Methods and compositions for treating pulmonary disorders using optically pure (R,R)-formoterol

• US 5,795,564 A
• Filed: 03/07/1996
• Issued: 08/18/1998
• Est. Priority Date: 04/05/1991
• Status: Expired due to Term

• Current Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Original Assignee: Sepracor Incorporated
• Inventors: Aberg, Gunnar, Morley, John
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/613,382
• Time in Patent Office: 894 Days
• Field of Search: 424/447, 424/451, 424/464, 424/45, 424/436, 514/630
• US Class Current: 424/45
• 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine

Abstract

A method and composition are disclosed utilizing the pure (R,R) isomer of formoterol, which is a potent bronchodilator with reduced adverse effects, having a low incidence of the development of tolerance and having increased bronchial distribution when administered by inhalation.

Claims

1. A method for eliciting a bronchodilator effect while avoiding the concomitant liability of hypersensitivity which comprises administering to a human in need of bronchodilation an amount of (R,R)-formoterol, or a pharmaceutically acceptable salt thereof, sufficient to alleviate bronchospasms but insufficient to cause hypersensitivity, said (R,R)-formoterol containing at least 99% by weight of (R,R)-formoterol and less than 1% by weight of (S,S)-formoterol.

2. The method of claim 1 wherein (R,R) formoterol is administered by subcutaneous injection, intravenous infusion, inhalation, transdermal delivery or oral administration.

3. The method according to claim 2 wherein the amount administered by inhalation is about 1 μ

g to about 100 μ

g per day.

4. The method according to claim 2 wherein the amount administered orally is about 0.1 to about 1 mg per day.

5. The method according to claim 1 wherein (R,R) formoterol or pharmaceutically acceptable salt thereof is administered together with a pharmaceutically acceptable carrier.

6. A method according to claim 2 wherein (R,R) formoterol fumarate dihydrate is administered.

7. A method according to claim 3 wherein said amount is administered in divided doses from two to four times a day.

8. A bronchodilator composition in the form of a tablet, capsule, transdermal patch or aerosol, which comprises a pharmaceutically acceptable carrier suitable for a tablet, capsule, transdermal patch or aerosol and an amount of (R,R)-formoterol, or a pharmaceutically acceptable salt thereof, sufficient to alleviate bronchospasms but insufficient to cause hypersensitivity, said (R,R)-formoterol containing at least 99% by weight of (R,R)-formoterol and less than 1% by weight of (S,S)-formoterol.

9. A composition according to claim 8 adapted for administration by inhalation wherein the amount of (R,R) formoterol is about 6 μ

g to about 25 μ

g.

10. A composition according to claim 9 which comprises (R,R) formoterol fumarate dihydrate.

11. A composition according to claim 8 adapted for oral administration.

12. A composition according to claim 11 wherein the amount of formoterol in an oral dosage form is from about 0.1 mg to about 1 mg.

13. A composition according to claim 8 adapted for transdermal administration.

14. A method for eliciting a bronchodilator effect that is more than twice the duration of the bronchodilator effect of a comparable dose of racemic formoterol, which comprises administering to a human in need of bronchodilation an amount of (R,R)-formoterol, or a pharmaceutically acceptable salt thereof, sufficient to alleviate bronchospasms, said (R,R)-formoterol producing a bronchodilator effect that is more than twice the duration of the bronchodilator effect of a comparable dose of racemic formoterol, and said (R,R)-formoterol containing at least 99% by weight of (R,R)-formoterol and less than 1% by weight of (S,S)-formoterol.

15. A method for eliciting a bronchodilator effect that is of longer duration than the bronchodilator effect of a comparable dose of racemic formoterol, which comprises administering to a human in need of bronchodilation an amount of (R,R)-formoterol, or a pharmaceutically acceptable salt thereof, sufficient to alleviate bronchospasms, said (R,R)-formoterol producing a bronchodilator effect that is of longer duration than the bronchodilator effect of a comparable dose of racemic formoterol, and said (R,R)-formoterol containing at least 99% by weight of (R,R)-formoterol and less than 1% by weight of (S,S)-formoterol.