[發明專利]一種穿心蓮內酯聚合物膠束及其制備方法與醫藥用途

無效

• 申請號: 201310364852.4
• 申請日: 2013-08-20
• 公開（公告）號: CN104415029A
• 公開（公告）日: 2015-03-18
• 發明（設計）人: 許卉;郎躍武;劉西曼;劉珂
• 申請（專利權）人: 蘇州雷納藥物研發有限公司
• 主分類號: A61K31/365
• 分類號: A61K31/365;A61K9/19;A61K47/34;A61P31/00;A61P35/00
• 代理公司: 暫無信息
• 代理人: 暫無信息

技術領域

本發明涉及穿心蓮內酯與兩親性嵌段共聚物形成的穩定聚合物膠束載藥系統及其制備方法與醫藥用途，屬納米藥物制劑領域。

背景技術

穿心蓮內酯（Andrographolide）為爵床科植物穿心蓮（Andrographis?Paniculata(bunn.f.)Nees）中提取得到的一種具有半日花烷骨架的二萜內酯類化合物，化學名3,19-dihydroxy-8(17),13-laboiadien-16,15-olide，化學結構如下所示：

研究表明，穿心蓮內酯具有抗炎、抗菌、抗病毒等廣泛的生理活性，能夠抑制TNF-α、IL-1β和LPS等誘導的腹膜炎模型中白細胞向腹腔的浸潤，抑制LPS引起的內毒素休克，以及嗜酸性粒細胞介導的過敏性呼吸道炎癥，對細菌性與病毒性上呼吸道感染及痢疾有特殊療效，被譽為天然抗生素【Basak?A,et?al.Inhibition?of?proprotein?convertases-1,-7and?furin?by?diterpines?of?Andrographis?paniculata?and?their?succinoyl?esters.Biochem?J1999,338(Pt1):107-113；Chiou?W?F,et?al.Andrographolide?suppresses?the?expression?of?inducible?nitric?oxide?synthase?in?macrophage?and?restores?the?vasoconstriction?in?rat?aorta?treated?with?lipopolysaccharide.Br?J?Pharmacol1998,125(2):327-334；Calabmse?C,et?al.A?phase?I?trial?of?andrographolide?in?HIV?positive?patients?and?normal?volunteers.Phytother?Res2000,14(5):333-338；Chiou?W?F,et?al.Mechanisms?of?suppression?of?inducible?nitric?oxide?synthase(iNOS)expression?in?RAW264.7cells?by?andrographolide.Br?J?Pharmacol2000,129(8):1553-1560；Batkhuu?J,et?al.Shen?Y?C,et?al.Andrographolide?prevents?oxygen?radical?production?by?human?neutrophils:possible?mechanism(s)involved?in?its?anti-inflammatory?effect.Br?J?Pharmacol2002,135(2):399-406；Xia?Y?F,et?al.Andrographolide?attenuates?inflammation?by?inhibition?of?NF-κB?activation?through?covalent?modification?of?reduced?cysteine62of?p50.J?Immunol2004,173(6):4207-4217；Hidalgo?M?A,et?al.Andrographolide?interferes?with?binding?of?nuclear?factor-kappaB?to?DNA?in?HL-60-derived?neutrophilic?cells.Br?J?Pharmacol2005,144(5):680-686.】。近年來的研究還發現，穿心蓮內酯可通過細胞毒活性、誘導細胞凋亡、誘導細胞周期阻滯以及抗腫瘤新生血管的生成等多種途徑對腫瘤細胞的體內外增殖發揮直接或間接的抑制作用，顯示廣譜抗腫瘤活性，是一種備受關注的天然抗腫瘤候選藥物【Zhou?J,et?al.Critical?role?of?pro-apoptotic?Bcl-2family?members?in?andrographolide-induced?apoptosis?in?human?cancer?cells.Biochem?Pharmacol2006,72(2):132-144.Cheung?H?Y,et?al.Andrographolide?isolated?from?andrographis?paniculata?induces?cell?cycle?arrest?and?mitochondrial-mediated?apoptosis?in?human?leukemic?HL-60cells.Planta?Med2005,71(12):1106-1111；Li?W,et?al.Secondary?metabolites?from?Andrographis?paniculata.Chem?Pharm?Bull(Tokyo)2007,55(3):455-458.】。