发明公开
EP1175390A4 DISODIUM SALTS, MONOHYDRATES, AND ETHANOL SOLVATES 有权
乙醇钠,乙醇钠,乙醇溶液

DISODIUM SALTS, MONOHYDRATES, AND ETHANOL SOLVATES
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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