COMBINATION THERAPY FOR THE TREATMENT OF INFLUENZA

• US 20090298797A1
• Filed: 05/20/2009
• Published: 12/03/2009
• Est. Priority Date: 05/23/2008
• Status: Abandoned Application

• Current Assignee: Bridgestone Corporation, University of Hong Kong (Government of Hong Kong Special Administrative Region)
• Original Assignee: University of Hong Kong (Government of Hong Kong Special Administrative Region)
• Inventors: Zheng, Bojian, Yuen, Kowk-Yung
• Application Number:
  US12/469,319
• Publication Number:
  US 20090298797A1
• Time in Patent Office: Days
• US Class Current: 514/161
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/606 having amino groups
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses

Abstract

Compositions and methods for treating one or more symptoms of influenza, preferably influenza due to infection with influenza A (H5N1) are provided. It has been discovered that administration of a combination of a neuraminidase inhibitor with two immunomodulators increases survivability in subjects 24, 48, or even 72 hours post infection compared to administration of the neuraminidase inhibitor alone. A preferred neuraminidase inhibitor is zanamivir. Preferred immunomodulators include, but are not limited to celecoxib and mesalazine. Another embodiment provides a method for treating influenza, preferably, influenza due to infection with avian influenza A (H5N1) by administering to subject infected with the influenza virus, an effective amount of a neuraminidase inhibitor to inhibit or reduce budding of the influenza virus from infected cells of the subject, and an effective amount of at least two immunomodulators effective to reduce or inhibit one or more symptoms of inflammation in the subject.

Claims

1. A pharmaceutical composition for treating influenza comprising an effective amount of a neuraminidase inhibitor to inhibit or reduce budding of influenza virus from infected cells of a subject and an effective amount of at least two immunomodulators effective to reduce or inhibit one or more symptoms of inflammation of the subject.

2. The pharmaceutical composition of claim 1 wherein the neuraminidase inhibitor is selected from the group consisting of zanamivir, oseltamivir and peramivir.

3. The pharmaceutical composition of claim 2 wherein the neuramindase inhibitor comprises zanamivir.

4. The pharmaceutical composition of claim 1 wherein the immunomodulators are anti-inflammatory agents.

5. The pharmaceutical composition of claim 4 wherein the anti-inflammatory agents are non-steroidal anti-inflammatory agents.

6. The pharmaceutical composition of claim 5 wherein the non-steroidal anti-inflammatory agents are selected from the group consisting of COX-2 inhibitors, aminosalicylate drugs and ligands for PPAR.

7. The pharmaceutical composition of claim 6 wherein the COX-2 inhibitor comprises celecoxib.

8. The pharmaceutical composition of claim 6 wherein the aminosalicylate drug comprises mesalazine.

9. The pharmaceutical composition of claim 1 wherein the neuramindase inhibitor comprises zanamivir, and

wherein the immunomodulators comprise celecoxib and mesalazine.

10. The pharmaceutical composition of claim 1 wherein the influenza is influenza A (H5N1).

11. The pharmaceutical composition of claim 1 wherein the composition extends survivability rates in subjects when administered 24, 48, or 72 hours post infection compared to administration of the neuraminidase inhibitor alone.

12. A unit dose formulation for treating one or more symptoms of influenza comprising an effective amount of zanamivir to inhibit influenza virus from budding from infect cells of a subject and an effective amount of celecoxib and mesalazine to inhibit one or more symptoms of inflammation of the subject.

13. A method for treating influenza comprising administering to subject infected with influenza virus an effective amount of a neuraminidase inhibitor to inhibit or reduce budding of influenza virus from infected cells of the subject and an effective amount of at least two immunomodulators effective to reduce or inhibit one or more symptoms of inflammation of the subject.

14. The method of claim 13 wherein the neuraminidase inhibitor is selected from the group consisting of zanamivir, oseltamivir and peramivir.

15. The method of claim 14 wherein the neuramindase inhibitor comprises zanamivir.

16. The method of claim 13 wherein the immunomodulators are non-steroidal anti-inflammatory agents.

17. The method of claim 16 wherein the non-steroidal anti-inflammatory agents are selected from the group consisting of COX-2 inhibitors, aminosalicylate drugs and ligands for PPAR.

18. The method of claim 13 wherein the neuramindase inhibitor comprises zanamivir, and

wherein the immunomodulators comprise celecoxib and mesalazine.

19. The method of claim 13 wherein the influenza is due to influenza A (H5N1) infection.

20. The method of claim 13 wherein administration at 24, 48, or 72 hours post infection compared to administration of the neuraminidase inhibitor alone increase survivability of the subject compared to administration of the neuraminidase inhibitor alone.