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1. 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。

2. 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。

3. 发明授权

US06323187B1 Therapeutic dinucleotide and derivatives 失效
标题翻译：治疗二核苷酸和衍生物
公开(公告)号：US06323187B1
公开(公告)日：2001-11-27
申请号：US09316571
申请日：1999-05-21
申请人： Benjamin R. Yerxa , William Pendergast , Janet L. Rideout , Maryse Picher , Richard C. Boucher, Jr. , M. Jackson Stutts
发明人： Benjamin R. Yerxa , William Pendergast , Janet L. Rideout , Maryse Picher , Richard C. Boucher, Jr. , M. Jackson Stutts
IPC分类号： A01N4304
CPC分类号： A61K31/7048 , A61K31/70 , C07H19/207 , C07H21/00
摘要： The present invention relates to P1-(cytidine 5′-)-P-(uridine 5′-)tetraphosphates and its salts, esters and amides, and formulations thereof which are highly stable and selective agonists of the P2Y2 and/or P2Y4 purinergic receptor. The compounds of the invention are useful in the treatment of chronic obstructive pulmonary diseases such as chronic bronchitis, primary ciliary dyskinesia, cystic fibrosis, as well as prevention of pneumonia due to immobility, and the induction of sputum and its expectoration. 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 and otitis media.
摘要翻译：本发明涉及P2Y2和/或P2Y4嘌呤能受体的高度稳定和选择性激动剂的P1-（胞苷5' - ） - （ - 尿苷5' - ）四磷酸及其盐，酯和酰胺及其制剂。本发明的化合物可用于治疗慢性阻塞性肺疾病如慢性支气管炎，原发性纤毛运动障碍，囊性纤维化，以及预防由于不动的肺炎，以及诱导痰及其咳痰。此外，由于它们具有清除保留的粘液分泌物和刺激睫状肌搏动频率的一般能力，本发明的化合物也可用于治疗鼻窦炎和中耳炎。

4. 发明申请

US20100330164A1 METHOD OF INCREASING TEAR PRODUCTION WITH PURINERGIC RECEPTOR AGONISTS 有权
标题翻译：增加与纯化受体激动剂进行生产的方法
公开(公告)号：US20100330164A1
公开(公告)日：2010-12-30
申请号：US12825051
申请日：2010-06-28
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： A61K31/7076 , A61K31/7072 , A61K9/127 , A61P27/04
CPC分类号： C07H19/10 , A61K9/0048 , A61K31/7084 , A61K45/06 , C07H19/20 , C07H21/00 , Y10S514/912 , Y10S514/915
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。

5. 发明授权

US07759322B2 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：US07759322B2
公开(公告)日：2010-07-20
申请号：US11821091
申请日：2007-06-20
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： A01N43/04 , A61K31/70
CPC分类号： C07H19/10 , A61K9/0048 , A61K31/7084 , A61K45/06 , C07H19/20 , C07H21/00 , Y10S514/912 , Y10S514/915
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。

6. 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。

7. 发明授权

US06916794B2 Method of enhancing drainage of lacrimal system with purinergic receptor agonists 有权
标题翻译：用嘌呤能受体激动剂增强泪液排出的方法
公开(公告)号：US06916794B2
公开(公告)日：2005-07-12
申请号：US10041826
申请日：2002-01-03
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： A61K9/06 , A61K9/00 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/127 , A61K9/14 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61K45/06 , A61K47/02 , A61K47/14 , A61K47/26 , A61K47/32 , A61K47/34 , A61K47/36 , A61P27/02 , A61P27/04 , C07H19/10 , C07H19/20 , C07H21/00 , A61K31/70
CPC分类号： C07H19/10 , A61K9/0048 , A61K31/7084 , A61K45/06 , C07H19/20 , C07H21/00 , Y10S514/912 , Y10S514/915
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。

8. 发明授权

US08097600B2 Method of increasing tear production with purinergic receptor agonists 有权
标题翻译：用嘌呤能受体激动剂增加泪液产生的方法
公开(公告)号：US08097600B2
公开(公告)日：2012-01-17
申请号：US12825051
申请日：2010-06-28
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： A01N43/04 , A61K31/70
CPC分类号： C07H19/10 , A61K9/0048 , A61K31/7084 , A61K45/06 , C07H19/20 , C07H21/00 , Y10S514/912 , Y10S514/915
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。

9. 发明授权

US06887858B1 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：US06887858B1
公开(公告)日：2005-05-03
申请号：US09171169
申请日：1998-02-06
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： A61K9/06 , A61K9/00 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/127 , A61K9/14 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61K45/06 , A61K47/02 , A61K47/14 , A61K47/26 , A61K47/32 , A61K47/34 , A61K47/36 , A61P27/02 , A61P27/04 , C07H19/10 , C07H19/20 , C07H21/00 , A61K31/70
CPC分类号： C07H19/10 , A61K9/0048 , A61K31/7084 , A61K45/06 , C07H19/20 , C07H21/00 , Y10S514/912 , Y10S514/915
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。

10. 发明授权

US07235535B2 Method of enhancing drainage of lacrimal system with purinergic receptor agonists 有权
标题翻译：用嘌呤能受体激动剂增强泪液排出的方法
公开(公告)号：US07235535B2
公开(公告)日：2007-06-26
申请号：US11114957
申请日：2005-04-25
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： A01N43/04 , A61K31/70 , C07H19/10 , C07H19/048
CPC分类号： C07H19/10 , A61K9/0048 , A61K31/7084 , A61K45/06 , C07H19/20 , C07H21/00 , Y10S514/912 , Y10S514/915
摘要： A method and preparation for enhancing drainage of lacrimal system 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：公开了一种用于增强需要这种治疗的受试者中泪液系统排泄的方法和制备方法。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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