Device for Acamprosate Transcutaneous Delivery to Reduce Alcohol Consumption.

描述（由申请人提供）：酒精依赖是一种慢性疾病，具有遗传，心理和环境基础。酒精的社会影响是广泛的;据估计，在美国有1760万人滥用或依赖酒精。（Grant等人，2004）。酒精依赖被认为是美国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。总的来说，仅在美国，酗酒的年度经济成本就超过1850亿美元（Harwood，2000年）。在过去的十年中，人们对使用药物治疗酒精依赖的兴趣越来越大（Swift，1999; Anton和Swift，2003）。阿坎酸/Campral（乙酰高牛磺酸钙）是一种新的，FDA批准的药物，可促进戒酒，并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，因为只有11%的口服剂量被吸收。此外，低生物利用度需要每天三次给药，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。在乙醇自我给药的动物模型中，阿坎酸治疗已显示减少乙醇摄入（Boismare等人，1984）而不是食物或液体摄入（Czachowski等人，2001; Naassila等人，1998），这是动物模型的优选给药方法，因此消除了口服生物利用度和胃肠副作用的问题。如果胃肠外给药方法可以应用于人类，它可以显着提高阿坎酸的有效性。来自学术界和工业界的一个独特的跨学科专家团队将在第一阶段开发一种可穿戴的非侵入性输送设备，该设备对阿坎酸具有较高的预期生物利用度。通过经由中空微针阵列非侵入性地通过皮肤的角质层从加压储器释放受控量的阿坎酸溶液，阿坎酸将绕过皮肤屏障，并经由皮肤毛细血管直接扩散到血液中。因此，预期阿坎酸的经皮、流量调节、微针阵列增强的递送将其较差的（11%）口服生物利用度增加高达5-7倍，使得在大鼠模型研究中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.