Treatment of acute coronary syndrome with an exendin

a technology of exendin and acute coronary syndrome, which is applied in the direction of peptide/protein ingredients, extracellular fluid disorder, metabolic disorder, etc., can solve the problems of increased time, and increased risk of recurrence, so as to reduce the risk of recurrence and improve the effect of tim

Inactive Publication Date: 2006-02-16
AMYLIN PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0015] (5) A method for treatment of a patient with ischemic heart disease, or is at risk for developing ischemic heart disease, and who exhibits one or more of the following symptoms: nausea, shortness of breath, palpitations, or dizziness, and further wherein the patient does not exhibit chest pain, comprising administering to the patient a therapeutically effective amount of a GLP-1 molecule, wherein the patient is not suffering a Q-wave MI. The above method, wherein the patient has a normal ECG.
[0016] (6) A method for increasing the time during which thrombolytic therapy will be effective following the first symptom o

Problems solved by technology

Heart disease is a major health problem throughout the world.
Myocardial infarctions are a significant source of mortality among those individuals with heart disease.
Excess FFAs can lead to free radical formation and consequent tissue damage.
These therapies do not treat directly the disturbed energy metabolism that results from ischemia and that induces tissue damage.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0078] Wistar rats were anesthetized with thiopentone sodium. The left anterior descending (LAD) coronary artery was occluded. After 25 minutes of occlusion, reperfusion was allowed for 2 hours. This animal model has been described previously. Zacharowski, et al., Br. J. Pharmacol. 128; 945-952 (1999).

[0079] GLP-1 (1.5 μg / kg / min) was infused into anesthetized rats (n=10), commencing 10 minutes prior to reperfusion and continuing throughout the 2-hour reperfusion. Controls were sham operated with no occlusion (n=7), LAD occlusion+reperfusion+administration of saline (n=12), and LAD occlusion and reperfusion with a buffer of 10 mM sodium acetate, 5.05% D-mannitol, pH 4.5, (“vehicle”) at 1.5 mL / kg / hour (n=10).

[0080] Following reperfusion, the coronary artery was reoccluded, and Evans Blue dye (4 ml, 2% w / v) was injected into the left ventricle of the heart via a right carotid artery cannula. Evans Blue stains perfused myocardium, while occluded vascular bed remains uncolored. Animals...

example 2

[0083] Two dogs were studied at baseline before, during, and for 6 hours after a 10-minute complete left circumflex coronary (LCx) occlusion. Each dog underwent occlusion / reperfusion in the presence and absence of GLP-1 infusion for 24 hours, beginning 1 minute prior to reperfusion. GLP-1 infusion enhanced the recovery of ventricular wall regional dysfunction following 10 minutes of coronary artery occlusion. The study shows that the recovery after ischemia and the reduced stunning in the presence of GLP-1 are not due to increased coronary flow compared to controls, but presumably reflect favorable changes in myocardial energetics.

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PUM

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Abstract

The invention relates to methods for treating a patient suffering from acute coronary syndrome, but who is not suffering from a Q-wave myocardial infarction, comprising administration of a therapeutically effective amount of a GLP-1 molecule. The GLP-1 can be self-administered, and can be administered in one or more doses, as needed, on an intermittent or continuous basis, to optimize metabolism in cardiac tissue and to prevent cardiac damage associated with ischemia.

Description

BACKGROUND OF THE INVENTION [0001] Heart disease is a major health problem throughout the world. Myocardial infarctions are a significant source of mortality among those individuals with heart disease. [0002] Acute coronary syndrome (“ACS”) denotes patients who have or are at high risk of developing an acute myocardial infarction (MI). This complex includes unstable angina (UA), non-Q-wave cardiac necrosis (NQCN) and Q-wave MI (QMI). Thompson et al., M.J.A. 171; 153 (1999). Typically, ACS is diagnosed when a patient has acute (i.e., sudden onset) chest pain of a cardiac origin that is either new or clearly different from pre-existing, chronic, stable angina; that is, ACS chest pain is more severe, more frequent, occurs at rest, or is longer than 15 minutes in duration. After ACS has been diagnosed, the patient is stratified into UA, NQCN, and QMI, using criteria that are described elsewhere in this application. UA, NQCN, and QMI are believed to represent different stages of plaque r...

Claims

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Application Information

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IPC IPC(8): A61K38/26A61K9/08A61F2/958A61K9/20A61K9/72A61K31/19A61K31/7004A61K33/14A61K38/12A61K38/22A61K45/00A61K48/00A61P9/10A61P43/00
CPCA61K38/26A61P43/00A61P9/00A61P9/04A61P9/10A61P3/10A61K38/16
Inventor COOLIDGE, THOMASEHLERS, MARIO
Owner AMYLIN PHARMA INC
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