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51. 发明授权

US4923854A Solubilization of hydrophobic materials using lysophospholipid 失效
标题翻译：使用溶血磷脂溶解疏水材料
公开(公告)号：US4923854A
公开(公告)日：1990-05-08
申请号：US821366
申请日：1986-01-22
申请人： Colin P. S. Tilcock , Pieter R. Cullis , Michael J. Hope , Andrew S. Janoff
发明人： Colin P. S. Tilcock , Pieter R. Cullis , Michael J. Hope , Andrew S. Janoff
IPC分类号： A61K9/00 , A61K9/08 , A61K9/10 , A61K9/127 , A61K31/57 , A61K31/685 , A61K38/00 , A61K38/22 , A61K45/00 , A61K47/00 , A61K47/24
CPC分类号： A61K9/1277 , A61K47/24 , A61K9/0019
摘要： A method and composition are described for the solubilization of hydrophobic materials using a lysophospholipid. The method includes drying a composition comprising a hydrophobic material-solubilizing effective amount of phospholipid from organic solvent and hydrating the resulting film with an aqueous medium at either a pH of between about 8.5 and about 14.0, or at pH 7.0 followed by reduction of the temperature to less then 0.degree. C.
摘要翻译：描述了使用溶血磷脂增溶疏水性材料的方法和组合物。该方法包括从有机溶剂中干燥含有疏水物质增溶有效量的磷脂的组合物，并用pH介于约8.5至约14.0之间或pH 7.0的水性介质水合所得膜，随后降低温度小于0℃

52. 发明授权

US4880635A Dehydrated liposomes 失效
标题翻译：脱水脂质体
公开(公告)号：US4880635A
公开(公告)日：1989-11-14
申请号：US759419
申请日：1985-07-26
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。

53. 再颁专利

USRE39042E1 Etherlipid-containing multiple lipid liposomes 失效
标题翻译：含脂质的多种脂质体
公开(公告)号：USRE39042E1
公开(公告)日：2006-03-28
申请号：US09976936
申请日：2001-10-11
申请人： Eric Mayhew , Andrew S. Janoff , Imran Ahmad , Suresh K. Bhatia
发明人： Eric Mayhew , Andrew S. Janoff , Imran Ahmad , Suresh K. Bhatia
IPC分类号： A61K9/127
CPC分类号： A61K9/1272 , Y10T428/2984
摘要： Described herein are liposomes containing etherlipids of the formula: as well as a phosphatidylcholine, a sterol, and a headgroup-derivatized lipid. These liposomes are useful in a variety of therapeutic regimens, including the treatment of cancers and inflammatory disorders.
摘要翻译：本文描述了含有下式的醚脂的脂质体：以及磷脂酰胆碱，固醇和头团衍生的脂质。这些脂质体可用于各种治疗方案，包括治疗癌症和炎症性疾病。

54. 发明授权

US06406713B1 Methods of preparing low-toxicity drug-lipid complexes 失效
标题翻译：制备低毒药物 - 脂质复合物的方法
公开(公告)号：US06406713B1
公开(公告)日：2002-06-18
申请号：US08430661
申请日：1995-04-28
申请人： Andrew S. Janoff , Thomas D. Madden , Pieter R. Cullis , John J. Kearns , Anthony G. Durning
发明人： Andrew S. Janoff , Thomas D. Madden , Pieter R. Cullis , John J. Kearns , Anthony G. Durning
IPC分类号： A61K9127
CPC分类号： A61K9/127 , A61K9/1277 , A61K9/1617 , A61K31/7048 , A61K47/544 , G03B2227/325 , Y10T428/2984
摘要： Methods and compositions are described for nonliposomal lipid complexes in association with toxic hydrophobic drugs such as the polyene antibiotic amphotericin B. Lipid compositions are preferably a combination of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in about a 7:3 mole ratio. The lipid complexes contain a bioactive agent, and may be made by a number of procedures, at high drug:lipid ratios. These compositions of high drug:lipid complexes (HDLCs) may be administered to mammals such as humans for the treatment of infections, with substantially equivalent or greater efficacy and reduced drug toxicities as compared to the drugs in their free form. Also disclosed is a novel liposome-loading procedure, which may also be used in the formation of the HDLCs.
摘要翻译：描述了与毒性疏水性药物如多烯抗生素两性霉素B相关的非脂质体脂质复合物的方法和组合物。脂质组合物优选以约7:3摩尔比组合磷脂二肉豆蔻酰磷脂酰胆碱（DMPC）和二肉豆蔻酰磷脂酰甘油（DMPG）。脂质复合物含有生物活性剂，并且可以以高药物：脂质比例通过多种方法制备。与其游离形式的药物相比，高药物：脂质复合物（HDLC）的这些组合物可以施用于哺乳动物例如人以治疗感染，具有基本相同或更大的功效和降低的药物毒性。还公开了一种新的脂质体加载程序，其也可用于HDLC的形成。

55. 发明授权

US06291690B1 Hydrophobic taxane derivatives 失效
标题翻译：疏水紫杉烷衍生物
公开(公告)号：US06291690B1
公开(公告)日：2001-09-18
申请号：US09567366
申请日：2000-05-09
申请人： Eric Mayhew , J. Craig Franklin , Suresh Bhatia , Paul A. Harmon , Andrew S. Janoff
发明人： Eric Mayhew , J. Craig Franklin , Suresh Bhatia , Paul A. Harmon , Andrew S. Janoff
IPC分类号： C07D30514
CPC分类号： B82Y5/00 , A61K9/127 , C07D305/14 , C07F9/65512
摘要： This invention provides a taxane derivative of the formula: wherein a hydrophobic organic moiety is attached to a taxane. R and R1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.
摘要翻译：本发明提供下式的紫杉烷衍生物：其中疏水性有机部分连接于紫杉烷。 R和R 1各自独立地为H或疏水性有机部分，只要R和R 1中的至少一个不为H.将疏水性有机部分连接到紫杉烷以获得紫杉烷衍生物通常稳定该衍生物的缔合其中包含脂质体脂质的脂质，其中施用衍生物 - 载体缔合的动物血浆中的载体。本文还提供含有紫杉烷衍生物和药学上可接受的介质的组合物; 理想地，培养基还含有脂质载体，并且该衍生物与载体相关联。本文还提供了将紫杉烷衍生物施用于动物，例如患有癌症的动物的方法。

56. 发明授权

US5942246A Etherlipid containing multiple lipid liposomes 失效
标题翻译：含有多种脂质体的醚脂
公开(公告)号：US5942246A
公开(公告)日：1999-08-24
申请号：US17366
申请日：1998-02-02
申请人： Eric Mayhew , Andrew S. Janoff , Imran Ahmad , Suresh K. Bhatia
发明人： Eric Mayhew , Andrew S. Janoff , Imran Ahmad , Suresh K. Bhatia
IPC分类号： A61K9/127 , A61K9/133
CPC分类号： A61K9/1272 , A61K31/685 , A61K9/1271 , Y10T428/2984
摘要： Liposomes are provided which contain etherlipids having the formula: ##STR1## as well as an unsaturated or partially unsaturated phospholipid, a sterol, and a phosphatidylethanolamine-based headgroup-derivatized lipid. These liposomes are useful in a variety of therapeutic regimens, including the treatment of cancers and inflammatory disorders.
摘要翻译：提供了含有具有下式的醚脂的脂质体：以及不饱和或部分不饱和的磷脂，固醇和基于磷脂酰乙醇胺的头组衍生的脂质。这些脂质体可用于各种治疗方案，包括治疗癌症和炎症性疾病。

57. 发明授权

US5840328A Treatment using arachidonic acid metabolite and particulate formulations 失效
标题翻译：使用花生四烯酸代谢物和颗粒制剂进行处理
公开(公告)号：US5840328A
公开(公告)日：1998-11-24
申请号：US371541
申请日：1995-01-11
申请人： Andrew S. Janoff , David F. Eierman
发明人： Andrew S. Janoff , David F. Eierman
IPC分类号： A61K9/127 , A61K31/557 , A61K9/16
CPC分类号： A61K9/127 , A61K31/557
摘要： A composition comprises a free arachidonic acid metabolite and endocystosable particles such as phagocytosable or opsonizable particles, or particles binding to phagocytic receptors to serum proteins, and the like. The composition, in the form of a therapeutic formulation may be administered alone, or with other bioactive agents, for the treatment of a disorder characterized by cell activation/adhesion, inflammation or toxemia. A second method of treating such disorders comprises the administration of an endocytosable particle.
摘要翻译：组合物包含游离的花生四烯酸代谢物和可以吞噬或可调节的颗粒的内囊泡颗粒，或与血清蛋白质的吞噬受体结合的颗粒等。治疗性制剂形式的组合物可以单独施用或与其它生物活性剂一起施用，用于治疗以细胞活化/粘附，炎症或毒血症为特征的病症。治疗这种疾病的第二种方法包括给予可内吞的颗粒。

58. 发明授权

US5811118A Methods of treatment using unilamellar liposomal arachidonic acid metabolite formulations 失效
标题翻译：使用单层脂质体花生四烯酸代谢物制剂的治疗方法
公开(公告)号：US5811118A
公开(公告)日：1998-09-22
申请号：US333975
申请日：1994-11-03
申请人： Marc J. Ostro , Andrew S. Janoff , Sharma R. Minchey
发明人： Marc J. Ostro , Andrew S. Janoff , Sharma R. Minchey
IPC分类号： A61K9/127 , A61K9/133 , A61K31/557 , A61K31/5575
CPC分类号： A61K9/127 , A61K31/557 , A61K31/5575 , A61K9/1278 , Y10S977/801 , Y10S977/907 , Y10S977/915
摘要： This invention provides a method of administering an arachidonic acid metabolite, such as prostaglandin E1, to an animal. The metabolite is given to the animal, typically a human, in association with a unilamellar liposome comprising a lipid and a release-inhibiting aqueous buffer. This method can be used to treat animals afflicted with disorders characterized by cell activation and adhesion, inflammation or toxemia.
摘要翻译：本发明提供了向动物施用花生四烯酸代谢物如前列腺素E1的方法。将代谢物与包含脂质和释放抑制性水性缓冲液的单层脂质体相关联地给予动物，通常为人。该方法可用于治疗以细胞活化和粘附，炎症或毒血症为特征的疾病。

59. 发明授权

US5703117A Hydrolysis-promoting hydrophobic taxane derivatives 失效
标题翻译：水解促进疏水紫杉烷衍生物
公开(公告)号：US5703117A
公开(公告)日：1997-12-30
申请号：US712684
申请日：1996-09-12
申请人： Eric Mayhew , Shaukat Ali , Andrew S. Janoff
发明人： Eric Mayhew , Shaukat Ali , Andrew S. Janoff
IPC分类号： A61K9/127 , A61K31/337 , A61P35/00 , C07D305/14 , A61K31/335
CPC分类号： A61K9/127 , C07D305/14
摘要： Provided herein is a taxane having a hydrocarbon attached at the 2' and/or 7 positions, the hydrocarbon's alpha position being occupied by a "hydrolysis-promoting group" ("HPG"). Substitution of an HPG for the methylene unit ordinarily occupying the alpha position allows for enhanced in vivo hydrolysis of the hydrocarbon-taxane bond, and hence, for enhanced taxane therapeutic activity. Also provided herein are taxane-containing compositions, and methods of administering taxanes to animals, including those afflicted with cancers.
摘要翻译：本文提供了具有在2'和/或7位上连接的烃的紫杉烷，烃的α位置被“水解促进基团”（“HPG”）占据。通常占据α位置的亚甲基单元的HPG的取代允许增强体系中的烃 - 紫杉烷键的体内水解，从而增强紫杉烷的治疗活性。本文还提供含紫杉烷的组合物，以及将紫杉烷类药物给予动物（包括患有癌症的那些）的方法。

60. 发明授权

US5681589A Liposomal ceramide-related liposomes and the therapeutic use thereof 失效
标题翻译：脂质体神经酰胺相关化合物及其治疗用途
公开(公告)号：US5681589A
公开(公告)日：1997-10-28
申请号：US545164
申请日：1995-10-19
申请人： Yong Wei , Eric Mayhew , Imran Ahmad , Andrew S. Janoff
发明人： Yong Wei , Eric Mayhew , Imran Ahmad , Andrew S. Janoff
IPC分类号： A61K9/127 , A61K31/13 , A61K31/135 , A61K31/16 , A61K31/164 , A61K31/165 , A61K31/18 , A61K31/695 , A61K38/00 , A61P35/00 , B01J13/02 , C07C211/21 , C07C211/22 , C07C211/45 , C07C211/49 , C07C215/02 , C07C219/02 , C07C229/02 , C07C233/18 , C07C233/31 , C07C311/03 , C07C311/11 , C07C317/28 , C07F7/18 , C07F9/06
CPC分类号： A61K9/1271 , C07F7/1852 , Y10T428/2984
摘要： This invention provides a compound having the formula R.sup.1 -Y.sup.1 --CHZ.sup.1 -CH(NY.sup.2 Y.sup.3)--CH.sub.2 -Z.sup.2, wherein: R.sup.1 is a straight-chained alkyl, alkenyl or alkynyl group having from 8 to 19 carbon atoms in the aliphatic chain; Y.sup.1 is --CH.dbd.CH--, --C.tbd.C-- or --CH(OH)CH(OH)--; Z.sup.1 is OH or a conversion-inhibiting group; Z.sup.2 is a conversion-inhibiting group; Y.sup.2 is H, a phenyl group, an alkyl-substituted phenyl group having from 1 to about 6 carbons in the alkyl chain, or an alkyl chain having from 1 to 6 carbons; Y.sup.3 is H or a group having the formula --C(O)R.sup.2 or --S(O).sub.2 R.sup.2 ; R.sup.2 is a straight-chained alkyl, alkenyl or alkynyl group having from 1 to 23 carbon atoms in the chain; and when Z.sup.2 is an amino, R.sup.2 is an aliphatic chain having from 1 to 9 or from 19 to 23 carbon atoms in the aliphatic chain.
摘要翻译：本发明提供具有式R1-Y1-CHZ1-CH（NY2Y3）-CH2-Z2的化合物，其中：R1是在脂族链中具有8至19个碳原子的直链烷基，烯基或炔基; Y1是-CH = CH-，-C3BON或-CH（OH）CH（OH） - ; Z1是OH或转化抑制基团; Z2是转化抑制基团; Y2是H，苯基，在烷基链中具有1至约6个碳的烷基取代的苯基或具有1至6个碳的烷基链; Y 3是H或具有式-C（O）R 2或-S（O）2 R 2的基团; R2是链中具有1至23个碳原子的直链烷基，烯基或炔基; 当Z 2是氨基时，R 2是在脂族链中具有1至9个或19至23个碳原子的脂族链。

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