公开(公告)号：KR100805675B1

公开(公告)日：2008-02-21

申请号：KR1020070022408

申请日：2007-03-07

Applicant: 한림제약(주)

Inventor： 김재신 ,  류종현 ,  이근혁 ,  전세화 ,  김진선

IPC: A61K31/4365 ,  A61K9/14

CPC classification number: A61K31/4365 ,  A61K9/20 ,  A61K47/08 ,  A61K47/10 ,  A61K47/22 ,  A61K47/26 ,  A61K2121/00

Abstract: A composition comprising clopidogrel besylate is provided to show high in vitro dissolution rate and have excellent stability without adding a separate additive such as an antioxidant by preparing the clopidogrel besylate in a solid dispersion with a copolymer of polyoxyethylene and polyoxypropylene and crospovidone as a disintegrant. A pharmaceutical composition comprises a clopidogrel besylate-containing solid dispersion prepared by dispersing 100 parts by weight of clopidogrel besylate, 3-15 parts by weight of a copolymer of polyoxyethylene and polyoxypropylene, 30-60 parts by weight of polyethyleneglycol and 5-20 parts by weight of crospovidone in 55-70 parts by weight of mannitol; and a pharmaceutically acceptable carrier such as a copolymer of polyoxyethylene and polyoxypropylene, crospovidone and a mixture thereof. A method for preparing the composition comprises the steps of: (a) dissolving clopidogrel besylate, a copolymer of polyoxyethylene and polyoxypropylene, polyethyleneglycol and crospovidone in 50-100% ethanol or an aqueous solution of ethanol; (b) dispersing the solution obtained from the step(a) in mannitol and then drying or spraying the solution of the step(a) with fluidizing the mannitol in a granulator to obtain a clopidogrel besylate-containing solid dispersion; and (c) mixing the clopidogrel besylate-containing solid dispersion with a pharmaceutically acceptable carrier. Further, the 0.2-0.4 wt.% of ethanol or an aqueous solution of ethanol is used based on the 100 wt.% of clopidogrel besylate.

Abstract translation: 提供了包含氯吡格雷苯磺酸盐的组合物，以显示高体外溶出速率并且具有优异的稳定性，而不用添加单独的添加剂如抗氧化剂，通过制备固体分散体中的氯吡格雷苯磺酸盐与聚氧乙烯和聚氧丙烯的共聚物和交聚维酮作为崩解剂。 药物组合物包含通过将100重量份苯磺酸氯吡格雷，3-15重量份的聚氧乙烯和聚氧丙烯的共聚物，30-60重量份的聚乙二醇和5-20重量份的聚乙二醇和 交联聚维酮的重量为55-70重量份的甘露糖醇; 和药学上可接受的载体，例如聚氧乙烯和聚氧丙烯的共聚物，交聚维酮及其混合物。 制备组合物的方法包括以下步骤：（a）将乙酸氯吡格雷，聚氧乙烯和聚氧丙烯的共聚物，聚乙二醇和交聚维酮溶于50-100％乙醇或乙醇水溶液中; （b）将从步骤（a）获得的溶液分散在甘露醇中，然后在制粒机中使甘露醇流化，干燥或喷雾步骤（a）的溶液，得到含氯吡格雷的固体分散体; 和（c）将含氯吡格雷苯磺酸盐的固体分散体与药学上可接受的载体混合。 此外，基于100重量％的氯吡格雷苯磺酸盐，使用0.2-0.4重量％的乙醇或乙醇水溶液。