公开(公告)号：KR1020080094473A

公开(公告)日：2008-10-23

申请号：KR1020070038959

申请日：2007-04-20

Applicant: 한국화학연구원

Inventor： 신병철 ,  정석현 ,  임덕휘 ,  성하수 ,  조선행

IPC: A61K9/16 ,  A61K9/56 ,  B82Y5/00

CPC classification number: A61K9/1271 ,  A61K9/1277 ,  A61K9/5123 ,  A61K9/5146 ,  A61K31/7048

Abstract: An anionic lipid nanosphere is provided to show increased encapsulation efficiency of an insoluble drug in an aqueous phase by introducing a polyethylene glycol(PEG) containing polyol onto the surface of particles formed from an anionic phospholipid, reduce toxicity of the drug against normal cells and increase in vivo circulation time of the drug by encapsulating a very strongly toxic drug into lipid nanosphere. An anionic lipid nanosphere for encapsulating an insoluble drug such as amphotericin B is characterized in that a PEG containing polymer is coated on the surface of particles formed by an anionic phospholipid. A method for preparing the anionic lipid nanosphere comprises the steps of: (a) mixing 100 parts by weight of lipid prepared by mixing phosphatidylcholine, anionic phospholipd and sterol in a weight ratio of 40-70:5-20:10-40 with 10-30 parts by weight of the polymer containing the PEG and dissolving a mixture in an organic solvent to prepare a lipid-PEG mixture solution; (b) dissolving an insoluble drug in C1-6 linear or branched alcohol to prepare a drug solution; (c) mixing the lipid-PEG mixture solution with the drug solution in a volumetric ratio of 1:1-1:9 to prepare a lipid-PEG-drug mixture solution; (d) dispersing the mixture solution into an aqueous phase in a volumetric ratio of 2:1-10:1 to form lipid nanosphere; and (e) after subjecting the lipid nanosphere solution obtained from the step(d) to distillation at a temperature of 20-50 deg.C under reduced pressure to remove the organic solvent therefrom, filtering it to prepare the anionic lipid nanosphere encapsulating the drug.

Abstract translation: 提供阴离子脂质纳米球，通过将含有聚乙二醇（PEG）的多元醇引入到由阴离子磷脂形成的颗粒表面上，在水相中显示不溶性药物的包封效率，降低药物对正常细胞的毒性并增加 药物的体内循环时间通过将非常强毒性的药物包封在脂质纳米球中。 用于包封不溶性药物如两性霉素B的阴离子脂质纳米球的特征在于将含PEG聚合物涂覆在由阴离子磷脂形成的颗粒的表面上。 制备阴离子脂质纳米球的方法包括以下步骤：（a）将100重量份通过将磷脂酰胆碱，阴离子磷脂和甾醇以40-70:5-20:10-40的重量比混合制备的脂质与10 -30重量份含有PEG的聚合物，并将混合物溶解在有机溶剂中以制备脂质-PEG混合溶液; （b）将不溶性药物溶解在C1-6直链或支链醇中以制备药物溶液; （c）以1：1-1：9的体积比混合脂质-PEG混合溶液与药液，制备脂质-PEG-药物混合溶液; （d）将混合溶液以2:1-10:1的体积比分散在水相中以形成脂质纳米球; 和（e）在将步骤（d）获得的脂质纳米圈溶液在20-50℃的温度下减压蒸馏除去有机溶剂之后，过滤以制备包封该药物的阴离子脂质纳米球 。