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1. 发明授权

US07169819B2 Pharmaceutical compositions of fenretinide having increased bioavailability and methods of using the same 有权
标题翻译：具有增加的生物利用度的芬维A胺的药物组合物及其使用方法
公开(公告)号：US07169819B2
公开(公告)日：2007-01-30
申请号：US10010914
申请日：2001-12-05
申请人： Shanker Gupta , Barry J. Maurer , C. Patrick Reynolds , B. Rao Vishnuvajjala
发明人： Shanker Gupta , Barry J. Maurer , C. Patrick Reynolds , B. Rao Vishnuvajjala
IPC分类号： A61K31/07 , A61K47/00 , A61P35/00
CPC分类号： A61K31/16 , A61K9/107 , A61K9/1075 , A61K31/164 , A61K31/167 , A61K47/10 , A61K47/44 , Y10S514/937 , Y10S514/938 , Y10S514/975
摘要： A pharmaceutical composition for parenteral delivery, comprising a retinide such as fenretinide in combination with a solvent capable of dispersing or solubilizing the retinide. The solvent comprises an alcohol, such as ethanol, in combination with an alkoxylated castor oil, such as CREMOPHOR® EL, or comprising a retinide, such as fenretinide, in an emulsion composed of a lipoid dispersed in an aqueous phase, a stabilizing amount of a non-ionic surfactant, optionally a solvent, and optionally an isotonic agent. In addition, a method of use in the treatment of hyperproliferative disorders, such as cancers is described.
摘要翻译：一种用于胃肠外递送的药物组合物，其包含视网膜如芬维A胺与能够分散或溶解视黄酸盐的溶剂的组合。溶剂包括醇，如乙醇，与烷氧基化蓖麻油（如ELEM）组合，或在分散在水相中的脂质组成的乳液中包含视黄酸盐，如芬维A胺，稳定剂非离子表面活性剂，任选的溶剂和任选的等渗剂的量。此外，描述了用于治疗过度增殖性疾病如癌症的方法。

2. 发明授权

US07476692B2 Pharmaceutical compositions of safingol and methods of using the same 有权
标题翻译：安息香的药物组合物及其使用方法
公开(公告)号：US07476692B2
公开(公告)日：2009-01-13
申请号：US10782459
申请日：2004-02-19
申请人： Shanker Gupta , C. Patrick Reynolds , Barry J. Maurer , B. Rao Vishnuvajjala
发明人： Shanker Gupta , C. Patrick Reynolds , Barry J. Maurer , B. Rao Vishnuvajjala
IPC分类号： A61K31/19 , A61K31/13
CPC分类号： A61K31/133 , A61K9/0019 , A61K9/08 , A61K9/107 , A61K9/19 , A61K31/19 , A61K31/685 , A61K31/739 , A61K47/10 , A61K47/12 , A61K47/26
摘要： The present invention provides stable aqueous solutions consisting essentially of: (a) a sphingolipid; (b) lactic acid; and (c) optionally a stabilizing agent; wherein the solution has a molar ratio of lactic acid to sphingolipid of 1:1 to 10:1. The present invention further provides an emulsion formulation consisting essentially of: (a) lactic acid; (b) a sphingolipid, wherein the sphingolipid is present in an amount of about 0.1 to about 30 mg/ml of emulsion; (b) optionally an isotonic agent; and (c) a phospholipid present in an amount of about 0.2 to about 200 mg/ml of emulsion. Methods of making and using the compositions are also provided.
摘要翻译：本发明提供基本上由以下组成的稳定的水溶液：（a）鞘脂; （b）乳酸; 和（c）任选的稳定剂; 其中所述溶液的乳酸与鞘脂的摩尔比为1:1至10:1。本发明还提供一种乳液制剂，其主要由以下物质组成：（a）乳酸; （b）鞘脂，其中所述神经鞘脂以约0.1至约30mg / ml的乳剂的量存在; （b）任选的等渗剂; 和（c）以约0.2至约200mg / ml的乳液的量存在的磷脂。还提供了制备和使用组合物的方法。

3. 发明授权

US06368831B1 Treatment of hyperproliferative disorders 有权
标题翻译：治疗过度增生性疾病
公开(公告)号：US06368831B1
公开(公告)日：2002-04-09
申请号：US09471944
申请日：1999-12-23
申请人： Barry J. Maurer , C. Patrick Reynolds
发明人： Barry J. Maurer , C. Patrick Reynolds
IPC分类号： C12N1509
CPC分类号： A61K31/165 , A61K31/07 , A61K31/535 , A61K31/70 , A61K45/06 , A61K2300/00
摘要： 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-generating retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) ceramide degredation inhibitor, such as compounds selected from the group consisting of (i) glucosylceramide synthesis inhibitors and/or 1-acylceramide synthesis inhibitors, (ii) sphingosine-1-phosphate synthesis inhibitors, and (iii) protein kinase C inhibitors. A preferred glucosyl ceramide synthesis inhibitor is 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingosine-1-phosphate synthesis inhibitor is D-erythro-N,N-dimethylsphingosine. A preferred protein kinase C inhibitor is L-threo-dihydrosphingosine.
摘要翻译：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，包括给所述受试者组合施用治疗有效量的：（a）产生神经酰胺的类视黄醇例如芬维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）神经酰胺降解抑制剂，例如选自（i）葡萄糖神经酰胺合成抑制剂和/或1-酰基神经酰胺合成抑制剂的化合物，（ii）鞘氨醇-1 磷酸盐合成抑制剂，和（iii）蛋白激酶C抑制剂。优选的葡糖基神经酰胺合成抑制剂是1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。优选的鞘氨醇-1-磷酸合成抑制剂是D-赤式-N，N-二甲基鞘氨醇。优选的蛋白激酶C抑制剂是L-苏式 - 二氢鞘氨醇。

4. 发明授权

US06352844B1 Treatment of hyperproliferative disorders 有权
标题翻译：治疗过度增生性疾病
公开(公告)号：US06352844B1
公开(公告)日：2002-03-05
申请号：US09342019
申请日：1999-06-28
申请人： Barry J. Maurer , Myles Cabot , C. Patrick Reynolds
发明人： Barry J. Maurer , Myles Cabot , C. Patrick Reynolds
IPC分类号： C12N1509
CPC分类号： A61K45/06 , A61K31/07 , A61K31/165 , A61K31/535 , A61K31/70 , Y10S424/15 , A61K2300/00
摘要： 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-generating retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) ceramide degredation inhibitor, such as compounds selected from the group consisting of (i) glucosylceramide synthesis inhibitors, (ii) sphingosine-1-phosphate synthesis inhibitors, and (iii) protein kinase C inhibitors. A preferred glucosyl ceramide synthesis inhibitor is 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingosine-1-phosphate synthesis inhibitor is D-erythro-N,N-dimethylsphingosine. A preferred protein kinase C inhibitor is L-threo-dihydrosphingosine.
摘要翻译：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，包括给所述受试者组合施用治疗有效量的：（a）产生神经酰胺的类视黄醇例如芬维A胺或其药学上可接受的盐; 和（b）至少一种（和在某些实施方案中至少两种）神经酰胺降解抑制剂，例如选自（i）葡糖基神经酰胺合成抑制剂，（ii）鞘氨醇-1-磷酸合成抑制剂和（iii））蛋白激酶C抑制剂。优选的葡糖基神经酰胺合成抑制剂是1-苯基-2-棕榈酰氨基-3-吗啉代-1-丙醇。优选的鞘氨醇-1-磷酸合成抑制剂是D-赤式-N，N-二甲基鞘氨醇。优选的蛋白激酶C抑制剂是L-苏式 - 二氢鞘氨醇。

5. 发明申请

US20100035911A1 DRUG COMBINATIONS TO TREAT HYPERPROLIFERATIVE DISORDERS 审中-公开
标题翻译：药物联合治疗高血压病
公开(公告)号：US20100035911A1
公开(公告)日：2010-02-11
申请号：US12301089
申请日：2007-05-16
申请人： Barry James Maurer , C. Patrick Reynolds
发明人： Barry James Maurer , C. Patrick Reynolds
IPC分类号： A61K31/167 , A61K31/4745 , A61K31/337 , A61P35/00 , A61K31/44
CPC分类号： A61K31/44 , A61K31/70
摘要： A method of treating a hyperproliferative disorder, including a cancer, in a subject in need of such treatment, comprising administering to said subject a pharmaceutical combination containing a treatment effective amount of: (a) a vitamin A derivative (i.e., a retinoid), or a pharmaceutically acceptable salt thereof, and an inhibitor of microtubule structure or function; or (b) a combination containing fenretinide (i.e., N-(4-hydrophenyl) retinamide, 4-HPR) and ABT-751 (i.e., N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4-methoxybenzenesulfonamide). Vitamin A derivatives that may be useful for this invention according to (a) include, but are not limited to, all-trans-retinoic acid, 13-cis-retinoic acid, and fenretinide. Microtubule inhibitors that may be useful for this invention according to (a) include, but are not limited to, inhibitors of the Vinca binding domain (e.g., vincristine, vinblastine, vinorelbine, and cryptophycin 52), inhibitors of the Taxane domain (e.g., paclitaxel, docetaxel, and epothilones), and inhibitors of the colchicine site (e.g., colchicine, ABT-751, CI-980, and combretastatin). A preferred retinoid according to (a) is fenretinide. A preferred microtubule inhibitor according to (b) is ABT-751.
摘要翻译：一种在需要这种治疗的受试者中治疗过度增殖性疾病（包括癌症）的方法，包括向所述受试者施用含有治疗有效量的药物组合：（a）维生素A衍生物（即类视黄醇）或其药学上可接受的盐，以及微管结构或功能的抑制剂; 或（b）含有芬维A胺（即N-（4-羟基苯基）视黄酰胺，4-HPR）和ABT-751（即N- [2 - [（4-羟基苯基）氨基] -3-吡啶基] - 4-甲氧基苯磺酰胺）。根据（a）可用于本发明的维生素A衍生物包括但不限于全反式视黄酸，13-顺式视黄酸和芬维A胺。根据（a）可用于本发明的微管抑制剂包括但不限于长春新碱结合结构域（例如长春新碱，长春碱，长春瑞滨和隐球菌52）的抑制剂，紫杉烷域的抑制剂（例如，紫杉醇，多西他赛和埃坡霉素）和秋水仙碱位点的抑制剂（例如秋水仙素，ABT-751，CI-980和考匹特他汀）。根据（a）的优选类视黄醇是芬维A胺。根据（b）的优选的微管抑制剂是ABT-751。

6. 发明授权

US06665430B2 Fluorescence digital imaging microscopy system 失效
公开(公告)号：US06665430B2
公开(公告)日：2003-12-16
申请号：US10217721
申请日：2002-08-13
申请人： C. Patrick Reynolds , Tomas Frgala
发明人： C. Patrick Reynolds , Tomas Frgala
IPC分类号： G06K900
CPC分类号： G01N21/6458 , G01N21/6428 , G01N21/6452
摘要： A method of preparing cell samples for viable cell number quantification with a fluorescence digital imaging microscopy system employing digital thresholding technique. The cell sample is stained with a first, fluorescent dye and treated with a second dye that is able to quench the fluorescence of the first dye. The fluorescent dye accumulates in viable cells only and is used to stain the viable cells. The second dye is excluded from viable cells but enters non-viable cells, thereby quenching the background fluorescence in non-viable cells and the medium. Two examples of dye combinations are described: fluorescein diacetate used as the fluorescent dye with eosin Y as the quenching dye; and calcein-AM used as the fluorescent dye with trypan blue as the quenching dye. By reducing the background fluorescence, the dynamic range and accuracy of viable cell number measurements are enhanced. In low viability cultures treated with fluorescein diacetate, background fluorescence completely masked viable cells, but digital thresholding and eosin treatment dramatically reduced background fluorescence, producing a linear response over 4 logs of viable cell density.

7. 发明授权

US06459805B1 Fluorescence digital imaging microscopy system 失效
公开(公告)号：US06459805B1
公开(公告)日：2002-10-01
申请号：US09066134
申请日：1998-04-24
申请人： C. Patrick Reynolds , Tomas Frgala
发明人： C. Patrick Reynolds , Tomas Frgala
IPC分类号： G06K900
CPC分类号： G01N21/6458 , G01N21/6428 , G01N21/6452
摘要： A method of preparing cell samples for viable cell number quantification with a fluorescence digital imaging microscopy system employing digital thresholding technique. The cell sample is stained with a first, fluorescent dye and treated with a second dye that is able to quench the fluorescence of the first dye. The fluorescent dye accumulates in viable cells only and is used to stain the viable cells. The second dye is excluded from viable cells but enters non-viable cells, thereby quenching the background fluorescence in non-viable cells and the medium. Two examples of dye combinations are described: fluorescein diacetate used as the fluorescent dye with eosin Y as the quenching dye; and calcein-AM used as the fluorescent dye with trypan blue as the quenching dye. By reducing the background fluorescence, the dynamic range and accuracy of viable cell number measurements are enhanced. In low viability cultures treated with fluorescein diacetate, background fluorescence completely masked viable cells, but digital thresholding and eosin treatment dramatically reduced background fluorescence, producing a linear response over 4 logs of viable cell density.

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