N-Acetylglucosamine Treatment of Osteoarthritis

N-乙酰氨基葡萄糖治疗骨关节炎

基本信息

批准号：
6691134
负责人：
YOSHITAKA ICHIKAWA
金额：
$ 10万
依托单位：
OPTIMER PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-15 至 2005-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6691134
关键词：
N acetylglucosamine antiarthritic agent arthritis therapy articular cartilage chondrocytes digital imaging drug design /synthesis /production hyaluronate laboratory rabbit morphometry nonhuman therapy evaluation osteoarthritis slow release drug synovial fluid

项目摘要

DESCRIPTION (provided by applicant): Osteoarthritis (OA) represents the most common joint disease, affecting approximately 40 million Americans. OA is a leading cause of severe activity limitations and disability. Therapies that definitively alter the course of the disease are not available. Pharmacologic management of OA is limited to pain control. Nonsteroidal anti-inflammatory drugs are widely used but are associated with significant adverse reactions. Oral glucosamine and chondroitin sulfate are consumed by a large number of patients. Although some studies suggest that this reduces the rate of joint space narrowing, this conclusion is not uniformly accepted. Viscosupplementation with hyaluronan acid or its derivatives has been approved as a therapy for patients with knee OA and clinical experience demonstrated excellent patient compliance. This establishes the need for second-generation products with improved efficacy towards symptom control and disease modification. The key advantage of intraarticular therapy is in the delivery of high local drug concentrations and a reduced risk for systemic adverse reactions. The following proposal is based on prior research to identify novel effective and safe approaches to this form of OA therapy. We observed chondroprotective activities of the glucosamine derivative,N-acetylglucosamine (GIcNAc). Intraarticular injections of aqueous solutions of GIcNAc in 6 rabbits with experimental OA demonstrated greater efficacy than hyaluronan in reducing not only joint inflammation but also cartilage degradation. Adverse reactions were not observed. Based on these findings we propose the hypothesis that intra articular administration of GIcNAc represents a novel, effective and safe approach to chondroprotection. The following aims will address this hypothesis: 1. Prepare formulations of GIcNAc and retention time in rodent joints. 2. Assess therapeutic efficacy of GIcNAc formulations in rabbits with experimentally induced OA. These studies have the potential to provide the basis for a safe and effective chondroprotective therapy for OA.

描述（由申请人提供）：骨关节炎（OA）代表了最常见的关节疾病，影响了约4000万美国人。 OA是严重活动限制和残疾的主要原因。明确改变疾病病程的疗法无法获得。 OA的药理学管理仅限于疼痛控制。非甾体类抗炎药被广泛使用，但与明显的不良反应有关。大量患者食用了口服葡萄糖胺和软骨素。尽管一些研究表明，这降低了关节空间的狭窄率，但该结论并不统一。透明质酸或其衍生物的粘质补充已被批准为膝关节OA患者的一种疗法，临床经验表明患者的依从性很高。这确定了对第二代产品的需求，其功效提高了症状控制和疾病的修饰。关节疗法的主要优势是递送高局部药物浓度和系统性不良反应的风险降低。以下建议基于先前的研究，以确定新型OA治疗的新型有效和安全的方法。我们观察到葡萄糖衍生物N-乙酰葡萄糖（GICNAC）的软骨保护活性。在6只兔子中，对GICNAC水溶液的关节内注射具有实验性OA的疗效比透明质酸不仅减少关节炎症，而且还要减少软骨降解。未观察到不良反应。根据这些发现，我们提出了以下假设：GICNAC的关节内给药代表了一种新型，有效且安全的软骨保护方法。以下目的将解决这一假设：1。准备GICNAC的配方和啮齿动物关节中的保留时间。 2。用实验诱导的OA评估GICNAC制剂在兔中的治疗功效。这些研究有可能为OA进行安全有效的软骨保护疗法提供基础。