Use of antimicrobial proteins and peptides for the treatment of otitis media and paranasal sinusitis

• US 20020141986A1
• Filed: 11/27/2001
• Published: 10/03/2002
• Est. Priority Date: 11/28/2000
• Status: Active Grant

• Current Assignee: House Ear Institute
• Original Assignee: House Ear Institute
• Inventors: Li, Jian-Dong, Lim, David J., Andalibi, Ali, Lee, Haa-Yung, Ganz, Tomas, Webster, Paul
• Granted Patent: US 6,716,813 B2
• Time in Patent Office: Days
• US Class Current: 424/94.61
• 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 38/1729 Cationic antimicrobial peptides, e.g. defensins
• CPC Class Codes: A61K 38/40 Transferrins, e.g. lactoferrins, ovotransferrins
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases

Abstract

Disclosed herein is a composition and a method for the treatment of otitis media and paranasal sinusitis using human defensins, lysozyme and/or lactoferrin as a new class of non-antibiotic antimicrobials. From studies of otitis media and paranasal sinusitis, it was observed that certain innate immune modulators were important in the bodies response to the infection. Therefore, these innate immune modulators, lysozyme, lactoferrin, and defensins were tested for use as a non-antibiotic treatment for infection, particularly infections such as otitis media and sinusitis.

Claims

1. A pharmaceutical preparation for the treatment of otitis and sinusitis, comprising at least one component selected from the group consisting of:

lactoferrins, lysozyme, and defensins in an amount effective to reduce the growth of microbes, a salt chelator and a pharmaceutically acceptable carrier.

2. The pharmaceutical preparation of claim 1 wherein said defensins are alpha defensins or beta defensins.

3. The pharmaceutical preparation of claim 1 wherein said beta defensins are beta defensin 1 or beta defensin 2.

4. The pharmaceutical preparation of claim 1 wherein said pharmaceutical is at a dose of about 0.1 to 100 mg/kg/dose.

5. The pharmaceutical preparation of claim 1 wherein said pharmaceutical is at a dose of about 0.5 to 50 mg/kg/dose.

6. The pharmaceutical preparation of claim 1 wherein said pharmaceutical is at a dose of about 0.1 to 1000 mg/kg/day.

7. The pharmaceutical preparation of claim 1 wherein said pharmaceutical is at a dose of about 0.8 to 800 mg/kg/day.

8. The pharmaceutical preparation of claim 1 comprising β

-defensin-2, lysozyme, and β

-defensin-1 in an excipient formulated for treatment of and administration to the middle ear.

9. A method for the treatment of microbial infections of the ear and sinuses in a mammal, comprising:

administering to said mammal a pharmaceutical preparation comprising at least one component selected from the group consisting of lactoferrins, lysozyme, and defensins in an amount effective for the reduction in numbers of the causative infective agents.

10. The method of claim 9 wherein said microbial infections of the ear and sinus are otitis media and paranasal sinusitis.

11. The method of claim 9 wherein said administration is orally, intranasally, by aerosolization or into the ear canal.

12. The method of claim 9 wherein said defensins are alpha defensins or beta defensins.

13. The method of claim 9 wherein said beta defensins are beta defensin 1 or beta defensin 2.

14. The method of claim 9 wherein said pharmaceutical is administered at a dose of about 0.1 to 100 mg/kg/dose.

15. The method of claim 9 wherein said pharmaceutical is administered at a dose of about 0.5 to 50 mg/kg/dose.

16. The method of claim 9 wherein said pharmaceutical is administered at a dose of about 0.1 to 1000 mg/kg/day.

17. The method of claim 9 wherein said pharmaceutical is administered at a dose of about 0.8 to 800 mg/kg/day.

18. The method of claim 9 wherein said pharmaceutical is administered 1 to 8 times per day.

19. The method of claim 9 wherein said pharmaceutical is a solution or suspension.

20. The method of claim 9 wherein said pharmaceutical further comprises a salt chelator.

21. The method of claim 9 wherein said pharmaceutical comprises lysozyme and lactoferrin.

22. The method of claim 9 wherein said pharmaceutical comprises lysozyme and a defensin.

23. The method of claim 9 wherein said defensin is β

-defensin-2.

24. The method of claim 9 wherein said pharmaceutical comprises lysozyme, beta defensin 1 and beta defensin 2.

25. The method of claim 9 wherein said mammal is a human.

26. The method of claim 9 wherein said mammal is an animal selected from the group consisting of:

a dog, a cat, a horse, a ferret, a mouse, a rat and a cow.

27. The method of claim 10, wherein the Otitis media is caused by a microbe selected from the group consisting of NTHi strain 12, M. catarrhalis, S. pneumoniae serotype 3, and S. pneumoniae serotype 6B.