发明公开
- 专利标题: DISODIUM SALTS, MONOHYDRATES, AND ETHANOL SOLVATES
- 专利标题(中): 乙醇钠,乙醇钠,乙醇溶液
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申请号: EP00921909申请日: 2000-04-05
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公开(公告)号: EP1175390A4公开(公告)日: 2002-09-04
- 发明人: BAY WILLIAM E , AGARWAL RAJESH K , CHAUDHARY KIRAN , MAJURU SHINGAI , GOLDBERG MICHAEL M , RUSSO JOANNE P
- 申请人: EMISPHERE TECH INC
- 专利权人: EMISPHERE TECH INC
- 当前专利权人: EMISPHERE TECH INC
- 优先权: US12775499 1999-04-05; US18614300 2000-03-01; US18614200 2000-03-01; US19128600 2000-03-21
- 主分类号: A61K47/16
- IPC分类号: A61K47/16 ; A61K9/08 ; A61K9/20 ; A61K9/48 ; A61K38/22 ; A61K47/12 ; A61K47/18 ; A61P3/14 ; C07C231/00 ; C07C231/12 ; C07C235/58 ; C07C235/60 ; C07D265/26 ; C07C229/00
摘要:
The inventors have discovered that the disodium salt of certain delivery agents has surprisingly greater efficacy for delivering active agents than the corresponding monosodium salt. Furthermore, the inventors have discovered that the disodium salts of these delivery agents form solvates with ethanol and hydrates with water. The delivery agents have formula (I) wherein R?1, R2, R3, and R4¿ are indepedently hydrogen, halogen, C¿1?-C4 alkyl, or C1-C4 alkoxy; and R?5¿ is a substituted or unsubstituted C¿2?-C16 alkylene, substituted or unsubstituted C2-C16 alkenylene, substituted or unsubstituted C1-C12 alkyl(arylene), or substituted or unsubstituted aryl(C1-C12 alkylene). The hydrates and solvates of present invention also have surprisingly greater efficacy for delivering active agents, such as heparin and calcitonin, than their corresponding monosodium salts and free acids. The present invention provides an alcohol solvate, such as ethanol solvate, of a disodium salt of a delivery agent of formula (I) above. Preferred delivery agents include, but are not limited to, N-(5-chlorosalicyloyl)-8-aminocaprylic acid (5-CNAC),N-(10-[2-hydroxybenzoyl]amino)decanoic acid (SNAD), and sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC). The invention also provides methods of preparing the disodium salt, ethanol solvate, and hydrate and compositions containing the disodium salt, ethanol solvate, and/or hydrate.
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