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1. 发明申请

WO2007014150A2 METHOD OF ADMINISTERING LIPOSOMES CONTAINING OLIGONUCLEOTIDES 审中-公开
标题翻译：含有寡核苷酸的脂质体的施用方法
公开(公告)号：WO2007014150A2
公开(公告)日：2007-02-01
申请号：PCT/US2006/028658
申请日：2006-07-24
申请人： NEOPHARM, INC. , SHERMAN, Jeffrey , PARKER, Kristen , AHMAD, Imran
发明人： SHERMAN, Jeffrey , PARKER, Kristen , AHMAD, Imran
IPC分类号： A61K48/00
CPC分类号： A61K48/0008 , A61K9/1272 , C12N15/1135 , C12N2310/11
摘要： The invention provides a method of treating a cellular proliferative disease, a method of inhibiting the growth of neoplastic cells and a method of reducing the expression of a raf sequence by administering an effective amount of a cationic liposomal composition. The cationic liposomal composition comprises c-raf Antisense Oligonucleotide (c-rafAON), a cationic cardiolipin analogue and, desirably, another lipid species. The preferred cationic cardiolipin analogue is l,3-Bis-(l,2-bis-tetradecyloxy-propyl-3- dimethylethoxyammoniumbromide)-propane-2-ol (PCL-2). The preferred lipids include cholesterol, dioleoylphosphatidylethanolamine (DOPE), 1,2 Dioleoyl-sn-glycero-3- phosphocholine (DOPC), alpha tocopheryl acid succinate and phosphatidylcholine. The effective amount of the cationic liposomal composition is about 60 mg/m 2 .
摘要翻译：本发明提供了治疗细胞增殖性疾病的方法，抑制肿瘤细胞生长的方法和通过施用有效量的阳离子脂质体组合物来降低raf序列的表达的方法。阳离子脂质体组合物包含c-raf反义寡核苷酸（c-rafAON），阳离子心磷脂类似物，并且理想地是另一种脂质物质。优选的阳离子心磷脂类似物是1,3-双 - （1,2-双 - 十四烷氧基 - 丙基-3-二甲基乙氧基溴化铵） - 丙-2-醇（PCL-2）。优选的脂质包括胆固醇，二油酰磷脂酰乙醇胺（DOPE），1,2-二油酰-sn-甘油-3-磷酸胆碱（DOPC），α-生育酚酸琥珀酸酯和磷脂酰胆碱。阳离子脂质体组合物的有效量为约60mg / m 2。

2. 发明申请

WO2006052906A2 SYNTHESIS OF CARDIOLIPIN ANALOGUES AND USES THEREOF 审中-公开
标题翻译：卡培他滨类似物的合成及其用途
公开(公告)号：WO2006052906A2
公开(公告)日：2006-05-18
申请号：PCT/US2005/040325
申请日：2005-11-08
申请人： NEOPHARM, INC. , AHMAD, Moghis, U. , UKKALAM, Murali, K. , ALI, Shoukath, M. , AHMAD, Imran
发明人： AHMAD, Moghis, U. , UKKALAM, Murali, K. , ALI, Shoukath, M. , AHMAD, Imran
IPC分类号： A61K31/663
CPC分类号： C07F9/106
摘要： The invention provides novel synthetic methodologies for preparing cardiolipin, migrated caridiolipin (1,2-positional isomer of cardiolipin) and their analogues having varying fatty acids and/or alkyl chains with varying length and degrees of saturation/unsaturation. The method comprises (a) reacting an optically pure 1,2- O -dialkyl- sn -glycerol or 1,2- O -dialkyl- sn -glycerol with one or more phosphoramidite reagent(s), wherein a phosphite triester is produced; (b) coupling the product of (a) with glycerol, wherein a protected cardiolipin is produced; and (c) deprotecting the protected cardiolipin, such that cardiolipin is prepared. The cardiolipins and analogues thereof, prepared by the present methods, can be incorporated into liposomes, which can also include active agents such as hydrophobic or hydrophilic drugs, antisense nucleotides or diagnostic agents. Such liposomes can be used to treat diseases or can be used in diagnostic and/or analytical assays.
摘要翻译：本发明提供了新的合成方法，用于制备心磷脂，迁移的卡立二磷（心磷脂的1,2位异构体）及其类似物，其具有不同长度和饱和度/不饱和度变化的脂肪酸和/或烷基链。该方法包括（a）使光学纯的1,2-O-二烷基-sn-甘油或1,2-二烷基-sn-甘油与一种或多种亚磷酰胺试剂反应，其中产生亚磷酸三酯; （b）将（a）的产物与甘油偶联，其中产生受保护的心磷脂; 和（c）使保护的心磷脂脱保护，使得制备心磷脂。通过本发明方法制备的心磷脂及其类似物可以掺入脂质体中，脂质体还可以包括活性剂如疏水或亲水药物，反义核苷酸或诊断剂。这样的脂质体可用于治疗疾病或可用于诊断和/或分析测定。

3. 发明申请

WO2006050072A3 MANUFACTURING PROCESS FOR LIPOSOMAL PREPARATIONS 审中-公开
公开(公告)号：WO2006050072A3
公开(公告)日：2006-05-11
申请号：PCT/US2005/038899
申请日：2005-10-28
申请人： NEOPHARM, INC. , AHMAD, Zafeer , ANYARAMBHATLA, Gopal , PREM, Sushil , AHMAD, Imran
发明人： AHMAD, Zafeer , ANYARAMBHATLA, Gopal , PREM, Sushil , AHMAD, Imran
IPC分类号： A61K9/127
摘要： The present invention provides a manufacturing process for liposomal preparations comprising water-insoluble or hydrophobic active principals. In accordance with one aspect of the inventive method, at least one active principal and lipid fraction are dissolved in an organic solvent. This solution is then subjected to reduced pressure (vacuum) in a container with or with out inert packing to remove the organic solvent, thereby forming a puffy cake comprising the active principal or principals and lipid fraction. This puffy cake is then mixed with an aqueous solution, under controlled conditions suitable to form a bulk liposomal preparation. Because the active principal is imbedded in the lipid bilayer, removal of the aqueous solution is optional.

4. 发明申请

WO2006029081A2 NUCLEOSIDE-LIPID CONJUGATES, THEIR METHOD OF PREPARATION AND USES THEREOF 审中-公开
标题翻译：核苷脂酸结合体，其制备方法及其用途
公开(公告)号：WO2006029081A2
公开(公告)日：2006-03-16
申请号：PCT/US2005/031543
申请日：2005-09-02
申请人： NEOPHARM, INC. , AHMAD, Moghis, U. , ALI, Shoukath, M. , KHAN, Abdul, R. , AHMAD, Imran
发明人： AHMAD, Moghis, U. , ALI, Shoukath, M. , KHAN, Abdul, R. , AHMAD, Imran
IPC分类号： A61K31/7072
CPC分类号： A61K31/7072 , A61K9/127 , Y02A50/385 , Y02A50/393 , Y02A50/463 , Y02A50/471
摘要： The invention provides methods for synthesizing nucleoside-lipid conjugates having varying fatty acid and alkyl chain lengths with or without unsaturation and their use in the treatment of cancer and viral diseases. More particularly, the invention provides methods for preparing gemcitabine-cardiolipin conjugates, and analogues thereof, cytarabine-cardiolipin conjugates, and analogues thereof. Additionally, the methods of the invention comprise administering a compound of invention as prodrug or a pharmaceutical preparation to combat mammalian diseases, preferably cancer, viral infections and bone disorders.
摘要翻译：本发明提供了具有不同脂肪酸和具有或不具有不饱和键的烷基链长度的核苷 - 脂质缀合物的方法及其在治疗癌症和病毒性疾病中的用途。更具体地，本发明提供了制备吉西他滨 - 心磷脂偶联物及其类似物的方法，阿糖胞苷 - 心磷脂缀合物及其类似物。此外，本发明的方法包括施用本发明化合物作为前药或药物制剂，以对抗哺乳动物疾病，优选癌症，病毒感染和骨骼疾病。

5. 发明申请

WO2007145782A3 PANT CUFF PROTECTOR AND SYSTEM THEREOF 审中-公开
公开(公告)号：WO2007145782A3
公开(公告)日：2007-12-21
申请号：PCT/US2007/012102
申请日：2007-05-18
申请人： LAMBERT, Michael, Louis , LAMBERT, Michael, Richard
发明人： LAMBERT, Michael, Louis , LAMBERT, Michael, Richard
IPC分类号： A41D1/06 , A41F17/04
摘要： A pant cuff protector for surrounding a portion of a pant leg is provided that, in one embodiment, includes a flexible U-shaped clip with two opposed ends. At least two pads are provided proximate each end to provide for gripping opposite sides of a shoe sole. The pant cuff protector holds the rear cuff of a pant tight against a heel of a person so the rear cuff does not drag on the ground.

6. 发明申请

WO2006102533A3 PHARMACEUTICALLY ACTIVE LIPID-BASED FORMULATION OF NUCLEOSIDE-LIPID CONJUGATES 审中-公开
公开(公告)号：WO2006102533A3
公开(公告)日：2006-09-28
申请号：PCT/US2006/010638
申请日：2006-03-23
申请人： NEOPHARM, INC. , ZHANG, Jia-Ai , UGWU, Sydney , MA, Lan , AHMAD, Moghis, U. , ALI, Shoukath, M. , KHAN, Abdul, R. , AHMAD, Imran
发明人： ZHANG, Jia-Ai , UGWU, Sydney , MA, Lan , AHMAD, Moghis, U. , ALI, Shoukath, M. , KHAN, Abdul, R. , AHMAD, Imran
IPC分类号： A01N43/04 , A61K31/70
摘要： Novel formulations of nucleoside-lipid conjugates, the methods of preparing them and the methods for administering them are provided. More particularly, methods for making liposomal formulations of nucleoside-cardiolipin and analogues thereof are provided. By encapsulating nucleoside prodrugs, drugs are protected from degradation, thereby extending the drugs' plasma half-life and intracellular release. In addition, compositions that demonstrate greater efficacy and higher cytotoxicity are produced. Accordingly, nucleoside-lipid conjugates that demonstrate greater in-vitro and in-vivo activity are produced.

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