公开(公告)号：US5932242A

公开(公告)日：1999-08-03

申请号：US720997

申请日：1996-10-15

申请人： J. Craig Franklin ,  Eric Mayhew ,  Walter Perkins ,  Andrew Janoff

发明人： J. Craig Franklin ,  Eric Mayhew ,  Walter Perkins ,  Andrew Janoff

IPC分类号： A61K9/127 ,  A61K31/661 ,  A61K31/685 ,  A61P35/00

CPC分类号： A61K9/1272 ,  A61K31/685 ,  Y10T428/2984

摘要： Pharmaceutical compositions are provided herein that contain, in addition to a pharmaceutically acceptable carrier, a lamellar lipid. The lipid is composed of an ether lipid and a lipid having a molecular shape that is complementary to the molecular shape of the glycerolipid. These compositions can be used therapeutically, for example, in the treatment of cancers and inflammatory conditions.

摘要翻译： 本文提供的药物组合物除了药学上可接受的载体外还含有片状脂质。 脂质由醚脂质和具有与甘油脂分子形状互补的分子形状的脂质组成。 这些组合物可用于治疗，例如治疗癌症和炎性病症。

公开(公告)号：US6017557A

公开(公告)日：2000-01-25

申请号：US950773

申请日：1997-10-15

申请人： J. Craig Franklin ,  Eric Mayhew ,  Walter Perkins ,  Andrew Janoff

发明人： J. Craig Franklin ,  Eric Mayhew ,  Walter Perkins ,  Andrew Janoff

IPC分类号： A61K9/127 ,  A61K31/661 ,  A61K31/685 ,  A61P35/00

CPC分类号： A61K9/1272 ,  A61K31/685 ,  Y10T428/2984

摘要： Lipid-based carriers are provided herein that have a lamellar lipid component composed of an etherlipid and a complementarily shaped lipid. This novel combination of lipids allows for the incorporation of etherlipids in the carriers at higher concentrations than would otherwise be possible. Pharmaceutical compositions containing the carriers can be used therapeutically, for example, in the treatment of cancers.

摘要翻译： 本文提供了具有由醚脂和互补形状的脂质组成的层状脂质组分的脂质载体。 脂质的这种新型组合允许以比其它方式更高的浓度将乙醚掺入载体中。 含有载体的药物组合物可用于治疗，例如治疗癌症。

公开(公告)号：US06500461B2

公开(公告)日：2002-12-31

申请号：US09314338

申请日：1999-05-19

申请人： Walter Perkins ,  Xingong Li ,  Donald Hirsh ,  Eric Mayhew ,  Imran Ahmad ,  Shaukat Ali ,  Andrew Janoff

发明人： Walter Perkins ,  Xingong Li ,  Donald Hirsh ,  Eric Mayhew ,  Imran Ahmad ,  Shaukat Ali ,  Andrew Janoff

IPC分类号： A61K914

CPC分类号： A61K47/6929 ,  A61K47/542

摘要： This invention provides vehicles capable of delivering high concentrations of poorly hydrophilic/poorly lipophilic compounds to animals, by combining compounds having biocompatible hydrophobic domains with conjugates having both hydrophobic and hydrophilic regions. Such formulations are suitable for a number of uses in animals, particularly the administration thereto of high concentrations of therapeutically useful compound, without an undue level of side effects.

摘要翻译： 本发明提供能够通过将具有生物相容性疏水域的化合物与具有疏水和亲水区两者的缀合物组合的化合物，将能够将高浓度亲水性差/亲脂性差的化合物递送给动物的载体。 这样的制剂适用于动物中的许多用途，特别是其给予高浓度的治疗有用的化合物，而没有不适当的副作用水平。

公开(公告)号：US06392063B1

公开(公告)日：2002-05-21

申请号：US09618872

申请日：2000-07-19

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： C07D30514

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 a-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.

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。 在一个实施方案中，水解促进基团立体特异性地连接到疏水紫杉烷的α-碳上。 通常占据α位置的通常占据α位置的亚甲基单元的HPG的取代允许烃 - 紫杉烷键的体内水解增强，因此增强紫杉烷治疗活性。 本文还提供了含紫杉烷的组合物，以及向动物（包括患有癌症或炎性疾病的患者）施用紫杉烷的方法。

公开(公告)号：US06667053B1

公开(公告)日：2003-12-23

申请号：US09540050

申请日：2000-03-31

申请人： Imran Ahmad ,  Eric Mayhew ,  Andrew Janoff

发明人： Imran Ahmad ,  Eric Mayhew ,  Andrew Janoff

IPC分类号： A61K9133

CPC分类号： A61K9/1272 ,  Y10T428/2984

摘要： A liposome having a lipid bilayer, where the lipid bilayer includes either the L or D stereoisomer of an ether lipid or a non-equal mixture of both. Most preferably the liposome also comprises (a) an underivatized phosphatidylcholine; (b) a sterol; (c) about 5-20 mole % of a phosphatidylethanolamine linked to a dicarboxylic acid at the ethanolamine group of the phosphatidylethanolamine, and (d) greater than about 10 mole % to less than about 30 mole % of either the L or D stereoisomer of an ether lipid. The liposome may be used as an anti-cancer or anti-inflammatory agent.

摘要翻译： 具有脂质双层的脂质体，其中脂质双层包括醚脂质的L或D立体异构体或两者的不相等的混合物。 最优选地，脂质体还包含（a）未衍生的磷脂酰胆碱; （b）固醇; （c）约5-20摩尔％的与磷脂酰乙醇胺的乙醇胺基上的二羧酸连接的磷脂酰乙醇胺，和（d）大于约10摩尔％至小于约30摩尔％的L或D立体异构体 醚类脂质。 脂质体可以用作抗癌剂或抗炎剂。

公开(公告)号：US6118011A

公开(公告)日：2000-09-12

申请号：US753650

申请日：1996-11-27

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： A61K9/127 ,  A61K31/335 ,  A61K31/337 ,  A61K31/66 ,  A61P35/00 ,  C07D305/14 ,  C07F9/655

CPC分类号： B82Y5/00 ,  A61K9/127 ,  C07D305/14 ,  C07F9/65512

摘要： This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 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。

公开(公告)号：US6107332A

公开(公告)日：2000-08-22

申请号：US249004

申请日：1999-02-12

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： A61K9/127 ,  A61P35/00 ,  C07D305/14 ,  A61K31/337

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 .alpha.-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.

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。 在一个实施方案中，水解促进基团立体特异性地连接到疏水紫杉烷的α-碳上。 通常占据α位置的通常占据α位置的亚甲基单元的HPG的取代允许烃 - 紫杉烷键的体内水解增强，因此增强紫杉烷治疗活性。 本文还提供了含紫杉烷的组合物，以及向动物（包括患有癌症或炎性疾病的患者）施用紫杉烷的方法。

公开(公告)号：US5939567A

公开(公告)日：1999-08-17

申请号：US988120

申请日：1997-12-10

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： A61K9/127 ,  A61K31/335 ,  A61K31/337 ,  A61K31/66 ,  A61P35/00 ,  C07D305/14 ,  C07F9/655

CPC分类号： B82Y5/00 ,  A61K9/127 ,  C07D305/14 ,  C07F9/65512

摘要： This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 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。

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：US5580899A

公开(公告)日：1996-12-03

申请号：US474888

申请日：1995-06-07

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： A61K9/127 ,  A61K31/335 ,  A61K31/337 ,  A61K31/66 ,  A61P35/00 ,  C07D305/14 ,  C07F9/655

CPC分类号： B82Y5/00 ,  A61K9/127 ,  C07D305/14 ,  C07F9/65512

摘要： This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 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。