Metal coordinated compositions

• US 20090143338A1
• Filed: 12/30/2008
• Published: 06/04/2009
• Est. Priority Date: 10/25/2004
• Status: Active Grant

• Current Assignee: Thomas Piccariello
• Original Assignee: Thomas Piccariello
• Inventors: Piccariello, Thomas
• Granted Patent: US 7,989,440 B2
• Time in Patent Office: Days
• US Class Current: 514/108
• CPC Class Codes: A61K 47/52 the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
• CPC Class Codes: A61K 47/547 Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
• 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: A61K 47/552 one of the codrug's components being an antibiotic
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 13/04 for urolithiasis
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/10 for petit-mal
• CPC Class Codes: A61P 25/12 for grand-mal
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/12 : Antihypertensives
• 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 21/02 : with ribosyl as saccharide radical

Abstract

A metal coordination complex of a biologically active moiety and a metal is disclosed. The complex confers to the biologically active moiety an improved performance which can include potency, stability, absorbability, targeted delivery, and combinations thereof.

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 thyronine, hydrochlorothiazide, hydrocodone, oxycodone, alendronate, and their derivatives, and

the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

2. A complex according to claim 1 wherein the biologically active moiety is selected from the group consisting of thyronine and its derivatives.

3. A complex according to claim 2, wherein the complex is bis(triiodothyroninato)zinc.

4. A complex according to claim 2, wherein the complex is bis(triiodothyroninato)magnesium.

5. A complex according to claim 1 wherein the biologically active moiety is selected from the group consisting of oxycodone and its derivatives.

6. A complex according to claim 5, wherein the complex is (oxycodone)magnesium.

7. A complex according to claim 5, wherein the complex is (oxycodone)zinc.

8. A complex according to claim 1 wherein the biologically active moiety is selected from the group consisting of hydrocodone and its derivatives.

9. A complex according to claim 8, wherein the complex is bis(hydrocodonato)magnesium.

10. A complex according to claim 8, wherein the complex is bis(hydrocodonato)zinc.

11. A complex according to claim 1 wherein the biologically active moiety is selected from the group consisting of hydrochlorothiazide and its derivatives.

12. A complex according to claim 11 wherein the complex is bis(hydrochlorothiazido)zinc.

13. A complex according to claim 1 wherein the biologically active moiety is selected from the group consisting of alendronate and its derivatives.

14. A complex according to claim 13 wherein the complex is bis(alendronato)zinc.

15. A complex according to claim 13 wherein the complex is bis(alendronato)magnesium.

16. A metal coordination complex of a biologically active moiety and a metal, wherein the biologically active moiety contains a β

-diketone, ketophenol or β

-ketoalcohol, functional group and

the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc,

wherein the biologically active moiety is not a tetracycline antibiotic.

17. A metal coordination complex of a biologically active moiety and a metal, wherein

the biologically active moiety contains an alcohol and an azole functional group, and

the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc,

wherein the biologically active moiety is not a tetracycline antibiotic.

18. A metal coordination complex of a biologically active moiety and a metal, wherein

the biologically active moiety contains a diamine functional group, and

the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

19. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with the biologically active moiety and a metal,

wherein the biologically active moiety is selected from the group consisting of thyronine, hydrocodone, oxycodone, and their derivatives, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

20. A method of claim 19 further comprising

adding an adjuvant selected from the group consisting of peptides, carbohydrates or lipids that confer desired performance parameters to the biologically active agent.

21. The method of claim 19, wherein the properties to be modulated are selected from the group consisting of potency, stability, absorbability, targeted delivery, and combinations thereof.

22. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety is selected from the group consisting of thyronine, hydrochlorothiazide, hydrocodone, oxycodone, alendronate, and their derivatives, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

23. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises furosemide or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, magnesium, and silicon.

24. The method of claim 23, wherein the metal is magnesium.

25. The method of claim 23, wherein the metal is calcium.

26. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises furosemide or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, and silicon.

27. The method of claim 26, wherein the metal is magnesium.

28. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises hydrochlorothiazide or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

29. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises hydrochlorothizide or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

30. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises hydrocodone or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

31. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises hydrocodone or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

32. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises oxycodone or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

33. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises oxycodone or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

34. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises alendronate or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

35. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises alendronate or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

36. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises thyronine or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

37. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises thyronine or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

38. A method of treating a patient having a condition that is responsive to a treatment with a metal coordination complex of a biologically active moiety and a metal, comprising:

administering to the patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety is selected from the group consisting of thyronine, hydrochlorothiazide, hydrocodone, oxycodone, alendronate, and their derivatives, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

39. A method of treating hypothyroidism, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises thyronine or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

40. The method of treating edema or hypertension, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises hydrochlorothiazide or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

41. A method of treating pain or a cough, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises hydrocodone or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

42. A method of treating pain, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises oxycodone or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

43. A method of treating osteoporosis, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises alendronate or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

44. A method of preventing osteoporosis, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises alendronate or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

45. A method of treating excess fluid retention, edema, or hypertension, comprising:

administering to a patient in need thereof an effective amount of a metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises furosemide or a derivative thereof, and

wherein the metal is selected from the group consisting aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

46. A metal coordination complex of a biologically active moiety and a metal,

wherein the biologically active moiety comprises mesalamine or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.

47. A method of modulating the properties of a biologically active moiety comprising

forming a metal coordination complex with a metal,

wherein the biologically active moiety comprises mesalamine or a derivative thereof, and

wherein the metal is selected from the group consisting of aluminum, bismuth, calcium, iron, magnesium, silicon, and zinc.