- 學位論文
新型注射型COX-2 NSAIDs之研發
Design and Development of Novel Injectable COX-2 NSAIDs
摘要
中文摘要 非固醇類抗發炎藥(NSAID)最常用於急性和慢性疼痛的治療，臨床上也用於發炎反應的治療。NSAIDs大致可分為傳統(traditional) NSAIDs 及 COX-2 specific NSAIDs，其中COX-2 specific NSAIDs的胃腸道副作用較少。目前臨床上的COX-2 NSAIDs僅有一種可透過靜脈注射及肌肉注射來使用。 注射型COX-2 NSAIDs 的研發，將增進臨床治療上的方便性，進而有助於病患的治療。本研究的主旨在於進行valdecoxib pentanamide 與 valdeoxib hepatanamide兩種新型的注射型COX-2 NSAIDs的藥效研究，藉著「大白鼠」、「小白鼠」、「天竺鼠」的動物實驗，探討經由「靜脈注射」及「肌肉注射」兩種不同的給藥途徑，進行dose-ranging studies，觀察各自產生的抗發炎（水腫）及止痛的作用。 實驗結果發現， 新合成的valdecoxib pentanamide 及valdecoxib hepatanamide，圴具有抗發炎的活性。依據 dose-response curve，隨著藥物濃度的增加，抗發炎的作用愈顯著 (216μmol/kg > 108μmol/kg > 54μmol/kg > 27μmol/kg) 。在止痛作用方面，valdecoxib pentanamide 及valdecoxib hepatanamide,圴具有止痛作用(216μmol/kg > 108μmol/kg > 54μmol/kg > 27μmol/kg) 。 關鍵詞：非類固醇抗發炎藥，前列腺素E2，第二型環氧化酵素抑制劑
並列摘要
ABSTRACT Nonsteroidal anti-inflammatory drugs (NSAIDs) have been most commonly available in the treatment of acute and chronic pain, and so has been in the inflammatory response. NSAIDs generally can be divided into two types: traditional and COX-2-specific. The latter is with fewer side effects on the whole body, and only one of its kinds is clinically available for intravenous and intamuscular infections. The research and development of injectable COX-2 NSAIDs will be conducive to the clinical treatment. The pharmacodynemics study was to investigate the two sorts of the novel injectable NSAIDs: valdecoxib pentanamide and valdeoxib hepatanamide. In the dose-ranging study using SD rats, ICR mice and Guinea pigs, the injection routes were intravenous and intamuscular for the effects of anti-inflammation and analgesia. The results indicated that the effects of anti-inflammatory of valdecoxib pentanamide and valdecoxib hepatanamide were obvious. According to the dose-dependent curve, the effect of anti-inflammatory is more apparent as the thickness of medicine is increase(216μmol/kg > 108μmol/kg > 54μmol/kg > 27μmol/kg). The effects of relieving pain of valdecoxib pentanamide 、valdecoxib hepatanamide and parecoxib were obvious(216μmol/kg > 108μmol/kg > 54μmol/kg > 27μmol/kg). Keywords: Nonsteroidal anti-inflammatory drugs (NSAIDs)， prostaglandin E2 ，cyclooxygenase-2 inhibiters.