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1. 发明申请

WO2003039540A2 D-AMINO ACID OXIDASE INHIBITORS FOR LEARNING AND MEMORY 审中-公开
标题翻译：用于学习和记忆的D-氨基酸氧化酶抑制剂
公开(公告)号：WO2003039540A2
公开(公告)日：2003-05-15
申请号：PCT/US2002/036051
申请日：2002-11-12
申请人： SEPRACOR INC. , HEEFNER, Donald, L. , CURRIE, Mark, G. , ROSSI, JR., Richard, Filip , ZEPP, Charles, M.
发明人： HEEFNER, Donald, L. , CURRIE, Mark, G. , ROSSI, JR., Richard, Filip , ZEPP, Charles, M.
IPC分类号： A61K31/405
CPC分类号： A61K31/34 , A61K31/401 , A61K31/404 , A61K31/405 , A61K31/473
摘要： Methods and pharmaceutical compositions which inhibit the activity of D-amino acid oxidase (DAO) are disclosed. Inhibition of DAO improves memory, learning and cognition in individuals suffering from neurodegenerative diseases such as Alzheimer's, Huntington's or Parkinson's diseases; the methods and pharmaceutical compositions which inhibit the activity of DAO also improve cognitive dysfunctions associated with aging and improve catatonic schizophrenia. Several genera of heterocycle-2-carboxylic acids are disclosed as DAO inhibitors.
摘要翻译：公开了抑制D-氨基酸氧化酶（DAO）活性的方法和药物组合物。 DAO的抑制改善了患有神经退行性疾病如阿尔茨海默病，亨廷顿舞蹈病或帕金森病的个体的记忆，学习和认知; 抑制DAO活性的方法和药物组合物也改善与衰老相关的认知功能障碍并改善紧张性精神分裂症。作为DAO抑制剂公开了几个杂环-2-羧酸的属。

2. 发明申请

WO2004043447A3 COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING HEARING IMPAIRMENT 审中-公开
标题翻译：用于治疗或预防听力障碍的组合物和方法
公开(公告)号：WO2004043447A3
公开(公告)日：2005-01-27
申请号：PCT/US0336269
申请日：2003-11-13
申请人： SEPRACOR INC , CURRIE MARK G , HEEFNER DONALD L , RUBIN PAUL , ZEPP CHARLES M
发明人： CURRIE MARK G , HEEFNER DONALD L , RUBIN PAUL , ZEPP CHARLES M
IPC分类号： A61K31/17 , A61K31/495 , A61P27/16
CPC分类号： A61K31/17 , A61K31/495
摘要： Ototoxic side-effects have either limited the application of an important group of antibiotics, aminoglycoside antibiotics, or have added further burden to those who have to resort to platinum-containing antineoplastic agents to treat life-threatening tumors. The present invention discloses pharmaceutical compositions that prevent or treat the ototoxic side-effects of aminoglycoside antibiotics and platinum-containing antineoplastic agents. The otoprotective compositions disclosed herein can also be used to treat noise induced hearing loss.
摘要翻译：耳毒性副作用限制了一组重要的抗生素，氨基糖苷类抗生素的应用，或者为那些不得不使用含铂抗肿瘤剂治疗危及生命的肿瘤的人增加了进一步的负担。本发明公开了预防或治疗氨基糖苷类抗生素和含铂抗肿瘤剂的耳毒性副作用的药物组合物。本文公开的保护性组合物也可用于治疗噪声引起的听力损失。

3. 发明申请

WO2003039540A3 D-AMINO ACID OXIDASE INHIBITORS FOR LEARNING AND MEMORY 审中-公开
公开(公告)号：WO2003039540A3
公开(公告)日：2003-05-15
申请号：PCT/US2002/036051
申请日：2002-11-12
申请人： SEPRACOR INC. , HEEFNER, Donald, L. , CURRIE, Mark, G. , ROSSI, JR., Richard, Filip , ZEPP, Charles, M.
发明人： HEEFNER, Donald, L. , CURRIE, Mark, G. , ROSSI, JR., Richard, Filip , ZEPP, Charles, M.
IPC分类号： A61K31/405
摘要： Methods and pharmaceutical compositions which inhibit the activity of D-amino acid oxidase (DAO) are disclosed. Inhibition of DAO improves memory, learning and cognition in individuals suffering from neurodegenerative diseases such as Alzheimer's, Huntington's or Parkinson's diseases; the methods and pharmaceutical compositions which inhibit the activity of DAO also improve cognitive dysfunctions associated with aging and improve catatonic schizophrenia. Several genera of heterocycle-2-carboxylic acids are disclosed as DAO inhibitors.

4. 发明申请

WO1996020592A1 METHOD FOR INACTIVATING NON-ENVELOPED VIRUSES USING A VIRICIDE-POTENTIATING AGENT 审中-公开
标题翻译：使用杀虫剂对非传染病毒灭活的方法
公开(公告)号：WO1996020592A1
公开(公告)日：1996-07-11
申请号：PCT/US1996000271
申请日：1996-01-02
申请人： HEMASURE INC. , ZEPP, Charles, M. , HEEFNER, Donald, L.
发明人： HEMASURE INC.
IPC分类号： A01N01/02
CPC分类号： C12N7/00 , A61L2/0011 , A61L2/0088 , A61L2/08 , A61L2/18 , C12N7/04 , C12N7/06 , C12N2710/10363 , C12N2750/14363 , C12N2770/32463 , C12N2770/32663
摘要： Method for inactivating non-enveloped viruses using a viricide-potentiating agent. In a preferred embodiment, the method may be used to inactivate non-enveloped viruses present within a sample of whole blood or a blood product and comprises (a) adding to the blood sample a photoactivatable viricide, such as a psoralen, hypericin, methylene blue, toluidine blue or the like, which, when activated, is effective in inactivating enveloped viruses; (b) adding to the blood sample a viricide-potentiating chemical agent that increases the sensitivity of non-enveloped viruses to the activated viricide; and (c) activating the photoactivatable viricide. Preferably, the viricide-potentiating chemical agent includes a first moiety which possesses an affinity for a component of the non-enveloped virus and a second moiety which includes a lipid tail, the first and second moieties being structurally interrelated so that, when the first moiety becomes associated with a component of the non-enveloped virus, the second moiety penetrates or at least partially surrounds the viral capsid of the non-enveloped virus. Examples of the chemical agent include cationic lipopolyamines, such as dioctadecylamidoglycylspermine.
摘要翻译：使用杀病毒剂增效剂灭活非包膜病毒的方法。在优选的实施方案中，该方法可用于灭活全血或血液制品样品中存在的非包膜病毒，并且包括（a）向血液样品中加入可光活化的杀戮剂，例如补骨脂素，金丝桃素，亚甲基蓝甲苯胺蓝等，其在活化时有效灭活包膜病毒; （b）向血液样品中加入增加非包膜病毒对活化杀戮剂的敏感性的杀病剂增效化学试剂; 和（c）活化可光活化杀戮剂。优选地，杀病毒剂增强化学试剂包括对非包膜病毒的组分具有亲和力的第一部分和包含脂质尾部的第二部分，第一和第二部分在结构上相互关联，使得当第一部分变得与非包膜病毒的组分相关联，第二部分渗透或至少部分地包围非包膜病毒的病毒衣壳。化学试剂的实例包括阳离子脂多胺，如双十八烷基酰氨基甘氨酰精胺。

5. 发明申请

WO1996008580A1 IN VITRO METHOD FOR PREDICTING THE EVOLUTIONARY RESPONSE OF HIV PROTEASE TO A DRUG TARGETED THEREAGAINST 审中-公开
标题翻译：用于预测艾滋病病毒蛋白酶对药物靶向药物的演变反应的体外方法
公开(公告)号：WO1996008580A1
公开(公告)日：1996-03-21
申请号：PCT/US1995011860
申请日：1995-09-18
申请人： SEPRACOR INC. , MELNICK, Laurence, M. , HEEFNER, Donald, L.
发明人： SEPRACOR INC.
IPC分类号： C12Q01/37
CPC分类号： C12N9/506 , C12N15/1048 , C12Q1/37 , C12Q1/6811 , G01N2333/16 , G01N2333/8142 , Y10S435/974 , Y10S435/975
摘要： An in vitro method for identifying distinct, first generation, drug-resistant, biologically active, HIV protease mutants that may emerge in vivo in response to a drug targeted thereagainst comprising: (a) preparing, in the presence of the drug, a library of all first-generation mutants of the protease differing therefrom by one to three amino acid substitutions, each of the protease mutants being generated as part of a polyprotein with reverse transcriptase; (b) isolating drug-resistant, biologically-active mutant proteases by assaying for activity of the reverse transcriptase; and (c) identifying the distinct amino acid changes leading to the drug-resistance of the active, mutant proteases so isolated. An in vitro method for evaluating the efficacy of a drug against a biologically active mutant or wild-type form of HIV protease comprising combining the drug and a mutant polyprotein, comprising an inactive HIV protease, HIV reverse transcriptase, and one or more protease cleavage sites, adding biologically-active mutant or wild-type protease, assaying for release of active reverse transcriptase, whereby reverse transcriptase activity indicates that the drug is not efficacious against the mutant or wild-type form of HIV protease tested.
摘要翻译：一种体外方法，其用于鉴定可能在其靶向靶向药物的体内可能出现的不同的第一代，耐药性，生物活性的HIV蛋白酶突变体，其包括：（a）在所述药物存在下，制备所有蛋白酶突变体的所有第一代突变体通过一至三个氨基酸取代基与之不同，每个蛋白酶突变体作为具有逆转录酶的多聚蛋白的一部分产生; （b）通过测定逆转录酶的活性来分离耐药性，生物活性的突变型蛋白酶; 和（c）鉴定导致如此分离的活性突变蛋白酶的耐药性的不同氨基酸变化。一种用于评估药物对生物活性突变体或野生型形式的HIV蛋白酶的功效的体外方法，包括将药物和突变体多蛋白（包括无活性的HIV蛋白酶，HIV逆转录酶和一个或多个蛋白酶切割位点），添加生物活性突变体或野生型蛋白酶，测定活性逆转录酶的释放，由此逆转录酶活性表明该药物对于所测试的HIV蛋白的突变体或野生型形式是无效的。

6. 发明申请

WO2004043447A2 COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING HEARING IMPAIRMENT 审中-公开
标题翻译：用于治疗或预防听觉障碍的组合物和方法
公开(公告)号：WO2004043447A2
公开(公告)日：2004-05-27
申请号：PCT/US2003/036269
申请日：2003-11-13
申请人： SEPRACOR, INC. , CURRIE, Mark, G. , HEEFNER, Donald, L. , RUBIN, Paul , ZEPP, Charles, M.
发明人： CURRIE, Mark, G. , HEEFNER, Donald, L. , RUBIN, Paul , ZEPP, Charles, M.
IPC分类号： A61K31/17
CPC分类号： A61K31/17 , A61K31/495
摘要： Ototoxic side-effects have either limited the application of an important group of antibiotics, aminoglycoside antibiotics, or have added further burden to those who have to resort to platinum-containing antineoplastic agents to treat life-threatening tumors. The present invention discloses pharmaceutical compositions that prevent or treat the ototoxic side-effects of aminoglycoside antibiotics and platinum-containing antineoplastic agents. The otoprotective compositions disclosed herein can also be used to treat noise induced hearing loss.
摘要翻译：耳毒性副作用限制了一组重要的抗生素，氨基糖苷类抗生素的应用，或者为那些不得不使用含铂抗肿瘤剂治疗危及生命的肿瘤的人增加了进一步的负担。本发明公开了预防或治疗氨基糖苷类抗生素和含铂抗肿瘤剂的耳毒性副作用的药物组合物。本文公开的保护性组合物也可用于治疗噪声引起的听力损失。

7. 发明申请

WO9857931A3 QUINOLINE-INDOLE ANTIMICROBIAL AGENTS, USES AND COMPOSITIONS RELATED THERETO 审中-公开
标题翻译：喹诺酮类抗生素代谢物，用途及组合物
公开(公告)号：WO9857931A3
公开(公告)日：1999-04-29
申请号：PCT/US9812762
申请日：1998-06-18
申请人： SEPRACOR INC , KUMARAVEL GNANASAMBANDAM , HOEMANN MICHAEL Z , MELIKIAN BADALIAN ANITA , CUNY GREGORY D , HAUSKE JAMES R , HEEFNER DONALD L , ROSSI RICHARD F
发明人： KUMARAVEL GNANASAMBANDAM , HOEMANN MICHAEL Z , MELIKIAN-BADALIAN ANITA , CUNY GREGORY D , HAUSKE JAMES R , HEEFNER DONALD L , ROSSI RICHARD F
IPC分类号： C07D491/048 , A61K31/4709 , A61K31/4725 , A61K31/4738 , A61K31/496 , A61K31/497 , A61K31/5377 , A61K31/541 , A61K31/551 , A61P31/04 , C07D209/12 , C07D209/14 , C07D215/52 , C07D401/04 , C07D401/14 , C07D405/04 , C07D405/14 , C07D409/04 , C07D453/02 , C07D471/04 , C07D491/04 , C07D491/056 , A61K31/395 , C07D471/08
CPC分类号： C07D401/14 , C07D209/12 , C07D209/14 , C07D215/52 , C07D401/04 , C07D405/04 , C07D409/04 , C07D471/04 , C07D491/04
摘要： Compounds of general formula (1), or a pharmaceutically acceptable salt and/or prodrug thereof, wherein each of A and B independently represent fused rings selected from a group consisting of monocyclic or polycyclic cycloalkyls, cycloalkenyls, aryls, and heterocyclic rings, said rings comprising from 4 to 8 atoms in a ring structure; X represents Cr, N, N(O), P, or As; Y represents CR2, R, O, PR, AsR, or Se; and pharmaceutical preparations that inhibit the growth of bacterial microorganism.
摘要翻译：通式（1）的化合物或其药学上可接受的盐和/或前药，其中A和B各自独立地表示选自单环或多环环烷基，环烯基，芳基和杂环的稠合环，所述环包含4至8个环结构的原子; X表示Cr，N，N（O），P或As; Y表示CR2，R，O，PR，AsR或Se; 以及抑制细菌微生物生长的药物制剂。

8. 发明申请

WO1995018530A1 INACTIVATION OF VIRUSES PRESENT IN BLOOD COMPONENTS USING CHEMICALLY-ACTIVATED COMPOUNDS 审中-公开
标题翻译：使用化学活化的化合物在血液组分中存在的病毒灭活
公开(公告)号：WO1995018530A1
公开(公告)日：1995-07-13
申请号：PCT/US1995000464
申请日：1995-01-09
申请人： HEMASURE INC. , ZEPP, Charles, M. , HEEFNER, Donald, L.
发明人： HEMASURE INC.
IPC分类号： A01N01/02
CPC分类号： C07F9/65512 , A61L2/0082 , A61L2/16 , C07F9/6561 , C12N7/06
摘要： A method of inactivating viral molecules present within a blood sample and compounds for use in same. The method involves adding to a virus-containing blood sample an effective quantity of a compound which both has an affinity for viral nucleic acid and which is activatable to an excited state in which the compound covalently binds viral nucleic acid. After permitting the compound to complex with viral nucleic acid, the compound is raised to its excited state by chemical activation. In a first preferred embodiment, psoralen, hypericin or a derivative of psoralen or hypericin is used as the activatable, viral-inactivating compound, and chemical activation of the compound is effected by the decomposition of a dioxetane proximate to the nucleic acid/compound complex. In a second preferred embodiment, the activatable, viral-inactivating compound is incorporated into a dioxetane molecule, and chemical activation of the compound is effected by decomposition of the dioxetane into a pair of carbonyl compounds.
摘要翻译：使血液样品中存在的病毒分子灭活的方法和用于其中的化合物。该方法包括向含病毒的血液样品中加入有效量的化合物，其对于病毒核酸具有亲和性，并且其可激活至激活状态，其中化合物共价结合病毒核酸。在使化合物与病毒核酸复合后，通过化学活化将化合物升至其激发态。在第一优选实施方案中，补骨脂素，金丝桃素或补骨脂素或金丝桃素的衍生物用作可激活的病毒灭活化合物，化合物的化学活化通过邻近核酸/化合物复合物的二氧杂环丁烷的分解来实现。在第二优选实施方案中，将可活化的病毒灭活化合物掺入二氧杂环丁烷分子中，化合物的化学活化通过将二氧杂环丁烷分解成一对羰基化合物来实现。

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