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1. 发明申请

WO2004028443A2 LIPOPHILIC DIESTERS OF CHELATING AGENT FOR INHIBITION OF ENZYME ACTIVITY 审中-公开
标题翻译：用于抑制酶活性的螯合剂的锂离子电池
公开(公告)号：WO2004028443A2
公开(公告)日：2004-04-08
申请号：PCT/IL2003/000225
申请日：2003-03-16
申请人： D-PHARM LTD. , STRIEM, Sarina , FRIEDMAN, Jonathan, Eduard , REZNITSKY-COHEN, Dalia , KOZAK, Alexander
发明人： STRIEM, Sarina , FRIEDMAN, Jonathan, Eduard , REZNITSKY-COHEN, Dalia , KOZAK, Alexander
IPC分类号： A61K
CPC分类号： A61K31/225
摘要： The present invention relates to the use of lipophilic diesters of the chelating agent 1,2-bis(2 aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) for inhibition of proteolytic activities of certain metalloproteinases and of calpain. The invention further relates to methods for preventing, treating or managing MMP-related and calpain-related diseases or disorders in mammals comprising administering to a mammal in need thereof, a pharmaceutical composition comprising a therapeutically effective amount of said lipophilic diesters of the chelating agent BAPTA.
摘要翻译：本发明涉及螯合剂1,2-双（2-氨基苯氧基）乙烷-N，N，N'，N'-四乙酸（BAPTA）的亲脂性二酯用于抑制某些金属蛋白酶的蛋白水解活性和钙蛋白酶。本发明还涉及用于预防，治疗或管理哺乳动物中MMP-相关和钙蛋白酶相关疾病或病症的方法，其包括向有需要的哺乳动物施用包含治疗有效量的螯合剂BAPTA的所述亲脂性二酯的药物组合物。

2. 发明申请

WO2005016229A2 USE OF LIPOPHILIC DIESTERS OF CHELATING AGENT FOR THE TREATMENT OF AMYLOIDOSIS AND ATHEROSCLEROSIS 审中-公开
标题翻译：麻醉药物治疗青光眼病和甲状腺功能亢进症的使用
公开(公告)号：WO2005016229A2
公开(公告)日：2005-02-24
申请号：PCT/IL2004/000746
申请日：2004-08-12
申请人： D-PHARM LTD. , ROSENBERG, Gilad, Israel , FRIEDMAN, Jonathan, Eduard , ANGEL, Itzchak , KOZAK, Alexander
发明人： ROSENBERG, Gilad, Israel , FRIEDMAN, Jonathan, Eduard , ANGEL, Itzchak , KOZAK, Alexander
IPC分类号： A61K
CPC分类号： A61K31/24
摘要： The present invention relates to the use of lipophilic diesters of the chelating agent 1,2-bis(2 aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA) for preventing, treating or managing atherosclerosis, amyloidosis-related diseases and disorders and other pathologies associated with proteins aggregations. In particular, these compounds are useful in treating cardiac and vascular amyloidosis, neurodegenerative diseases and disorders and cerebral amyloid angiopathy (CAA).
摘要翻译：本发明涉及螯合剂1,2-双（2-氨基苯氧基）乙烷-N，N，N'，N'-四乙酸（BAPTA）的亲脂性二酯用于预防，治疗或控制动脉粥样硬化，淀粉样变性 - 相关疾病和病症以及与蛋白质聚集相关的其他病理学。特别地，这些化合物可用于治疗心脏和血管淀粉样变性，神经变性疾病和病症以及脑淀粉样血管病（CAA）。

3. 发明申请

WO2003000173A3 USE OF BRANCHED-CHAIN FATTY ACIDS AND DERIVATIVES THEREOF FOR THE TREATMENT OF PAIN 审中-公开
公开(公告)号：WO2003000173A3
公开(公告)日：2003-01-03
申请号：PCT/IL2002/000502
申请日：2002-06-24
申请人： D-PHARM LIMITED , KOZAK, Alexander , DUVDEVANI, Revital , YOUNIS, Firas, M.
发明人： KOZAK, Alexander , DUVDEVANI, Revital , YOUNIS, Firas, M.
IPC分类号： C07C55/00
摘要： The present invention relates to compounds and pharmaceutical compositions useful for treating pain. The invention also relates to methods of treating or alleviating pain in mammals, comprising administering to a mammal suffering from pain, a pain-alleviating amount of a compound of the general formula (I) or (II).

4. 发明申请

WO2003000173A2 USE OF BRANCHED-CHAIN FATTY ACIDS AND DERIVATIVES THEREOF FOR THE TREATMENT OF PAIN 审中-公开
标题翻译：使用分支链脂肪酸及其衍生物治疗疼痛
公开(公告)号：WO2003000173A2
公开(公告)日：2003-01-03
申请号：PCT/IL2002/000502
申请日：2002-06-24
申请人： D-PHARM LIMITED , KOZAK, Alexander , DUVDEVANI, Revital , YOUNIS, Firas, M.
发明人： KOZAK, Alexander , DUVDEVANI, Revital , YOUNIS, Firas, M.
IPC分类号： A61K
CPC分类号： C07F9/11 , A61K31/16 , A61K31/20 , A61K31/22 , A61K31/66 , C07C53/128 , C07C69/30 , C07C233/05 , C07F9/10 , C07F9/12
摘要： The present invention relates to compounds and pharmaceutical compositions useful for treating pain. The invention also relates to methods of treating or alleviating pain in mammals, comprising administering to a mammal suffering from pain, a pain-alleviating amount of a compound of the general formula (I) or (II).
摘要翻译：本发明涉及可用于治疗疼痛的化合物和药物组合物。本发明还涉及治疗或减轻哺乳动物疼痛的方法，其包括向患有疼痛的哺乳动物施用减轻疼痛的量的通式（I）或（II）的化合物。

5. 发明申请

WO2015092789A1 ONIUM SALTS OF LIPOPHILIC DIESTERS OF CHELATING AGENTS 审中-公开
标题翻译：烟囱石油公司的石油销售
公开(公告)号：WO2015092789A1
公开(公告)日：2015-06-25
申请号：PCT/IL2014/051100
申请日：2014-12-16
申请人： D-PHARM LTD.
发明人： KOZAK, Alexander , ROSENBERG, Gilad , SHAPIRO, Israel , VINNIKOVA, Marina
IPC分类号： A61K31/22 , A61K31/223 , C07C229/16 , C07C381/12 , C07F9/54
CPC分类号： C07C229/18 , C07F9/5442
摘要： The present invention provides water soluble onium salts other than ammonium salts (e.g. phosphonium salt, sulfonium salt) of lipophilic diesters of 1,2-bis(2 aminophenoxy)ethane- N,N,N',N'-tetraacetic acid denoted herein as BAPTA-DE which are stable lipophilic derivatives of divalent metal ions chelators having increased stability under physiological conditions. The invention further concerns pharmaceutical compositions thereof and their use in the treatment of conditions or diseases related to abnormal levels of divalent metal ions, said treatment results in minimizing the risk of developing unwanted side effects associated with the therapeutic use of their sodium salt analogues.
摘要翻译：本发明提供了在本文中表示的1,2-双（2氨基苯氧基）乙烷-N，N，N'，N'-四乙酸的亲脂性二酯的铵盐（例如鏻盐，锍盐）以外的水溶性鎓盐 BAPTA-DE，其是在生理条件下具有增加的稳定性的二价金属离子螯合剂的稳定的亲脂性衍生物。本发明还涉及其药物组合物及其在治疗与二价金属离子的异常水平相关的病症或疾病中的用途，所述治疗使得与其钠盐类似物的治疗用途相关的不希望的副作用发生风险最小化。

6. 发明申请

WO2015092788A1 COMPOSITIONS COMPRISING LIPOPHILIC DIESTERS OF CHELATING AGENTS NON-COVALENTLY ASSOCIATED WITH ORGANIC AMINES 审中-公开
标题翻译：组合物包含与有机氨基相关的螯合剂的锂离子电池
公开(公告)号：WO2015092788A1
公开(公告)日：2015-06-25
申请号：PCT/IL2014/051099
申请日：2014-12-16
申请人： D-PHARM LTD.
发明人： TSIMANIS, Alexander , KREYNIN, Haim , KOZAK, Alexander , SHAPIRO, Israel , VINNEKOVA, Marina , ROSENBERG, Gilad
IPC分类号： A61K31/194 , A61P7/00 , A61K38/03
CPC分类号： A61K31/23
摘要： The present invention provides pharmaceutical compositions comprising lipophilic diesters of l,2-bis(2-aminophenoxy)ethane-N,N,N',N' -tetraacetic acid denoted herein as B APTA-DE, or salts thereof, in non-covalent association with a free amino acid, wherein a stoichiometric ratio of the free amino acid and the lipophilic diester in the composition is at least 3: 1, M denotes a hydrogen ion and/or a physiologically acceptable cation, and wherein R is selected from the group consisting of C n H 2n+1 (n=1-10), C n H 2n+1 (OCH 2 CH 2 ) m (n=1-20, m=1-6), (C n H 2n+1 )2N(CH2)m (n=1-6, m=1-6) and substituted or unsubstituted ArCH 2 ; the substituents on the aromatic rings being in the ortho position. The invention further concerns use of said pharmaceutical compositions in the treatment of neurological conditions or diseases related to abnormal levels of divalent metal ions, said treatment resulting in minimizing the risk of developing undesired side effects associated with the therapeutic use of the lipophilic diester salts.
摘要翻译：本发明提供药物组合物，其包含以非共价键形式表示为B APTA-DE的1,2-双（2-氨基苯氧基）乙烷-N，N，N'，N' - 四乙酸或其盐的亲脂性二酯与游离氨基酸缔合，其中组合物中游离氨基酸和亲脂性二酯的化学计量比为至少3:1，M表示氢离子和/或生理上可接受的阳离子，并且其中R选自 CnH2n + 1（n = 1-10），CnH2n + 1（OCH2CH2）m（n = 1-20，m = 1-6），（CnH2n + 1）2N（CH2）m（n = 6，m = 1-6）和取代或未取代的ArCH 2; 芳环上的取代基处于邻位。本发明还涉及所述药物组合物在治疗与二价金属离子的异常水平相关的神经病症或疾病方面的应用，所述治疗导致最小化与治疗性使用亲脂性二酯盐相关的不期望的副作用的风险。

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