公开(公告)号：WO2009045345A1

公开(公告)日：2009-04-09

申请号：PCT/US2008/011207

申请日：2008-09-26

Applicant: CHILDRENS HOSPITAL LOS ANGELES RESEARCH INSTITUTE ,  MAURER, Barry James ,  REYNOLDS, Charles Patrick

Inventor： MAURER, Barry James ,  REYNOLDS, Charles Patrick

IPC: A61K31/167 ,  A61K31/4196 ,  A61K31/496 ,  A61P35/00

CPC classification number: A61K31/496 ,  A61K31/167 ,  A61K31/4196

Abstract: The present invention provides methods of increasing an amount of a treatment agent in the body, a cancer or tumor. The methods include administering an inhibitor of the metabolic degradation or conversion of the treatment agent to a subject undergoing treatment for a hyperproliferative disorder with said treatment agent. Methods of treating hyperproliferative disorders, tumors and cancers are also provided.

Abstract translation: 本发明提供增加体内，癌症或肿瘤中治疗剂量的方法。 所述方法包括将所述治疗剂的代谢降解抑制剂或转化为经历所述治疗剂的过度增殖性疾病治疗的受试者。 还提供了治疗过度增生性疾病，肿瘤和癌症的方法。

公开(公告)号：WO2005049827A3

公开(公告)日：2005-06-02

申请号：PCT/US2004/037175

申请日：2004-11-08

Applicant: CHILDREN'S HOSPITAL LOS ANGELES ,  MAURER, Barry, James ,  REYNOLDS, Charles, Patrick

Inventor： MAURER, Barry, James ,  REYNOLDS, Charles, Patrick

IPC: C12N15/09

Abstract: The present invention relates to a method of treating a hyperproliferative disorder comprising administering a ceramide generating retinoid comprising a retinoic acid derivative or a pharmaceutically acceptable salt thereof, and D-threo-PPMP as a ceramide degradation inhibitor or a pharmaceutically acceptable salt thereof, wherein the hyperproliferative disorder is a tumor; and wherein the ceramide generating retinoid is administered in an amount effective to produce necrosis, apoptosis or both in the tumor, and the ceramide degradation inhibitor is administered in an amount effective to increase the necrosis, apoptosis or both in the tumor over that expected to be produced by the sum of that produced by the ceramide generating retinoid and the ceramide degradation inhibitor when administered separately.

公开(公告)号：WO2005049827A2

公开(公告)日：2005-06-02

申请号：PCT/US2004037175

申请日：2004-11-08

Applicant: CHILDREN S HOSPITAL LOS ANGELE ,  MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

Inventor： MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

IPC: A61K31/16 ,  A61K31/225 ,  A61K45/06 ,  C12N15/09

CPC classification number: A61K45/06 ,  A61K31/16 ,  A61K31/225 ,  A61K2300/00

Abstract: The present invention relates to a method of treating a hyperproliferative disorder comprising administering a ceramide generating retinoid comprising a retinoic acid derivative or a pharmaceutically acceptable salt thereof, and D-threo-PPMP as a ceramide degradation inhibitor or a pharmaceutically acceptable salt thereof, wherein the hyperproliferative disorder is a tumor; and wherein the ceramide generating retinoid is administered in an amount effective to produce necrosis, apoptosis or both in the tumor, and the ceramide degradation inhibitor is administered in an amount effective to increase the necrosis, apoptosis or both in the tumor over that expected to be produced by the sum of that produced by the ceramide generating retinoid and the ceramide degradation inhibitor when administered separately.

Abstract translation: 本发明涉及治疗过度增殖性病症的方法，其包括施用神经酰胺产生性视黄酸，其包含视黄酸衍生物或其药学上可接受的盐和作为神经酰胺降解抑制剂的D-苏型-PPMP或其药学上可接受的盐，其中所述 过度增殖性疾病是一种肿瘤; 并且其中产生神经酰胺的视黄醇以有效产生肿瘤中的坏死，细胞凋亡或两者的量施用，神经酰胺降解抑制剂以有效增加肿瘤中的坏死，细胞凋亡或两者的量施用超过预期为 其产生量是神经酰胺产生类视黄醇和神经酰胺降解抑制剂单独给药产生的总和。

公开(公告)号：WO2005049827B1

公开(公告)日：2005-08-25

申请号：PCT/US2004037175

申请日：2004-11-08

Applicant: CHILDREN S HOSPITAL LOS ANGELE ,  MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

Inventor： MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

IPC: A61K31/16 ,  A61K31/225 ,  A61K45/06 ,  C12N15/09

CPC classification number: A61K45/06 ,  A61K31/16 ,  A61K31/225 ,  A61K2300/00

Abstract: The present invention relates to a method of treating a hyperproliferative disorder comprising administering a ceramide generating retinoid comprising a retinoic acid derivative or a pharmaceutically acceptable salt thereof, and D-threo-PPMP as a ceramide degradation inhibitor or a pharmaceutically acceptable salt thereof, wherein the hyperproliferative disorder is a tumor; and wherein the ceramide generating retinoid is administered in an amount effective to produce necrosis, apoptosis or both in the tumor, and the ceramide degradation inhibitor is administered in an amount effective to increase the necrosis, apoptosis or both in the tumor over that expected to be produced by the sum of that produced by the ceramide generating retinoid and the ceramide degradation inhibitor when administered separately.

公开(公告)号：WO2011060332A2

公开(公告)日：2011-05-19

申请号：PCT/US2010/056626

申请日：2010-11-12

Applicant: TEXAS TECH UNIVERSITY ,  MAURER, Barry, James ,  REYNOLDS, Charles, Patrick

Inventor： MAURER, Barry, James ,  REYNOLDS, Charles, Patrick

CPC classification number: A61K31/133 ,  A61K31/131 ,  A61K31/167 ,  A61K31/5375

Abstract: A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-increasing retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) compounds selected from the groups consisting of (i) a non-18 carbon chain length L-threo-sphinganine(s) or pharmaceuticeutically acceptable salt thereof, (ii) glucosylceramide or glucosyl(dihydro)ceramide synthesis inhibitor(s), and (iii) sphingomyelin or dihydrosphingomyelin synthase inhibitor(s). Preferred L-threo-sphinganines are of carbon chain length 17 carbons, 19 carbons and 20 carbons. A preferred glucosylceramide or glucosyl(dihydro)ceramide synthesis inhibitor is D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingomyelin or dihydrosphingomyelin synthesis inhibitor is D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred hyperproliferative disorder is brain cancers.

Abstract translation: 在需要这种治疗的受试者中治疗过度增殖性病症的方法，包括给予所述受试者联合治疗有效量的：（a）增加神经酰胺的类维生素A例如芬维A胺 或其药学上可接受的盐; （b）至少一种（并且在某些实施方案中至少两种）选自以下的化合物：（i）非18碳链长度的L-苏型 - 二氢鞘氨醇或其药学上可接受的盐，（ii） 葡糖基神经酰胺或葡糖基（二氢）神经酰胺合成抑制剂，和（iii）鞘磷脂或二氢鞘磷脂合酶抑制剂。 优选的L-苏糖 - 二氢鞘氨醇的碳链长度为17个碳，19个碳和20个碳。 优选的葡糖神经酰胺或葡糖基（二氢）神经酰胺合成抑制剂是D-苏式-1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。 优选的鞘磷脂或二氢鞘磷脂合成抑制剂是D-苏式-1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。 一种优选的过度增殖性疾病是脑癌。

公开(公告)号：WO2011060332A3

公开(公告)日：2011-09-15

申请号：PCT/US2010056626

申请日：2010-11-12

Applicant: UNIV TEXAS TECH ,  MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

Inventor： MAURER BARRY JAMES ,  REYNOLDS CHARLES PATRICK

IPC: C07C215/10 ,  A61K31/133 ,  A61K31/16 ,  A61P35/00

CPC classification number: A61K31/133 ,  A61K31/131 ,  A61K31/167 ,  A61K31/5375

Abstract: A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-increasing retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) compounds selected from the groups consisting of (i) a non-18 carbon chain length L-threo-sphinganine(s) or pharmaceuticeutically acceptable salt thereof, (ii) glucosylceramide or glucosyl(dihydro)ceramide synthesis inhibitor(s), and (iii) sphingomyelin or dihydrosphingomyelin synthase inhibitor(s). Preferred L-threo-sphinganines are of carbon chain length 17 carbons, 19 carbons and 20 carbons. A preferred glucosylceramide or glucosyl(dihydro)ceramide synthesis inhibitor is D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingomyelin or dihydrosphingomyelin synthesis inhibitor is D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred hyperproliferative disorder is brain cancers.

Abstract translation: 一种治疗需要这种治疗的受试者的过度增殖性疾病的方法，包括给予所述受试者组合治疗有效量的：（a）神经酰胺增量的类视色素如芬维A胺或其药学上可接受的盐; 和（b）至少一种（以及在某些实施方案中为至少两种）选自以下的化合物：（i）非18碳链长的L-苏棱 - 鸟嘌呤或其药学上可接受的盐，（ii） （二氢）神经酰胺合成抑制剂，和（iii）鞘磷脂或二氢鞘磷脂合成酶抑制剂。 优选的L-苏式 - 鞘氨醇具有碳链长度为17个碳，19个碳和20个碳。 优选的葡萄糖神经酰胺或（二氢）神经酰胺合成抑制剂是D-苏式-1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。 优选的鞘磷脂或二氢鞘磷脂合成抑制剂是D-苏式-1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。 优选的过度增生性疾病是脑癌。