D9-THC for Marijuana Addiction

说明(申请人提供)：？9-四氢大麻酚(？9-THC)已被证明可以缓解大麻戒断症状，因此具有治疗大麻类药物依赖的潜力。然而，口服给药的生物利用度很差，而且变化很大。此外，它还要求一天几次给药。提高生物利用度和/或减少给药频率的制剂有望提高9-THC的治疗效果。 在第一阶段，我们的技术目标是基于生物制药原理开发改进的口服和/或仓库制剂？9-THC，并选择具有可接受的体外控制释放特性的稳定配方。？9-THC是非常疏水和对氧敏感的，这两个因素都是制造口服生物利用度和稳定性的制剂的挑战。利用专有的SuperFluid(Tm)技术，我们建议将9-THC包裹在可生物降解的聚合物纳米球中，使其能够转运到胃中，改善其稳定性并提高生物利用度。 在第二阶段，我们将对开发的配方进行药理学、毒理学和药代动力学评价(S)。我们还将提供GMP放大的稳定剂型，在动物模型和/或人类中具有可接受的体外和体内生物利用度。 说明：开发的9-THC控释口服制剂将用于治疗大麻依赖和戒断症状、癌症疼痛、与癌症化疗和艾滋病恶病质或消瘦相关的恶心。

DESCRIPTION (provided by applicant): ?9-tetrahydrocannabinol (?9-THC) has been shown to alleviate marijuana withdrawal symptoms and thus has potential for treating cannabinoid dependence. However, the bioavailability of ?9-THC administered orally is poor and variable. In addition, it also requires drug administration several times a day. Formulations to improve bioavailability and/or to reduce dosing frequency would be expected to improve the therapeutic effectiveness of ?9-THC. In Phase I, our technical objectives are to develop improved oral and/or depot formulations of ?9-THC based on biopharmaceutical rationale, and select a formulation that is stable with acceptable in vitro controlled release characteristics. ?9-THC is very hydrophobic and oxygen-sensitive, both factors that are challenges in making formulations that are orally bioavailable and stable. Utilizing proprietary SuperFluids(tm) technologies, we propose to encapsulate ?9-THC in biodegradable polymer nanospheres that will allow transport to the stomach, improve its stability and enhance bioavailability. In Phase II, we will carry out pharmacological, toxicological and pharmacokinetic evaluations of the developed formulation(s). We will also provide a GMP scale-up of a stable dosage form with acceptable in vitro and in vivo bioavailability in animal models and/or in humans. Narrative: The developed controlled release, oral formulation of ?9-THC will be commercialized for treating marijuana dependence and withdrawal symptoms, cancer pain, nausea associated with cancer chemotherapy and AIDS cachexia or wasting.