Boron-containing small molecules

Patent metadata

Field	Value
Publication number	US-9566289-B2
Application number	US-201615046322-A
Country	US
Kind code	B2
Filing date	Feb 17, 2016
Priority date	Feb 16, 2005
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

This invention relates to compounds useful for treating fungal infections, more specifically topical treatment of onychomycosis and/or cutaneous fungal infections. This invention is directed to compounds that are active against fungi and have properties that allow the compound, when placed in contact with a patient, to reach the particular part of the skin, nail, hair, claw or hoof infected by the fungus. In particular the present compounds have physiochemical properties that facilitate penetration of the nail plate.

First claim

What is claimed is:

1. A pharmaceutical formulation, comprising:
1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable topical carrier.

2. The pharmaceutical formulation of claim 1 , wherein the pharmaceutically acceptable topical carrier comprises one or more members selected from polymers, thickeners, buffers, neutralizers, chelating agents, preservatives, surfactants or emulsifiers, antioxidants, waxes or oils, emollients, sunscreens, and a solvent or mixed solvent system.

3. The pharmaceutical formulation of claim 1 , wherein the pharmaceutically acceptable topical carrier comprises a solvent system and a chelating agent; wherein the solvent system comprises ethanol and propylene glycol; and wherein
the chelating agent is ethylene diamine tetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical formulation, comprising:
1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a pharmaceutically acceptable salt thereof;
a solvent system and
a chelating agent.

5. The pharmaceutical formulation of claim 4 , wherein the solvent system comprises ethanol.

6. The pharmaceutical formulation of claim 4 , wherein the solvent system consists of ethanol.

7. The pharmaceutical formulation of claim 4 , wherein the solvent system comprises ethanol and propylene glycol.

8. The pharmaceutical formulation of claim 4 , wherein the chelating agent is ethylene diamine tetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof.

9. The pharmaceutical formulation of claim 8 , wherein the ethylene diamine tetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof, is present in a concentration of from about 0.005% to about 2.0% w/w.

10. The pharmaceutical formulation of claim 4 , wherein the 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a pharmaceutically acceptable salt thereof, is present in a concentration of about 5% w/w.

11. The pharmaceutical formulation of claim 4 , wherein the formulation is suitable for the treatment of onychomycosis of a toenail due to Trichophyton rubrum or Trichophyton mentagrophytes by topical application of the formulation to the toenail.

12. A pharmaceutical formulation, comprising:
about 5% w/w 1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a pharmaceutically acceptable salt thereof;
propylene glycol;
ethanol; and
ethylene diamine tetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof.

13. The pharmaceutical formulation of claim 12 , wherein the formulation is suitable for the treatment of onychomycosis of a toenail due to Trichophyton rubrum or Trichophyton mentagrophytes by topical application of the formulation to the toenail.

14. The pharmaceutical formulation of claim 12 , wherein the ethylene diamine tetraacetic acid (EDTA) or a pharmaceutically acceptable salt thereof, is present in a concentration of from about 0.005% to about 2.0% w/w.

15. The pharmaceutical formulation of claim 14 , wherein the formulation is suitable for the treatment of onychomycosis of a toenail due to Trichophyton rubrum or Trichophyton mentagrophytes by topical application of the formulation to the toenail.

Assignees

• Anacor Pharmaceuticals Inc

Inventors

• Baker Stephen J
• Akama Tsutomu
• Hernandez Vincent S
• Hold Karin M
• Maples Kirk
• Plattner Jacob J
• Sanders Virginia
• Zhang Yong-Kang
• Fieldson Gregory T
• Leyden James J

Classifications

• A61P31/10

  Antimycotics · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title

• A61K9/0012

  Galenical forms characterised by the site of application · CPC title

• C07H23/00

  Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title