Combination of azelastine and steroids

• US 8,163,723 B2
• Filed: 09/10/2010
• Issued: 04/24/2012
• Est. Priority Date: 06/14/2002
• Status: Expired due to Term

• Current Assignee: Cipla (EU) Limited
• Original Assignee: Cipla (EU) Limited
• Inventors: Lulla, Amar, Malhotra, Geena
• Primary Examiner(s): Richter, Johann
• Assistant Examiner(s): Nielsen, Thor
• Application Number:
  US12/879,515
• Publication Number:
  US 20100331289A1
• Time in Patent Office: 592 Days
• Field of Search: None
• US Class Current: 514/171
• 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 31/55 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

A pharmaceutical product or formulation, which comprises azelastine or a pharmaceutically acceptable salt, solvate or physiologically functional derivative thereof, and a steroid, or a pharmaceutical acceptable salt, solvate or physiologically functional derivative thereof, preferably the product or formulation being in a form suitable for nasal or ocular administration.

Claims

1. A method for the prophylaxis or treatment in a mammal of a condition for which administration of one or more anti-histamines and/or one or more steroids is indicated, comprising intranasal administration to said mammal of a therapeutically effective amount of a pharmaceutical composition comprising (a) azelastine, or a pharmaceutically acceptable salt thereof;

and (b) pharmaceutically acceptable ester of fluticasone.

2. The method of claim 1, wherein said pharmaceutically acceptable salt of azelastine is azelastine HCl.

3. The method of claim 1, wherein said pharmaceutically acceptable ester of fluticasone is fluticasone propionate or fluticasone valerate.

4. The method of claim 1, wherein said pharmaceutical composition is in the form of a nasal spray.

5. The method of claim 1, wherein said pharmaceutical composition is in the form of nasal drops.

6. The method of claim 1, wherein said pharmaceutical composition is the form of an insufflation powder.

7. The method of claim 1, wherein said mammal is a human.

8. The method of claim 1, wherein said condition is allergic rhinitis.

9. The method of claim 1, wherein said condition is allergic conjunctivitis.

12. The method of claim 1, wherein said pharmaceutical composition is an aqueous suspension comprising from about 0.0005% to about 2% (weight/weight) of azelastine or a pharmaceutically acceptable salt of azelastine, and from about 0.0357% to about 1.5% (weight/weight) of pharmaceutically acceptable ester of fluticasone.

13. The method of claim 12, wherein said pharmaceutical composition is an aqueous suspension comprising from about 0.001% to about 1% (weight/weight) of azelastine or a pharmaceutically acceptable salt of azelastine, and from about 0.0357% to about 1.5% (weight/weight) of a pharmaceutically acceptable ester of fluticasone.

14. The method of claim 12, wherein said pharmaceutical composition is an aqueous suspension comprising 0.1% or 0.15% (weight/weight) of azelastine HCl and from about 0.0357% to about 1.5% (weight to weight) of fluticasone propionate or fluticasone valerate.

15. The method of claim 5, wherein said pharmaceutical composition further comprises at least one surfactant selected from the group consisting of a polysorbate surfactant, poloxamer surfactant, and combinations thereof.

16. The method of claim 15, wherein said pharmaceutical composition comprises from about 50 micrograms to about 1 milligram of said surfactant per ml of the formulation.

17. The method of claim 1, wherein said pharmaceutical composition further comprises at least one isotonic agent selected from the group consisting of sodium chloride, saccharose, glucose, glycerine, sorbitol, 1,2-propylene glycol, and combinations thereof.

18. The method of claim 1, wherein said pharmaceutical composition further comprises at least one additional component selected from the group consisting of a buffer, a preservative, a suspending agent, a thickening agent, and combinations thereof.

19. The method of claim 18, wherein said buffer is a citric acid-citrate buffer.

20. The method of claim 18, wherein said preservative is selected from the group consisting of edetic acid and its alkali salts, lower alkyl p-hydroxybenzoates, chlorhexidine, phenyl mercury borate, benzoic acid or a salt thereof, a quaternary ammonium compound, sorbic acid or a salt thereof, and combinations thereof.

21. The method of claim 18, wherein said suspending agent or thickening agent is selected from the group consisting of cellulose derivatives, gelatin, polyvinylpyrrolidone, tragacanth, ethoxose, alginic acid, polyvinyl alcohol, polyacrylic acid, pectin, and combinations thereof.

22. The method of claim 1, wherein said formulation comprises a pH of from 3 to 7.

23. The method of claim 1, wherein said formulation comprises a pH from 4.5 to 6.5.

24. The method of claim 15, wherein said surfactant comprises a polysorbate.

25. The method of claim 17, wherein said isotonic agent comprises glycerine.

26. The method of claim 18, wherein said preservative comprises edetate disodium and benzalkonium chloride.

27. The method of claim 18, wherein said suspending agent or said thickening agent comprises cellulose derivatives.

28. The method of claim 1, wherein the pharmaceutical composition further comprises edetate disodium, glycerine, a thickening agent comprising microcrystalline cellulose and sodium carboxy methyl cellulose, polysorbate 80, benzalkonium chloride, phenyl ethyl alcohol, and purified water.

10. The method of 1, wherein said pharmaceutical composition comprises a pharmaceutically acceptable ester of fluticasone in an amount from about 50 micrograms/ml to about 5 mg/ml of the composition.

11. The method of claim 10, wherein the pharmaceutical composition has a particle size of less than 10 μ

m.