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1. 发明申请

WO1997040809A2 METHOD OF ENHANCING EFFECT OF NEUROTROPHIN WITH ANALOGUES OF p75NTR367-379 审中-公开
标题翻译：增强神经营养因子与p75 367-379类似物的作用的方法
公开(公告)号：WO1997040809A2
公开(公告)日：1997-11-06
申请号：PCT/CA1997000271
申请日：1997-04-23
申请人： QUEEN'S UNIVERSITY AT KINGSTON , RIOPELLE, Richard, J. , WEAVER, Donald, F. , ROSS, Gregory, M. , SHAMOVSKY, Igor, L.
发明人： QUEEN'S UNIVERSITY AT KINGSTON
IPC分类号： A61K00/00
CPC分类号： C07K14/70578 , A61K38/00
摘要： The present invention provides methods and compositions for enhancing an effect or effects of a neurotrophin, preferably, but not limited to, enhancing the growth and survival promoting properties of neurotrophins. The cytoplasmic region of the common neurotrophin receptor (p75 ) (rat, human, chick) contains a putative membrane-associating domain implicated in intracellular signalling. A peptide (R3) identical to this domain (p75 367-379) and various analogues of this peptide displayed circular dichroism spectra in aqueous and non-polar environments identical to the amphiphilic tetradecapeptide mastoparan (MP), and were internalized by PC12 rat pheochromocytoma cells. The R3 peptide enhanced neurite growth in PC12 cells, chick embryo primary sensory neurons, and fetal rat primary sensory neurons in vitro in the presence of sub-saturating concentrations of NGF. Peptide analogues of R3 not faithful to the distance and angular relationships of ionic groups, and the putative amphiphilic structure of p75 367-379, while still providing some enhancement, nevertheless displayed reduced potency to enhance NGF-mediated neurite growth. The common neurotrophin receptor p75 activates and translocates the nuclear transcription factor NFkB and displays pro-apoptotic effects similar to other members of the TNF receptor superfamily. A peptide mimic of the amphiphilic domain 367-379 of p75 that enhances TrkA mediated neurite growth by NGF, was used to affinity purify cytoplasmic proteins from PC12 cells. Isolated proteins contained a predominant species with an apparent molecular weight of 65 kDa. The affinity purified 65 kDa protein, as well as a protein of similar molecular mass from crude cell extracts, were identified by immunoblotting with antibody to NFkB. The 65 kDa species was chemically cross-linked to the radiolabeled analogue of the peptide mimic of p75 and immunoprecipitated by antibody to NFkB. These observations, taken together with the finding that a p75 -selective NGF antagonist blocked mediated neurite growth in limiting NGF conditions, support the view that p75 participates in neurite growth via a signaling pathway involving the translocation of NFkB.
摘要翻译：本发明提供了用于增强神经营养因子的作用或效果的方法和组合物，优选但不限于增强神经营养因子的生长和存活促进性质。常见的神经营养因子受体（p75 ）（大鼠，人，小鸡）的细胞质区域含有涉及细胞内信号传导的推定的膜结合域。与该结构域相同的肽（R3）（p75 367-379）和该肽的各种类似物在与两亲性十四肽mastoparan（MP）相同的水性和非极性环境中显示圆二色性光谱，并且被PC12内化大鼠嗜铬细胞瘤细胞。在亚饱和浓度的NGF的存在下，R3肽在体外增强了PC12细胞，鸡胚原代感觉神经元和胎儿大鼠初级感觉神经元中的神经突生长。不符合离子基团的距离和角度关系的R3的肽类似物，以及p75 367-379的推定的两亲结构，同时仍然提供一些增强，但是显示降低的效力以增强NGF介导的神经突生长。常见的神经营养因子受体p75 激活和转位核转录因子NFkB，并显示类似于TNF受体超家族其他成员的促凋亡作用。使用通过NGF增强TrkA介导的神经突生长的p75 的两亲结构域367-379的肽模拟物用于从PC12细胞中亲和纯化细胞质蛋白。分离的蛋白质含有表观分子量为65kDa的主要物种。通过用NFkB的抗体进行免疫印迹鉴定亲和纯化的65kDa蛋白质，以及来自粗细胞提取物的相似分子量的蛋白质。将65kDa物质与p75 的肽模拟物的放射性标记的类似物进行化学交联，并通过抗NFkB的抗体免疫沉淀。这些观察结果与P75 选择性NGF拮抗剂在限制NGF条件下阻断介导的神经突生长的发现一起支持p75 通过涉及NFkB易位的信号通路参与神经突生长的观点。

2. 发明申请

WO1998006048A2 MOLECULAR MODELLING OF NEUROTROPHIN-RECEPTOR BINDING 审中-公开
标题翻译：神经营养受体结合的分子建模
公开(公告)号：WO1998006048A2
公开(公告)日：1998-02-12
申请号：PCT/CA1997000539
申请日：1997-07-31
申请人： QUEEN'S UNIVERSITY AT KINGSTON , SHAMOVSKY, Igor, L. , ROSS, Gregory, M. , RIOPELLE, Richard, J. , WEAVER, Donald, F.
发明人： QUEEN'S UNIVERSITY AT KINGSTON
IPC分类号： G06F17/50
CPC分类号： G06F19/16 , C07K14/475
摘要： The present invention relates to a computational method for identifying the bioactive conformations of peptide domains, in particular, the geometries of complexes of neurotrophins and their receptors. The bioactive conformation of the Nerve Growth Factor (NGF) amino and carboxyl termini (Trk binding domain) was determined. The complex of the NGF termini splits into two distinct regions: a rigid region (residues 9-11 and 112'-118') and a flexible loop (residues 1-8), the geometry of the rigid region, which is maintained by electrostatic interaction between Glu and Arg , is conserved in active molecules only. The separation of the flexible loop from the rigid region is necessary in order to eliminate an influence of the loop on the biologically active conformation of the rigid region. The present invention also relates to a method for identifying and theoretically modelling specific receptor binding sites for Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) on their receptors, TrkA and TrkB, respectively. The present invention also relates to a method for identifying and theoretically modelling a receptor binding site for neurotrophins, such as NGF, BDNF, NT-3, and NT-4/5, of the common neurotrophin receptor p75 .
摘要翻译：本发明涉及用于鉴定肽结构域的生物活性构象的计算方法，特别是神经营养因子及其受体的复合物的几何形状。确定神经生长因子（NGF）氨基和羧基末端（Trk结合结构域）的生物活性构象。 NGF末端的复合物分成两个不同的区域：刚性区域（残基9-11和112'-118'）和柔性环（残基1-8），刚性区域的几何形状由静电 Glu 11和Arg <118>之间的相互作用仅在活性分子中保守。柔性环与刚性区的分离是必要的，以消除环对刚性区的生物活性构象的影响。本发明还涉及用于分别鉴定神经生长因子（NGF）和脑衍生神经营养因子（BDNF）的特异性受体结合位点对其受体TrkA和TrkB进行理论建模的方法。本发明还涉及用于鉴定和理论模拟常见神经营养因子受体p75 的神经营养因子（如NGF，BDNF，NT-3和NT-4/5）的受体结合位点的方法。

3. 发明申请

WO1997049735A1 NERVE PROCESS GROWTH MODULATORS 审中-公开
标题翻译：神经过程生长调节剂
公开(公告)号：WO1997049735A1
公开(公告)日：1997-12-31
申请号：PCT/CA1997000437
申请日：1997-06-20
申请人： QUEEN'S UNIVERSITY AT KINGSTON , DOW, Kimberly, E. , GORINE, Boris I. , RIOPELLE, Richard, J. , THATCHER, Gregory
发明人： QUEEN'S UNIVERSITY AT KINGSTON
IPC分类号： C08B37/16
CPC分类号： C08B37/0012 , A61K31/724
摘要： Nerve process growth modulation can be achieved using derivatized cyclodextrins. Processes for making sulfated and aminated beta -cyclodextrin derivatives are also described in which a compound of the formula R''2 NCH X' X' where R'' is an alkyl containing 1-5 carbon atoms and X' is selected from bromine and iodine is used to halogenate the cyclodextrin.
摘要翻译：使用衍生的环糊精可以实现神经过程生长调节。还描述了制备硫酸化和胺化的β-环糊精衍生物的方法，其中式R''2NCH X'X' - 的化合物其中R“是含有1-5个碳原子的烷基和X '选自溴，碘用于卤化环糊精。

4. 发明申请

WO1997039760A1 COMBINATION THERAPY FOR TREATMENT OF ERECTILE DYSFUNCTION 审中-公开
标题翻译：治疗溃疡性功能障碍的组合治疗
公开(公告)号：WO1997039760A1
公开(公告)日：1997-10-30
申请号：PCT/CA1997000264
申请日：1997-04-23
申请人： QUEEN'S UNIVERSITY AT KINGSTON , ADAMS, Michael, A. , HEATON, Jeremy, P., W. , MAURICE, Donald, H.
发明人： QUEEN'S UNIVERSITY AT KINGSTON
IPC分类号： A61K33/26
CPC分类号： A61K31/34 , A61K31/198 , A61K31/21 , A61K31/295 , A61K31/5377 , A61K38/063 , A61K45/06
摘要： In the field of treatment of erectile dysfunction there is disclosed a novel therapy in which the actions of an agent or agents, produce a combination of effects to induce effective erection (and avoid priapism) while reducing or entirely avoiding pain. The method taught combines a first action of an agent which is to antagonize a drug-induced pain stimulus within nociceptive nerves of penile tissue with a second action of either the same agent or of a second agent, which enhances, synergistically, smooth muscle relaxation. The synergism allows for at least an equivalent effect of smooth muscle relaxation to be obtained at significantly lower doses of a smooth muscle relaxing agent such as PGE1 which in standard therapy is also in 40-45 % of cases pain-inducing at doses which achieve effective erection. Thus, in an anatomical site where nociceptive tissue is in close proximity to one or more effector systems, the method enhances the effector system while reducing nociception in the nociceptive tissue which nociception would be caused by an agent such as PGE1 which is used to trigger the effector system.
摘要翻译：在治疗勃起功能障碍的领域中，公开了一种新颖的治疗方法，其中药剂或药剂的作用产生组合的效应以诱导有效勃起（并避免阴茎异常勃起），同时减少或完全避免疼痛。所述方法结合了药剂的第一作用，其是在相同药剂或第二药剂的第二作用下拮抗阴茎组织伤害性神经内的药物诱发的疼痛刺激，其增强，协同地平滑肌肉松弛。协同作用允许在明显较低剂量的平滑肌松弛剂（例如PGE1）下获得平滑肌松弛的至少等效效果，其在标准治疗中也是在实现有效的剂量下疼痛诱导的40-45％的病例勃起。因此，在伤害性组织紧邻一个或多个效应系统的解剖部位中，该方法增强了效应系统，同时减少了伤害感受性组织中的伤害感受，其中伤害感受会由诸如PGE1的药剂引起，其用于触发效应系统。

5. 发明申请

WO1994010303A1 MULTIDRUG RESISTANCE GENE 审中-公开
标题翻译：多抗性基因
公开(公告)号：WO1994010303A1
公开(公告)日：1994-05-11
申请号：PCT/CA1993000439
申请日：1993-10-27
申请人： QUEEN'S UNIVERSITY AT KINGSTON
发明人： QUEEN'S UNIVERSITY AT KINGSTON , DEELEY, Roger, G. , COLE, Susan, P., C.
IPC分类号： C12N15/12
CPC分类号： C12N15/8509 , A01K2217/05 , A01K2217/075 , A01K2217/30 , A01K2267/03 , A61K38/00 , C07K14/705 , C07K16/28 , C07K16/30 , C07K2317/34
摘要： A novel protein associated with multidrug resistance in living cells and capable of conferring multidrug resistance on a cell is disclosed and nucleic acids encoding the novel isoforms are disclosed. Transformant cell lines which express the nucleic acid encoding the novel protein are also disclosed. Further, diagnostic and treatment methods using the novel protein, nucleic acids and cell lines are also disclosed.
摘要翻译：公开了与活细胞中多药耐药相关并且能够赋予细胞多药耐药性的新型蛋白质，并公开了编码新型同种型的核酸。还公开了表达编码新蛋白质的核酸的转化体细胞系。此外，还公开了使用新型蛋白质，核酸和细胞系的诊断和治疗方法。

6. 发明申请

WO1993024530A1 SERUM AMYLOID A PROTEIN 审中-公开
标题翻译：血清AMYLOID A蛋白
公开(公告)号：WO1993024530A1
公开(公告)日：1993-12-09
申请号：PCT/CA1993000155
申请日：1993-05-14
申请人： QUEEN'S UNIVERSITY AT KINGSTON
发明人： QUEEN'S UNIVERSITY AT KINGSTON , KISILEVSKY, Robert
IPC分类号： C07K15/06
CPC分类号： C07K14/775 , A61K38/00
摘要： A method is provided for potentiating the efflux of cholesterol from the macrophage, the method including the steps of increasing the affinity of high-density lipoprotein for macrophages by the administration of a serum amyloid A/high-density lipoprotein complex, exposing the macrophage to the complex, and potentiating macrophage cholesterol efflux.
摘要翻译：提供了一种增强胆固醇从巨噬细胞流出的方法，该方法包括通过施用血清淀粉样蛋白A /高密度脂蛋白复合物增加高密度脂蛋白对巨噬细胞的亲和力的步骤，将巨噬细胞暴露于复杂和增强的巨噬细胞胆固醇流出。

7. 发明申请

WO1993003073A1 AZO POLYMERS FOR REVERSIBLE OPTICAL STORAGE 审中-公开
标题翻译：用于可逆光存储的AZO聚合物
公开(公告)号：WO1993003073A1
公开(公告)日：1993-02-18
申请号：PCT/CA1992000318
申请日：1992-07-28
申请人： QUEEN'S UNIVERSITY AT KINGSTON
发明人： QUEEN'S UNIVERSITY AT KINGSTON , NATANSOHN, Almeria, L. , ROCHON, Paul, L. , XIE, Shuang
IPC分类号： C08F20/00
CPC分类号： G11B7/0055 , G11B7/245 , Y10S430/146
摘要： A novel series of azo polymers, copolymers and polymer blends for reversible optical storage devices are described. Various azobenzenes can be bound in the side chain or within the main chain of long chain polymers such as polyester, polystyrene and poly methacrylates with very short or no spacers to form amorphous polymers which as a film or deposited on a transparent substrate can be used to record optical information using a linearly polarized laser beam which induces optical anisotropy in the film. The information can be erased thermally by heating above the glass transition temperature, or optically by overwriting with light polarized in a predefined zero direction or with circularly polarized light.

8. 发明申请

WO1998021346A1 ENHANCED TRANSPORT WITH A PLASTID MEMBRANE TRANSPORT PROTEIN 审中-公开
标题翻译：增强运输与塑料膜运输蛋白质
公开(公告)号：WO1998021346A1
公开(公告)日：1998-05-22
申请号：PCT/CA1997000799
申请日：1997-11-04
申请人： QUEEN'S UNIVERSITY AT KINGSTON , KO, Kenton , PANG, Peng
发明人： QUEEN'S UNIVERSITY AT KINGSTON
IPC分类号： C12N15/67
CPC分类号： C12N15/65 , C07K14/415 , C12N15/67 , C12N15/70 , C12N15/8209 , C12N15/8216 , C12N15/8221
摘要： A novel method to enhance translocation of molecules across or into cellular membranes using a plastid protein transport gene is described. The method can also be used to incorporate substances into membranes of organisms. Nucleic acid constructs include those which express a plastid protein transport protein or its equivalent in cells of all organisms.
摘要翻译：描述了使用质体蛋白质转运基因增强分子穿过或进入细胞膜的易位的新方法。该方法也可以用于将物质掺入生物膜中。核酸构建体包括在所有生物的细胞中表达质体蛋白质转运蛋白或其等同物的构建体。

9. 发明申请

WO1997046674A1 SPRUCE BUDWORM ANTIFREEZE PROTEINS, GENES AND METHODS OF USING SAME 审中-公开
标题翻译： SPRUCE BUDWORM抗体蛋白，基因及其使用方法
公开(公告)号：WO1997046674A1
公开(公告)日：1997-12-11
申请号：PCT/CA1997000371
申请日：1997-06-03
申请人： QUEEN'S UNIVERSITY AT KINGSTON , WALKER, Virginia, K. , DAVIES, Peter, L. , RAHAVARD, Mitra , TYSHENKO, Michael, G.
发明人： QUEEN'S UNIVERSITY AT KINGSTON
IPC分类号： C12N15/12
CPC分类号： A01N1/0221 , A01K2217/05 , A01N1/02 , A01N1/0205 , C07K14/43563 , C09K5/20
摘要： A class of thermal hysterisis, antifreeze proteins (THPs) has been isolated and purified from Choristoneura sp., including the spruce budworm C. fumiferana. The invention provides for nucleic acids which encode these antifreeze proteins. The invention also provides for antibodies reactive to these antifreeze proteins. The invention also includes a method for decreasing the freezing point of an aqueous solution by adding these antifreeze proteins to the solution.
摘要翻译：已经从Choristoneura sp。分离和纯化一类热滞后，防冻蛋白（THPs），包括云杉芽孢C. fumiferana。本发明提供编码这些防冻蛋白的核酸。本发明还提供对这些抗冻蛋白具有反应性的抗体。本发明还包括通过将这些防冻蛋白加入溶液来降低水溶液的凝固点的方法。

10. 发明申请

WO1995028930A1 DOSAGE FORMS AND METHOD FOR AMELIORATING MALE ERECTILE DYSFUNCTION 审中-公开
标题翻译：用于改善男性精神功能障碍的剂型和方法
公开(公告)号：WO1995028930A1
公开(公告)日：1995-11-02
申请号：PCT/US1995004897
申请日：1995-04-21
申请人： PENTECH PHARMACEUTICALS, INC. , QUEEN'S UNIVERSITY AT KINGSTON
发明人： PENTECH PHARMACEUTICALS, INC. , QUEEN'S UNIVERSITY AT KINGSTON , EL-RASHIDY, Ragab , HEATON, Jeremy, P., W. , MORALES, Alvaro , ADAMS, Michael, A.
IPC分类号： A61K31/485
CPC分类号： A61K31/00 , A61K9/0056 , A61K9/006 , A61K31/473 , A61K31/485 , A61K49/0004
摘要： Pyschogenic impotence or erectile dysfunction can be identified in psychogenic male patients and can be ameliorated, without substantial undesirable side effects, by sublingual administration of apomorphine dosage forms that contain about 2.5 to about 10 milligrams of apomorphine and dissolve within a time period of about 2 to about 5 minutes.
摘要翻译：潜心性勃起功能障碍或勃起功能障碍可以通过舌下施用含有约2.5至约10毫克阿扑吗啡的阿扑吗啡剂型，并在约2〜约5分钟。

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