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1. 发明申请

US20080214490A1 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：US20080214490A1
公开(公告)日：2008-09-04
申请号：US12043845
申请日：2008-03-06
申请人： William Pendergast , Sammy Ray Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
发明人： William Pendergast , Sammy Ray Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
IPC分类号： A61K31/7076 , A61P15/02
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 agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.
摘要翻译：本发明提供了通过用P2Y2和/或P2Y4N4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。公开了合适的激动剂，例如UTP，CTP，ATP，二核苷酸及其类似物。

2. 发明授权

US07432252B1 Method of promoting cervical and vaginal secretions 有权
标题翻译：促进子宫颈和阴道分泌物的方法
公开(公告)号：US07432252B1
公开(公告)日：2008-10-07
申请号：US09531851
申请日：2000-03-20
申请人： William Pendergast , Sammy Ray Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
发明人： William Pendergast , Sammy Ray Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
IPC分类号： A61K31/70
CPC分类号： C07H21/00
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 agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.
摘要翻译：本发明提供了通过用P2Y2和/或P2Y4N4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。公开了合适的激动剂，例如UTP，CTP，ATP，二核苷酸及其类似物。

3. 发明授权

US06624150B2 Method of treating gastrointestinal tract disease with purinergic receptor agonists 失效
公开(公告)号：US06624150B2
公开(公告)日：2003-09-23
申请号：US09747777
申请日：2000-12-22
申请人： Benjamin R. Yerxa , Janet L. Rideout , William Pendergast , Sammy Ray Shaver , Zhen Zhang , Ward M. Peterson , Matthew Cowlen
发明人： Benjamin R. Yerxa , Janet L. Rideout , William Pendergast , Sammy Ray Shaver , Zhen Zhang , Ward M. Peterson , Matthew Cowlen
IPC分类号： A61K3170
CPC分类号： A61K31/7064 , A61K31/00 , A61K31/7048 , A61K31/7068 , A61K31/7072 , A61K31/7076 , 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.

4. 发明授权

US06420347B1 Method of treating ciliary dyskinesia with uridine triphosphates and related compounds 失效
标题翻译：用尿苷三磷酸和相关化合物治疗睫状肌运动障碍的方法
公开(公告)号：US06420347B1
公开(公告)日：2002-07-16
申请号：US09101840
申请日：1998-07-17
申请人： Karla M. Jacobus , Benjamin R. Yerxa , William Pendergast , Richard C. Boucher, Jr. , Janet L. Rideout , David J. Drutz , Michael K. James , Monroe Jackson Stutts , Cary Geary , Edwardo R. Lazarowski
发明人： Karla M. Jacobus , Benjamin R. Yerxa , William Pendergast , Richard C. Boucher, Jr. , Janet L. Rideout , David J. Drutz , Michael K. James , Monroe Jackson Stutts , Cary Geary , Edwardo R. Lazarowski
IPC分类号： A61K3170
CPC分类号： A61K31/70
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类似物或任何其它类似物睫毛拍频。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。

5. 发明授权

US06673779B2 Method of treating ciliary dyskinesia with dinucleoside polyphosphate compounds or UTP analogues 有权
标题翻译：用二核苷多磷酸盐化合物或UTP类似物治疗睫状肌运动障碍的方法
公开(公告)号：US06673779B2
公开(公告)日：2004-01-06
申请号：US10163804
申请日：2002-06-05
申请人： Karla M. Jacobus , Benjamin R. Yerxa , William Pendergast , Richard C. Boucher, Jr. , Janet L. Rideout , David J. Drutz , Michael K. James , Monroe Jackson Stutts , Cara Geary , Eduardo R. Lazarowski
发明人： Karla M. Jacobus , Benjamin R. Yerxa , William Pendergast , Richard C. Boucher, Jr. , Janet L. Rideout , David J. Drutz , Michael K. James , Monroe Jackson Stutts , Cara Geary , Eduardo R. Lazarowski
IPC分类号： A61K3170
CPC分类号： A61K31/7076 , A61K9/0048 , A61K31/70 , A61K31/7072 , C07H19/10 , C07H19/20 , C07H21/00
摘要： The present invention is directed to a method of stimulating ciliary beat frequency to promote mucociliary or cough clearance of retained mucus secretions from the lungs, sinuses, upper airways, ears, eyes, genito-urinary tract, spermatozoa, ovaries, fallopian tubes, neutrophils, and macrophages of a patient. The method comprises administering uridine triphosphates, adenosine triphosphates, cytidine triphosphates, or dinucleoside tetraphosphates and the derivatives thereof to an affected body of a patient, to treat dysfunction of the mucociliary clearance system as a result of impaired ciliary movement in the patient.
摘要翻译：本发明涉及一种刺激睫状脉搏频率以促进从肺，鼻窦，上呼吸道，耳朵，眼睛，生殖泌尿道，精子，卵巢，输卵管，嗜中性粒细胞，粘液分泌物中保留的粘液分泌物的粘液纤毛或咳嗽清除的方法，和巨噬细胞。该方法包括给患者的受影响的体内施用三磷酸尿苷，三磷酸腺苷，胞苷三磷酸或二核苷四磷酸及其衍生物，以治疗患者睫状肌移动受损的粘液纤毛清除系统的功能障碍。

6. 发明授权

US06462028B2 Method of promoting cervical and vaginal secretions 有权
标题翻译：促进子宫颈和阴道分泌物的方法
公开(公告)号：US06462028B2
公开(公告)日：2002-10-08
申请号：US09199912
申请日：1998-11-25
申请人： William Pendergast , Sammy R. Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
发明人： William Pendergast , Sammy R. Shaver , David J. Drutz , Janet L. Rideout , Benjamin R. Yerxa
IPC分类号： C07H1910
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 agonists such as UTP, CTP, ATP, dinucleotides and analogs thereof are disclosed.
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。公开了合适的激动剂，例如UTP，CTP，ATP，二核苷酸及其类似物。

7. 发明授权

US06451288B1 Method of treating lung diseases with uridine 5′-diphosphate and analogs thereof 有权
标题翻译：用尿苷5'-二磷酸治疗肺部疾病的方法及其类似物
公开(公告)号：US06451288B1
公开(公告)日：2002-09-17
申请号：US09645161
申请日：2000-08-24
申请人： Richard C. Boucher, Jr. , Sammy Ray Shaver , William Pendergast , Benjamin Yerxa , Janet L. Rideout , Robert Dougherty , Dallas Croom
发明人： Richard C. Boucher, Jr. , Sammy Ray Shaver , William Pendergast , Benjamin Yerxa , Janet L. Rideout , Robert Dougherty , Dallas Croom
IPC分类号： A61K912
CPC分类号： A61K31/7068 , A61K9/0073 , A61K31/7072 , A61K45/06 , C07H19/10 , Y10S514/826 , Y10S514/851 , A61K2300/00
摘要： Compounds of Formula I: wherein: X1, and X2 are each independently either O− or S−; X3 and X4 are each independently either —H or —OH, with the proviso that X3 and X4 are not simultaneously —H; R1 is selected from the group consisting of O, imido, methylene and dihalomethylene; R2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido; R3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; and R4 is selected from the group consisting of —OR′, —SR′, —NR′, and —NR′R″, wherein R′ and R″ are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R′ is absent when R4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.
摘要翻译：式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地为-H或-OH，条件是X 3和X 4不同时为-H; R 1为选自由O，亚氨基，亚甲基和二卤代亚甲基组成的组; R 2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R 3选自H，烷基，酰基，芳基和芳基烷基; 和R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基，芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4位上的碳时，R'不存在，用于水合肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。还描述了含有式I化合物和式I的新化合物的药物组合物。

8. 发明授权

US6143279A Uridine 5'-diphosphate and analogs useful for treating lung diseases 有权
标题翻译：尿苷5'-二磷酸和类似物可用于治疗肺部疾病
公开(公告)号：US6143279A
公开(公告)日：2000-11-07
申请号：US143297
申请日：1998-08-28
申请人： Richard C. Boucher, Jr. , Sammy Ray Shaver , William Pendergast , Benjamin Yerxa , Janet L. Rideout , Robert Dougherty , Dallas Croom
发明人： Richard C. Boucher, Jr. , Sammy Ray Shaver , William Pendergast , Benjamin Yerxa , Janet L. Rideout , Robert Dougherty , Dallas Croom
IPC分类号： A61K9/00 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K45/06 , A61P11/00 , C07H19/10 , A61K9/12
CPC分类号： A61K31/7068 , A61K31/7072 , A61K45/06 , A61K9/0073 , C07H19/10 , Y10S514/826 , Y10S514/851
摘要： Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ;X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H;R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido;R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; andR.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.
摘要翻译：式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地是-H或-OH，条件是X 3和X 4不同时为-H; R1选自O，亚氨基，亚甲基和二卤代亚甲基; R2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R3选自H，烷基，酰基，芳基和芳基烷基; 并且R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基，芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4-位上的碳时，R'不存在，用于水分肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。还描述了含有式I化合物和式I的新化合物的药物组合物。

9. 发明授权

US6022527A Method of treating lung diseases with uridine 5'-diphosphate and analogs thereof 有权
标题翻译：用尿苷5'-二磷酸治疗肺部疾病的方法及其类似物
公开(公告)号：US6022527A
公开(公告)日：2000-02-08
申请号：US352390
申请日：1999-07-13
申请人： Richard C. Boucher, Jr. , Sammy Ray Shaver , William Pendergast , Benjamin Yerxa , Janet L. Rideout , Robert Dougherty , Dallas Croom
发明人： Richard C. Boucher, Jr. , Sammy Ray Shaver , William Pendergast , Benjamin Yerxa , Janet L. Rideout , Robert Dougherty , Dallas Croom
IPC分类号： A61K9/00 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K45/06 , A61P11/00 , C07H19/10 , A61K9/12
CPC分类号： A61K31/7068 , A61K31/7072 , A61K45/06 , A61K9/0073 , C07H19/10 , Y10S514/826 , Y10S514/851
摘要： Compounds of Formula I: ##STR1## wherein: X.sub.1, and X.sub.2 are each independently either O.sup.- or S.sup.- ;X.sub.3 and X.sub.4 are each independently either --H or --OH, with the proviso that X.sub.3 and X.sub.4 are not simultaneously --H;R.sub.1 is selected from the group consisting of O, imido, methylene and dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, alkoxyl, nitro and azido;R.sub.3 is selected from the group consisting of H, alkyl, acyl, aryl, and arylalkyl; andR.sub.4 is selected from the group consisting of --OR', --SR', --NR', and --NR'R", wherein R' and R" are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, alkoxyl, and aryloxyl, with the proviso that R' is absent when R.sub.4 is double bonded from an oxygen or sulfur atom to the carbon at the 4-position of the pyrimidine ring, are used in methods of hydrating lung mucus secretions and treating lung disorders such as cystic fibrosis, ventilator-associated pneumonia, chronic bronchitis, chronic obstructive pulmonary disorder and primary ciliary dyskinesia. Pharmaceutical compositions containing compounds of Formula I, and novel compounds of Formula I are also described.
摘要翻译：式I化合物：其中：X 1和X 2各自独立地为O-或S-; X 3和X 4各自独立地是-H或-OH，条件是X 3和X 4不同时为-H; R1选自O，亚氨基，亚甲基和二卤代亚甲基; R2选自H，卤素，烷基，取代的烷基，烷氧基，硝基和叠氮基; R3选自H，烷基，酰基，芳基和芳基烷基; 并且R 4选自-OR'，-SR'，-NR'和-NR'R“，其中R'和R”独立地选自H，烷基，取代的烷基，芳基，取代的芳基，芳基烷基，烷氧基和芳氧基，条件是当R4与氧或硫原子双键连接到嘧啶环的4-位上的碳时，R'不存在，用于水分肺粘液分泌物和治疗肺部疾病如囊性纤维化，呼吸机相关肺炎，慢性支气管炎，慢性阻塞性肺病和原发性纤毛运动障碍。还描述了含有式I化合物和式I的新化合物的药物组合物。

10. 发明授权

US06921755B2 Method of treating dry eye disease with purinergic receptor agonists 有权
标题翻译：用嘌呤能受体激动剂治疗干眼病的方法
公开(公告)号：US06921755B2
公开(公告)日：2005-07-26
申请号：US10010055
申请日：2001-11-09
申请人： Benjamin R. Yerxa , Karla M. Jacobus , William Pendergast , Janet L. Rideout
发明人： Benjamin R. Yerxa , Karla M. Jacobus , William Pendergast , Janet L. Rideout
IPC分类号： A61K45/06 , A61K31/70
CPC分类号： A61K45/06 , Y10S514/912
摘要： A method and preparation for the stimulation of tear secretion in a subject in need of such treatment is disclosed. The method comprises administering to the ocular surfaces of the subject a purinergic receptor agonist such as uridine 5′-triphosphate (UTP), dinucleotides, cytidine 5′-triphosphate (CTP), adenosine 5′-triphosphate (ATP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate tear fluid secretion and enhance drainage of the lacrimal system. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intra-operative instillation or suppository form.
摘要翻译：公开了用于刺激需要这种治疗的受试者的泪液分泌的方法和制剂。该方法包括向受试者的眼表面施用嘌呤能受体激动剂如尿苷5'-三磷酸（UTP），二核苷酸，胞苷5'-三磷酸（CTP），腺苷5'-三磷酸（ATP）或其治疗上有用的类似物和衍生物，其量有效地刺激泪液分泌并增强泪液系统的引流。还公开了药物制剂及其制备方法。施用该方法的方法将包括：通过液体，凝胶，霜剂或作为隐形眼镜或选择性释放膜的一部分局部给药; 或通过鼻滴或喷雾进行全身给药，通过喷雾器或其它装置吸入，口服形式（液体或丸剂），可注射的，术中滴注或栓剂形式。

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