AEROSOLIZED TYLOXAPOL IN THE AIRWAYS DISEASE OF CYSTIC FIBROSIS

雾化泰洛沙泊治疗气道囊性纤维化疾病

• 批准号: 6304927
• 负责人: BRUCE C MARSHALL
• 金额: $ 0.16万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6304927
• 关键词: aerosols; bioassay; clinical research; cystic fibrosis; detergents; drug adverse effect; drug screening /evaluation; experimental designs; human subject; particle; volunteer

The production of thick, tenacious, purulent bronchial secretions is the hallmark of cystic fibrosis. These secretions are difficult to clear, obstruct the airway, and contribute greatly to the progression of obstructive lung disease by stagnating the inflammatory process within airways. This stagnation prolongs the exposure of the airway in patients with cystic fibrosis to harmful digestive enzymes and oxidizing radicals associated with the inflammatory response. The thickness of the secretions in patients with cystic fibrosis are due, in part, to the presence of DNA from the nuclei of degenerating inflammatory cells, particularly neutrophils. Another factor contributing to the tenacity of sputum is the presence of a network of cross-linked protein filaments made up of a protein called actin. An effective and inexpensive agent capable of "thinning" the airway secretions of patients with cystic fibrosis would be extremely useful, and this study is testing the hypothesis that tyloxapol can achieve this end. Tyloxapol is a dramatically effective mucolytic (mucous thinner) for cystic fibrosis secretions when tested in a test tube. Tyloxapol is also a powerful antioxidant, capable of scavenging injurious radicals produced in abundance in the airway of patients with cystic fibrosis. Finally, tyloxapol is a potent inhibitor of the production of inflammatory molecules by activated scavenger cells found in the airway secretions in patients with cystic fibrosis. The combination of these three activities is not found in any single, effective, inexpensive drug. This study is designed to develop the methods necessary to deliver aerosolized tyloxapol to the airway and to study the safety of the use of tyloxapol in normal subjects. A study is then planned to test the effectiveness of aerosolized tyloxapol in patients with cystic fibrosis.

囊性纤维化的特征是产生粘稠、坚韧的脓性支气管分泌物。 这些分泌物难以清除，阻塞气道，并通过停滞气道内的炎症过程而极大地促进阻塞性肺病的进展。 这种停滞使囊性纤维化患者的气道暴露于与炎症反应相关的有害消化酶和氧化自由基。 囊性纤维化患者分泌物的厚度部分是由于存在来自变性炎性细胞，特别是中性粒细胞的细胞核的DNA。另一个导致痰液韧性的因素是存在一种由肌动蛋白组成的交联蛋白丝网络。 一种有效而廉价的药物能够“稀释”囊性纤维化患者的气道分泌物将是非常有用的，这项研究正在测试泰洛沙泊可以达到这一目的的假设。泰洛沙泊是一种非常有效的粘液溶解剂（粘液稀释剂），用于在试管中测试囊性纤维化分泌物。 泰洛沙泊也是一种强大的抗氧化剂，能够清除囊性纤维化患者气道中大量产生的有害自由基。 最后，泰洛沙泊是囊性纤维化患者气道分泌物中发现的活化清道夫细胞产生炎症分子的有效抑制剂。 这三种活性的组合在任何单一的，有效的，廉价的药物中都找不到。本研究旨在开发将泰洛沙泊雾化吸入气道所需的方法，并研究正常受试者使用泰洛沙泊的安全性。 然后计划进行一项研究，以测试雾化泰洛沙泊在囊性纤维化患者中的有效性。