Co-crystallization of hemp oil constituents and assessment for bioaccessibility using the TIM-1 in vitro gastrointestinal digestion model

使用 TIM-1 体外胃肠消化模型共结晶大麻油成分并评估生物可及性

• 批准号: 518092-2017
• 负责人: Rogers, Michael
• 金额: $ 1.82万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=640239
• 关键词: Co; crystallization; hemp; oil; constituents

In Canada, cannabis may be prescribed as a physician-recommended herbal therapy. While cannabis is typicallysmoked, inhalation of burned dry plant matter has obvious inherent health risks. Oral administration offersseveral key advantages, including elimination of pulmonary health risks and more accurate dosing of activeingredients such as THC and CBD. Oral administration does, however, suffer certain shortcomings andchallenges as well. Bioavailability is defined as the proportion of a drug or other substance that enterscirculation when introduced into the body and so is able to have an active effect. This is therefore an importantproperty to assess when developing cannabis formulations for oral administration. Research has thus far shownthat extensive liver metabolism reduces the oral bioavailability of THC to roughly 2-14%, while inhalation ofmarijuana smoke offers a systemic bioavailability generally ranging between 10-35%. Others have reportedTHC bioavailability after oral ingestion to be approximately 6% compared to 25% after smoking. The goal ofour current research project is to develop novel formulations of cannabinoids in an effort to improve oralbioavailability. Assessing for bioavailability poses some serious challenges, as human or animal subjects arerequired and plasma samples must be drawn. The TIM-1 simulated in vitro gastrointestinal digestion modeldeveloped by TNO in the Netherlands is an advanced dissolution model with high correlation to in vivo testingand has been validated for use in drug delivery testing. Novel formulations can be assessed for bioavailabilityin a quick and cost-effective manner without the need for ethical approval when dealing with human or animaltest subjects. This will allow rapid assessments of formulations and significantly increase the rate of innovationand discovery into enhancing oral bioavailability of cannabinoids.

在加拿大，大麻可以作为医生推荐的草药疗法。虽然大麻通常是烟熏的，但吸入燃烧过的干植物物质具有明显的固有健康风险。口服给药提供了几个关键优势，包括消除肺部健康风险和更准确的活性成分剂量，如THC和CBD。然而，口服给药确实也存在某些缺点和挑战。生物利用度定义为药物或其他物质进入体内后进入循环的比例，因此能够产生积极的效果。因此，在开发口服给药的大麻制剂时，这是一个需要评估的重要特性。迄今为止的研究表明，广泛的肝脏代谢将THC的口服生物利用度降低到大约2- 14%，而吸入大麻烟雾提供的全身生物利用度通常在10- 35%之间。其他人则认为口服THC后的生物利用度约为6%，而吸烟后为25%。我们目前的研究项目的目标是开发大麻素的新配方，以提高口服生物利用度。评估生物利用度带来了一些严重的挑战，因为需要人类或动物受试者并且必须采集血浆样本。荷兰TNO开发的TIM-1模拟体外胃肠道消化模型是一种先进的溶出模型，与体内试验高度相关，并已被验证可用于药物释放试验。新的制剂可以快速和成本效益的方式进行生物利用度评估，而不需要在处理人类或动物试验受试者时获得伦理批准。这将允许快速评估配方，并显着提高创新和发现的速度，以提高大麻素的口服生物利用度。