公开(公告)号：US4721612A

公开(公告)日：1988-01-26

申请号：US721630

申请日：1985-04-10

申请人： Andrew S. Janoff ,  Mircea C. Popescu ,  Alan L. Weiner ,  Lois E. Bolcsak ,  Paul S. Tremblay

发明人： Andrew S. Janoff ,  Mircea C. Popescu ,  Alan L. Weiner ,  Lois E. Bolcsak ,  Paul S. Tremblay

IPC分类号： G01N33/52 ,  A61K20060101 ,  A61K9/00 ,  A61K9/10 ,  A61K9/127 ,  A61K9/52 ,  A61K31/59 ,  A61K39/44 ,  A61K47/00 ,  A61K47/28 ,  A61K49/04 ,  A61K51/00 ,  B01J13/02 ,  G01N31/00 ,  G01N33/48 ,  G01N33/544 ,  A61J3/07 ,  A61K43/00

CPC分类号： A61K9/1272 ,  A61K9/1271 ,  A61K2039/55555 ,  Y10S436/829 ,  Y10S514/887 ,  Y10S514/967 ,  Y10T428/2984 ,  Y10T436/117497

摘要： Methods and compositions are described for the preparation of lipid vesicles, the bilayers of which comprise a salt form of an organic acid derivative of a sterol such as the tris-salt form of a sterol hemisuccinate. The method is rapid, efficient, and does not require the use of organic solvents. The sterol hemisuccinate vesicles may be used to entrap compounds which are insoluble in aqueous solutions. Such preparations are especially useful for entrapping bioactive agents of limited solubility thus enabling administration in vivo.

摘要翻译： 描述了用于制备脂质囊泡的方法和组合物，其双层包含固醇的有机酸衍生物的盐形式，例如半琥珀酸固醇的三盐形式。 该方法快速，高效，不需要使用有机溶剂。 固醇半琥珀酸钠泡囊可用于捕获不溶于水溶液的化合物。 这种制剂对于捕获有限溶解度的生物活性剂特别有用，因此能够在体内施用。

公开(公告)号：US06482850B2

公开(公告)日：2002-11-19

申请号：US09940672

申请日：2001-08-29

申请人： Shaukat Ali ,  J. Craig Franklin ,  Imran Ahmad ,  Eric Mayhew ,  Soumendu Bhattacharya ,  Gil Koehane ,  Andrew S. Janoff

发明人： Shaukat Ali ,  J. Craig Franklin ,  Imran Ahmad ,  Eric Mayhew ,  Soumendu Bhattacharya ,  Gil Koehane ,  Andrew S. Janoff

IPC分类号： A01N4302

CPC分类号： C07D305/14 ,  A61K9/127

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”). In one embodiment, the hydrolysis promoting group is stereospecifically attached to the &agr;-carbon of the hydrophobic taxane. The 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 or inflammatory diseases.

公开(公告)号：US06261792B1

公开(公告)日：2001-07-17

申请号：US08441567

申请日：1995-05-15

申请人： Andrew S. Janoff ,  Joyce Rauch ,  Theodore F. Taraschi

发明人： Andrew S. Janoff ,  Joyce Rauch ,  Theodore F. Taraschi

IPC分类号： C12Q156

CPC分类号： G01N33/92 ,  G01N33/564 ,  G01N33/86 ,  G01N2405/04 ,  Y10S435/962

摘要： For use in a lipid-dependent diagnostic assay, a stable aqueous suspension of a phospholipid which normally has a hexagonal (HII) organization when dispersed in an aqueous medium without detergent, the suspension containing the phospholipid, a detergent, and an aqueous phase. In the stable suspension, the phospholipid remains in suspension at a temperature of 25° C. for at least one hour. The suspension is suitable for providing the phospholipid to an assay for lupus anticoagulants which includes the step of pre-incubating a test sample with the phospholipid.

摘要翻译： 为了用于脂质依赖性诊断测定法，当分散在不含洗涤剂的水性介质中时，通常具有六边形（HII）组织的磷脂的稳定水性悬浮液，含有磷脂的悬浮液，洗涤剂和水相。 在稳定的悬浮液中，磷脂在25℃的温度下保持悬浮至少1小时。 该悬浮液适用于将磷脂提供给用于狼疮抗凝剂的测定法，其包括用磷脂预孵育测试样品的步骤。

公开(公告)号：US06180137B2

公开(公告)日：2001-01-30

申请号：US09390395

申请日：1999-09-03

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： A61K9127

CPC分类号： A61K9/1272 ,  A61K9/1271 ,  A61K31/685 ,  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。

公开(公告)号：US6051600A

公开(公告)日：2000-04-18

申请号：US805184

申请日：1997-02-27

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 ,  C07D305/14 ,  A61K31/335

CPC分类号： A61K31/337 ,  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。

公开(公告)号：US5922350A

公开(公告)日：1999-07-13

申请号：US876938

申请日：1997-06-16

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。

公开(公告)号：US5614216A

公开(公告)日：1997-03-25

申请号：US442079

申请日：1995-05-16

申请人： Andrew S. Janoff

发明人： Andrew S. Janoff

IPC分类号： A61K9/127

CPC分类号： A61K31/685 ,  Y10S514/958

摘要： A synthetic lung surfactant composition and process for depositing a monolayer of a phosphatidylcholine lung surfactant to the alveoli of a mammal. The composition comprises a phosphatidylcholine lung surfactant, a phosphatidylethanolamine, and cholesterol in proportions such that the composition is in lamellar form at or below a first temperature and in non-lamellar form at a second temperature which is higher than the first temperature. A preferred phosphatidylcholine lung surfactant for use in this invention is dipalmitoyl phosphatidylcholine (DPPC), which is known to be the major lipid constituent of natural mammalian lung surfactant, and a preferred phosphatidylethanolamine is dioleoyl phosphatidylethanolamine (DOPE). In particular embodiments, the composition is in lamellar form at about room temperature (25.degree. C.), and in non-lamellar form at a temperature in the range of about 30.degree. to 37.degree. C., which is at or below normal human body temperature (37.degree. C.). The composition may also include one or more therapeutic peptides or other pharmaceutical agents. The synthetic lung surfactant may be used to treat a mammal for respiratory distress syndrome caused by an insufficiency of natural lung surfactant.

摘要翻译： 一种合成肺表面活性剂组合物和用于将磷脂酰胆碱肺表面活性剂的单层沉积到哺乳动物的肺泡的方法。 组合物包含磷脂酰胆碱肺表面活性剂，磷脂酰乙醇胺和胆固醇，其比例使得组合物在低于第一温度或低于第一温度的层状形式，并且在高于第一温度的第二温度下以非层状形式。 用于本发明的优选的磷脂酰胆碱肺表面活性剂是二棕榈酰磷脂酰胆碱（DPPC），其已知是天然哺乳动物肺表面活性剂的主要脂质组分，优选的磷脂酰乙醇胺是二油酰磷脂酰乙醇胺（DOPE）。 在具体实施方案中，组合物在约室温（25℃）下为薄片形式，并且在约30-37℃的温度范围内以非层状形式，其处于或低于正常人 体温（37℃）。 组合物还可以包括一种或多种治疗性肽或其它药剂。 合成肺表面活性剂可用于治疗由天然肺表面活性剂不足引起的呼吸窘迫综合征的哺乳动物。

公开(公告)号：US5288499A

公开(公告)日：1994-02-22

申请号：US758587

申请日：1991-09-12

申请人： Andrew S. Janoff ,  Mircea C. Popescu ,  Alan L. Weiner ,  Lois E. Bolcsak ,  Paul A. Tremblay ,  Christine E. Swenson

发明人： Andrew S. Janoff ,  Mircea C. Popescu ,  Alan L. Weiner ,  Lois E. Bolcsak ,  Paul A. Tremblay ,  Christine E. Swenson

IPC分类号： A61K9/00 ,  A61K9/127 ,  A61K9/133 ,  A61K37/22

CPC分类号： A61K9/1271 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0034 ,  A61K9/02 ,  A61K9/12 ,  A61K9/1272 ,  C12N15/88 ,  A61K2039/55555 ,  A61K47/12 ,  A61K47/28 ,  Y10S424/15 ,  Y10S436/829 ,  Y10S514/887 ,  Y10S514/967 ,  Y10T428/2984

摘要： Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to compositions comprising a mixture of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.

摘要翻译： 描述了用于制备包含在脂质囊泡中的生物活性剂的方法和组合物，其双层包含固醇类的有机酸衍生物的盐形式，例如三羟甲基半琥珀酸酯的三盐形式，以及包含混合物 胆固醇半琥珀酸盐的三（羟甲基）氨基甲烷盐与抗真菌化合物或肽。 这些组合物在体内具有各种应用。

公开(公告)号：US5231112A

公开(公告)日：1993-07-27

申请号：US425727

申请日：1989-10-23

申请人： Andrew S. Janoff ,  Mircea C. Popescu ,  Alan L. Weiner ,  Lois E. Bolcsak ,  Paul A. Tremblay ,  Christine E. Swenson

发明人： Andrew S. Janoff ,  Mircea C. Popescu ,  Alan L. Weiner ,  Lois E. Bolcsak ,  Paul A. Tremblay ,  Christine E. Swenson

IPC分类号： A61K9/00 ,  A61K9/127 ,  A61K9/133

CPC分类号： A61K9/1271 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0034 ,  A61K9/02 ,  A61K9/12 ,  A61K9/1272 ,  C12N15/88 ,  A61K2039/55555 ,  A61K47/12 ,  A61K47/28 ,  Y10S424/15 ,  Y10S436/829 ,  Y10S514/887 ,  Y10S514/967 ,  Y10T428/2984

摘要： Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to bompositions comprising a mixture of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.

摘要翻译： 描述了用于制备包埋在脂质囊泡中的生物活性剂的方法和组合物，其双层包含固醇的有机酸衍生物的盐形式，例如三羟甲基半琥珀酸盐的三盐形式，以及包含混合物 胆固醇半琥珀酸盐的三（羟甲基）氨基甲烷盐与抗真菌化合物或肽。 这些组合物在体内具有各种应用。

公开(公告)号：US07491409B1

公开(公告)日：2009-02-17

申请号：US09914615

申请日：2000-03-01

申请人： Paul R. Meers ,  Tong Shangguan ,  Donna Cabral-Lilly ,  Patrick Ahl ,  Andrew S. Janoff

发明人： Paul R. Meers ,  Tong Shangguan ,  Donna Cabral-Lilly ,  Patrick Ahl ,  Andrew S. Janoff

IPC分类号： A61K9/127

CPC分类号： A61K9/1272 ,  A61K9/127

摘要： This invention provides a method to prepare liposome-encapsulated bioactive agents such as nucleic acids, comprising complexation of the bioactive agents in reverse micelles prior to forming liposomes, as well as methods of using the liposomes so formed and formulations to deliver nucleic acids to cells.

摘要翻译： 本发明提供了一种制备脂质体包封的生物活性剂如核酸的方法，其包括在形成脂质体之前在反胶束中络合生物活性剂，以及使用如此形成的脂质体和制剂将核酸递送至细胞的方法。