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21. 发明申请

US20110097720A1 SCREENING METHOD FOR SELECTED AMINO LIPID-CONTAINING COMPOSITIONS 审中-公开
标题翻译：选择含氨基脂肪的组合物的筛选方法
公开(公告)号：US20110097720A1
公开(公告)日：2011-04-28
申请号：US12811503
申请日：2008-12-31
申请人： Marco A. Ciufolini , Thomas D. Madden , Michael J. Hope , Barbara Mui , De Fougerolles Antonin , Tatiana Novobrantseva , Anna Borodovsky , Akin Akinc , Mark Tracy , Pieter Rutter Cullis
发明人： Marco A. Ciufolini , Thomas D. Madden , Michael J. Hope , Barbara Mui , De Fougerolles Antonin , Tatiana Novobrantseva , Anna Borodovsky , Akin Akinc , Mark Tracy , Pieter Rutter Cullis
IPC分类号： C12Q1/68 , C12Q1/02
CPC分类号： G01N33/5088 , A01K2207/05 , A01K2227/105 , A01K2267/0381 , C12N15/111 , C12N15/1137 , C12N2310/14 , C12N2320/10 , C12Q1/6876 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178 , C12Y304/21021 , G01N33/5023 , G01N33/5067 , G01N33/86 , G01N2333/745 , G01N2333/96447
摘要： The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-Dilinoley 1-4-dimethylaminomethyl-[1,3]-dioxolane by screening for an effect of the agent on the liver of a model subject.
摘要翻译：本发明的特征在于通过筛选试剂对模型受试者的肝脏的影响来鉴定治疗相关组合物的方法，所述组合物包括治疗剂和2,2-二苯胺基-4-二甲基氨基甲基 - [1,3] - 二氧杂环戊烷。

22. 发明申请

US20110086826A1 LIPOSOMAL CAMPTOTHECINS AND USES THEREOF 审中-公开
标题翻译：脂质体及其用途
公开(公告)号：US20110086826A1
公开(公告)日：2011-04-14
申请号：US12963888
申请日：2010-12-09
申请人： Thomas D. MADDEN , Sean F. SEMPLE
发明人： Thomas D. MADDEN , Sean F. SEMPLE
IPC分类号： A61K31/575 , A61K9/127 , A61K31/4745 , A61P35/00 , A61P7/02
CPC分类号： A61K9/127 , A61K9/1272 , A61K9/1278 , A61K31/4745 , A61K45/06 , A61K2300/00
摘要： This invention relates to improved liposomal camptothecin compositions and methods of manufacturing and using such compositions for treating neoplasia and for inhibiting angiogenesis.
摘要翻译：本发明涉及改进的脂质体喜树碱组合物以及制备和使用这些组合物治疗瘤形成和抑制血管生成的方法。

23. 发明授权

US07452550B2 Liposomal antineoplastic drugs and uses thereof 有权
标题翻译：脂质体抗肿瘤药物及其用途
公开(公告)号：US07452550B2
公开(公告)日：2008-11-18
申请号：US11430522
申请日：2006-05-09
申请人： Thomas D. Madden , Sean C. Semple , Quet F. Ahkong
发明人： Thomas D. Madden , Sean C. Semple , Quet F. Ahkong
IPC分类号： A61K9/127
CPC分类号： A61K9/127 , A61K9/0019 , A61K31/4745 , A61K31/496
摘要： This invention relates to liposomal antineoplastic agents (e.g., camptothecin) compositions and methods of using such compositions for treating neoplasia and for inhibiting angiogenesis. The compositions and methods are useful for modulating the plasma circulation half-life of an active agent.
摘要翻译：本发明涉及脂质体抗肿瘤剂（例如喜树碱）组合物和使用这些组合物治疗瘤形成和抑制血管生成的方法。组合物和方法可用于调节活性剂的血浆循环半衰期。

24. 发明授权

US5885613A Bilayer stabilizing components and their use in forming programmable fusogenic liposomes 失效
标题翻译：双层稳定组分及其在形成可编程融合脂质体中的应用
公开(公告)号：US5885613A
公开(公告)日：1999-03-23
申请号：US485608
申请日：1995-06-07
申请人： John W. Holland , Thomas D. Madden , Pieter R. Cullis
发明人： John W. Holland , Thomas D. Madden , Pieter R. Cullis
IPC分类号： A61K9/127 , A61K47/18 , B01J13/02
CPC分类号： A61K9/1272 , Y10T428/2984
摘要： The present invention provides a fusogenic liposome comprising a lipid capable of adopting a non-lamellar phase, yet capable of assuming a bilayer structure in the presence of a bilayer stabilizing component; and a bilayer stabilizing component reversibly associated with the lipid to stabilize the lipid in a bilayer structure. Such fusogenic liposomes are extremely advantageous because the rate at which they become fusogenic can be not only predetermined, but varied as required over a time scale ranging from minutes to days. Control of liposome fusion can be achieved by modulating the chemical stability and/or exchangeability of the bilayer stabilizing component(s). The fusogenic liposomes of the present invention can be used to deliver drugs, peptide, proteins, RNA, DNA or other bioactive molecules to the target cells of interest.
摘要翻译：本发明提供了一种融合脂质体，其包含能够采用非层状相的脂质，但能够在双层稳定成分存在下具有双层结构; 和与脂质可逆地相关的双层稳定组分以稳定双层结构中的脂质。这种融合脂质体是非常有利的，因为它们变得融合的速率不仅可以预先确定，而且可以在数分钟到数天的时间范围内根据需要而变化。脂质体融合的控制可通过调节双层稳定化组分的化学稳定性和/或可交换性来实现。本发明的融合脂质体可用于将药物，肽，蛋白质，RNA，DNA或其他生物活性分子递送至感兴趣的靶细胞。

25. 发明授权

US5837279A Encapsulation of ionizable agents in liposomes 失效
标题翻译：电离剂在脂质体中的封装
公开(公告)号：US5837279A
公开(公告)日：1998-11-17
申请号：US450831
申请日：1995-05-25
申请人： Andrew S. Janoff , Pieter R. Cullis , Marcel B. Bally , Michael W. Fountain , Richard S. Ginsberg , Michael J. Hope , Thomas D. Madden , Hugh P. Schieren , Regina L. Jablonski
发明人： Andrew S. Janoff , Pieter R. Cullis , Marcel B. Bally , Michael W. Fountain , Richard S. Ginsberg , Michael J. Hope , Thomas D. Madden , Hugh P. Schieren , Regina L. Jablonski
IPC分类号： C07D475/08 , A61K9/00 , A61K9/10 , A61K9/127 , A61K31/435 , A61K31/505 , A61K31/519 , A61K31/70 , A61K31/7028 , A61K31/7034 , A61K31/704 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/715 , A61K45/00 , A61K45/08 , A61K47/26 , A61K47/36 , A61K47/48 , A61P35/00 , B01J13/02 , B01J13/04 , C07D519/00 , C07H15/252 , C07H19/09
CPC分类号： A61K9/1277 , A61K9/1271 , A61K9/1278
摘要： Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration. Concentration gradients capable of generating transmembrane potentials can be created across the liposome membranes either before or after dehydration, and the transmembrane potentials resulting from these gradients can be used to load charged materials, e.g., drugs, into the liposomes.
摘要翻译：通过在一种或多种保护性糖例如二糖类海藻糖和蔗糖的存在下，减压干燥脂质体制剂来制备脱水脂质体。优选地，保护性糖存在于脂质体膜的内表面和外表面。在脱水之前冻干脂质体制剂是任选的。或者，如果：（1）脂质体是具有多个脂质层的类型，则可以省略保护性糖; （2）脱水是在没有预先冻结的情况下进行的; 和（3）脱水进行到终点，导致制剂中留有足够的水（例如，至少12摩尔水/摩尔脂质），使得大部分多脂质层的完整性保持在补液。可以在脱水之前或之后在脂质体膜上产生能够产生跨膜电位的浓度梯度，并且由这些梯度产生的跨膜电位可用于将带电材料（例如药物）加载到脂质体中。

26. 发明授权

US5736155A Encapsulation of antineoplastic agents in liposomes 失效
标题翻译：抗肿瘤剂在脂质体中的封装
公开(公告)号：US5736155A
公开(公告)日：1998-04-07
申请号：US461212
申请日：1995-06-05
申请人： Marcel B. Bally , Pieter R. Cullis , Michael J. Hope , Thomas D. Madden , Lawrence D. Mayer
发明人： Marcel B. Bally , Pieter R. Cullis , Michael J. Hope , Thomas D. Madden , Lawrence D. Mayer
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K9/1278 , A61K9/1271 , A61K9/1277
摘要： Methods for encapsulating ionizable antineoplastic agents in liposomes using transmembrane potentials are provided. Trapping efficiencies approaching 100% and rapid loading are readily achieved. Dehydration protocols which allow liposomes to be conveniently used in the administration of antineoplastic agents in a clinical setting are also provided. In accordance with other aspects of the invention, transmembrane potentials are used to reduce the rate of release of ionizable drugs from liposomes.
摘要翻译：提供了使用跨膜电位将可电离抗肿瘤剂包封在脂质体中的方法。捕获效率接近100％，快速加载容易实现。还提供允许脂质体在临床环境中方便地用于施用抗肿瘤剂的脱水方案。根据本发明的其他方面，使用跨膜电位来降低可离子化药物从脂质体释放的速率。

27. 发明授权

US5389378A Benzoporphyrin vesicles and their use in photodynamic therapy 失效
标题翻译：苯并卟啉囊泡及其在光动力疗法中的应用
公开(公告)号：US5389378A
公开(公告)日：1995-02-14
申请号：US990923
申请日：1992-12-15
申请人： Thomas D. Madden
发明人： Thomas D. Madden
IPC分类号： A61K9/127 , A61K31/40 , A61K41/00
CPC分类号： A61K41/0071 , A61K31/40 , A61K9/127 , Y10T428/2984
摘要： This invention relates to benzoporphyrin containing vesicles which are suitable for pharmaceutical application. In particular, the present invention relates to a liposomal preparation of benzoporphyrin (BPD) incorporated into vesicles comprising a liposome forming lipid such as EPC or DMPC at a drug to lipid ratio of greater than 100 .mu.g/umole lipid which will allow adequate drug dosing with relatively low lipid concentration. In an additional aspect of the present invention, sized liposomes are described which are storage stable. Certain sized BPD-containing vesicles (no greater than about 120 nm in diameter) permit sterilization by terminal filtration. Further, a lyophilized preparation of the BPD-lipid mixture can be obtained from aqueous buffer under conditions which do not result in vesicle fusion/aggregation or BPD precipitation. Liposomes according to the present invention are able to accommodate surprisingly large amounts of BPD within the bilayer of the liposome, rather than in the encapsulated buffer. The advantages of this surprising aspect of the present invention includes the ease of manufacture and the cost savings associated with an efficient use of BPD are also presented.
摘要翻译：本发明涉及适用于药物应用的含有苯并卟啉的囊泡。特别地，本发明涉及掺入到泡囊中的苯并卟啉（BPD）的脂质体制剂，其包含形成脂质体的脂质如EPC或DMPC，药物与脂质之比大于100μg/ 脂质浓度相对较低。在本发明的另一方面，描述了储存稳定的大小的脂质体。某些尺寸的含BPD的囊泡（直径不大于约120nm）允许通过末端过滤进行灭菌。此外，可以在不导致囊泡融合/聚集或BPD沉淀的条件下从水性缓冲液中获得BPD-脂质混合物的冻干制剂。根据本发明的脂质体能够容纳在脂质体的双层内令人惊讶的大量BPD，而不是在封装的缓冲液中。本发明的这个令人惊奇的方面的优点包括易于制造和与有效使用BPD相关联的成本节约。

28. 发明授权

US4963297A Spontaneous vesticulation of multilamellar liposomes 失效
标题翻译：多层脂质体的自发兴奋
公开(公告)号：US4963297A
公开(公告)日：1990-10-16
申请号：US136267
申请日：1987-12-22
申请人： Thomas D. Madden
发明人： Thomas D. Madden
IPC分类号： A61K9/127 , A61K9/133
CPC分类号： A61K9/1277 , Y10S436/829 , Y10T428/2984
摘要： A new method is disclosed for making unilamellar vesicles from multilamellar vesicles. Such vesicles are formed without the use of physical of chemical disruption processes known in the art for forming unilamellar vesicles. The liposomes are incubated at neutral pH at or near the transition temperature of the lipids used, in low ionic strength media such as distilled water. The liposomes may comprise bioactive agents and may be used in vivo or in vitro.
摘要翻译：公开了一种从多层囊泡制造单层囊泡的新方法。形成这样的囊泡，而不使用本领域已知的用于形成单层囊泡的化学破坏过程的物理。将脂质体在等离子体强度介质如蒸馏水中，在所用脂质的转变温度或接近温度的中性pH下孵育。脂质体可以包含生物活性剂并且可以在体内或体外使用。

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