EDTA and other chelators with or without antifungal antimicrobial agents for the prevention and treatment of fungal infections

• US 6,509,319 B1
• Filed: 10/04/2000
• Issued: 01/21/2003
• Est. Priority Date: 08/26/1997
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Raad, Issam, Hachem, Ray, Sherertz, Robert
• Primary Examiner(s): Peselev, Elli
• Application Number:
  US09/680,061
• Time in Patent Office: 839 Days
• Field of Search: 424/450, 424/141.1, 514/31
• US Class Current: 514/31
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• 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 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00

Abstract

A pharmaceutical composition comprising at least one antifungal agent and at least one chelator, and a method for administering the pharmaceutical composition to a patient having a fungal infection. Another aspect provides a pharmaceutical composition comprising at least one chelator, at least one antifungal agent and at least one monoclonal antibody, wherein the monoclonal antibody is operatively attached to the chelator, and a method of administering this composition to a patient having a fungal infection.

Claims

1. A pharmaceutical composition comprising at least one polyene antifungal agent and at least one chelator, the polyene antifungal agent and chelator being selected and present in amounts that provide a greater than additive antifungal action in vitro.

2. The pharmaceutical composition of claim 1, wherein the chelator is selected from the group of chelators consisting of EDTA free acid, EDTA 2Na, EDTA 3Na, EDTA 4Na, EDTA 2K, EDTA 2Li, EDTA 2NH₄, EDTA 3K, Ba(II)-EDTA, Ca(II)-EDTA, Co(II)-EDTA, Cu(II)-EDTA, Dy(III)-EDTA, Eu(III)-EDTA, Fe(III)-EDTA, In(III-EDTA, La(III)-EDTA, CyDTA, DHEG, DTPA-OH, DTPA, EDDA, EDDP, EDDPO, EDTA-OH, EDTPO, EGTA, HBED, HDTA, HIDA, IDA, Methyl-EDTA, NTA, NTP, NTPO, O-Bistren, and TTHA.

3. The pharmaceutical composition of claim 1, wherein the antifungal agent is selected from the group of antifungal agents consisting of Ambisome, ABLC, Liposomal Amphotericin, ABCD, Liposomal Nystatin, Amphotericin B, Nystatin, and Natamycin.

4. The pharmaceutical composition of claim 2, wherein the chelator is EDTA.

5. The pharmaceutical composition of claim 3, wherein the antifungal agent is Amphotericin B.

6. The pharmaceutical composition of claim 1, wherein the chelator is EDTA and the antifungal agent is Amphotericin B.

7. The pharmaceutical composition of claim 1, further comprising at least one monoclonal antibody specific for a targeted species of fungus.

8. The pharmaceutical composition of claim 7, where the monoclonal antibody is operatively attached to said chelator.

9. A pharmaceutical composition comprising at least one chelator, at least one antifungal agent and at least one monoclonal antibody, wherein said monoclonal antibody is operatively attached to said chelator.

10. The pharmaceutical composition of claim 9, wherein the chelator is selected from the group of chelators consisting of EDTA free acid, EDTA 2Na, EDTA 3Na, EDTA 4Na, EDTA 2K, EDTA 2Li, EDTA 2NH₄, EDTA 3K, Ba(II)-EDTA, Ca(II)-EDTA, Co(II)-EDTA, Cu(II)-EDTA, Dy(III)-EDTA, Eu(III)-EDTA, Fe(III)-EDTA, In(III-EDTA, La(III)-EDTA, CyDTA, DHEG, DTPA-OH, DTPA, EDDA, EDDP, EDDPO, EDTA-OH, EDTPO, EGTA, HBED, HDTA, HIDA, IDA, Methyl-EDTA, NTA, NTP, NTPO, O-Bistren, and TTHA.

11. The pharmaceutical composition of claim 9, wherein the antifungal agent is selected from the group of antifungal agents consisting of Voriconazole, SCH 56592, ER30346, UK 9746, UK 9751, T 8581, Flutrimazole, Cilofungin LY121019, Echinocandin, Pneumocandin, Pradimicins, Benanomicin, Ambisome, ABLC, Liposomal Amphotericin, ABCD, Liposomal Nystatin, Nikkomycin Z, Terbinafine, BF-796, MTCH 24, BTG-137586, RMP-7/Amphotericin B, Omoconazole, Amphotericin B, Nystatin, Natamycin, Clotrimazole, Miconazole, Ketoconazole, Terconazole, Econazole, Itraconazole, Fluconazole, Griseofulvin, and Flucytosine.

12. The pharmaceutical composition of claim 10, wherein the chelator is EDTA.

13. The pharmaceutical composition of claim 11, wherein the antifungal agent is Amphotericin B.

14. The pharmaceutical composition of claim 9, wherein the chelator is EDTA and the antifungal agent is Amphotericin B.

15. The pharmaceutical composition of claim 9, further defined as comprising about 0.001 mg to about 1000 mg of chelator.

16. The pharmaceutical composition of claim 9, further defined as comprising about 0.001 mg to about 1000 mg of antifungal agent.