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11. 发明申请

WO1997029756A1 METHOD OF TREATING OTITIS MEDIA WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯及相关化合物处理脂肪介质的方法
公开(公告)号：WO1997029756A1
公开(公告)日：1997-08-21
申请号：PCT/US1997002299
申请日：1997-02-14
申请人： INSPIRE PHARMACEUTICALS, INC. , DRUTZ, David, J. , RIDEOUT, Janet, L. , JACOBUS, Karla, M.
发明人： INSPIRE PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： A61K31/7076 , A61K31/7072
摘要： A method of promoting drainage of congested middle ear fluid in a subject in need of such treatment is disclosed. The method comprises administering to the middle ear of the subject a uridine triphosphate such as uridine 5'-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to promote drainage of congested middle ear fluid by hydrating mucous secretions in the middle ear or by stimulating ciliary beat frequency in the middle ear or eustachian tube. The method is useful for treating patients afflicted with otitis media and other middle ear diseases, otitis externa, and inner ear diseases including Ménière's Disease. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal drops or spray), oral, inhaled by nebulization, topical, injected or suppository form.
摘要翻译：公开了一种在需要这种治疗的受试者中促进拥挤的中耳液的引流的方法。该方法包括向受试者的中耳施用尿苷三磷酸，例如尿苷5'-三磷酸（UTP），UTP的类似物或任何其它类似物，其量可有效地促进通过保湿粘液促进拥挤的中耳液的引流中耳分泌物或通过刺激中耳或咽鼓管中的睫状肌搏动频率。该方法可用于治疗患有中耳炎和其他中耳疾病，外耳炎和内耳疾病（包括梅尼埃病）的患者。还公开了药物制剂及其制备方法。给药方法包括任何液体悬浮液（包括滴鼻剂或喷雾剂），口服，通过雾化，局部，注射或栓剂形式吸入。

12. 发明申请

WO0145691A3 METHOD OF TREATING GASTROINTESTINAL TRACT DISEASE WITH PURINERGIC RECEPTOR AGONISTS 审中-公开
标题翻译：用纯化受体激动剂治疗胃肠疾病的方法
公开(公告)号：WO0145691A3
公开(公告)日：2002-04-18
申请号：PCT/US0035439
申请日：2000-12-22
申请人： INSPIRE PHARMACEUTICALS INC , YERXA BENJAMIN R , RIDEOUT JANET L , PENDERGAST WILLIAM , SHAVER SAMMY R , ZHANG ZHEN , PETERSON WARD M , COWLEN MATHEW
发明人： YERXA BENJAMIN R , RIDEOUT JANET L , PENDERGAST WILLIAM , SHAVER SAMMY R , ZHANG ZHEN , PETERSON WARD M , COWLEN MATHEW
IPC分类号： C07H19/048 , A61K9/02 , A61K31/00 , A61K31/706 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7084 , A61K45/00 , A61P1/00 , A61P1/02 , A61P1/04 , A61P1/10 , A61P1/12 , A61P31/10 , A61P43/00 , C07H19/10 , C07H19/20 , C07H19/207 , A61K31/70
CPC分类号： A61K31/7072 , A61K31/00 , A61K31/7068 , A61K31/7084
摘要： The invention provides a method of regulating water and mucin secretions and fluid transport in the gastrointestinal tract. The invention also provides a method for treating a gastrointestinal disease in which the mucosal barrier of the gastrointestinal system is impaired. The invention additionally provides a method for correcting disorders of fluid secretion or absorption in the gastrointestinal system. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor agonist, in an amount effective to regulate water and mucin secretions or to correct abnormal fluid transport in the gastrointestinal tract. The pharmaceutical composition used in this invention comprises a P2Y purinergic receptor agonist such as uridine 5'-diphosphate (UDP), uridine 5'-triphosphate (UTP), cytidine 5'-diphosphate (CDP), cytidine 5'-triphosphate (CTP), adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), and their analogs; and dinucleotide polyphosphate compounds of general Formula (IV). Said compound is prepared in an oral form, an injectable form, or a suppository form, and administered to a patient.
摘要翻译：本发明提供调节胃肠道中水分和粘蛋白分泌物和液体输送的方法。本发明还提供了一种治疗消化道疾病的方法，其中胃肠系统的粘膜屏障受损。本发明另外提供了一种校正胃肠系统中的流体分泌或吸收紊乱的方法。该方法包括向患者施用含有嘌呤能P2Y受体激动剂的药物组合物，其量可有效调节水和粘蛋白分泌物或纠正在胃肠道中的异常流体转运。用于本发明的药物组合物包含P2Y嘌呤能受体激动剂如尿苷5'-二磷酸（UDP），尿苷5'-三磷酸（UTP），胞苷5'-二磷酸（CDP），胞苷5'-三磷酸（CTP），腺苷5'-二磷酸（ADP），腺苷5'-三磷酸（ATP）及其类似物; 和通式（IV）的二核苷酸多磷酸酯化合物。所述化合物以口服形式，可注射形式或栓剂形式制备，并施用于患者。

13. 发明申请

WO9834942A2 CERTAIN DINUCLEOTIDES AND THEIR USE AS MODULATORS OF MUCOCILIARY CLEARANCE AND CILIARY BEAT FREQUENCY 审中-公开
标题翻译：某些蛋白质及其作为微粒间隔和半球形频率的调制器使用
公开(公告)号：WO9834942A2
公开(公告)日：1998-08-13
申请号：PCT/US9802702
申请日：1998-02-06
申请人： INSPIRE PHARMACEUTICALS INC , PENDERGAST WILLIAM , YERXA BENJAMIN R , RIDEOUT JANET L , SIDDIQI SUHAIB M
发明人： PENDERGAST WILLIAM , YERXA BENJAMIN R , RIDEOUT JANET L , SIDDIQI SUHAIB M
IPC分类号： C07H19/207 , A61K9/00 , A61K31/7084 , A61P11/00 , A61P27/02 , A61P27/16 , A61P43/00 , C07H19/10 , C07H19/20 , C07H21/00 , C07H
CPC分类号： C07H19/10 , A61K9/0048 , C07H19/20 , C07H21/00
摘要： The present invention relates to certain novel dinucleotides and formulations thereof which are highly selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. They are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, PCD, cystic fibrosis, as well as prevention of pneumonia due to immobility. Furthermore, because of their general ability to clear retained mucus secretions and stimulate ciliary beat frequency, the compounds of the present invention are also useful in the treatment of sinusitis, otitis media and nasolacrimal duct obstruction. They are also useful for treatment of dry eye disease and retinal detachment.
摘要翻译：本发明涉及作为P2Y2和/或P2Y4嘌呤能受体的高选择性激动剂的某些新型二核苷酸及其制剂。它们可用于治疗慢性阻塞性肺疾病如慢性支气管炎，PCD，囊性纤维化，以及由于不动而预防肺炎。此外，由于其清除保留的粘液分泌物和刺激睫状肌痉挛频率的一般能力，本发明的化合物也可用于治疗鼻窦炎，中耳炎和鼻泪管阻塞。它们也可用于治疗干眼症和视网膜脱离。

14. 发明申请

WO0030629A3 METHOD OF PROMOTING CERVICAL AND VAGINAL SECRETIONS 审中-公开
标题翻译：促进宫颈和阴道分泌的方法
公开(公告)号：WO0030629A3
公开(公告)日：2001-06-07
申请号：PCT/US9927634
申请日：1999-11-19
申请人： INSPIRE PHARMACEUTICALS INC , PENDERGAST WILLIAM , SHAVER SAMMY R , DRUTZ DAVID J , RIDEOUT JANET L
发明人： PENDERGAST WILLIAM , SHAVER SAMMY R , DRUTZ DAVID J , RIDEOUT JANET L
IPC分类号： C07H19/10 , A61K31/00 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7084 , A61P15/02 , C07H19/20 , C07H19/207 , C07H21/00
CPC分类号： C07H21/00 , A61K31/00
摘要： The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y2, and/or P2Y4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable purinergic receptor agonists include nucleotide triphosphates such as uridine 5-triphosphate, cytidine 5'-triphosphate and adenosine 5'-triphosphate; dinucleotide polyphosphates such as P , P -di(uridine-5') tetraphosphate; and their analogs. These purinergic receptor agonists are useful in stimulating cervical and vaginal secretions and treating vaginal dryness in mammals.
摘要翻译：本发明提供了通过用P2Y2和/或P2Y4嘌呤能受体激动剂治疗来刺激哺乳动物的宫颈和阴道分泌物的方法。讨论了与绝经，化疗和各种疾病状态相关的阴道干燥的治疗以及外阴疼痛的治疗。合适的嘌呤能受体激动剂包括三磷酸核苷酸，如五磷酸尿苷，胞苷5'-三磷酸和腺苷5'-三磷酸; 二磷酸二核苷酸如P 1，P 4 - 二（尿苷-5'）四磷酸; 及其类似物。这些嘌呤能受体激动剂可用于刺激宫颈和阴道分泌物并治疗哺乳动物的阴道干燥。

15. 发明申请

WO1998019685A1 METHOD OF TREATING BRONCHITIS WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯和相关化合物处理BRONCHITIS的方法
公开(公告)号：WO1998019685A1
公开(公告)日：1998-05-14
申请号：PCT/US1997018766
申请日：1997-10-21
申请人： INSPIRE PHARMACEUTICALS, INC. , SHAFFER, Christy, L. , BOUCHER, Richard, C. , RIDEOUT, Janet, L. , JACOBUS, Karla, M.
发明人： INSPIRE PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： A61K31/7076 , A61K31/7072
摘要： A method of promoting clearance of retained mucous secretions in the bronchi, bronchioles and small terminal airways of a subject in need of such treatment is disclosed. The method comprises administering to the bronchi of the subject a uridine phosphate such as uridine 5'Îtriphosphate (UTP), or P1,P4-di(uridine-5Î) tetraphosphate (U2P4), an analog of UTP, or any other analog, in an amount effective to promote mucociliary clearance and/or cough clearance of retained fluid in the bronchi, bronchioles and small terminal airways. Methods of administering the same would include; aerosol inhalation, any liquid suspension (including nasal drops or spray), oral form (liquid or pill), injected, intra-operative instillation or suppository form.
摘要翻译：公开了一种促进需要这种治疗的受试者的支气管，细支气管和小型终端气道中保留的粘液分泌物的清除的方法。该方法包括向受试者的支气管施用尿苷磷酸酯，例如尿苷5'-三磷酸（UTP）或P1，P4-二（尿苷-5α）四磷酸（U2P4），UTP的类似物或任何其它类似物，有效促进支气管，细支气管和小型终端气道中保留液体的粘膜纤毛清除和/或咳嗽清除的量。其施用方法包括：气溶胶吸入，任何液体悬浮液（包括滴鼻剂或喷雾剂），口服形式（液体或药丸），注射液，手术液中滴注或栓剂形式。

17. 发明申请

WO9735591A2 METHOD OF TREATING CILIARY DYSKINESIA WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯及相关化合物处理胆固醇的方法
公开(公告)号：WO9735591A2
公开(公告)日：1997-10-02
申请号：PCT/US9705101
申请日：1997-03-27
申请人： INSPIRE PHARMACEUTICALS INC , JACOBUS KARLA M , YERXA BEN , PENDERGAST WILLIAM , BOUCHER RICARD C JR , RIDEOUT JANET L , DRUTZ DAVID J , JAMES MICHAEL K , STUTTS MONROE JACKSON , GEARY CARY , LAZAROWSKI EDWARDO R
发明人： JACOBUS KARLA M , YERXA BEN , PENDERGAST WILLIAM , BOUCHER RICARD C JR , RIDEOUT JANET L , DRUTZ DAVID J , JAMES MICHAEL K , STUTTS MONROE JACKSON , GEARY CARY , LAZAROWSKI EDWARDO R
IPC分类号： C07H19/10 , A61K9/06 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/70 , A61K31/00 , A61K31/505 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61P11/00 , A61P13/00 , A61P15/00 , A61P27/00 , A61P27/02 , A61P27/16 , A61P37/00 , A61P37/04 , C07H19/20 , C07H21/02
CPC分类号： A61K31/7076 , A61K31/7072
摘要： A method of stimulating ciliary beat frequency in a subject in need of such treatment is disclosed. The method comprises administering to the airways, ears, eyes, or genito-urinary tract of the subject a triphosphate nucleotide such as uridine 5'-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to stimulate ciliary beat frequency. This method is useful for treating patients afflicted with ciliary dyskinesia, Kartagener's syndrome, or any other disease involving dysfunction of ciliary movement, such as male infertility caused by impairment of propulsion of the spermatozoa or immune deficiency caused by impairment of ciliary movement in neutrophils or macrophages. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal spray or nasal or eye drops), oral, inhaled by nebulization, topical, injected, suppository, intra-operative by instillation or application, or ex vivo direct application to spermatozoa.
摘要翻译：公开了一种在需要这种治疗的受试者中刺激睫状肌搏动频率的方法。该方法包括向受试者的气道，耳朵，眼睛或生殖泌尿道施用有效刺激的量的三磷酸核苷酸，例如尿苷5'-三磷酸（UTP），UTP类似物或任何其他类似物睫毛拍频。该方法可用于治疗患有睫状肌运动障碍，Kartagener综合征或涉及睫状肌运动功能障碍的任何其他疾病，例如由嗜中性粒细胞或巨噬细胞的睫状肌运动损伤引起的精子推进或免疫缺陷引起的男性不育症。还公开了药物制剂及其制备方法。给药方法包括任何液体悬浮液（包括鼻喷雾或鼻腔或滴眼液），口服，通过雾化吸入，局部注射，注射，栓剂，通过滴注或施用手术，或离体直接施用于精子。

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