Transdermal compositions containing levosimendan

• US 6,183,771 B1
• Filed: 03/23/1999
• Issued: 02/06/2001
• Est. Priority Date: 07/05/1996
• Status: Expired due to Term

• Current Assignee: Orion Corporation (Smiths Group International Holdings Ltd.)
• Original Assignee: Orion Corporation (Smiths Group International Holdings Ltd.)
• Inventors: Hirvonen, Jouni, Urtti, Arto, Lehtonen, Lasse, Antila, Saila
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HOWARD, SHARON LEE
• Application Number:
  US09/214,295
• Time in Patent Office: 686 Days
• Field of Search: 424/402, 424/448, 424/449, 424/484, 424/486, 514/846
• US Class Current: 424/449
• CPC Class Codes: A61K 31/50 Pyridazines; Hydrogenated pyridazines
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Transdermal administration of levosimenden or (−)-[[4-(1,4,5,6-tetahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof is disclosed. Transdermal preparations of levosimenden can be in the form of e.g. ointment, emulsion, lotion, solution, gel, cream, patch or transdermal delivery device including iontophoretic device.

Claims

1. A transdermal preparation, comprising, as a therapeutically active ingredient, (−

)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]-hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof.

2. The preparation according to claim 1, wherein the preparation is in the form of an ointment, an emulsion, a lotion, a solution, a gel, a cream, or a patch.

3. The preparation according to claim 1, wherein the preparation is a transdermal delivery system, comprising (a) a drug impermeable backing layer and (b) an adhesive layer, wherein the active ingredient is dispersed in the adhesive layer.

4. The preparation according to claim 1, wherein the preparation is a transdermal delivery system, comprising (a) a drug impermeable backing layer;

(b) an adhesive layer; and

(c) a matrix layer, in which the active ingredient is dispersed.

5. The preparation according to claim 4, wherein the matrix layer is made of a polymer material.

6. The preparation according to claim 1, wherein the preparation is an iontophoretic transdermal delivery system.

8. The preparation according to claim 1, wherein the preparation is a transdermal delivery system, comprising

(a) a drug impermeable backing layer;

(b) an adhesive layer;

(c) a drug permeable membrane, wherein the membrane is positioned relative to the backing layer so that at least one drug reservoir compartment is defined between the membrane and the backing layer; and

(d) the active ingredient or a composition thereof within the drug reservoir.

7. A method (for treating heart failure) comprising administering transdermally to a subject in need of such treatment a therapeutically effective amount of (−

)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]-hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof.

9. The method according to claim 7, wherein (−

)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof is administered from about 1 μ

g/h to about 1000 μ

g/h.

10. The method according to claim 9, wherein (−

)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof is administered through a skin area of from about 2 cm² to about 100 cm².

11. The method according to claim 7 wherein the dose of (−

)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile or a pharmaceutically acceptable salt thereof administered is from about 0.1 mg to about 500 mg per day.

12. The method according to claim 11, wherein the dose is from about 0.5 mg to about 10 mg per day.