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1. 发明授权

US5455027A Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon 失效
标题翻译：聚（环氧烷）氨基酸共聚物和药物载体和基于其的带电共聚物
公开(公告)号：US5455027A
公开(公告)日：1995-10-03
申请号：US23069
申请日：1993-02-25
申请人： Samuel Zalipsky , Durgadas Bolikal , Aruna Nathan , Joachim B. Kohn
发明人： Samuel Zalipsky , Durgadas Bolikal , Aruna Nathan , Joachim B. Kohn
IPC分类号： A61K47/30 , A61K47/48 , A61K49/00 , A61L15/26 , A61L27/18 , C08G63/685 , C08G65/32 , C08G69/10 , C08G69/40 , C08G69/44 , C08G81/00 , H01M6/18 , A61K31/74 , A61K31/765 , A61K31/785
CPC分类号： A61K47/48315 , A61K47/48215 , A61L15/26 , A61L27/18 , C08G63/6854 , C08G81/00 , Y10S530/81
摘要： Copolymers of poly(alkylene oxides) and amino acids or peptide sequences are disclosed, which amino acids or peptide sequences have pendant functional groups that are capable of being conjugated with pharmaceutically active compounds for drug delivery systems and cross-linked to form polymer matrices functional as hydrogel membranes. The copolymers can also be formed into conductive materials. Methods are also disclosed for preparing the polymers and forming the drug conjugates, hydrogel membranes and conductive materials.
摘要翻译：公开了聚（环氧烷）和氨基酸或肽序列的共聚物，其中氨基酸或肽序列具有侧链官能团，其能够与用于药物递送系统的药学活性化合物缀合并交联以形成作为水凝胶膜。共聚物也可以形成导电材料。还公开了制备聚合物并形成药物共轭物，水凝胶膜和导电材料的方法。

2. 发明授权

US5219564A Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon 失效
标题翻译：聚（环氧烷）氨基酸共聚物和药物载体和基于其的带电共聚物
公开(公告)号：US5219564A
公开(公告)日：1993-06-15
申请号：US726301
申请日：1991-07-05
申请人： Samuel Zalipsky , Durgadas Bolikal , Aruna Nathan , Joachim B. Kohn
发明人： Samuel Zalipsky , Durgadas Bolikal , Aruna Nathan , Joachim B. Kohn
IPC分类号： A61K47/30 , A61K47/48 , A61K49/00 , A61L15/26 , A61L27/18 , C08G63/685 , C08G65/32 , C08G69/10 , C08G69/40 , C08G69/44 , C08G81/00 , H01M6/18
CPC分类号： A61K47/48315 , A61K47/48215 , A61L15/26 , A61L27/18 , C08G63/6854 , C08G81/00 , Y10S530/81
摘要： Copolymers of poly(alkylene oxides) and amino acids or peptide sequences are disclosed, which amino acids or peptide sequences have pendant functional groups that are capable of being conjugated with pharmaceutically active compounds for drug delivery systems and cross-linked to form polymer matrices functional as hydrogel membranes. The copolymers can also be formed into conductive materials. Methods are also disclosed for preparing the polymers and forming the drug conjugates, hydrogel membranes and conductive materials.
摘要翻译：公开了聚（环氧烷）和氨基酸或肽序列的共聚物，其中氨基酸或肽序列具有侧链官能团，其能够与用于药物递送系统的药物活性化合物缀合并交联以形成作为水凝胶膜。共聚物也可以形成导电材料。还公开了制备聚合物并形成药物共轭物，水凝胶膜和导电材料的方法。

3. 发明授权

US07592307B2 Releasable linkage and compositions containing same 有权
标题翻译：可释放的连接物和含有它们的组合物
公开(公告)号：US07592307B2
公开(公告)日：2009-09-22
申请号：US11810931
申请日：2007-06-06
申请人： Samuel Zalipsky , Radwan Kiwan
发明人： Samuel Zalipsky , Radwan Kiwan
IPC分类号： A01N37/18 , A61K38/00 , C08B11/00 , C25D3/60 , A61K9/127
CPC分类号： A61K47/554 , A61K47/54 , A61K47/542 , A61K47/543 , A61K47/544 , A61K47/60
摘要： A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.
摘要翻译：描述了由共价但可逆地连接到含胺，羟基或羧基的配体的亲水性聚合物组成的缀合物。所得的缀合物能够通过硫醇介导的切割释放母体胺，羟基或含羧基的化合物。该系统允许以其可硫裂解的大分子缀合物的形式递送各种氨基，羟基或羧基的药物。

4. 发明授权

US07303760B2 Method for treating multi-drug resistant tumors 有权
标题翻译：多药耐药肿瘤治疗方法
公开(公告)号：US07303760B2
公开(公告)日：2007-12-04
申请号：US10714085
申请日：2003-11-14
申请人： Samuel Zalipsky , Alberto Gabizon
发明人： Samuel Zalipsky , Alberto Gabizon
IPC分类号： A61K9/127 , C07F9/02 , C07F53/00 , C07F321/00
CPC分类号： A61K31/407 , A61K47/543 , A61K47/6911
摘要： Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.
摘要翻译：描述了向多药耐药细胞施用丝裂霉素C并降低化合物的毒性的方法。在该方法中，丝裂蛋白C以前体药物缀合物的形式提供，其中药物通过可裂解的二硫代苄基键连接到疏水部分，例如脂质。二硫代苄基键易受到轻度硫解的裂解，导致丝裂霉素C以其原始形式释放。在非还原条件下，连接是稳定的。可以将前体药物缀合物掺入用于体内施用的体内脂质体中，并响应内源性体内还原条件或响应外源性还原剂的施用而释放丝裂霉素C.

5. 发明授权

US07276248B2 Conjugate having a cleavable linkage for use in a liposome 有权
标题翻译：具有用于脂质体的可切割连接的缀合物
公开(公告)号：US07276248B2
公开(公告)日：2007-10-02
申请号：US11202913
申请日：2005-08-12
申请人： Samuel Zalipsky , Alberto A. Gabizon
发明人： Samuel Zalipsky , Alberto A. Gabizon
IPC分类号： A61K9/127 , C07F9/02 , C07F53/00 , C07C321/00
CPC分类号： A61K9/1271 , A61K9/0019 , A61K31/196 , A61K31/407 , A61K31/519 , A61K31/56 , A61K38/14 , A61K47/54 , A61K47/542 , A61K47/543 , A61K47/544 , A61K47/554 , A61K47/60 , A61K47/6911 , C07C323/19 , C07D239/553 , C07D487/14 , C07H17/08 , C07H19/12 , C07H19/16 , Y10T428/2984
摘要： Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.
摘要翻译：描述了通过可切割二硫代苄基键连接到治疗剂的疏水部分（例如脂质）的缀合物。二硫代苄基键易受到轻度硫解的裂解，导致治疗剂以其原始形式释放。在非还原条件下，连接是稳定的。缀合物可以并入脂质体中，用于体内施用和响应于体内还原条件或响应于外源性还原剂的施用释放治疗剂。

6. 发明授权

US07160554B2 Enhanced circulation effector composition and method 有权
标题翻译：增强循环效应器组成和方法
公开(公告)号：US07160554B2
公开(公告)日：2007-01-09
申请号：US10438502
申请日：2003-05-14
申请人： Samuel Zalipsky , Martin C. Woodle , Francis J. Martin , Yechezkel Barenholz , Herve Bercovier
发明人： Samuel Zalipsky , Martin C. Woodle , Francis J. Martin , Yechezkel Barenholz , Herve Bercovier
IPC分类号： A61K9/127
CPC分类号： A61K9/0019 , A61K9/1271 , A61K31/00 , A61K38/12 , A61K38/1774 , A61K47/61 , A61K47/62 , A61K47/6911 , Y10S424/812 , A61K2300/00
摘要： A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.
摘要翻译：公开了包含小的表面结合效应分子的脂质体组合物。脂质体具有亲水性聚合物链的表面层，用于增强血流中的循环时间。效应分子连接到聚合物链的末端。在一个实施方案中，效应物是多粘菌素B，用于治疗败血性休克。

7. 发明授权

US07150882B2 Enhanced circulation effector composition and method 失效
公开(公告)号：US07150882B2
公开(公告)日：2006-12-19
申请号：US10832636
申请日：2004-04-26
申请人： Samuel Zalipsky , Martin C. Woodle , Francis J. Martin , Yechezkel Barenholz , Herve Bercovier
发明人： Samuel Zalipsky , Martin C. Woodle , Francis J. Martin , Yechezkel Barenholz , Herve Bercovier
IPC分类号： A61K9/127
CPC分类号： A61K9/0019 , A61K9/1271 , A61K31/00 , A61K38/12 , A61K38/1774 , A61K47/61 , A61K47/62 , A61K47/6911 , Y10S424/812 , A61K2300/00
摘要： A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

8. 发明授权

US07108863B2 Liposome composition for improved intracellular delivery of a therapeutic agent 有权
公开(公告)号：US07108863B2
公开(公告)日：2006-09-19
申请号：US10108154
申请日：2002-03-26
申请人： Samuel Zalipsky , Theresa M. Allen , Shi Kun Huang
发明人： Samuel Zalipsky , Theresa M. Allen , Shi Kun Huang
IPC分类号： A61B5/055 , A61B8/00 , A61K9/127
CPC分类号： A61K9/1272 , A61K9/1271 , A61K47/6913
摘要： A liposomal composition and a method of using the same for achieving intracellular delivery of a liposome-entrapped agent is described. The liposomes are composed of a pH sensitive lipid and include a targeting ligand to direct the liposomes to a target cell. The liposomes also include a stabilizing component, such a polymer-derivatized lipid, where the polymer is attached to the lipid by a releasable linkage. Administration of the liposomes results in cellular internalization and destabilization of the liposome for intracellular delivery of the entrapped agent.

9. 发明申请

US20060159736A1 Liposome formulations of boronic acid compounds 审中-公开
标题翻译：硼酸化合物的脂质体制剂
公开(公告)号：US20060159736A1
公开(公告)日：2006-07-20
申请号：US11267076
申请日：2005-11-04
申请人： Samuel Zalipsky , Francis Martin
发明人： Samuel Zalipsky , Francis Martin
IPC分类号： A61K31/7024 , A61K31/69 , A61K9/127
CPC分类号： A61K47/26 , A61K9/0019 , A61K9/127 , A61K9/1271 , A61K31/69 , A61K31/7024 , A61K47/10
摘要： A liposome composition comprised of liposomes having the peptide boronic acid proteasome inhibitor compound bortezomib entrapped in the liposomes is described. The boronic acid compound is entrapped in the liposomes in the form of a boronate ester, subsequent to interaction with a liposome-entrapped polyol. In one embodiment, the liposomes have an outer coating of hydrophilic polymer chains and are used to treat a solid tumor in a subject.
摘要翻译：描述了脂质体组合物，其包含被脂质体包埋的具有肽硼酸蛋白酶体抑制剂化合物硼替佐米的脂质体。在与脂质体包被的多元醇相互作用后，硼酸化合物以硼酸酯的形式包埋在脂质体中。在一个实施方案中，脂质体具有亲水性聚合物链的外涂层，并且用于治疗受试者中的实体瘤。

10. 发明授权

US06974589B1 Neutral-cationic lipid for nucleic acid and drug delivery 有权
标题翻译：用于核酸和药物递送的中性阳离子脂质
公开(公告)号：US06974589B1
公开(公告)日：2005-12-13
申请号：US09685940
申请日：2000-10-10
申请人： Shi Kun Huang , Samuel Zalipsky , Wei-Ming Zhang , Bei Jin , Yolanda P. Quinn
发明人： Shi Kun Huang , Samuel Zalipsky , Wei-Ming Zhang , Bei Jin , Yolanda P. Quinn
IPC分类号： C07D233/02 , A61K9/127 , A61K31/7105 , A61K31/711 , A61K47/22 , A61K47/44 , A61K48/00 , A61P35/00 , A61P43/00 , C07D233/54
CPC分类号： A61K9/1271 , A61K9/1272 , A61K47/542 , A61K47/543 , A61K48/00 , C07D233/54 , C07D233/64 , Y10T428/2984
摘要： A lipid represented by the formula: wherein each of R1 and R2 is an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms; n=0–20; L is selected from the group consisting of (i) —X—(C═O)—Y—, (ii) —X—(C═O)—, and (iii) —X—CH2—, wherein X and Y are independently selected from oxygen, NH, and a direct bond; and Z is a weakly basic moiety that has a pK of less than about 7.4 and greater than about 4.0 is described.
摘要翻译：由下式表示的脂质：其中R 1和R 2各自为具有约8至约24个碳原子的烷基或链烯基链; n = 0-20; L选自（i）-X-（CO）-Y-，（ii）-X-（CO） - 和（iii）-X-CH 2 - 其中X和Y独立地选自氧，NH和直接键; 并且Z是具有小于约7.4且大于约4.0的pK的弱碱性部分。

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