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11.发明授权Cationic amphiphiles containing dialkylamine lipophilic groups for intracellular delivery of therapeutic molecules 失效含有二烷基胺亲脂基团的阳离子两亲物用于细胞内递送治疗分子
公开(公告)号：US5719131A
公开(公告)日：1998-02-17
申请号：US546110
申请日：1995-10-20
申请人： David J. Harris , Edward R. Lee , Craig S. Siegel , Seng H. Cheng , Simon J. Eastman , John Marshall , Ronald K. Scheule
发明人： David J. Harris , Edward R. Lee , Craig S. Siegel , Seng H. Cheng , Simon J. Eastman , John Marshall , Ronald K. Scheule
CPC分类号： A61K9/1272 , A61K47/48023 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003 , C12N15/88 , Y10S516/07
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译： 提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。 还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。 另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。
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12.发明授权
公开(公告)号：US5650096A
公开(公告)日：1997-07-22
申请号：US352479
申请日：1994-12-09
申请人： David J. Harris , Edward R. Lee , Craig S. Siegel , Seng H. Cheng , Simon J. Eastman , John Marshall
发明人： David J. Harris , Edward R. Lee , Craig S. Siegel , Seng H. Cheng , Simon J. Eastman , John Marshall
CPC分类号： C07J43/003 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , A61K9/1272 , C07J41/0005 , C07J41/0055 , C07J41/0061 , Y10S514/975
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active molecules into cells. Typically, the amphiphiles contain lipophilic groups derived from steroids or from mono or dialkylamines, and two cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles, with or without colipids, and therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, polypeptides and low molecular weight organic compounds. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells.
摘要翻译： 提供了新的阳离子两亲物，其促进生物活性分子进入细胞。 通常，两亲物含有衍生自类固醇或单或二烷基胺的亲脂基团，以及两种阳离子基团，其在生理pH下可质子化，衍生自胺，烷基胺或多烷基胺。 还提供了通常通过使一种或多种阳离子两亲物的分散体与或不与咔啉和治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA，多肽和低分子量有机化合物。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。
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13.发明授权Cationic amphiphiles containing amino acid or dervatized amino acid groups for intracellular delivery of therapeutic molecules 失效含有氨基酸或衍生化氨基酸基团的阳离子两亲物用于治疗分子的细胞内递送
公开(公告)号：US5767099A
公开(公告)日：1998-06-16
申请号：US546086
申请日：1995-10-20
IPC分类号： A61K9/127 , A61K47/48 , A61K48/00 , C07J41/00 , C07J43/00 , C12N15/88 , A61K31/70 , A61K31/56 , B61F17/28 , A61K17/28
CPC分类号： A61K9/1272 , A61K47/48023 , A61K47/48038 , A61K47/48046 , A61K47/48123 , A61K48/00 , C07J41/0005 , C07J41/0055 , C07J41/0061 , C07J43/003 , C12N15/88 , Y10S516/07 , Y10S516/915
摘要： Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.
摘要翻译： 提供了新的阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 两亲物含有衍生自类固醇的单亲或二烷基胺或烷基或酰基的亲脂基团; 和在生理pH下可质子化的阳离子基团，衍生自胺，烷基胺或多烷基胺。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。 还公开了新型和高效的质粒构建体，包括在为炎症复杂的临床病症提供基因治疗方面特别有效的质粒构建体。 另外，描述了通过静脉内施用治疗组合物靶向用于基因治疗的器官。
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14.发明授权Cationic amphiphiles containing linkers derived from neutral or positively charged amino acids 失效含有源自中性或带正电氨基酸的连接体的阳离子两亲物
公开(公告)号：US5948925A
公开(公告)日：1999-09-07
申请号：US851917
申请日：1997-05-06
CPC分类号： C07J41/0055
摘要： Cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.
摘要翻译： 提供阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。
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15.发明授权Imidazole-containing cationic amphiphiles for intracellular delivery of therapeutic molecules 失效含咪唑的阳离子两亲物用于细胞内递送治疗分子
公开(公告)号：US5912239A
公开(公告)日：1999-06-15
申请号：US833370
申请日：1997-04-04
申请人： Craig S. Siegel , Edward R. Lee , David J. Harris
发明人： Craig S. Siegel , Edward R. Lee , David J. Harris
IPC分类号： A61K9/127 , C07J43/00 , A61K31/575
CPC分类号： A61K9/1272 , C07J43/003
摘要： Cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.
摘要翻译： 提供阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。
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公开(公告)号：US06323191B1
公开(公告)日：2001-11-27
申请号：US09334936
申请日：1999-06-17
申请人： David J. Harris , Edward R. Lee , Canwen Jiang , Seng H. Cheng , Mathieu Lane
发明人： David J. Harris , Edward R. Lee , Canwen Jiang , Seng H. Cheng , Mathieu Lane
IPC分类号： A01N4500
CPC分类号： A61K47/28 , A61K31/00 , A61K31/56 , A61K31/573 , A61K31/6615 , Y10S514/851
摘要： Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride (Cl−) channel regulated by phosphorylation and intracellular nucleotides. CFTR is the major Cl− transport pathway in airway epithelial cells. The abnormal transepithelial Cl− transport and subsequent defective fluid transport caused by CF is a result of the genetic mutations of the gene coding for the CFTR protein. The present invention is directed to the novel use of ionophores as artificial Cl− transport pathways into CF epithelia to treat the defective Cl− and fluid transport lonophores and in particular, small molecule ionophores, represent a potential novel means of treating CF. The invention also includes using an ionophore to generate chloride secretion on intact monolayers of airway epithelia cells and other epithelia cells by administering an ionophore to a mammal.
摘要翻译： 囊性纤维化跨膜电导调节因子（CFTR）是通过磷酸化和细胞内核苷酸调节的氯化物（Cl-）通道。 CFTR是气道上皮细胞中主要的Cl-转运途径。 由CF引起的异常跨上皮性Cl-转运和随后的有缺陷的流体转运是编码CFTR蛋白的基因的遗传突变的结果。 本发明涉及离子载体作为人造Cl-转运途径进入CF上皮以治疗有缺陷的Cl-和液体转运离子的新颖应用，特别是小分子离子载体，代表了治疗CF的潜在的新方法。 本发明还包括使用离子载体通过向哺乳动物施用离子载体来在气道上皮细胞和其它上皮细胞的完整单层上产生氯化物分泌。
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公开(公告)号：US5952516A
公开(公告)日：1999-09-14
申请号：US852864
申请日：1997-05-08
申请人： Craig S. Siegel , Edward R. Lee , David J. Harris
发明人： Craig S. Siegel , Edward R. Lee , David J. Harris
CPC分类号： C07J41/0055
摘要： Cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.
摘要翻译： 提供阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。
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公开(公告)号：US5942634A
公开(公告)日：1999-08-24
申请号：US853680
申请日：1997-05-09
申请人： Craig S. Siegel , Edward R. Lee , David J. Harris
发明人： Craig S. Siegel , Edward R. Lee , David J. Harris
CPC分类号： C07J41/0061 , C07J41/0055 , C07J51/00
摘要： Cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.
摘要翻译： 提供阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。
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19.发明授权
公开(公告)号：US5925628A
公开(公告)日：1999-07-20
申请号：US828234
申请日：1997-03-31
申请人： Edward R. Lee , David J. Harris , Craig S. Siegel
发明人： Edward R. Lee , David J. Harris , Craig S. Siegel
IPC分类号： A61K9/127 , C07J41/00 , A61K31/575 , C07J9/00
CPC分类号： C07J41/0055 , A61K9/1272 , C07J41/0061
摘要： Cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.
摘要翻译： 提供阳离子两亲物，其促进生物活性（治疗性）分子进入细胞。 还提供了通常通过使一种或多种阳离子两亲物的分散体与治疗分子接触而制备的治疗组合物。 根据本发明的实践可以递送到细胞中的治疗分子包括DNA，RNA和多肽。 本发明治疗组合物的代表性用途包括提供基因治疗以及向细胞递送反义多核苷酸或生物活性多肽。 关于基因治疗的治疗组合物，通常以与阳离子两亲物络合的质粒的形式提供DNA。
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公开(公告)号：US20080035219A1
公开(公告)日：2008-02-14
申请号：US11838357
申请日：2007-08-14
CPC分类号： B60P3/36 , F16L41/03 , F17C2265/066 , Y10T137/87249
摘要： A gas delivery system for a recreational vehicle comprising an inlet hose configured to be connected to a source of gas, a manifold connected to the inlet hose, a plurality of supply hoses connected to the manifold, and a plurality of appliances configured to be positioned within the recreational vehicle, with each one of the appliances being connected to one of the supply hoses. Gas can be supplied to each of the appliances via the inlet hose, the manifold and one of the supply hoses.
摘要翻译： 一种用于娱乐车辆的气体输送系统，包括被配置为连接到气源的入口软管，连接到入口软管的歧管，连接到歧管的多个供应软管，以及被配置为位于内部 娱乐车辆，其中每个设备连接到一个供应软管。 可以通过入口软管，歧管和供应软管之一向每个设备提供气体。
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