Controlling Type 2 Diabetes with Proprietary Natural Extracts in Medical Foods

利用医疗食品中的专有天然提取物控制 2 型糖尿病

• 批准号: 8518837
• 负责人: Alexander M Gosslau
• 金额: $ 29.32万
• 依托单位: WELLGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518837
• 关键词: Address; Adult; Advanced Glycosylation End Products; Adverse effects; Affect; Aging; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Biological Assay; Biological Factors; Biological Markers; Black Tea; Blood Glucose; CCL2 gene; Cardiovascular Diseases; Cells; Centers for Disease Control and Prevention (U.S.); Chronic; Clinical; Clinical Trials; Conduct Clinical Trials; Control Groups; Development; Disease; Disease Progression; Down-Regulation; Drug Targeting; E-Selectin; Epidemic; Fasting; Foundations; Gene Expression; Genes; Glycosylated hemoglobin A; Goals; Human; Hyperglycemia; IL8 gene; Ibuprofen; Inflammation; Inflammation Mediators; Inflammatory; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin-6; Isoprostanes; Kidney Diseases; Lead; Marketing; Measurement; Measures; Medical; Metformin; Modeling; Modification; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Non-Steroidal Anti-Inflammatory Agents; Obesity; Oranges; Organ; PTGS2 gene; Patients; Pharmaceutical Preparations; Phase; Pioglitazone; Play; Production; Property; Proteins; Pyruvaldehyde; Rattus; Reaction; Reactive Oxygen Species; Regimen; Renal function; Resistance; Retinal Diseases; Risk; Role; TNF gene; Theaflavins; Therapeutic; Time; Toxic effect; Triglycerides; Vascular Cell Adhesion Molecule-1; aging population; base; blood glucose regulation; combat; cost; design; diabetic; economic cost; efficacy testing; heart function; liver function; medical food; novel; public health relevance; receptor; response

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.

描述（由申请人提供）：2型糖尿病（T2 D）是一种炎症性疾病，影响美国2600万人（11%），预计到2050年将影响美国30%以上的成年人。T2 D的经济成本每年超过2000亿美元。2型糖尿病患者由于胰岛素产生低、胰岛素转运差或细胞抵抗而患有高血糖症 导致视网膜病变、肾病、神经病变和心血管疾病的胰岛素。T2 D中的慢性炎症是疾病进展的主要原因。肥胖症在美国也以流行率发生，引起慢性低度炎症，从而促成T2 D。尽管目前的治疗方法可以维持血糖控制并降低胰岛素抵抗，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。 我们认为天然产物有潜力填补这一治疗空白，同时减少潜在的副作用和需要二次治疗的代偿反应。为了对抗导致T2 D及其并发症的炎症，我们开发了两种天然衍生产品：WG 0401和WG 0301，它们都是专有的，新颖的，充分表征的，生物活性增强的天然提取物。两种提取物都显示出强烈的抗炎作用，如在基于人类细胞的生物测定和炎症动物模型中所证明的。在先前进行的临床试验中，这两种药物在人体中的耐受性良好，并且可以被普遍认为是安全的（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的，有效的医疗食品，以控制导致T2 D的慢性炎症的潜在病理作用。目标1.证明WG 0401和WG 0301将减少导致T2 D并发症的炎性代谢物。将在已接受WG 0401或WG 0301治疗的Zucker糖尿病肥胖大鼠T2 D动物模型中测量T2 D的生物标志物和在T2 D中起主要作用的炎性代谢物。成功的结果将显示治疗组内或对照组和治疗组大鼠之间的统计学显著改善。目标二。我们认为，抑制炎症基因减少了目标1中测量的代谢物。我们将通过WG 0401和WG 0301测量基因产物与炎症代谢物和/或炎症和T2 D生物标志物的下调之间的相关性，并与二甲双胍和布洛芬进行比较。正相关的观察支持我们的假设。目标3。根据上述结果选择两种产品之一进行进一步开发。 该项目的成功完成将使II期临床试验的设计和启动成为可能，使用我们的一种提取物来管理T2 D。