Localized delivery of cardiac inotropic agents

• US 20070021358A1
• Filed: 05/25/2006
• Published: 01/25/2007
• Est. Priority Date: 05/25/2005
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Edelman, Elazer, Lovich, Mark
• Granted Patent: US 8,551,961 B2
• Time in Patent Office: Days
• US Class Current: 514/26
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/4168 having a nitrogen attached in position 2, e.g. clonidine
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 38/2242 Atrial natriuretic factor complex: Atriopeptins, atrial natriuretic protein [ANP]; Cardionatrin, Cardiodilatin
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

The present invention provides novel methods for the localized delivery of inotropic agents to the heart, including specific regions of the heart, such as the ventricles, for example in a subject undergoing cardiothoracic surgery, with the aim of supporting the myocardial contractile function of the heart.

Claims

1. A method of locally delivering a cardiac inotropic agent to the heart of a subject, comprising administering locally to a subject in need thereof a therapeutically effective amount of at least one inotropic agent.

2. The method of claim 1, wherein the inotropic agent is an agent that interacts with the sympathetic nervous system and modulates calcium entry, G-proteins, ATP, or GTP, wherein the inotropic agent is selected from the group consisting of sympathomimetic compounds, phosphodiesterase inhibitors, BNP, ANP, and digitalis glycosides, and derivatives and analogues thereof.

3. The method of claim 1, wherein the inotropic agent is a sympathomimetic compound selected from the group consisting of epinephrine, norepinephrine, dobutamine, isoproterenol, salbutamol, salmeterol, terbutaline, phenylephrine, ephedrine, clonidine and dopamine, and derivatives and analogues thereof.

4. The method of claim 1, wherein the inotropic agent is a phosphodiesterase inhibitor selected from the group consisting of milrinone, enoximone and amrinone, and derivatives and analogues thereof.

5. The method of claim 1, wherein the subject is a surgical patient and is selected from the group consisting of a cardiac surgery patient, a thoracic surgery patient, and a general surgery patient.

6. The method of claim 1, wherein the subject is a cardiac surgery patient, and wherein the cardiac surgery patient is selected from the group consisting of a cardiac surgery patient requiring support from a cardiopulmonary bypass circuit and a cardiac patient not requiring support from a cardiopulmonary bypass circuit.

7. The method of claim 1, wherein the subject has a condition selected from the group consisting of trauma, shock, acute congestive heart failure and chronic congestive heart failure.

8. The method of claim 1, wherein the therapeutically effective amount of the inotropic agent is sufficient to effect myocardial contractility.

9. The method of claim 1, wherein the inotropic agent is delivered locally to the heart by its inclusion in a delivery vehicle.

10. The method of claim 1, wherein the inotropic agent is delivered locally to the heart by its inclusion in a delivery vehicle, and wherein the delivery vehicle is selected from the group consisting of a drug-impregnated, coated or relasing sheet, patch, matrix, hydrogel, foam, gel, cream, spray, microshpere, microcapsule, composite and an ointment.

11. The method of claim 1, wherein the local administration comprises administering said inotropic agent directly to the heart via an open surgical wound.

12. The method of claim 1, wherein the local administration comprises administering said inotropic agent directly to the heart percutaneously.

13. A method of reducing postoperative complications of cardiopulmonary bypass (CPB) surgery in a subject, comprising locally administering to a subject in need thereof an effective amount of an inotropic agent in conjunction with said CPB surgery of said subject.

14. The method of claim 13, wherein the inotropic agent is administered to said subject during a time period selected from the group consisting of prior to said CPB surgery, during said CPB surgery, subsequent to said CPB surgery and combinations thereof.

15. The method of claim 13, wherein the inotropic agent is selected from the group consisting a sympathomimetic compound or a phosphodiesterase inhibitor.

16. The method of claim 13, wherein the therapeutically effective amount of the inotropic agent is sufficient to effect myocardial contractility.

17. The method of claim 13, wherein the inotropic agent is delivered locally to the heart by its inclusion in a delivery vehicle.

18. The method of claim 13, wherein the inotropic agent is delivered locally to the heart by its inclusion in a delivery vehicle, and wherein the delivery vehicle is selected from the group consisting of a drug-impregnated, coated or relasing sheet, patch, matrix, hydrogel, foam, gel, cream, spray, microshpere, microcapsule, composite and an ointment.