Medicaments comprising steroids and a novel anticholinergic

• US 20030223937A1
• Filed: 03/19/2003
• Published: 12/04/2003
• Est. Priority Date: 04/12/2002
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Pairet, Michel, Pieper, Michael P., Meade, Christopher John Montague, Meissner, Helmut, Banholzer, Rolf, Speck, Georg, Pohl, Gerald, Morschhaeuser, Gerd, Reichl, Richard
• Granted Patent: US 7,084,153 B2
• Time in Patent Office: Days
• US Class Current: 424/46
• 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 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• 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 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61K 9/008 comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]

Abstract

A pharmaceutical composition comprising:

(a) a salt of formula 1

wherein:

X⁻ is an anion with a single negative charge; and

(b) a steroid 2,

processes for preparing such pharmaceutical composition, and their use in the treatment of respiratory complaints.

Claims

1. A pharmaceutical composition comprising:

(a) a salt of formula 1

wherein;

X⁻

is an anion with a single negative charge; and

(b) a steroid 2.

2. The pharmaceutical composition according to claim 1, further comprising a pharmaceutically acceptable excipient.

3. The pharmaceutical composition according to claim 1, wherein X⁻

is selected from chloride, bromide, iodide, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate, and p-toluenesulfonate

4. The pharmaceutical composition according to claim 1, wherein pharmaceutical composition comprises more than one steroid 2.

5. The pharmaceutical composition according to claim 1, wherein the steroid 2 is selected from flunisolide, beclomethasone, triamcinolone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, ST-126, and dexamethasone.

6. The pharmaceutical composition according to claim 5, wherein the steroid 2 is selected from budesonide, fluticasone, mometasone, ciclesonide, and ST-126.

7. The pharmaceutical composition according to claim 1, wherein the weight ratio of the salt of formula 1′

to the steroid 2 is in the range from about 1;

250 to 250;

1.

8. The pharmaceutical composition according to claim 1, wherein the weight ratio of the salt of formula 1′

to the steroid 2 is in the range from about 1;

150 to 150;

1.

9. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is suitable for inhalation.

10. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is an inhalable powder, a propellant-containing metered-dose aerosol, or a propellant-free inhalable solution or suspension.

11. The pharmaceutical composition according to claim 10, wherein the pharmaceutical composition is an inhalable powder comprising the salt of formula 1′

and the steroid 2 in admixture with a physiologically acceptable excipient selected from monosaccharides, disaccharides, oligo- and polysaccharides, polyalcohols, salts, or mixtures thereof.

12. The pharmaceutical composition according to claim 11, wherein the excipient has a maximum average particle size of 250 μ

m or less.

13. The pharmaceutical composition according to claim 12, wherein the excipient has a maximum average particle size of between 10 μ

m and 150 μ

m.

15. The pharmaceutical composition according to claim 10, wherein the pharmaceutical composition is a propellant-containing metered-dose aerosol comprising the salt of formula 1′

and the steroid 2 in dissolved or dispersed form.

16. The pharmaceutical composition according to claim 15, wherein the propellant gas is a hydrocarbon or halohydrocarbon.

17. The pharmaceutical composition according to claim 16, wherein the propellant gas is selected from n-propane;

n-butane;

isobutane;

or the chlorinated and/or fluorinated derivatives of methane, ethane, propane, butane, cyclopropane, or cyclobutane.

18. The pharmaceutical composition according to claim 16, wherein the propellant gas is selected from TG11, TG12, TG134a, TG227, or a mixture thereof.

19. The pharmaceutical composition according to claim 15, wherein the pharmaceutical composition comprises 5% by weight or less of active substance 1 and 2.

20. The pharmaceutical composition according to claim 10, wherein the pharmaceutical composition is a propellant-free inhalable solution or suspension further comprising a solvent selected from water, ethanol, or a mixture thereof.

21. The pharmaceutical composition according to claim 20, further comprising a cosolvent or excipient.

22. The pharmaceutical composition according to claim 21, wherein the cosolvent is selected from an alcohol, a glycol, glycerol, a polyoxyethylene alcohol, and a polyoxyethylene fatty acid ester.

23. The pharmaceutical composition according to claim 22, wherein the cosolvent is selected from isopropyl alcohol, propyleneglycol, polyethyleneglycol, polypropyleneglycol, or glycol ether.

24. The pharmaceutical composition according to claim 21, wherein the excipient is selected from a surfactant, a stabilizer, a complexing agent, an antioxidant, a preservative, a flavoring, and a vitamin.

25. The pharmaceutical composition according to claim 24, wherein the excipient is edetic acid or a salt of edetic acid.

14. A pharmaceutical composition consisting essentially of:

(a) a salt of formula 1

wherein;

X⁻

is an anion with a single negative charge; and

(b) a steroid 2.