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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

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。

3. 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。

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

US06765090B2 Method for large-scale production of di(uridine 5')-tetraphosphate and salts thereof 有权
标题翻译：二（尿苷5'） - 四磷酸及其盐的大规模生产方法
公开(公告)号：US06765090B2
公开(公告)日：2004-07-20
申请号：US09805332
申请日：2001-03-12
申请人： Benjamin R. Yerxa , William Pendergast
发明人： Benjamin R. Yerxa , William Pendergast
IPC分类号： C07H1904
CPC分类号： C07H21/00 , Y10S514/912
摘要： The present invention provides new methods for the synthesis of the therapeutic dinucleotide, P1,P4-di(uridine 5′-tetraphosphate), and demonstrates applicability to the production of large quantities. The methods of the present invention substantially reduce the time period required to synthesize diuridine tetraphosphate, preferably to three days or less. The novel tetrammonium and tetrasodium salts of P1,P4-di(uridine 5′-tetraphosphate) (Formula I) prepared by these methods are stable, soluble, nontoxic, and easy to handle during manufacture. wherein: X is Na, NH4 or H, provided that all X groups are not H.
摘要翻译：本发明提供了合成治疗性二核苷酸P 1，P 4 - 二（尿苷5'） - 四磷酸的新方法，并证明其适用于大量生产。本发明的方法基本上减少了合成二尿苷四磷酸酯所需的时间，优选为3天以下。通过这些方法制备的P 1，P 4 - 二（尿苷5'） - 四磷酸（式I）的新型四铵盐和四钠盐在制备过程中是稳定的，可溶的，无毒的，易于处理。其中：X 是Na，NH4或H，条件是所有X基团不是H.

7. 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。

8. 发明授权

US07531525B2 P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-)tetraphosphate, tetra-(alkali metal) salt, for treating cystic fibrosis 有权
标题翻译： P1-（2'-脱氧胞苷5' - ）P4-（尿苷5' - ）四磷酸盐，四（碱金属盐），用于治疗囊性纤维化
公开(公告)号：US07531525B2
公开(公告)日：2009-05-12
申请号：US11690385
申请日：2007-03-23
申请人： Benjamin R. Yerxa , Ward M. Peterson , Janet L. Rideout , William Pendergast
发明人： Benjamin R. Yerxa , Ward M. Peterson , Janet L. Rideout , William Pendergast
IPC分类号： A61K31/7072 , C07H19/10
CPC分类号： C07H19/10 , A61K31/7072 , A61K31/7084 , C07H19/04 , C07H19/20 , C07H21/00 , Y10S514/851
摘要： The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The present invention also provides a method of treating cystic fibrosis. The present invention further provides P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-) tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-) tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.
摘要翻译：本发明提供治疗水肿性视网膜病变的方法。该方法包括施用包含水解抗性P2Y受体激动剂的药物制剂，以刺激从视网膜下和视网膜空间中除去病理性外来流体，从而减少与视网膜脱离和视网膜水肿相关的所述流体的积聚。 P2Y受体激动剂可以与通常用于治疗水肿性视网膜疾病的治疗剂和辅助剂一起施用。本发明还提供治疗囊性纤维化的方法。本发明还提供了P1-（2'-脱氧胞苷5' - ）P4-（尿苷5'-）四磷酸盐，四钠（碱金属）盐，例如四钠，四锂，四钾和混合（四碱金属）盐。本发明还提供了药学上可接受的载体中包含P1-（2'-脱氧胞苷5' - ）P4-（尿苷5'-）四磷酸盐，四 - （碱金属盐）的药物制剂。

9. 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。

10. 发明授权

US07223744B2 Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof 有权
标题翻译：包含二核苷多磷酸盐及其盐的药物制剂
公开(公告)号：US07223744B2
公开(公告)日：2007-05-29
申请号：US10962016
申请日：2004-10-07
申请人： Benjamin R. Yerxa , Ward M. Peterson , Janet L. Rideout , William Pendergast
发明人： Benjamin R. Yerxa , Ward M. Peterson , Janet L. Rideout , William Pendergast
IPC分类号： C07H21/00 , A61K37/70
CPC分类号： C07H19/10 , A61K31/7072 , A61K31/7084 , C07H19/04 , C07H19/20 , C07H21/00 , Y10S514/851
摘要： The present invention provides a method of treating edematous retinal disorders. The method comprises administration of a pharmaceutical formulation comprising a hydrolysis-resistant P2Y receptor agonist to stimulate the removal of pathological extraneous fluid from the subretinal and retinal spaces and thereby reduce the accumulation of said fluid associated with retinal detachment and retinal edema. The P2Y receptor agonist can be administered with therapeutic and adjuvant agents commonly used to treat edematous retinal disorders. The pharmaceutical formulation useful in this invention comprises a P2Y receptor agonist with enhanced resistance to extracellular hydrolysis, such as dinucleoside polyphosphate compounds, or hydrolysis-resistant mononucleoside triphosphate salts. The present invention also provides P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-)tetraphosphate, tetra-(alkali metal) salts such as tetrasodium, tetralithium, tetrapotassium, and mixed (tetra-alkali metal) salts. The present further provides a pharmaceutical formulation comprising a P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-)tetraphosphate, tetra-(alkali metal) salt, in a pharmaceutically acceptable carrier.
摘要翻译：本发明提供治疗水肿性视网膜病变的方法。该方法包括施用包含水解抗性P2Y受体激动剂的药物制剂，以刺激从视网膜下和视网膜空间中除去病理性外来流体，从而减少与视网膜脱离和视网膜水肿相关的所述流体的积聚。 P2Y受体激动剂可以与通常用于治疗水肿性视网膜疾病的治疗剂和辅助剂一起施用。可用于本发明的药物制剂包含具有增强的细胞外水解抗性的P2Y受体激动剂，例如二核苷多磷酸酯化合物或耐水解的单核苷三磷酸盐。本发明还提供了P 1 - （2'-脱氧胞苷5' - ）P 4 - （尿苷5'-）四磷酸盐，四（碱金属盐）盐作为四钠，四锂，四钾和混合（四碱金属）盐。本发明还提供一种药物制剂，其包含P 1 - （2'-脱氧胞苷5' - ）P 4 - （尿苷5' - ）四磷酸酯，四 - （碱金属）盐，在药学上可接受的载体中。

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