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    • 5. 发明申请
    • PULMONARY HYDROPHOBIC SURFACTANT-ASSOCIATED PROTEINS
    • 肺血浆表面活性剂相关蛋白
    • WO1988003170A1
    • 1988-05-05
    • PCT/US1987002536
    • 1987-10-02
    • WHITSETT, Jeffrey, A.FOX, J., LawrencePILOT-MATIAS, Tami, J.MEUTH, Joseph, L.SARIN, Virender, K.
    • C12P21/00
    • A61K31/685A61K31/575A61K31/66A61K35/42A61K38/1709C07K14/785C07K16/18C07K2319/00C07K2319/035C12N9/00C12N15/72A61K2300/00
    • Novel, isolated, substantially pure, hydrophobic surfactant-associated proteins of 4,000-7,000 dalton simple molecular weight, SAP(Val) and SAP(Phe); multimers thereof, and substitution, addition and deletion analogs and fragments thereof. When SAP(Val) and/or SAP(Phe) is combined with lipids, its surfactant-like property imparts to the combination significant pulmonary biophysical activity. Such a combination results in enhanced adsorption of the lipids with properties similar to that of natural pulmonary surfactant material. SAP(Val) and/or SAP(Phe) in combination with lipids is highly useful for replacing or supplementing natural pulmonary surfactant material for reducing or maintaining normal surface tension in the lungs, especially in the lungs of patients suffering from hyaline membrane disease, HMD, or other syndromes associated with the lack or insufficient amounts of natural pulmonary surfactant material. A combination of SAP(Val) and/or SAP(Phe) and lipids may be administered as an aerosol spray or in aqueous normal saline with or without calcium chloride for treating or preventing HMD and other surfactant deficiency states. Also disclosed are methods of isolating the SAP(Val) from animal tissue and methods for making SAP(Val) and SAP(Phe) by recombinant DNA techniques and direct peptide synthesis; genomic clones of SAP(Val) and SAP(Phe); expression systems and products for SAP(Val) DNA; and polyclonal and monoclonal antibodies to SAP(Val) and SAP(Phe).
    • 具有4,000-7,000道尔顿简单分子量的新型,分离的,基本上纯的疏水表面活性剂相关蛋白质SAP(Val)和SAP(Phe); 多聚体及其取代,添加和缺失类似物及其片段。 当SAP(Val)和/或SAP(Phe)与脂质组合时,其表面活性剂样特性赋予组合显着的肺生物物理活性。 这种组合导致具有与天然肺表面活性剂材料类似的性质的脂质的增强的吸附。 与脂质组合的SAP(Val)和/或SAP(Phe)可用于替代或补充天然肺表面活性物质,以降低或维持肺中正常的表面张力,特别是在患有透明膜病的患者的肺中,HMD ,或与天然肺表面活性物质的量不足或不足量相关的其他综合征。 SAP(Val)和/或SAP(Phe)和脂质的组合可以作为气溶胶喷雾剂或含有或不含氯化钙的水性生理盐水施用,用于治疗或预防HMD和其它表面活性剂缺乏状态。 还公开了将SAP(Val)与动物组织分离的方法和通过重组DNA技术和直接肽合成制备SAP(Val)和SAP(Phe)的方法; SAP(Val)和SAP(Phe)的基因组克隆; SAP(Val)DNA的表达系统和产品; 和针对SAP(Val)和SAP(Phe)的多克隆和单克隆抗体。