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 the formula [structure] wherein R 1 , R 2 , R 3 , and R 4 are independently hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy; and R 5 is a substituted or unsubstituted C 2 -C 16 alkylene, substituted or unsubstituted C 2 -C 16 alkenylene, substituted or unsubstituted C 1 -C 12 alkyl(arylene), or substituted or unsubstituted aryl(C 1 -C 12 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 the formula above. The invention also provides a hydrate of a disodium salt of a delivery agent of the formula 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.

Claims

8 · 2 independent · depth 3

8 granted claims

›1.independentA solid pharmaceutical composition comprising from about 50% to about 100% by weight of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic ac…+6

›2.↳ 1The solid pharmaceutical composition of claim 1, wherein the biologically active agent is human growth hormone.d2

›3.↳ 1The solid pharmaceutical composition of claim 1, wherein the biologically active agent is parathyroid hormone or a biologically active fragment thereo…d2

›4.↳ 1The solid pharmaceutical composition of claim 1, wherein the composition comprises from about 90% to about 100% by weight of the disodium salt of N-(5…d2+1

›5.↳ 1The solid pharmaceutical composition of claim 1, wherein the composition comprises from about 90% to about 100% by weight of the disodium salt of N-(5…d2+1

›8.independentA solid pharmaceutical composition comprising at least from about 96% to 100% by weight of the disodium salt of N-(5-chlorosalicyloyl)-8-aminocaprylic…

Classifications

5 codes

IPC · International Patent Classification

Section A — Human necessities

A61K31/195

Section C — Chemistry; metallurgy

C07C229/00

USPC · US Patent Classification

514/563562/444562/450

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Pendency

1.3 y

466 days filing → grant

Office actions

non-final + final

Responses

1 RCE

Examiner

Taylor Victor Oh

art unit 1625 · TC 1600

Law firm

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Priority chain

2 priority documents

Priority

5 Apr 1999

earliest claimed

›Priority documents — 2

Type	Document	Date
provisional	US 60127754	5 Apr 1999
related publication	US 20100099621 A1	22 Apr 2010

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