Coordination complexes, pharmaceutical solutions comprising coordination complexes, and methods of treating patients

• US 9,624,256 B2
• Filed: 05/29/2014
• Issued: 04/18/2017
• Est. Priority Date: 10/25/2004
• Status: Expired due to Fees

• Current Assignee: Synthonics Incorporated (Synthonics Technologies, Inc.)
• Original Assignee: Synthonics Incorporated (Synthonics Technologies, Inc.)
• Inventors: Piccariello, Thomas, Price, John D., Oberlender, Robert A., Mulhare, Michaela E., Spencer, Mary C., Palmer, Scott B.
• Primary Examiner(s): NAZARIO GONZALEZ, PORFIRIO
• Application Number:
  US14/290,877
• Publication Number:
  US 20140274936A1
• Time in Patent Office: 1,055 Days
• Field of Search: 544 64, 514492, 556137
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/295 Iron group metal compounds
• CPC Class Codes: A61K 31/351 not condensed with another ring
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/55 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07F 15/02 Iron compounds
• CPC Class Codes: C07F 15/04 Nickel compounds
• CPC Class Codes: C07F 15/045 without a metal-carbon linkage
• CPC Class Codes: C07F 3/00 Compounds containing elements of Groups 2 or 12 of the Periodic Table
• CPC Class Codes: C07F 3/003 without C-Metal linkages
• CPC Class Codes: C07F 3/02 Magnesium compounds
• CPC Class Codes: C07F 3/06 Zinc compounds
• CPC Class Codes: C07H 17/02 Heterocyclic radicals containing only nitrogen as ring hetero atoms

Abstract

A coordination complex having a physiologically acceptable pK_a includes a metal and a biologically active agent. The pK_a of the coordination complex is less than the pK_a of the biologically active agent. A pharmaceutical solution for treating a patient includes a coordination complex and water, wherein the coordination complex is at least partially soluble in the water at physiological pH and in a therapeutically efficacious concentration. A method for treating a patient includes administering a pharmaceutical solution including a coordination complex and water to a patient in need of a biologically active agent.

Claims

1. A metal coordination complex of a biologically active moiety and a metal, wherein the biologically active moiety is selected from the group consisting of:

fingolimod, acamprosate, tixocortol, pregabalin, 7-phenyl-2,4,6-hepta-trienal hydroxamic acid, (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid, eglumegad, (2S,2′

R,3′

R)-2-(2′

,3′

-dicarboxycyclo-propyl)glycine, remacemide, zonisamide, balsalazide, dobutamine, ganciclovir, modafinil, ribavirin, zoledronic acid, and their derivatives.

2. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a metal coordination complex of a biologically active moiety and a metal, wherein the biologically active moiety is selected from the group consisting of:

fingolimod, acamprosate, tixocortol, pregabalin, 7-phenyl-2,4,6-hepta-trienal hydroxamic acid, (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid, eglumegad, (2S,2′

R,3′

R)-2-(2′

,3′

-dicarboxycyclo-propyl)glycine, remacemide, zonisamide, balsalazide, dobutamine, ganciclovir, modafinil, ribavirin, zoledronic acid, and their derivatives.

3. The composition of claim 2, wherein the metal is selected from:

s-block metals, d-block metals, and p-block metals.

4. The composition of claim 2, wherein the biologically active moiety is fingolimod.

5. The composition of claim 2, wherein the biologically active moiety is acamprosate.

6. The composition of claim 2, wherein the biologically active moiety is tixocortol.

7. The composition of claim 2, wherein the biologically active moiety is pregabalin.

8. The composition of claim 2, wherein the biologically active moiety is 7-phenyl-2,4,6-hepta-trienal hydroxamic acid.

9. The composition of claim 2, wherein the biologically active moiety is (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid.

10. The composition of claim 2, wherein the biologically active moiety is eglumegad.

11. The composition of claim 2, wherein the biologically active moiety is (2S,2′

R,3′

R)-2-(2′

,3′

-dicarboxycyclo-propyl)glycine.

12. The composition of claim 2, wherein the biologically active moiety is remacemide.

13. The composition of claim 2, wherein the biologically active moiety is zonisamide.

14. The composition of claim 2, wherein the biologically active moiety is balsalazide.

15. The composition of claim 2, wherein the biologically active moiety is dobutamine.

16. The composition of claim 2, wherein the biologically active moiety is ganciclovir.

17. The composition of claim 2, wherein the biologically active moiety is modafinil.

18. The composition of claim 2, wherein the biologically active moiety is ribavirin.

19. The composition of claim 2, wherein the biologically active moiety is zoledronic acid.

20. The pharmaceutical composition of claim 2, wherein the biologically active moiety is selected from the group consisting of:

fingolimod, acamprosate, tixocortol, pregabalin, 7-phenyl-2,4,6-hepta-trienal hydroxamic acid, (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid, eglumegad, (2S,2′

R,3′

R)-2-(2′

,3′

-dicarboxycyclo-propyl)glycine, remacemide, zonisamide, balsalazide, dobutamine, ganciclovir, modafinil, ribavirin, and zoledronic acid.

21. The complex of claim 20, wherein the metal is selected from:

s-block metals, d-block metals, and p-block metals.