Animal model for chronic obstructive pulmonary disease and cystic fibrosis
    1.
    发明授权
    Animal model for chronic obstructive pulmonary disease and cystic fibrosis 有权
    慢性阻塞性肺疾病和囊性纤维化的动物模型

    公开(公告)号:US08952214B2

    公开(公告)日:2015-02-10

    申请号:US12823243

    申请日:2010-06-25

    IPC分类号: A01K67/027

    摘要: A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel β subunit, wherein said promoter construct directs expression of the epithelial sodium channel β subunit in lung epithelial cells of said animal, and wherein said transgenic mammal has increased lung mucus retention as compared to the corresponding wild-type mammal. The animal is useful in screening compounds for activity in treating lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

    摘要翻译: 描述了一种非人类转基因哺乳动物,其基因组包含与编码上皮钠通道的异源DNA可操作地连接的启动子构建体; 亚基,其中所述启动子构建体指导上皮钠通道的表达; 所述动物的肺上皮细胞中的亚单位,并且其中所述转基因哺乳动物与相应的野生型哺乳动物相比具有增加的肺粘液滞留。 该动物用于筛选用于治疗肺部疾病如囊性纤维化和慢性阻塞性肺疾病的活性的化合物。

    ANIMAL MODEL FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND CYSTIC FIBROSIS
    2.
    发明申请
    ANIMAL MODEL FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND CYSTIC FIBROSIS 有权
    慢性阻塞性肺疾病和CYSTIC FIBROSIS的动物模型

    公开(公告)号:US20100263064A1

    公开(公告)日:2010-10-14

    申请号:US12823243

    申请日:2010-06-25

    IPC分类号: A01K67/027 A61K49/00

    摘要: A nonhuman transgenic mammal is described whose genome comprises a promoter construct operably linked to a heterologous DNA encoding an epithelial sodium channel β subunit, wherein said promoter construct directs expression of the epithelial sodium channel β subunit in lung epithelial cells of said animal, and wherein said transgenic mammal has increased lung mucus retention as compared to the corresponding wild-type mammal. The animal is useful in screening compounds for activity in treating lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease.

    摘要翻译: 描述了一种非人类转基因哺乳动物,其基因组包含与编码上皮钠通道的异源DNA可操作地连接的启动子构建体; 亚基,其中所述启动子构建体指导上皮钠通道的表达; 所述动物的肺上皮细胞中的亚单位,并且其中所述转基因哺乳动物与相应的野生型哺乳动物相比具有增加的肺粘液滞留。 该动物用于筛选用于治疗肺部疾病如囊性纤维化和慢性阻塞性肺疾病的活性的化合物。

    Method of detecting lung disease
    6.
    发明授权
    Method of detecting lung disease 失效
    检测肺部疾病的方法

    公开(公告)号:US06133247A

    公开(公告)日:2000-10-17

    申请号:US776772

    申请日:1997-01-22

    摘要: A method of facilitating the obtaining of a mucus sample from at least one lung of a subject comprises administering to at least one lung of the subject, in an amount effective to hydrate lung mucous secretions and/or stimulate cilia beat frequency therein, uridine 5'-triphosphate, an active analog thereof, or a pharmaceutically acceptable salt of either thereof, and, optionally, concurrently administering to said at least one lung a physiologically acceptable salt in an amount effective to hydrate lung mucus secretions therein. A sputum or mucus sample is then collected from said at least one lung, which sample can then be analyzed for lung disease. Pharmaceutical compositions useful for carrying out the method comprise UTP or a salt thereof, alone or in combination with a physiologically acceptable salt, or a pharmaceutically acceptable salt of either thereof. The composition may be a liquid/liquid suspension composition or a dry powder composition.

    摘要翻译: PCT No.PCT / US96 / 12377 Sec。 371日期1997年1月22日 102(e)1997年1月22日PCT PCT 1996年7月24日PCT公布。 出版物WO97 / 05195 日期1997年2月13日有助于从受试者的至少一个肺获得粘液样品的方法包括以有效水合肺粘膜分泌物和/或刺激纤毛节拍频率的剂量给予受试者的至少一个肺 其中,尿苷5'-三磷酸,其活性类似物或其任何一种的药学上可接受的盐,并且任选地,以有效水合物中的肺粘液分泌物的量向所述至少一个肺施用生理上可接受的盐。 然后从所述至少一个肺采集痰液或粘液样品,然后可以分析该样品的肺部疾病。 可用于实施该方法的药物组合物包含UTP或其盐单独或与其生理学上可接受的盐或其药学上可接受的盐组合。 组合物可以是液体/液体悬浮液组合物或干粉组合物。

    Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs
    9.
    发明授权
    Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs 失效
    用于治疗气道疾病和用于输送气道药物的化合物和方法

    公开(公告)号:US07666395B2

    公开(公告)日:2010-02-23

    申请号:US10992454

    申请日:2004-11-18

    摘要: Chronic obstructive airway diseases are treated by administering an osmotically active compound such as a salt, sugar, sugar alcohol, or organic osmolyte to the afflicted airway surface. The compound may be administered as a liquid or dry powder aerosol formulation. Diseases that can be treated by the method include cystic fibrosis, chronic bronchitis, and ciliary dyskinesia. The formulations of the invention can also be used in conjunction with other active agents such as bronchodilators, sodium channel blockers, antibiotics, enzymes, or purinoceptor agonists on airway surfaces.

    摘要翻译: 通过向受影响的气道表面施用渗透性活性化合物如盐,糖,糖醇或有机渗透液来治疗慢性阻塞性气道疾病。 化合物可以作为液体或干粉气溶胶制剂施用。 可以通过该方法治疗的疾病包括囊性纤维化,慢性支气管炎和睫状肌运动障碍。 本发明的制剂还可以与气道表面上的其它活性剂如支气管扩张剂,钠通道阻断剂,抗生素,酶或嘌呤受体激动剂联合使用。

    Methods of hydrating mucosal surfaces
    10.
    发明授权
    Methods of hydrating mucosal surfaces 失效
    保湿粘膜表面的方法

    公开(公告)号:US07056524B2

    公开(公告)日:2006-06-06

    申请号:US09789256

    申请日:2001-02-20

    IPC分类号: A61F13/02 A61K31/4965

    摘要: A method of hydrating nasal airway surfaces in a subject in need of such treatment comprises topically applying a sodium channel blocker to a nasal airway surface of the subject in an amount effective to inhibit the reabsorption of water by the surface. The channel blocker may be a pyrazinoylguanidine sodium channel blocker, such as benzamil, phenamil, amiloride, or a pharmaceutically acceptable salts thereof. The method may further comprise the step of topically applying a P2Y2 receptor agonist to a nasal airway surface of the subject in an amount effective to stimulate chloride secretion by the nasal airway surface. In a preferred embodiment, the sodium channel blocker is a covalent conjugate of a pyrazinoylguanidine sodium channel blocker and a non-absorbable carrier moiety (e.g., albumin, polyethylene glycol). Such compounds may also be administered to other mucosal surfaces where it is desired to inhibit the reabsorption of water.

    摘要翻译: 在需要这种治疗的受试者中水合鼻气道表面的方法包括以有效抑制表面再吸收水的量将钠通道阻滞剂局部施用于受试者的鼻气道表面。 通道阻断剂可以是吡嗪酰胍胍钠通道阻滞剂,例如苯甲酰胺,苯胺胺,阿米洛利或其药学上可接受的盐。 该方法可以进一步包括以有效刺激鼻气道表面的氯化物分泌的量将P2Y2受体激动剂局部施用于受试者的鼻气道表面的步骤。 在优选的实施方案中,钠通道阻断剂是吡嗪酰基胍钠通道阻滞剂和不可吸收载体部分(例如白蛋白,聚乙二醇)的共价缀合物。 也可以将这样的化合物施用于需要抑制水的再吸收的其它粘膜表面。