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CA-3110173-C - USE OF GHRP-6 AS LATE CARDIOPROTECTIVE AND CARDIAC RESTORATION MEDICAMENT

CA3110173CCA 3110173 CCA3110173 CCA 3110173CCA-3110173-C

Abstract

The present invention relates to the use of the growth hormone releasing peptide 6 (GHRP-6) for the manufacture of a late cardioprotective and cardiac restoration medicament. Said late cardioprotective and cardiac restoration medicament comprises GHRP-6 and a pharmaceutically acceptable excipient or vehicle. The invention also relates to a method for the treatment of a disease that involves a low cardiac output, wherein a therapeutically effective amount of a late cardioprotective and cardiac restoration medicament comprising GHRP-6 is administered to a subject in need. Said medicament allows for the late treatment, even days later, of the myocardium that has undergone episodes of stunning, hibernation, ischemia and the consequences thereof.

Inventors

  • Jorge Amador Berlanga Acosta
  • Gerardo Enrique Guillen Nieto
  • Diana Garcia Del Barco Herrera
  • Francisco HERNANDEZ BERNAL
  • Sonia Gonzalez Blanco
  • Raimundo Ubieta Gomez

Assignees

  • CENTRO DE INGENIERIA GENETICA Y BIOTECNOLOGIA

Dates

Publication Date
20260505
Application Date
20190819
Priority Date
20180821

Claims (6)

  1. CLAIMS 1. A growth hormone releasing peptide-6 (GHRP-6) for use in the treatment of a pathology selected from the group consisting of acute myocardial infarction (AMI) with ST segment elevation or depression, acute coronary syndrome, acute or chronic ischemic myocardial disease, heart failure and episodes of ischemia / reperfusion of the heart muscle, to rescue ventricular mass from stunning or hibernation states, low-cardiac output syndrome, and cardiogenic shock, wherein the GHRP-6 is for administration 12 hours after an episode of ischemia is established.
  2. 2. The GHRP-6 for use according to claim 1 wherein the GHRP-6 is for administration to patients awaiting a heart transplant to correct and optimize the systemic homeostasis and health in general.
  3. 3. The GHRP-6 for use according to claim 1 wherein the GHRP-6 is for administration by central intravenous route, peripheral intravenous route, or within the coronary tree.
  4. 4. The GHRP-6 for use according to claim 3 ·wherein the GHRP-6 is for administration as part of an endoluminal dilation procedure.
  5. 5. The GHRP-6 for use according to claim 1 wherein the GHRP-6 is for administration at 25-200 μg/kg of the patient body weight as a bolus.
  6. 6. The GHRP-6 for use according to claim 1 wherein the GHRP-6 is for administration between 13 and 96 hours a'l'.ter an episode of ischemia is established.

Description

1 USE OF GHRP-6 AS LATE CARDIOPROTECTIVE AND CARDIAC RESTORATION MEDICAMENT Technical field 5 The present invention relates to human medicine, in particular to the use of the growth hormone releasing peptide-6 (GHRP-6) to restore the normal physiology of heart cells that have been subjected to long periods of hypoxia. This use of the peptide expands the window of therapeutic opportunity, transforming the paradigm that lethal non-return time occurs after the sixth hour of acute coronary events on 10 development. The GHRP-6 promotes reversal of cytotoxic events resulting from ventricular dyskinesia and diastolic dysfunction in order to restore myocardial function and improve the perfusion of coronary, myocardium and the rest of the animal and human tissues and organs. 15 Prior art Cardiovascular diseases remain at the top of the diseases that cause greater morbidity and mortality in the general population. In United States of America, occurs about 1.5 million cases of myocardial infarction per year; according to the Centers for Disease Control and Prevention (CDC), is the leading cause of mortality in that 20 country. The World Health Organization (WHO) noted that in 2012, 17.5 million people died from cardiovascular disease, representing 31 % of all deaths recorded in the world, and of these 7.4 million were due to Coronary Cardiopathy. More than three quarters of deaths from cardiovascular diseases come from Low and Middle Income Countries (Ar6s, F., Boraita, A., et al. Rev. Esp. Cardiel. 2000; 53: 1063-94). 25 In general, heart diseases are grouped as follows: Coronary Disease, Angina Pectoris, Myocardial Acute Infarct (MAI), Heart Failure, Congestive Heart Failure and Cardiomyopathies. Coronary heart disease leads to the establishment of ischemic heart disease, which is defined as the imbalance between myocardial oxygen demand and blood supply, as cited in World Health Organization (2015), 2 Cardiovascular Diseases: http://www.who.int/en/news-room/factsheets/ detail/cardiovascular-diseases-(cvds). From all these diseases afore mentioned, the Acute Myocardial Infarct (AMI) reaches the highest rate of acute mortality. It occurs due to the sudden and sustained 5 interruption of blood flow, causing the cells to die if irrigation is not restored soon. If the patient survives to a first attack, he is at risk of suffering another one within the next 6 months, or dying after associated complications thereof. Total recovery is hard to achieve after this first event, and specific treatment and care must be followed, since 5 out of 10 patients die during the first year after the infarction. Most coronary 10 episodes constitute medical emergencies and urgencies; occur suddenly, with acute or overacute course, galloping involution of the patient, and unexpected. This presupposes the impossibility of predicting or anticipating an event of myocardial hypoxia. The survival of cells in hypoxia depends on several factors, especially the duration of 15 ischemia and the metabolic demand in question, according to the type of cell. Thus, the duration of the ischemia to which they have been subjected, at the time the restoration of blood flow occurs, is the main determinant of the success of reperfusion therapy. The shorter the ischemia time, the less the damage to the tissue, the less the damage at the time of reperfusion, and therefore, the lower 20 number of associated subsequent complications. Acute coronary syndrome is the operative term that describes a collection of clinical symptoms compatible with acute myocardial ischemia. Despite investigations by more than four decades, acute coronary events remain a leading cause of morbidity and mortality in many countries. The early mechanical or pharmacological 25 reperfusion continues to be the paradigm, the golden rule, and apparently the only current alternative to rescue ventricular mass from necrosis before the ischemic / reperfusion. The most recent literature highlights the importance of practicing reperfusion during the first 12 hours of the onset of symptoms (European Society of Cardiology. Clinical practice guide for the management of acute coronary syndrome 3 in patients without persistence ST segment elevation, Rev Esp. Cardiol. 2012; 65 (2): 173.e1-e55). One of the major limitations in the prior art is the total absence of drugs that can be applied with therapeutic character, to acutely restore myocardial pump function, 5 reduce its damage and restore systemic hemodynamic balance. This is because, most of the candidates developed up to date require prophylactic or pre-conditioning use, the intervention should be applied before the hypoxic event, which is not predictable. Blood thinners, platelet antiaggregants, antihypertensives and beta blockers drugs are aimed at maintaining adequate blood flow, to prevent obstructions 10 and the resulting heart attacks, but not to restore the contractile mechanics and adequate cardiac output to the demands of the body. Thus, anot