Method and compositions for polymer nanocarriers containing therapeutic molecules
    11.
    发明授权
    Method and compositions for polymer nanocarriers containing therapeutic molecules 有权
    含有治疗分子的聚合物纳米载体的方法和组合物

    公开(公告)号:US07927629B2

    公开(公告)日:2011-04-19

    申请号:US11925834

    申请日:2007-10-27

    CPC分类号: A61K9/5153

    摘要: A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.

    摘要翻译: 控制聚合物纳米载体包封的蛋白质颗粒的物理特性的方法包括改变或选择双乳液的初级乳液的全两亲双嵌段共聚物中的疏水性聚合物嵌段的重量百分数,冻融技术。 使用两亲二嵌段共聚物的冻融循环和分子量为至多300,000Da的蛋白质形成初级乳液。 疏水聚合物嵌段百分比的选择改变所得纳米颗粒的一种或多种特性,例如形状。 因此,一方面,生产丝状聚合物纳米载体包封的蛋白质(即活性酶)颗粒的方法包括使用(i)两亲性二嵌段共聚物(其分子量约为)的冷冻 - 解冻循环形成初级乳液 10,000至约100,000Da,并且包含疏水性聚合物嵌段和亲水性聚合物嵌段的共轭物,其中两亲性二嵌段共聚物包含大于疏水性聚合物嵌段重量的81%至约95% 和分子量大于或等于约300,000Da的蛋白质。 公开了包含这种丝状纳米载体颗粒的各种组合物,以及用于诊断和治疗的方法。

    COMPOSITIONS CONTAINING THROMBOMODULIN DOMAINS AND USES THEREOF
    15.
    发明申请
    COMPOSITIONS CONTAINING THROMBOMODULIN DOMAINS AND USES THEREOF 审中-公开
    含有酪氨酸蛋白酶域的组合物及其用途

    公开(公告)号:US20110262466A1

    公开(公告)日:2011-10-27

    申请号:US13124295

    申请日:2009-10-16

    摘要: Compositions are provided comprising a thrombomodulin domain linked to a targeting moiety that binds to a determinant on the surface of a target endothelial cell or red blood cell, wherein the thrombomodulin domain may be the extracellular domain, the N-terminal lectin-like domain, or an epidermal growth factor (EGF)-like domain. The targeting moiety may be a single chain antigen-binding domain (scFv), and the targeting moiety and thrombomodulin domain of the composition may be linked as a continuous polypeptide chain. Methods of delivery and use of a composition described herein are provided, as well as methods of treating or preventing thrombosis, inflammation, tissue ischemia, sepsis, acute lung injury (ALI), acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease is provided.

    摘要翻译: 提供了组合物,其包含与靶向部分连接的血栓调节蛋白结构域,所述靶向部分与靶内皮细胞或红细胞的表面上的决定簇结合,其中所述血栓调节蛋白结构域可以是细胞外结构域,N-末端凝集素样结构域,或 表皮生长因子(EGF)样结构域。 靶向部分可以是单链抗原结合结构域(scFv),并且组合物的靶向部分和血栓调节蛋白结构域可以作为连续的多肽链连接。 提供本文所述的组合物的递送和使用方法,以及治疗或预防血栓形成,炎症,组织缺血,败血症,急性肺损伤(ALI),急性心肌梗塞(AMI),缺血性卒中,脑血管疾病, 提供肺栓塞或缺血性外周血管疾病。

    Antioxidant polymer nanocarriers for use in preventing oxidative injury
    16.
    发明授权
    Antioxidant polymer nanocarriers for use in preventing oxidative injury 有权
    用于预防氧化损伤的抗氧化聚合物纳米载体

    公开(公告)号:US07597907B2

    公开(公告)日:2009-10-06

    申请号:US11266785

    申请日:2005-11-04

    摘要: The present invention is a method for encapsulating active protein in a polymeric nanocarrier. The instant method employs homogenization at subzero temperatures so that enzyme activity is retained. Enzymes which can be encapsulated by the present method include, for example, antioxidant enzymes and xenobiotic detoxifying enzymes. Encapsulation of an enzyme protects it from protease degradation and increases therapeutic half-life. Advantageously, polymeric nanoparticles of the invention are permeable to enzyme substrates and therefore enzymes encapsulated by the instant method can exert their effect without release from the nanocarrier. Methods for decomposing a reactive oxygen species, protecting against vascular oxidative stress, and detoxifying a xenobiotic are also provided.

    摘要翻译: 本发明是将活性蛋白质包封在聚合物纳米载体中的方法。 本方法在亚零温度下使用均匀化,从而保留酶活性。 可以通过本方法包封的酶包括例如抗氧化酶和异生物解毒酶。 酶的包封可以防止蛋白酶降解并增加治疗半衰期。 有利地,本发明的聚合物纳米颗粒对酶底物是可渗透的,因此通过本发明方法包封的酶可以发挥其作用而不从纳米载体释放。 还提供了分解活性氧物质,保护血管氧化应激和解毒异种生物的方法。

    Targeting recombinant therapeutics to circulating red blood cells
    20.
    发明授权
    Targeting recombinant therapeutics to circulating red blood cells 有权
    靶向重组治疗循环红细胞

    公开(公告)号:US08333973B2

    公开(公告)日:2012-12-18

    申请号:US12811443

    申请日:2008-12-31

    IPC分类号: A61K39/00

    摘要: Fusion proteins comprising a single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.

    摘要翻译: 提供了包含与抗血栓形成剂,抗炎剂或其前体药物连接的单克隆抗体的单链抗原结合结构域(scFv)的融合蛋白,其中多肽与结合位点(抗原 )在红细胞的表面上以每个红细胞大于5,000拷贝的密度表达。 包含这些融合蛋白的药物组合物,以及通过这些融合蛋白的递送将抗血栓形成剂递送到红细胞表面的方法,以及治疗或预防血栓形成,组织缺血,急性心肌梗塞(AMI),缺血性 还提供了通过施用融合蛋白或包含其的组合物的中风,脑血管疾病,肺栓塞或缺血性外周血管疾病。