公开(公告)号：US5767099A

公开(公告)日：1998-06-16

申请号：US546086

申请日：1995-10-20

申请人： David J. Harris ,  Edward R. Lee ,  Craig S. Siegel ,  Eric A. Rowe ,  Shirley C. Hubbard

发明人： David J. Harris ,  Edward R. Lee ,  Craig S. Siegel ,  Eric A. Rowe ,  Shirley C. Hubbard

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。