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    • 2. 发明申请
    • HIGH-DENSITY LIPOPROTEIN-LIKE PEPTIDE-PHOSPHOLIPID SCAFFOLD (
    • 高密度脂蛋白胆固醇 - 磷脂酰胆碱(“HPPS”)纳米颗粒
    • WO2009073984A1
    • 2009-06-18
    • PCT/CA2008/002203
    • 2008-12-12
    • UNIVERSITY HEALTH NETWORKZHENG, GangZHANG, ZhihongCORBIN, IanCHEN, Juan
    • ZHENG, GangZHANG, ZhihongCORBIN, IanCHEN, Juan
    • C07K17/02A61K47/48A61K48/00A61K49/00A61K51/04A61P35/00C12N15/10C12N15/11G01N33/566G01N33/574C07K14/485C07K14/71C12N15/87
    • A61K49/0082A61K47/6917A61K47/6919A61K49/0002A61K49/0032A61K49/0056B82Y5/00G01N33/54346G01N33/587G01N2800/00
    • The present invention provides a non-naturally occurring High-Density Lipoprotein-like peptide-phospholipid scaffold ("HPPS") nanoparticle. More particularly, the invention provides a non-naturally occurring peptide-lipid nanoscaffold comprising: (a) at least one phospholipid; (b) at least one unsaturated lipid, preferably an unsaturated sterol ester, further preferably an unsaturated cholesterol ester, further preferably cholsteryl oleate; and (c) at least one peptide, the peptide comprising an amino acid sequence capable of forming at least one amphipathic a- helix; wherein the components a), b) and c) associate to form the peptide-phospholipid nanoscaffold. In embodiments of the present invention, a cell surface receptor ligand is incorporated into the HPPS. In one embodiment, the cell surface receptor ligand is covalently bonded to the peptide scaffold of the HPPS nanoparticles. In other embodiments, a cell surface receptor ligand is coupled to a lipid anchor and is displayed on the surface of the HPPS nanoparticles by incorporation of the lipid anchor into the phospholipids monolayer of the HPPS nanoparticle. The present invention also provides pharmaceutical formulations comprising HPPS nanoparticles and methods of making the HPPS nanoparticles.
    • 本发明提供非天然存在的高密度脂蛋白样肽 - 磷脂支架(“HPPS”)纳米颗粒。 更具体地,本发明提供非天然存在的肽 - 脂质纳米支架,其包含:(a)至少一种磷脂; (b)至少一种不饱和脂质,优选不饱和甾醇酯,更优选不饱和胆固醇酯,更优选油酸胆甾醇酯; 和(c)至少一种肽,所述肽包含能够形成至少一种两亲α-螺旋的氨基酸序列; 其中组分a),b)和c)缔合形成肽 - 磷脂纳米支架。 在本发明的实施方案中,将细胞表面受体配体掺入HPPS中。 在一个实施方案中,细胞表面受体配体共价键合到HPPS纳米颗粒的肽支架上。 在其它实施方案中,将细胞表面受体配体偶联到脂质锚定物上,并通过将脂质锚点掺入HPPS纳米颗粒的磷脂单层中而显示在HPPS纳米颗粒的表面上。 本发明还提供了包含HPPS纳米颗粒的药物制剂和制备HPPS纳米颗粒的方法。