Nasal and Ophthalmic Delivery of Aqueous Corticosteroid Solutions

• US 20090312724A1
• Filed: 06/05/2009
• Published: 12/17/2009
• Est. Priority Date: 06/28/2007
• Status: Abandoned Application

• Current Assignee: CyDex Pharmaceuticals, Inc. (Ligand Pharmaceuticals, Inc.)
• Original Assignee: CyDex Pharmaceuticals, Inc. (Ligand Pharmaceuticals, Inc.)
• Inventors: Zimmerer, Rupert O., Pipkin, James D., Siebert, John M.
• Application Number:
  US12/479,576
• Publication Number:
  US 20090312724A1
• Time in Patent Office: Days
• US Class Current: 604/294
• 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 31/335 having oxygen as the only ring hetero atom, e.g. fungichromin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• 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 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61M 31/00 Devices for introducing or retaining media, e.g. remedies, in cavities of the body A61M25/00 takes precedence ; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008

Abstract

The present invention is directed to methods of treating nasal and/or ophthalmic diseases, symptoms, or disorders that are therapeutically responsive to corticosteroid therapy by delivering aqueous solution formulations comprising a corticosteroid to nasal and ophthalmic tissues. The invention is also directed to methods, systems, devices, and compositions for delivering aqueous solution formulations comprising a corticosteroid and an antihistamine to nasal and ophthalmic tissues.

Claims

1. A method for treating an allergic symptom or disorder in a subject in need thereof, comprising:

nasally administering to the subject a corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier,

wherein the allergic symptom or disorder includes a non-nasal symptom selected from the group consisting of itchy/gritty eyes, tearing/watery eyes, red/burning eyes, itchy ears/palate and combinations thereof.

2. The method of claim 1, wherein the allergic symptom or disorder further comprises symptoms selected from the group consisting of runny nose, itchy nose, nasal congestion, sneezing and combinations thereof.

3. The method of claim 1, wherein said corticosteroid solution further comprises a therapeutically effective amount of an antihistamine.

4. The method of claim 3, wherein the antihistamine is azelastine, olopatadine pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof;

the corticosteroid is budesonide; and

the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β

-cyclodextrin).

5. The method of claim 4, wherein the azelastine is present in an amount of about 30 μ

g to about 275 μ

g per unit dose, or the olopatadine is present in an amount of about 150 μ

g to about 1400 μ

g per unit dose, the budesonide is present in an amount of about 5 μ

g to about 500 μ

g per unit dose, and the CAPTISOL is present in an amount of 100 μ

g to 100 mg per unit dose.

6. The method of claim 1, wherein the corticosteroid solution is administered 1-2 times per day.

7. A method for treating an ocular symptom or disorder in a subject in need thereof, comprising:

nasally administering to the subject a corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier,

wherein the allergic symptom or disorder includes a non-nasal symptom selected from the group consisting of itchy/gritty eyes, tearing/watery eyes, red/burning eyes, itchy ears/palate and combinations thereof.

8. The method of claim 7, wherein said corticosteroid solution further comprises a therapeutically effective amount of an antihistamine.

9. The method of claim 8, wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof;

the corticosteroid is budesonide; and

the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β

-cyclodextrin).

10. The method of claim 9, wherein the azelastine is present in an amount of about 30 μ

g to about 275 μ

g per unit dose or the olopatadine is present in an amount of about 150 μ

g to about 1400 μ

g per unit dose, the budesonide is present in an amount of about 5 μ

g to about 500 μ

g per unit dose, and the CAPTISOL is present in an amount of 100 μ

g to 100 mg per unit dose.

11. The method of claim 7, wherein the corticosteroid solution is administered 1-2 times per day.

12. A method for treating ocular inflammation in a subject in need thereof, comprising:

ophthalmically administering to the subject a corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier,

wherein the corticosteroid solution provides more rapid reduction in ocular inflammation compared with a corticosteroid suspension at the same unit dose.

13. The method of claim 12, wherein said corticosteroid solution further comprises a therapeutically effective amount of an antihistamine.

14. The method of claim 13, wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof;

the corticosteroid is budesonide; and

the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β

-cyclodextrin).

15. The method of claim 14, wherein the azelastine is present in an amount of about 30 μ

g to about 275 μ

g per unit dose or the olopatadine is present in an amount of about 150 μ

g to about 1400 μ

g per unit dose, the budesonide is present in an amount of about 5 μ

g to about 500 μ

g per unit dose, and the CAPTISOL is present in an amount of 100 μ

g to 100 mg per unit dose.

16. The method of claim 12, wherein the corticosteroid solution is administered 1-2 times per day.

17. A metered dose device for nasal or ophthalmic administration comprising:

corticosteroid solution comprising a therapeutically effective amount of corticosteroid, a therapeutically effective amount of an antihistamine, SAE-CD, and a pharmaceutically acceptable aqueous liquid carrier.

18. The device of claim 17, wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof;

the corticosteroid is budesonide; and

the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β

-cyclodextrin).

19. The device of claim 18, wherein the azelastine is present in an amount of about 30 μ

g to about 275 μ

g per unit dose or the olopatadine is present in an amount of about 150 μ

g to about 1400 μ

g per unit dose, the budesonide is present in an amount of about 5 μ

g to about 500 μ

g per unit dose, and the CAPTISOL is present in an amount of 100 μ

g to 100 mg per unit dose.

20. A system for treating an allergic symptom comprising:

corticosteroid solution comprising a therapeutically effective amount of a corticosteroid, a therapeutically effective amount of an antihistamine, SAE-CD and a pharmaceutically acceptable aqueous liquid carrier, and a metered dose device for nasal or ophthalmic administration of the corticosteroid solution to the subject.

21. The system of claim 20, wherein the allergic symptom is selected from the group consisting of runny nose, itchy nose, nasal congestion, sneezing, itchy/gritty eyes, red/burning eyes, tearing/watery eyes and itchy ears/palate and combinations thereof.

22. The system of claim 21, wherein the allergic symptom is selected from the group consisting of itchy/gritty eyes, tearing/watery eyes, red/burning eyes, itchy ears and palate and combinations thereof.

23. The system of claim 20, wherein the antihistamine is azelastine, olopatadine, pharmaceutically acceptable salts thereof, pharmaceutically active metabolites thereof, optically active isomers or racemates, and mixtures thereof;

the corticosteroid is budesonide; and

the SAE-CD is CAPTISOL cyclodextrin (sulfobutylether β

-cyclodextrin).

24. The system of claim 23 wherein the azelastine is present in an amount of about 30 μ

g to about 275 μ

g per unit dose or the olopatadine is present in an amount of about 150 μ

g to about 1400 μ

g per unit dose, the budesonide is present in an amount of about 5 μ

g to about 500 μ

g per unit dose, and the CAPTISOL is present in an amount of 100 μ

g to 100 mg per unit dose.