Formulations and methods for treating rhinosinusitis
View Patent ↗The invention involves methods and formulations for treating or preventing rhinosinusitis, including but not limited to, bacterial-induced, viral-induced and/or fungus-induced rhinosinusitis in mammals, and/or rhinosinusitis not induced by an infective agent, such as bacteria, fungus or virus. In one embodiment, the formulation of the present invention comprises an anti-inflammatory agent (e.g. fluticasone propionate) having a specific particle size distribution profile. The formulation may also comprise an antifungal agent, antibiotic or antiviral agent.
1. A formulation for the treatment of symptoms associated with rhinosinusitis in a mammal suffering from rhinosinusitis, the formulation comprising an aqueous suspension comprising:
(a) about 10 mcg to about 2000 mcg of an anti-inflammatory agent, the anti-inflammatory agent comprises suspended solid particles of fluticasone or pharmaceutically acceptable salt thereof, said suspended solid particles of fluticasone comprise the following particle size distribution profile:
i. about 10% of the anti-inflammatory particles has an average particle size of less than 0.40 microns;
ii. about 25% of the anti-inflammatory particles have an average particle size of less than 0.8 microns;
iii. about 50% of the anti-inflammatory particles have an average particle size of less than 1.5 microns;
iv. about 75% of the anti-inflammatory particles have an average particle size of less than 3.0 microns; and
v. about 90% of the anti-inflammatory particles have an average particle size distribution of less than 5.3 microns; and
(b) an antifungal agent, wherein the formulation is suitable for administration by the intranasal route of the mammal; wherein the formulation is sterile and free of benzalkonium chloride.
2. A formulation for the treatment of symptoms associated with rhinosinusitis in a mammal suffering from said rhinosinusitis, the formulation comprising an aqueous suspension comprising:
(a) about 10 mcg to about 2000 mcg of an anti-inflammatory agent, the anti-inflammatory agent comprises suspended solid particles of beclomethasone or pharmaceutically acceptable salt thereof, said suspended solid particles of beclomethasone comprise the following particle size distribution profile:
i. about 10% of the anti-inflammatory particles has an average particle size of less than 0.30 microns;
ii. about 25% of the anti-inflammatory particles have an average particle size of less than 0.55 microns;
iii. about 50% of the anti-inflammatory particles have an average particle size of less than 1.1 microns; and
iv. about 75% of the anti-inflammatory particles have an average particle size of less than 1.8 microns; and
v. about 90% of the anti-inflammatory particles have an average particle size distribution of less than 2.7 microns; and
(b) an antifungal agent, wherein the formulation is suitable for administration by the intranasal route of the mammal; wherein the formulation is sterile and free of benzalkonium chloride.
3. The formulation of claims 1 or 2 , comprising about 25 mcg to about 400 mcg of the anti-inflammatory agent.
4. The formulation of claims 1 or 2 , comprising about 75 to about 300 mcg of the anti-inflammatory agent.
5. The formulation of claims 1 or 2 , comprising about 200 mcg of the anti-inflammatory agent, and wherein the formulation is sterile and free of benzalkonium chloride yet has a relatively long period of stability such that after storage for 12 months at a temperature between 15 to 30° C., greater than 80% of the anti-inflammatory agent and greater than 80% of the antifungal agent originally present in the formulation still remains in the formulation.
6. A formulation for the treatment of symptoms associated with rhinosinusitis in a mammal suffering thereof, the formulation comprises an aqueous suspension that comprises an anti-inflammatory agent, the anti-inflammatory agent comprises 0.04% to 0.06% by weight of suspended solid particles of fluticasone or pharmaceutically acceptable salt thereof, said suspended solid particles of fluticasone comprise the following particle size distribution profile:
i. about 10% of the anti-inflammatory particles have an average particle size of less than 0.40 microns;
ii. about 25% of the anti-inflammatory particles have an average particle size of less than 0.8 microns;
iii. about 50% of anti-inflammatory particles have an average particle size of less than 1.5 microns;
iv. about 75% of the anti-inflammatory particles have a particle size of less than 3.0 microns;
v. about 90% of the anti-inflammatory particles have a particle size of less than 5.3 microns;
an antifungal agent, wherein the formulation is suitable for the administration by the intranasal route of the mammal; wherein the formulation is sterile and free of benzalkonium chloride.
7. A formulation for the treatment of symptoms associated with rhinosinusitis in a mammal suffering thereof, the formulation comprises an aqueous suspension that comprises an anti-inflammatory agent, the anti-inflammatory agent comprises 0.04% to 0.05% by weight of suspended solid particles of beclomethasone or pharmaceutically acceptable salt thereof, said suspended solid particles of beclomethasone comprise the following particle size distribution profile:
i. about 10% of the anti-inflammatory particles have an average particle size of less than 0.30 microns;
ii. about 25% of anti-inflammatory particles have an average particle size of less than 0.55 microns;
iii. about 50% of the anti-inflammatory particles have an average particle size of less than 1.1 microns;
iv. about 75% of the anti-inflammatory particles have a particle size of less than 1.8 microns;
v. about 90% of the anti-inflammatory particles have a particle size of less than 2.7 microns;
an antifungal agent, wherein the formulation is suitable for the administration by the intranasal route of the mammal; wherein the formulation is sterile and free of benzalkonium chloride.
8. The formulations of claims 6 or 7 , comprising about 25 mcg to about 400 mcg of the anti-inflammatory agent.
9. The formulation of claims 6 or 7 , comprising about 75 mcg to about 300 mcg of the anti-inflammatory agent.
10. The formulations of claims 6 or 7 , comprising about 200 mcg of said anti-inflammatory agent.
11. The formulations of claims 9 or 10 , wherein the formulation is sterile and free of benzalkonium chloride yet has a relatively long period of stability such that after storage for 12 months at a temperature between 15 to 30° C., greater than 95% of the anti-inflammatory agent and greater than 95% of the antifungal agent originally present in the formulation still remains in the formulation.
12. The formulations of claims 9 or 10 , wherein the formulation is suitable for intranasal administration by a spray pump, by nebulization or metered dose spray pump.
13. The formulation of claims 1 , 2 , 9 or 10 , further comprising about 0.01% to about 90% by weight on a dried weight basis of one or more of the following compounds:
(a) polysorbate 80;
(b) disodium edetate dihydrate, USP;
(c) sodium citrate dihydrate, USP;
(d) sodium chloride, USP; and
(e) purified water, USP.
14. The formulation of claim 13 , wherein the:
(a) polysorbate 80 is present in an amount of about 0.4 mg/ml;
(b) disodium edetate dihydrate, USP is present in an amount of about 1 mg/ml;
(c) sodium citrate dihydrate, USP is present in an amount of about 0.065 mg/ml; and
(d) sodium chloride, USP is present in an amount of about 8.8 mg/ml.
15. The formulation of claim 13 , wherein said formulation is a sterile aqueous suspension suitable for administration to the nasal-paranasal mucosa.
16. The formulations of claims 9 or 10 , further comprising an antiviral agent.