Stabilized polynucleotide complexes and methods
    2.
    发明授权
    Stabilized polynucleotide complexes and methods 失效
    稳定的多核苷酸复合物和方法

    公开(公告)号:US07323297B1

    公开(公告)日:2008-01-29

    申请号:US08485430

    申请日:1995-06-07

    IPC分类号: C12Q1/68 A01N43/04 A61K31/70

    CPC分类号: A61K31/70

    摘要: The invention comprises stabilized polynucleotide complexes that have a cryoprotectant and are lyophilized. Cryoprotectant compounds comprise carbohydrates or sugars, preferably lactose and sucrose, but also glucose, maltodextrins, mannitol, sorbitol, trehalose, and others. Other suitable cryoprotectants include amino acids such as betaines and prolines. Polynucleotide complexes stabilized according to the invention can be used for transfection, and exhibit improved tranfection efficiency with respect to polynucleotide complexes without cryoprotection.

    摘要翻译: 本发明包括具有冷冻保护剂并被冻干的稳定的多核苷酸复合物。 冷冻保护剂化合物包含碳水化合物或糖,优选乳糖和蔗糖,还包括葡萄糖,麦芽糖糊精,甘露醇,山梨醇,海藻糖等。 其他合适的冷冻保护剂包括氨基酸,例如甜菜碱和脯氨酸。 根据本发明稳定的多核苷酸复合物可用于转染,并且相对于没有冷冻保护的多核苷酸复合物显示出改善的转染效率。

    Separation of active complexes
    3.
    发明授权
    Separation of active complexes 失效
    分离活性配合物

    公开(公告)号:US5972600A

    公开(公告)日:1999-10-26

    申请号:US482110

    申请日:1995-06-07

    摘要: The invention separates defined, active complexes by a characteristic from Defined, active complexes that share a particular physicochemical characteristic such as density, surface charge or particle size are separated from complexes formed by the association of a polynucleotide with a transfecting component that increases transfection activity, such as a lipid, cationic lipid, liposome, peptide, cationic peptide, dendrimer or polycation. In a preferred embodiment, polynucleotide-transfecting component complexes are ultracentrifuged to resolve one or more bands corresponding to complexes having a specific polynucleotide-transfecting component interaction. Polynucleotide complexes having a cationic liposome transfecting component resolve into two primary bands corresponding to complexes formed either under excess lipid conditions or under excess polynucleotide conditions. In an alternate embodiment, polynucleotide-transfecting component complexes are resolved using cross-flow electrophoresis to identify complexes having specific interactions and to separate them from excess initial components.

    摘要翻译: 本发明通过来自定义的特征分离定义的活性复合物,其共享具有特定物理化学特性如密度,表面电荷或粒度的活性配合物与由多核苷酸与增加转染活性的转染成分缔合形成的复合物分离, 例如脂质,阳离子脂质,脂质体,肽,阳离子肽,树枝状聚合物或聚阳离子。 在优选的实施方案中,将多核苷酸转染组分复合物超速离心以分离对应于具有特异性多核苷酸转染组分相互作用的复合物的一个或多个条带。 具有阳离子脂质体转染组分的多核苷酸复合物分解成对应于在过量脂质条件下或在过量多核苷酸条件下形成的复合物的两个主要条带。 在替代实施方案中,使用交叉流电泳来分离多核苷酸转染组分复合物以鉴定具有特异性相互作用的复合物并将其与过量的初始组分分离。

    pH sensitive lipids based on ortho ester linkers, composition and method
    5.
    发明授权
    pH sensitive lipids based on ortho ester linkers, composition and method 失效
    基于原酸酯接头的pH敏感性脂质,组成和方法

    公开(公告)号:US06897196B1

    公开(公告)日:2005-05-24

    申请号:US09778388

    申请日:2001-02-07

    IPC分类号: A61K9/127 A61K31/00 A01N43/04

    CPC分类号: A61K9/1272 A61K31/00

    摘要: The invention comprises lipid derivatives that rapidly degrade in the pH range from 4.0 to 7.0 and lipidic delivery systems that contain them. These lipid derivatives can be used to modify the delivery properties of the lipidic delivery systems to enable prolonged circulation times or more rapid drug unloading in the target tissue. The lipid derivatives are amphipathic compounds comprising a hydrophilic head group joined to a hydrophobic group by an acid-labile ortho ester linkage. The delivery systems of the invention exhibit degradation of less than 10% within 3 hours at a pH of 7.4 and degradation greater than 50% within 60 min at a pH of 5.0.

    摘要翻译: 本发明包括在4.0至7.0的pH范围内迅速降解的脂质衍生物和含有它们的脂质递送系统。 这些脂质衍生物可用于改变脂质递送系统的递送性质,以使靶组织中的延长循环时间或更快速的药物卸载。 脂质衍生物是包含通过酸不稳定原酸酯键连接到疏水基团的亲水性头基的两亲性化合物。 本发明的递送系统在pH为7.4时在3小时内显示小于10%的降解,并且在pH5.0的60分钟内降解大于50%。

    Targeted drug delivery with a hyaluronan ligand
    10.
    发明授权
    Targeted drug delivery with a hyaluronan ligand 有权
    用透明质酸配体靶向药物递送

    公开(公告)号:US06593308B2

    公开(公告)日:2003-07-15

    申请号:US09454811

    申请日:1999-12-03

    IPC分类号: A01N4304

    CPC分类号: A61K9/1271 A61K47/6911

    摘要: The invention is a drug delivery system of a delivery vehicle having a low molecular weight hyaluronan ligand with an affinity for CD44 receptors. Preferably, the delivery vehicle is a liposome but other suitable delivery vehicles include microspheres, micelles, emulsions, lipid discs, polymers, viral particles and viruses. The systems of the invention may further comprise a drug, which can be any anticancer agent or other therapeutic or diagnostic agent. The invention also comprises methods of delivering a drug to a cell that expresses CD44 by contacting the cell with the drug delivery system. Further methods include treating a patient with cancer and targeting drug delivery to cells that express CD44 by attaching a glycosaminoglycan ligand.

    摘要翻译: 本发明是具有对CD44受体具有亲和力的低分子量透明质酸配体的递送载体的药物递送系统。 优选地,递送载体是脂质体,但是其它合适的递送载体包括微球,胶束,乳剂,脂质盘,聚合物,病毒颗粒和病毒。 本发明的系统还可以包含药物,其可以是任何抗癌剂或其它治疗或诊断剂。 本发明还包括通过使细胞与药物递送系统接触来将药物递送至表达CD44的细胞的方法。 其他方法包括治疗患有癌症的患者,并通过连接糖胺聚糖配体将药物递送靶向表达CD44的细胞。