Controlling Type 2 Diabetes with Proprietary Natural Extracts in Medical Foods

描述(申请人提供)：2型糖尿病(T2D)是一种炎症性疾病，在美国有2600万人(11%)，预计到2050年将有超过30%的美国成年人受到影响。T2D每年的经济成本超过2000亿美元。患有T2D的患者由于胰岛素产量低、胰岛素转运不良或细胞抵抗而患上高血糖。 胰岛素可导致视网膜病变、肾病、神经病变和心血管疾病。T2D的慢性炎症是疾病进展的主要原因。在美国，肥胖也是以流行的速度发生的，它会导致慢性低度炎症，从而导致T2D。尽管目前的治疗方法可以维持血糖控制并减少胰岛素抵抗，但与慢性炎症和器官损伤相关的并发症促使人们努力开发针对炎症级联反应中特定步骤的药物。我们认为，天然产品有可能填补这一治疗空白，同时减少潜在的副作用和需要二次治疗的代偿性反应。为了对抗导致T2D及其并发症的炎症，我们开发了两种天然衍生产品：WG0401和WG0301，这两种产品都是专利的、新颖的、特征良好的、生物活性增强的天然提取物。这两种提取物都显示出强大的抗炎作用，这在基于人体细胞的生物测试和动物炎症模型中得到了证明。在之前进行的临床试验中，这两种药物在人体内的耐受性都很好，通常可以被认为是安全的(GRAS)，从而减少了将产品推向市场的时间和费用。我们的目标是开发一种新颖、有效的医疗食品，以控制导致T2D的慢性炎症的潜在病理影响。目的1.证实WG0401和WG0301可减少导致T2D并发症的炎性代谢产物。在T2D中起主要作用的T2D和炎性代谢物的生物标记物将在使用WG0401或WG0301治疗的T2D的Zucker糖尿病肥胖大鼠动物模型中进行测量。成功的结果将在治疗组内或对照组和接受治疗的大鼠之间显示统计上的显著改善。目的2.我们认为抑制炎症基因减少了目标1中测量到的代谢物。我们将测量WG0401和WG0301下调炎症和T2D的炎性代谢物和/或生物标志物基因产物之间的相关性，并与二甲双胍和布洛芬进行比较。对正相关性的观察支持了我们的假设。目的3.根据以上结果选择两种产品中的一种进行进一步开发。该项目的成功完成将使我们能够设计和启动第二阶段的临床试验，使用我们的一种提取物来管理T2D。

DESCRIPTION (provided by applicant): Type 2 Diabetes (T2D) is an inflammatory disease affecting 26 million people in the US (11%) and is predicted to affect more than 30% of adults in the US by 2050. The economic cost of T2D is over $200 billion a year. People with T2D suffer from hyperglycemia due to low insulin production, poor transport of insulin, or cellular resistance to insulin which can lead to retinopathy, nephropathy, neuropathy, and cardiovascular disease. Chronic inflammation in T2D is a leading cause of the progression of the disease. Obesity, also occurring at epidemic rates in the US, causes chronic low- grade inflammation thus contributing to T2D. Although current therapies can maintain glucose control and reduce insulin resistance, complications associated with chronic inflammation and organ damage drive the effort to develop drugs targeting specific steps in the inflammatory cascade. We propose that natural products have the potential to fill this therapeutic gap while reducing potential side effects and compensatory reactions requiring secondary treatment. To combat the inflammation that leads to T2D and its complications, we developed two naturally derived products: WG0401 and WG0301, which are both proprietary, novel, well-characterized, bioactive enhanced natural extracts. Both extracts show strong effects against inflammation as demonstrated in human cell-based bioassays and animal models of inflammation. Both were well tolerated in humans in previously conducted clinical trials and can be Generally Regarded As Safe (GRAS), thereby reducing the time and expense of getting a product to market. Our goal is to develop a novel, effective medical food to control the underlying pathological effects of chronic inflammation that lead to T2D. Aim 1. Demonstrate that WG0401 and WG0301 will reduce inflammatory metabolites that lead to complications of T2D. Biomarkers for T2D and inflammatory metabolites that play major roles in T2D will be measured in the Zucker diabetic fatty rat animal model of T2D that have been treated with WG0401 or WG0301. Successful results will show statistically significant improvement within treatment groups or between controls and treated rats. Aim 2. We propose that the inhibition of inflammatory genes reduces the metabolites measured in Aim 1. We will measure correlations between the gene products and the down-regulation of inflammatory metabolites and/or biomarkers for inflammation and T2D by WG0401 and WG0301 and compare to metformin and ibuprofen. Observation of a positive correlation supports our hypothesis. Aim 3. Select one of the two products based on the results above for further development. Successful completion of this project will enable the design and initiation of clinical trials in Phase II, using one of our extracts for the management of T2D.