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

• US 6,716,813 B2
• Filed: 11/27/2001
• Issued: 04/06/2004
• Est. Priority Date: 11/28/2000
• Status: Expired due to Fees

• 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
• Primary Examiner(s): Spivack, Phyllis G.
• Assistant Examiner(s): DELACROIX MUIRHEI, CYBILLE
• Application Number:
  US09/998,547
• Publication Number:
  US 20020141986A1
• Time in Patent Office: 861 Days
• Field of Search: 514/2, 514/12
• US Class Current: 514/2.5
• 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 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 method for the treatment of microbial infections of ears and sinuses in a human, comprising administering to said human a pharmaceutical preparation comprising lactoferrins, lysozyme and defensins in an amount effective for a reduction of said microbial infection, wherein said microbial infection comprises a bacteria selected from the group consisting of Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis, said pharmaceutical preparation further comprising a pharmaceutically acceptable carrier, wherein said carrier has a concentration of sodium chloride salt below about 100 mM.

2. The method of claim 1 wherein said microbial infections of the ear and sinus are otitis media and paranasal sinusitis.

3. The method of claim 1 wherein said administration is orally, intranasally, by aerosolization or into the ear canal.

4. The method of claim 1 wherein said defensins are alpha defensins or beta defensin.

5. The method of claim 4, wherein said beta defensins are beta defensin 1 or beta defensin 2.

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

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

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

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

10. The method of claim 1, wherein said pharmaceutical preparation is administered 1 to 8 times per day.

11. The method of claim 1, wherein said pharmaceutical preparation is a solution or suspension.

12. The method of claim 1 wherein said pharmaceutical comprises lysozyme and lactoferrin.

13. The method of claim 1, wherein said pharmaceutical preparation comprises lysozyme and a defensin.

14. The method of claim 1 wherein said defensin is β

-defensin-2.

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

16. The method of claim 1, wherein said NTHi is a strain 12, and wherein said S. pneumoniae is a serotype 3 or a serotype 6B.