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。

公开(公告)号：US06864243B1

公开(公告)日：2005-03-08

申请号：US09570231

申请日：2000-05-12

申请人： Ward M. Peterson

发明人： Ward M. Peterson

IPC分类号： A61K9/02 ,  A61K9/06 ,  A61K9/08 ,  A61K9/10 ,  A61K9/12 ,  A61K9/127 ,  A61K9/14 ,  A61K9/70 ,  A61K9/72 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/7076 ,  A61K31/7084 ,  A61K45/00 ,  A61P25/02 ,  A61P27/02 ,  A61P27/06 ,  A61P29/00 ,  A61P43/00 ,  C07H19/10 ,  C07H19/20 ,  C07H19/207 ,  A61K31/70 ,  C07H21/00

CPC分类号： C07H19/10 ,  C07H19/20 ,  C07H19/207

摘要： The present invention provides a method of preventing or treating retinal degeneration arising from pathophysiological or physical conditions. The method comprises administering to a patient a pharmaceutical composition comprising a purinergic P2Y receptor ligand, in an amount effective to elevate its extracellular concentration to activate retinal glial and neuronal cell surface P2Y receptors and mount a neuroprotective response. Methods of administering including intravitreal bolus and sustained administrations, transscleral delivery, topical, and systemic administrations. The pharmaceutical composition useful in this invention comprises a P2Y purinergic receptor agonist, which include uridine 5′-di-and triphosphate (UDP, UTP) and their analogs, adenosine 5′-diphosphate (ADP) and its analogs, cytidine 5′-di-and triphosphate (CDP, CTP) and their analogs, and dinucleoside polyphosphate compounds.

摘要翻译： 本发明提供了预防或治疗由病理生理或身体状况引起的视网膜变性的方法。 该方法包括向患者施用包含嘌呤能P2Y受体配体的药物组合物，其量可有效地提高其细胞外浓度以激活视网膜神经胶质细胞和神经元细胞表面P2Y受体并且起到神经保护作用。 施用方法包括玻璃体内推注和持续施用，经巩膜递送，局部和全身施用。 可用于本发明的药物组合物包含P2Y嘌呤能受体激动剂，其包括尿苷5'-二 - 和三磷酸（UDP，UTP）及其类似物腺苷5'-二磷酸（ADP）及其类似物胞苷5'-二 和三磷酸（CDP，CTP）及其类似物，以及二核苷多磷酸盐化合物。

公开(公告)号：US06818629B2

公开(公告)日：2004-11-16

申请号：US10397795

申请日：2003-03-25

申请人： Ward M. Peterson ,  Benjamin R. Yerxa

发明人： Ward M. Peterson ,  Benjamin R. Yerxa

IPC分类号： C07H2100

CPC分类号： C07H19/10 ,  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 triphosphates.

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抗水解性单核苷三磷酸酯。

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.