公开(公告)号：US07084128B2

公开(公告)日：2006-08-01

申请号：US10347255

申请日：2003-01-15

申请人： Benjamin R. Yerxa ,  Robert Plourde, Jr. ,  Edward G. Brown ,  Ward M. Peterson

发明人： Benjamin R. Yerxa ,  Robert Plourde, Jr. ,  Edward G. Brown ,  Ward M. Peterson

IPC分类号： A61K31/70 ,  C07H21/00

CPC分类号： C07H19/20 ,  Y10S514/912 ,  Y10S514/913

摘要： The present invention is directed to a method of reducing intraocular pressure. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a purinerginic receptor ligand, which is a mononucleoside polyphosphate or dinucleoside polyphosphate defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as glaucoma, including primary and secondary glaucoma. The method can be used alone to reduce intraocular pressure. The method can also be used in conjunction with other therapeutic agents or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure.

公开(公告)号：US06730707B2

公开(公告)日：2004-05-04

申请号：US09915486

申请日：2001-07-25

申请人： Jesus J. Pintor ,  Maria A. Peral ,  Ward M. Peterson ,  Robert Plourde, Jr. ,  Edward G. Brown ,  Benjamin R. Yerxa

发明人： Jesus J. Pintor ,  Maria A. Peral ,  Ward M. Peterson ,  Robert Plourde, Jr. ,  Edward G. Brown ,  Benjamin R. Yerxa

IPC分类号： A61K4732

CPC分类号： A61K31/404 ,  A61K31/4045 ,  A61K31/55 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention provides a method of reducing intraocular pressure by administering pharmaceutical compositions comprising indole derivatives. The pharmaceutical compositions useful in this invention comprise indole derivatives and melatonin analogs of Formulae I-IV. A preferred embodiment is a method of lowering intraocular pressure using 5-(methoxycarbonylamino)-N-acetyltryptamine (5-MCA-NAT), also known as GR 135531, which has a prolonged duration of action and greater efficacy in lowering intraocular pressure compared to melatonin. The present invention further provides a method of treating disorders associated with ocular hypertension, and a method of treating various forms of glaucoma; the method comprises administering an effective dose of a pharmacuetical composition comprising an indole derivative with or without agents commonly used to treat such disorders.

摘要翻译： 本发明提供通过给药包含吲哚衍生物的药物组合物降低眼内压的方法。 用于本发明的药物组合物包含式I-IV的吲哚衍生物和褪黑素类似物。 优选的实施方案是使用5-（甲氧基羰基氨基）-N-乙酰基色胺（5-MCA-NAT）（也称为GR135531）降低眼内压的方法，其具有延长的作用时间和降低眼内压的更高功效， 褪黑激素 本发明还提供了治疗与高眼压相关的疾病的方法和治疗各种形式的青光眼的方法; 该方法包括施用有效剂量的药物组合物，所述药物组合物包含吲哚衍生物，所述药物组合物含或不含通常用于治疗所述疾病的试剂。

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。

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：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.

公开(公告)号：US20080214614A1

公开(公告)日：2008-09-04

申请号：US11958214

申请日：2007-12-17

申请人： John W. Lampe ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

发明人： John W. Lampe ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

IPC分类号： A61K31/454 ,  C07D401/12 ,  C07D403/12 ,  A61K31/416 ,  A61P27/02

CPC分类号： C07D401/12 ,  A61F9/00781 ,  A61K9/0048 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

摘要： The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂的合成细胞骨架活性化合物。 本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。 在本发明的一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 该方法包括向受试者施用治疗有效量的式I或式II的细胞骨架活性化合物，其中所述量可有效影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞粘附的变化。

公开(公告)号：US08604218B2

公开(公告)日：2013-12-10

申请号：US13273043

申请日：2011-10-13

申请人： John W. Lampe ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

发明人： John W. Lampe ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

IPC分类号： C07D231/56 ,  C07D421/00

CPC分类号： C07D401/12 ,  A61F9/00781 ,  A61K9/0048 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

摘要： The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

公开(公告)号：US20130012543A1

公开(公告)日：2013-01-10

申请号：US13614641

申请日：2012-09-13

申请人： John W. LAMPE ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

发明人： John W. LAMPE ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

IPC分类号： C07D401/14 ,  A61P27/02 ,  C07D409/14 ,  A61K31/454 ,  C07D405/14

CPC分类号： C07D401/12 ,  A61F9/00781 ,  A61K9/0048 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

摘要： The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂的合成细胞骨架活性化合物。 本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。 在本发明的一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 该方法包括向受试者施用治疗有效量的式I或式II的细胞骨架活性化合物，其中所述量可有效影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞粘附的变化。

公开(公告)号：US20120046275A1

公开(公告)日：2012-02-23

申请号：US13273043

申请日：2011-10-13

申请人： John W. Lampe ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

发明人： John W. Lampe ,  Paul S. Watson ,  David J. Slade ,  Ward M. Peterson ,  Christopher S. Crean ,  Jason L. Vittitow ,  Jonathan Bryan DeCamp ,  Nicholas F. Pelz

IPC分类号： A61K31/416 ,  C07D401/12 ,  A61P27/02 ,  A61K31/4725 ,  C07D403/12 ,  A61K31/55 ,  C07D231/56 ,  A61K31/454

CPC分类号： C07D401/12 ,  A61F9/00781 ,  A61K9/0048 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

摘要： The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

摘要翻译： 本发明涉及作为rho相关蛋白激酶抑制剂的合成细胞骨架活性化合物。 本发明还涉及包含这些化合物和药学上可接受的载体的药物组合物。 本发明另外涉及预防或治疗与细胞骨架重组相关的疾病或病症的方法。 在本发明的一个实施方案中，该方法治疗增加的眼内压，例如原发性开角型青光眼。 该方法包括向受试者施用治疗有效量的式I或式II的细胞骨架活性化合物，其中所述量可有效影响肌动球蛋白相互作用，例如通过导致细胞松弛和细胞粘附的变化。