METHOD OF TREATING MIDDLE EAR INFECTIONS

• US 20160243029A1
• Filed: 04/29/2016
• Published: 08/25/2016
• Est. Priority Date: 09/21/2001
• Status: Active Grant

• Current Assignee: Alcon Pharmaceuticals Limited (Alcon Incorporated)
• Original Assignee: Alcon Pharmaceuticals Limited (Alcon Incorporated)
• Inventors: Wall, G. Michael, Conroy, Peter J.
• Granted Patent: US 9,402,805 B1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/545 Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins, cefaclor, or cephalexine
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0046 Ear
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 27/16 Otologicals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Aqueous suspension formulations containing dexamethasone and ciprofloxacin are disclosed for the treatment of middle ear infections in human patients having an open tympanic membrane.

Claims

1. A method of treating a human patient comprising the steps of:

(a) diagnosing the patient as having otitis media and an open tympanic membrane and/or having acute otitis externa in at least one ear; and

(b) topically applying into the ear canal of the patients ear an aqueous suspension composition containing a combination of ciprofloxacin and dexamethasone, wherein the composition comprises a) 0.01-0.5% (wt.) dexamethasone;

b) 0.1-0.4% (wt.) ciprofloxacin;

c) 0.1-0.9% (wt.) tonicity agent;

d) 0.01-0.2% (wt.) of a nonionic surfactant; and

e) a buffer;

wherein three or four drops of the aqueous suspension composition are administered to the patients ear twice a day, and wherein each drop is 30-35 μ

L.

2. The method of claim 1 wherein the dexamethasone is dexamethasone alcohol and the ciprofloxacin is ciprofloxacin hydrochloride, monohydrate.

3. The method of claim 1 wherein the aqueous suspension composition contains 0.1% (wt.) dexamethasone and 0.3% (wt.) ciprofloxacin.

4. The method of claim 1 wherein the dexamethasone has an average particle size on a mean volume basis of less than 3 μ

m.

5. The method of claim 1 wherein said tonicity agent is NaCl.

6. The method of claim 5 wherein said NaCl is present in an amount sufficient to cause the composition to have an osmolality of 250-350 mOsm.

7. The method of claim 1 wherein said nonionic surfactant is tyloxapol.

8. The method of claim 7 wherein said tyloxapol is present at a concentration of 0.05% (wt.).

9. The method of claim 1 wherein said aqueous suspension further comprises a suspending agent.

10. The method of claim 9 wherein said suspending agent is hydroxyethylcellulose.

11. The method of claim 10 wherein said hydroxyethylcellulose is present at a concentration of 0.2% (wt.).

12. The method of claim 1 wherein the aqueous suspension composition consists essentially of a) 0.1% (wt.) dexamethasone alcohol;

b) 0.35% (wt.) ciprofloxacin hydrochloride, monohydrate;

c) NaCl in an amount sufficient to cause the composition to have an osmolality of 250-350 mOsm;

d) 0.2% (wt.) hydroxyethyl cellulose;

e) 0.05% (wt.) tyloxapol;

f) a buffer comprising sodium acetate and acetic acid;

g) 0.01% (wt.) benzalkonium chloride;

h) 0.01% (wt.) edetate disodium;

i) 0.6% (wt.) boric acid; and

wherein the composition has a pH of about 4.5.

13. The method of claim 1 wherein the method further comprises the step of pumping the tragus to force the aqueous suspension composition through the open tympanic membrane and into the middle ear.

14. The method of claim 1 wherein the otitis media is acute otitis media.

15. The method of claim 1 wherein the otitis media is chronic suppurative otitis media.

16. The method of claim 1 wherein the patient is a pediatric patient.

17. The method of claim 1 wherein the aqueous suspension composition containing a combination of ciprofloxacin and dexamethasone is packaged with directions for use that indicate the composition may be used to treat otitis media in patients with an open tympanic membrane.

18. The method of claim 1 wherein the aqueous suspension has a pH of 3-6.

19. The method of claim 1 wherein said treating comprises treating otorrhea associated with a middle ear infection.

20. The method of claim 1 wherein said treating comprises treating acute otitis externa associated with a middle ear infection.

21. The method of claim 1 wherein said treating comprises treating granulation tissue associated with a middle ear infection.

22. The method of claim 1 wherein four drops of said aqueous suspension composition are administered to the patients ear twice a day.

23. A kit for treating otic infections, the kit comprising an aqueous suspension composition comprising a) 0.01-0.5% (wt.) dexamethasone;

b) 0.1-0.4% (wt.) ciprofloxacin;

c) 0.1-0.9% (wt.) tonicity agent;

d) 0.01-0.2% (wt.) of a nonionic surfactant; and

e) a buffer, said composition in a sealed container together with instructions for use thereof, and wherein said instructions indicate that four drops of the aqueous suspension composition are administered to a patients ear twice a day and/or wherein said instructions indicate that three drops of the aqueous suspension composition are administered to a patients ear twice a day.