Compounds for treating biofilm infection

• US 10,272,158 B2
• Filed: 07/02/2015
• Issued: 04/30/2019
• Est. Priority Date: 07/03/2014
• Status: Active Grant

• 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: Smyth, Hugh, Du, Ju
• Primary Examiner(s): Lau, Jonathan S
• Application Number:
  US15/323,482
• Publication Number:
  US 20170143842A1
• Time in Patent Office: 1,398 Days
• 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 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

In some aspects, pegylated aminoglycoside compounds are provided. In some embodiments, m-PEG-tobramycin compounds may be used to treat a biofilm infection or reduce or treat established biofilms. The present invention provides, in various aspects, compounds and methods for the treatment of infections, such as biofilm infections or chronic biofilm infections. The chronic biofilm infection may occur in wounds, implanted devices, immunocompromised patients, people with cystic fibrosis, eye infections, etc.

Claims

1. A compound comprising an aminoglycoside covalently bound to a poly(ethylene glycol), wherein the compound has the structure

2. The compound of claim 1, wherein n=100-2000.

3. The compound of claim 2, wherein n=100-750.

4. The compound of claim 2, wherein n=250-1000.

5. The compound of claim 1, wherein the compound has a molecular weight ranging from about 100 daltons to about 100,000 daltons.

6. The compound of claim 5, wherein the compound has a molecular weight ranging from about 2000 daltons to about 10,000 daltons.

7. The compound of claim 1, wherein the compound is comprised in a pharmaceutical composition.

8. The compound of claim 7, wherein the pharmaceutical composition is formulated for topical, inhalational, parenteral, intravenous, or injection administration.

9. The compound of claim 7, wherein the pharmaceutical composition comprises a second antimicrobial, antibacterial, or antifungal compound.

10. The compound of claim 9, wherein the second compound is an aminoglycoside.

11. The compound of claim 10, wherein the second compound is tobramycin.

12. A medical device, wherein at least a portion of a surface of the device is coated with the compound of claim 1.

13. The medical device of claim 12, wherein all of the surface is coated with the compound.

14. The medical device of claim 12, wherein the medical device is a glove, a catheter, a stent, a staple, a pin, an electrical nerve stimulation device, a screw, a rod, a wire, a collar, a tube, or a surgical drain.

15. The medical device of claim 14, wherein the medical device is a catheter.

16. The medical device of claim 15, wherein the catheter is an intravenous catheter, a drainage catheter, or a urinary catheter.

17. The medical device of claim 12, wherein the medical device wherein the coating further comprises a second antimicrobial, antibacterial, or antifungal compound.

18. The medical device of claim 17, wherein the second compound is an aminoglycoside.

19. The medical device of claim 18, wherein the second compound is tobramycin.

20. A method of treating a biofilm infection in a subject comprising administering to the subject a therapeutic amount of a pegylated aminoglycoside compound of claim 1.