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1. 发明授权

US07084128B2 Method for reducing intraocular pressure 失效
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.

2. 发明授权

US06730707B2 Method for reducing intraocular pressure using indole derivatives 失效
标题翻译：使用吲哚衍生物降低眼内压的方法
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。

3. 发明授权

US06897201B2 Compositions and methods for the treatment of glaucoma or ocular hypertension 失效
标题翻译：用于治疗青光眼或高眼压症的组合物和方法
公开(公告)号：US06897201B2
公开(公告)日：2005-05-24
申请号：US10087551
申请日：2002-02-27
申请人： Jose L. Boyer , Benjamin R. Yerxa , Robert Plourde, Jr. , Edward G. Brown
发明人： Jose L. Boyer , Benjamin R. Yerxa , Robert Plourde, Jr. , Edward G. Brown
IPC分类号： A61K31/7068 , A61K31/7072 , A61K31/7084 , A61K31/7125 , A61P27/00 , A61P27/06 , C07H19/04 , C07H19/10 , C07H19/20 , C07H19/207 , C07H21/00 , A61K31/70 , A01N43/04
CPC分类号： A61K31/7084 , A61K31/7068 , A61K31/7072 , C07H19/04 , C07H19/10 , C07H19/20 , C07H19/207 , C07H21/00
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 nucleoside 5′-pyrophosphate pyranoside or analogue, which is defined by general Formula I. The method of the present invention is useful in the treatment or prevention of ocular hypertension, such as found in 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 another therapeutic agent or adjunctive therapy commonly used to treat glaucoma to enhance the therapeutic effect of reducing the intraocular pressure. The present invention also provides a novel composition comprising a nucleoside 5′-pyrophosphate pyranoside or analogues.
摘要翻译：本发明涉及降低眼内压的方法。该方法包括向受试者施用包含有效量的由通式I定义的核苷5'-焦磷酸吡喃糖苷或类似物的药物组合物。本发明的方法可用于治疗或预防高眼压症，例如在青光眼中发现，包括原发性和继发性青光眼。该方法可单独使用以降低眼内压。该方法还可以与通常用于治疗青光眼的另一种治疗剂或辅助治疗联合使用，以增强降低眼内压的治疗效果。本发明还提供了包含核苷5'-焦磷酸吡喃糖苷或类似物的新型组合物。

4. 发明授权

US07435724B2 Degradation-resistant mononucleoside phosphate compounds 失效
标题翻译：降解抗性单核苷磷酸化合物
公开(公告)号：US07435724B2
公开(公告)日：2008-10-14
申请号：US11285221
申请日：2005-11-21
申请人： James G. Douglass, III , Benjamin R. Yerxa , Sammy R. Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean , José L. Boyer
发明人： James G. Douglass, III , Benjamin R. Yerxa , Sammy R. Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean , José L. Boyer
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C07H19/10 , C07H19/20
摘要： The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.
摘要翻译：本发明涉及具有二核苷酸药物益处的单核苷磷酸化合物。这些单核苷酸磷酸酯可以由已经通过在聚磷酸酯单核苷酸的末端磷酸酯上连接降解抗性取代基而被修饰的单核苷酸制成。通过连接该降解抗性的取代基，降解的稳定性与某些二核苷酸的匹配或超过某些二核苷酸。本发明的单核苷磷酸化合物可用于预防和治疗与血小板聚集有关的上皮组织疾病或疾病或病症。

5. 发明授权

US07612047B2 Degradation-resistant mononucleoside phosphate compounds 失效
标题翻译：降解抗性单核苷磷酸化合物
公开(公告)号：US07612047B2
公开(公告)日：2009-11-03
申请号：US12208265
申请日：2008-09-10
申请人： James G. Douglass, III , Benjamin R. Yerxa , Sammy R. Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean , José L. Boyer
发明人： James G. Douglass, III , Benjamin R. Yerxa , Sammy R. Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean , José L. Boyer
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C07H19/10 , C07H19/20
摘要： The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.
摘要翻译：本发明涉及具有二核苷酸药物益处的单核苷磷酸化合物。这些单核苷酸磷酸酯可以由已经通过在聚磷酸酯单核苷酸的末端磷酸酯上连接降解抗性取代基而被修饰的单核苷酸制成。通过连接该降解抗性的取代基，降解的稳定性与某些二核苷酸的匹配或超过某些二核苷酸。本发明的单核苷磷酸化合物可用于预防和治疗与血小板聚集有关的上皮组织疾病或疾病或病症。

6. 发明申请

US20090076256A1 DEGRADATION-RESISTANT MONONUCLEOSIDE PHOSPHATE COMPOUNDS 失效
标题翻译：耐腐蚀单核苷酸磷酸酯化合物
公开(公告)号：US20090076256A1
公开(公告)日：2009-03-19
申请号：US12208265
申请日：2008-09-10
申请人： James G. Douglass, III , Benjamin R. Yerxa , Sammy R. Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean , Jose L. Boyer
发明人： James G. Douglass, III , Benjamin R. Yerxa , Sammy R. Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean , Jose L. Boyer
IPC分类号： C07H19/20
CPC分类号： C07H19/10 , C07H19/20
摘要： The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation-resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation-resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides. The mononucleoside phosphate compounds of the present invention are useful in preventing and treating epithelial tissue diseases or diseases or disorders associated with platelet aggregation.
摘要翻译：本发明涉及具有二核苷酸药物益处的单核苷磷酸化合物。这些单核苷酸磷酸酯可以由已经通过在聚磷酸酯单核苷酸的末端磷酸酯上连接降解抗性取代基而被修饰的单核苷酸制成。通过连接该降解抗性的取代基，降解的稳定性与某些二核苷酸的匹配或超过某些二核苷酸。本发明的单核苷磷酸化合物可用于预防和治疗与血小板聚集有关的上皮组织疾病或疾病或病症。

7. 发明授权

US07115585B2 Compositions for treating epithelial and retinal tissue diseases 有权
标题翻译：用于治疗上皮和视网膜组织疾病的组合物
公开(公告)号：US07115585B2
公开(公告)日：2006-10-03
申请号：US10082998
申请日：2002-02-27
申请人： Benjamin R. Yerxa , James G. Douglass, III , Sammy Ray Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean
发明人： Benjamin R. Yerxa , James G. Douglass, III , Sammy Ray Shaver , Ward M. Peterson , Edward G. Brown , Christopher S. Crean
IPC分类号： A61K31/70 , C07H19/20
CPC分类号： A61K31/7072 , A61K31/7084 , C07H19/04 , C07H19/10 , C07H19/20 , C07H19/207 , C07H21/00
摘要： The present invention relates to mononucleoside phosphate compounds that have the benefits of a dinucleotide pharmaceutical. These mononucleoside phosphates can be made from a mononucleotide that has been modified by attaching a degradation resistant substituent on the terminal phosphate of a polyphosphate mononucleotide. By attaching this degradation resistant substituent, the stability from degradation matches or exceeds those of certain dinucleotides.
摘要翻译：本发明涉及具有二核苷酸药物益处的单核苷磷酸化合物。这些单核苷酸磷酸酯可以由已经通过在聚磷酸酯单核苷酸的末端磷酸酯上连接降解抗性取代基而被修饰的单核苷酸制成。通过连接这种降解抗性的取代基，降解的稳定性与某些二核苷酸的匹配或超过某些二核苷酸。

8. 发明授权

US06881725B2 Method for treating pain 失效
标题翻译：治疗疼痛的方法
公开(公告)号：US06881725B2
公开(公告)日：2005-04-19
申请号：US10355699
申请日：2003-01-31
申请人： Benjamin R. Yerxa , Ward M. Peterson , Christopher S. Crean
发明人： Benjamin R. Yerxa , Ward M. Peterson , Christopher S. Crean
IPC分类号： C07H19/20 , A61K31/675 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61P23/00 , A61P25/04 , A61P25/06 , A61P29/00 , C07H19/207 , C07H21/00 , A61K31/70
CPC分类号： A61K31/7076 , A61K31/675 , A61K31/7072 , A61K31/7084 , Y10S514/851
摘要： The present invention is directed to a method of treating pain. The method comprises administering to a subject a pharmaceutical composition comprising an effective amount of a P2X receptor antagonist. The methods of the present invention are useful in reducing pain, such as traumatic pain, neuropathic pain, organ pain and pain associated with diseases. The P2X receptor antagonists particularly useful for this invention are mononucleoside polyphosphate derivatives or dinucleoside polyphosphate derivatives of general Formula I. The compounds of the present method can be used alone to treat pain. The compounds of the present method can also be used in conjunction with other therapeutic agents or adjunctive therapies commonly used to treat pain, thus enhancing the overall pain-reducing effect in a subject in need of such treatment.
摘要翻译：本发明涉及治疗疼痛的方法。该方法包括向受试者施用包含有效量的P2X受体拮抗剂的药物组合物。本发明的方法可用于减轻疼痛，例如创伤性疼痛，神经性疼痛，器官疼痛和与疾病相关的疼痛。特别可用于本发明的P2X受体拮抗剂是通式I的单核苷多磷酸衍生物或二核苷多磷酸衍生物。本发明方法的化合物可单独用于治疗疼痛。本发明方法的化合物还可以与通常用于治疗疼痛的其它治疗剂或辅助疗法结合使用，从而增强需要这种治疗的受试者的整体疼痛减轻作用。

9. 发明授权

US08008274B2 P1-(2′-deoxycytidine 5′-)P4-(uridine 5′-)tetraphosphate, tetra-(alkali metal) salt, for treating sinusitis 有权
标题翻译：用于治疗鼻窦炎的P1-（2'-脱氧胞苷5' - ）P4-（尿苷5' - ）四磷酸盐，四（碱金属）盐）
公开(公告)号：US08008274B2
公开(公告)日：2011-08-30
申请号：US12436679
申请日：2009-05-06
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 also provides a method of treating sinusitis. 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。本发明还提供治疗鼻窦炎的方法。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。

10. 发明申请

US20090306010A1 P1-(2'-DEOXYCYTIDINE 5'-)P4-(URIDINE 5'-)TETRAPHOSPHATE, TETRA-(ALKALI METAL) SALT, FOR TREATING DISORDERS 有权
标题翻译： P1-（2'-DEOXYCYTIDINE 5' - ）P4-（URIDINE 5' - ）TETRAPHOSPHATE，TETRA-（ALKALI METAL）SALT，用于治疗疾病
公开(公告)号：US20090306010A1
公开(公告)日：2009-12-10
申请号：US12436679
申请日：2009-05-06
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 , A61P11/00
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 also provides a method of treating sinusitis. 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。本发明还提供治疗鼻窦炎的方法。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。

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