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1. 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。

2. 发明申请

US20120121691A1 Method for Increasing the Production of a Specific ACYL-Chain Dihydroceramide(s) for Improving the Effectiveness of Cancer Treatments 审中-公开
标题翻译：增加特异性ACYL-链二氢神经酰胺以提高癌症治疗有效性的方法
公开(公告)号：US20120121691A1
公开(公告)日：2012-05-17
申请号：US13297132
申请日：2011-11-15
申请人： Barry James Maurer
发明人： Barry James Maurer
IPC分类号： A61K31/20 , A61P35/00 , A61K9/127
CPC分类号： A61K31/202 , A61K31/07 , A61K31/20 , A61K31/201 , A61K31/203 , A61K45/06 , A61K2300/00
摘要： A method to improve the effectiveness of cancer treatments by increasing the production of specific ACYL-chain dihydroceramide(s). Increase of native chain-length dihydroceramides is directly cytotoxic to human acute lymphoblastic leukemia cell line MOLT-4 ALL cells with a cytotoxic potency that is dependent upon the specific fatty acid acyl-chain length and saturation of the dihydroceramides. The combination of sphinganine and GT-11 lead to cell death in the absence of an increase of reactive oxygen species, suggesting that the ability of fenretinide to increase cytotoxic ROS is mechanistically independent of dihydroceramides increase and related cytotoxicity. Most unexpectedly, supplementing the exposure of cancer cells to a dihydroceramide-increasing anti-hyperproliferative agent(s), such as fenretinide, with specifically-chosen fatty acids can increase the cytotoxicity of the anti-hyperproliferative agent to the cancer cells to a beneficial effect.
摘要翻译：通过增加特定ACYL-链二氢神经酰胺的生产来提高癌症治疗的有效性的方法。天然链长二氢神经酰胺的增加直接对人急性淋巴细胞白血病细胞系MOLT-4 ALL细胞具有细胞毒性，其依赖于二氢神经酰胺的特定脂肪酸酰基链长度和饱和度。在没有增加活性氧的情况下，鞘氨醇和GT-11的组合导致细胞死亡，这表明芬维A胺增加细胞毒性ROS的能力在机械上与二氢神经酰胺增加和相关的细胞毒性无关。最意想不到的是，补充癌细胞暴露于具有特异选择的脂肪酸的二氢神经酰胺增加的抗过度增殖剂（如芬维利肽）的暴露可以增加抗过度增殖剂对癌细胞的细胞毒性，从而达到有益效果。

3. 发明申请

US20110152267A1 Compositions and Methods for Treating Hyperproliferative Disorders 审中-公开
标题翻译：治疗过度增生性疾病的组合物和方法
公开(公告)号：US20110152267A1
公开(公告)日：2011-06-23
申请号：US12945808
申请日：2010-11-12
申请人： Barry James Maurer , Charles Patrick Reynolds
发明人： Barry James Maurer , Charles Patrick Reynolds
IPC分类号： A61K31/5375 , C07C215/24 , A61K31/167 , A61P35/00
CPC分类号： A61K31/133 , A61K31/131 , A61K31/167 , A61K31/5375
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-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.
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。

4. 发明申请

US20100311765A1 METABOLIC DEGRADATION INHIBITORS FOR ANTI-HYPERPROLIFERATIVE AGENTS 审中-公开
标题翻译：代谢降解抑制剂用于抗高血压药物
公开(公告)号：US20100311765A1
公开(公告)日：2010-12-09
申请号：US12679795
申请日：2008-09-26
申请人： Barry James Maurer , Charles Patrick Reynolds
发明人： Barry James Maurer , Charles Patrick Reynolds
IPC分类号： A61K31/4164 , A61K31/496 , A61K31/4196 , A61K31/16 , A61P35/04
CPC分类号： A61K31/496 , A61K31/167 , A61K31/4196
摘要： 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.
摘要翻译：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。

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