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公开(公告)号：US08071082B2
公开(公告)日：2011-12-06
申请号：US11780754
申请日：2007-07-20
IPC分类号： A61K31/765 , A61K9/00 , A61K48/00 , C12N15/11 , C08F26/00
CPC分类号： C12N15/87 , A61K9/5138 , A61K47/34 , C08G63/6856 , C08G73/02 , C08L79/02
摘要： Poly(beta-amino esters) are end-modified to form materials useful in the medical as well as non-medical field. An amine-terminated poly(beta-amino ester) is reacted with an electrophile, or an acrylate-terminated poly(beta-amino ester) is reacted with a nucleophile. The inventive end-modified polymers may be used in any field where polymers have been found useful including the drug delivery arts. The end-modified polymers are particularly useful in delivery nucleic acids such as DNA or RNA. The invention also provides compositions including the inventive end-modified polymers, methods of preparing the inventive polymers, and method of using the inventive polymers.
摘要翻译： 聚（β-氨基酯）被末端修饰以形成用于医疗和非医学领域的材料。 使胺封端的聚（β-氨基酯）与亲电子试剂或丙烯酸酯封端的聚（β-氨基酯）与亲核试剂反应。 本发明的末端改性聚合物可用于已经发现聚合物有用的任何领域，包括药物递送领域。 末端修饰的聚合物特别可用于递送核酸如DNA或RNA。 本发明还提供包含本发明的端基改性聚合物，制备本发明聚合物的方法和使用本发明聚合物的方法的组合物。
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公开(公告)号：US20080242626A1
公开(公告)日：2008-10-02
申请号：US11780754
申请日：2007-07-20
IPC分类号： A61K31/7088 , C08F18/14 , A61P43/00
CPC分类号： C12N15/87 , A61K9/5138 , A61K47/34 , C08G63/6856 , C08G73/02 , C08L79/02
摘要： Poly(beta-amino esters) are end-modified to form materials useful in the medical as well as non-medical field. An amine-terminated poly(beta-amino ester) is reacted with an electrophile, or an acrylate-terminated poly(beta-amino ester) is reacted with a nucleophile. The inventive end-modified polymers may be used in any field where polymers have been found useful including the drug delivery arts. The end-modified polymers are particularly useful in delivery nucleic acids such as DNA or RNA. The invention also provides compositions including the inventive end-modified polymers, methods of preparing the inventive polymers, and method of using the inventive polymers.
摘要翻译： 聚（β-氨基酯）被末端修饰以形成用于医疗和非医学领域的材料。 使胺封端的聚（β-氨基酯）与亲电子试剂或丙烯酸酯封端的聚（β-氨基酯）与亲核试剂反应。 本发明的末端改性聚合物可用于已经发现聚合物有用的任何领域，包括药物递送领域。 末端修饰的聚合物特别可用于递送核酸如DNA或RNA。 本发明还提供包含本发明的端基改性聚合物，制备本发明聚合物的方法和使用本发明聚合物的方法的组合物。
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公开(公告)号：US09006487B2
公开(公告)日：2015-04-14
申请号：US11453222
申请日：2006-06-14
申请人： Daniel G. Anderson , Andreas Zumbuehl , Elizaveta Sergeyevna Leshchiner (Turkhanova) , Robert S. Langer , Michael Goldberg
发明人： Daniel G. Anderson , Andreas Zumbuehl , Elizaveta Sergeyevna Leshchiner (Turkhanova) , Robert S. Langer , Michael Goldberg
IPC分类号： C07C239/00 , C07C229/00 , C12N15/88 , A61K31/785 , C07B53/00 , G01N33/92 , A61K48/00 , A61K9/16 , C07C229/12 , C07C229/14 , C07C229/16 , C07C229/18 , C07C237/06 , C07D211/26 , C07D233/61 , C07D243/08 , C07D295/12 , C07D307/14 , C07D317/28
CPC分类号： C07D233/61 , A61K9/1617 , A61K47/18 , A61K47/22 , A61K48/00 , A61K48/0033 , C07C227/10 , C07C229/12 , C07C229/14 , C07C229/16 , C07C229/18 , C07C231/12 , C07C237/06 , C07D211/26 , C07D243/08 , C07D295/12 , C07D307/14 , C07D317/28 , C12N15/88
摘要： Nitrogen-containing lipids prepared from the conjugate addition of amines to acrylates, acrylamides, or other carbon-carbon double bonds conjugated to electron-withdrawing groups are described. Methods of preparing these lipids from commercially available starting materials are also provided. These amine-containing lipids or salts forms of these lipids are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these lipids, they are particularly suited for the delivery of polynucleotides. Complexes or nanoparticles containing the inventive lipid and polynucleotide have been prepared. The inventive lipids may also be used to in preparing microparticle for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.
摘要翻译： 描述了从共轭加成胺到丙烯酸酯，丙烯酰胺或与吸电子基团共轭的其它碳 - 碳双键制备的含氮脂质。 还提供了从市售的起始原料制备这些脂质的方法。 这些含脂质的脂质或这些脂质的盐形式优选是可生物降解的和生物相容的，并可用于各种药物递送系统。 鉴于这些脂质的氨基部分，它们特别适用于递送多核苷酸。 已经制备了含有本发明的脂质和多核苷酸的复合物或纳米颗粒。 本发明的脂质也可用于制备用于药物递送的微粒。 考虑到缓冲其周围环境的pH值，它们特别适用于提供不稳定剂。
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公开(公告)号：US20110009641A1
公开(公告)日：2011-01-13
申请号：US11453222
申请日：2006-06-14
申请人： Daniel G. Anderson , Andreas Zumbuehl , Elizaveta Sergeyevna Leshchiner (Turkhanova) , Robert S. Langer , Michael Goldberg
发明人： Daniel G. Anderson , Andreas Zumbuehl , Elizaveta Sergeyevna Leshchiner (Turkhanova) , Robert S. Langer , Michael Goldberg
IPC分类号： C07D233/61 , C07C229/04 , C07C233/01
CPC分类号： C07D233/61 , A61K9/1617 , A61K47/18 , A61K47/22 , A61K48/00 , A61K48/0033 , C07C227/10 , C07C229/12 , C07C229/14 , C07C229/16 , C07C229/18 , C07C231/12 , C07C237/06 , C07D211/26 , C07D243/08 , C07D295/12 , C07D307/14 , C07D317/28 , C12N15/88
摘要： Nitrogen-containing lipids prepared from the conjugate addition of amines to acrylates, acrylamides, or other carbon-carbon double bonds conjugated to electron-withdrawing groups are described. Methods of preparing these lipids from commercially available starting materials are also provided. These amine-containing lipids or salts forms of these lipids are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these lipids, they are particularly suited for the delivery of polynucleotides. Complexes or nanoparticles containing the inventive lipid and polynucleotide have been prepared. The inventive lipids may also be used to in preparing microparticle for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.
摘要翻译： 描述了从共轭加成胺到丙烯酸酯，丙烯酰胺或与吸电子基团共轭的其它碳 - 碳双键制备的含氮脂质。 还提供了从市售的起始原料制备这些脂质的方法。 这些含脂质的脂质或这些脂质的盐形式优选是可生物降解的和生物相容的，并可用于各种药物递送系统。 鉴于这些脂质的氨基部分，它们特别适用于递送多核苷酸。 已经制备了含有本发明的脂质和多核苷酸的复合物或纳米颗粒。 本发明的脂质也可用于制备用于药物递送的微粒。 考虑到缓冲其周围环境的pH值，它们特别适用于提供不稳定剂。
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公开(公告)号：US20140212503A1
公开(公告)日：2014-07-31
申请号：US14005707
申请日：2012-03-17
IPC分类号： A61K9/14 , A61K47/22 , A61K31/713
CPC分类号： A61K9/146 , A61K9/0019 , A61K9/14 , A61K31/713 , A61K47/22 , C12N15/111 , C12N15/87 , C12N2310/14 , C12N2320/32 , C12N2810/10
摘要： The present invention provides three-dimensional, nanoscale delivery systems, particularly well adapted for delivery of nucleic acids and/or nucleic acid associated entities.
摘要翻译： 本发明提供了三维，纳米级的递送系统，特别适用于递送核酸和/或核酸相关实体。
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公开(公告)号：US20120308650A1
公开(公告)日：2012-12-06
申请号：US13487524
申请日：2012-06-04
CPC分类号： A61K9/5036 , A61K9/0024 , A61K9/5161 , A61K35/39 , A61K45/06 , C08B37/0084
摘要： Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.
摘要翻译： 本文公开了具有增强的生物相容性和定制的理化性质的共价改性的藻酸盐聚合物，以及其制备和使用方法。 共价修饰的藻酸盐可用作细胞的包封和移植的基质。 还公开了用于表征改性藻酸盐聚合物的生物相容性和物理化学性质的高通量方法。
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公开(公告)号：US20120065358A1
公开(公告)日：2012-03-15
申请号：US13301315
申请日：2011-11-21
IPC分类号： C08G63/685
CPC分类号： A61K47/34 , A61K9/5146 , A61K31/711 , A61K31/713 , A61K47/59 , A61K47/593 , A61K47/6929 , B82Y5/00 , C08G63/685 , C08G73/02 , C08G73/0273 , C08G73/06 , C08G73/0611 , C08G73/0616 , C12N15/88
摘要： Poly(β-amino esters) prepared from the conjugate addition of bis(secondary amines) or primary amines to a bis(acrylate ester) are described. Methods of preparing these polymers from commercially available starting materials are also provided. These tertiary amine-containing polymers are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the poly(amine) nature of these polymers, they are particularly suited for the delivery of polynucleotides. Nanoparticles containing polymer/polynucleotide complexes have been prepared. The inventive polymers may also be used to encapsulate other agents to be delivered. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.
摘要翻译： 描述了从双（仲胺）或伯胺向双（丙烯酸酯）共轭加成制备的聚（＆（bgr。 - 氨基酯））。 还提供了从市售的原料制备这些聚合物的方法。 这些含叔胺的聚合物优选是可生物降解的和生物相容的并且可以用于各种药物递送系统中。 鉴于这些聚合物的聚（胺）性质，它们特别适用于递送多核苷酸。 已经制备了含有聚合物/多核苷酸复合物的纳米颗粒。 本发明的聚合物也可以用于包封待递送的其它试剂。 考虑到缓冲其周围环境的pH值，它们特别适用于提供不稳定剂。
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公开(公告)号：US07943179B2
公开(公告)日：2011-05-17
申请号：US11002542
申请日：2004-12-02
IPC分类号： A61K9/16
CPC分类号： A61K9/1617 , A61K9/1623 , A61K9/1647 , A61K9/1658
摘要： A drug delivery system comprising pH triggerable particles is described. The pH triggerable particles comprise and agent(s) to be delivered, which is encapsulated in a matrix comprising a pH trigger agent and a polymer. Agents including nucleic acids may be delivered intracellularly using the inventive pH triggerable particles. Upon exposure to an acidic environment such as the endosome or phagosome of a cell, the particles dissolve or disrupt due to protonation or an increase in solubility of the pH triggering agent. Pharmaceutical compositions and methods of preparing and administering these particles are also described. These particles may be particularly useful in genetic vaccination.
摘要翻译： 描述了包含pH可触发颗粒的药物递送系统。 pH可触发颗粒包含待运送的试剂，其被包封在包含pH触发剂和聚合物的基质中。 包含核酸的试剂可以使用本发明的pH可触发颗粒在细胞内递送。 当暴露于诸如细胞的内体或吞噬体的酸性环境中时，由于质子化或pH引发剂的溶解度的增加，颗粒溶解或破坏。 还描述了制备和施用这些颗粒的药物组合物和方法。 这些颗粒在基因疫苗接种中可能特别有用。
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公开(公告)号：US07427394B2
公开(公告)日：2008-09-23
申请号：US10446444
申请日：2003-05-28
IPC分类号： A61K31/765 , C08G69/44 , C08G63/44 , C07C327/00
CPC分类号： C08G69/44 , A61K9/5138 , A61K47/59 , A61K47/593 , A61K47/645 , A61K47/6925 , B82Y5/00 , C08G63/40 , C08G63/6856 , C08G73/02 , C08G73/0273 , C08G73/028 , C08G73/06 , C08G73/0611 , C08G73/0616 , C08L67/02 , C08L67/04 , C08L77/04 , C08L79/02 , C08L89/00 , C08L99/00 , C12N15/88 , C08L2666/02
摘要： Poly(β-amino esters) prepared from the conjugate addition of bis(secondary amines) or primary amines to a bis(acrylate ester) are described. Methods of preparing these polymers from commercially available starting materials are also provided. These tertiary amine-containing polymers are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the poly(amine) nature of these polymers, they are particularly suited for the delivery of polynucleotides. Nanoparticles containing polymer/polynucleotide complexes have been prepared. The inventive polymers may also be used to encapsulate other agents to be delivered. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings. A system for preparing and screening polymers in parallel using semi-automated robotic fluid delivery systems is also provided.
摘要翻译： 描述了从双（仲胺）或伯胺向双（丙烯酸酯）共轭加成制备的聚（β-氨基酯）。 还提供了从市售的原料制备这些聚合物的方法。 这些含叔胺的聚合物优选是可生物降解的和生物相容的并且可以用于各种药物递送系统中。 鉴于这些聚合物的聚（胺）性质，它们特别适用于递送多核苷酸。 已经制备了含有聚合物/多核苷酸复合物的纳米颗粒。 本发明的聚合物也可以用于包封待递送的其它试剂。 考虑到缓冲其周围环境的pH值，它们特别适用于提供不稳定剂。 还提供了使用半自动机器人流体输送系统并行制备和筛选聚合物的系统。
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公开(公告)号：US09867781B2
公开(公告)日：2018-01-16
申请号：US13400382
申请日：2012-02-20
IPC分类号： A61K9/16 , A61K9/00 , A61K31/573 , A61K45/06 , A61K35/39 , G01N33/50 , A61L27/38 , A61L27/48 , A61L27/52 , A61L27/54 , C12N5/071
CPC分类号： A61K9/1641 , A61K9/0019 , A61K31/573 , A61K35/39 , A61K45/06 , A61L27/3804 , A61L27/48 , A61L27/52 , A61L27/54 , A61L2300/41 , A61L2300/622 , A61L2300/64 , C12N5/0676 , C12N2502/1157 , C12N2533/40 , C12N2533/74 , G01N33/5088 , A61K2300/00 , C08L5/04 , C08L5/08
摘要： A composition containing biocompatible hydrogel encapsulating mammalian cells and anti-inflammatory drugs is disclosed. The encapsulated cells have reduced fibrotic overgrowth after implantation in a subject. The compositions contain a biocompatible hydrogel having encapsulated therein mammalian cells and anti-inflammatory drugs or polymeric particles loaded with anti-inflammatory drugs. The anti-inflammatory drugs are released from the composition after transplantation in an amount effective to inhibit fibrosis of the composition for at least ten days. Methods for identifying and selecting suitable anti-inflammatory drug-loaded particles to prevent fibrosis of encapsulated cells are also described. Methods of treating a disease in a subject are also disclosed that involve administering a therapeutically effective amount of the disclosed encapsulated cells to the subject.
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