Compounds for use in inducing myocardial perfusion recovery
Inventors
Sams Nielsen, Anette • Edvinsson, Lars Ingvar Herbert
Assignees
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Publication Number
US-11890324-B2
Publication Date
2024-02-06
Expiration Date
Abstract
A calcitonin gene-related peptide (CGRP) compound can be selected from N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)-butyrylamino]ethoxy}ethoxy)acetyl][Ser1]alpha-human CGRP peptide (α-CGRP-analogue), or derivatives thereof; or N-alpha-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]-ethoxy}ethoxy)acetyl][Ser1]beta-human CGRP peptide (β-CGRP-analogue), or derivatives thereof. The CGRP compound can be used to induce myocardial perfusion recovery, in connection with AMI, by activating any CGRP family of receptors with a larger CGRP compound: CGRP potency ratio in the coronary artery than in the mesenteric artery.
Core Innovation
The invention relates to a method for the treatment of acute myocardial infarction (AMI) by administering a calcitonin gene-related peptide (CGRP) compound. The CGRP compound is a specific CGRP peptide, namely N-alpha-[2-(2-{2-[(S)]-4-carboxy-4-(17-carboxyheptadecanoylamino)-butyryl-amino]-ethoxy}ethoxy)acetyl][Ser1]beta-human CGRP peptide (β-CGRP-analogue), or pharmaceutically acceptable salts and solvates thereof.
The method includes administering the CGRP compound at least once per day for one to thirty consecutive days immediately after the incident. The disclosed approach includes inducing myocardial perfusion recovery in connection with AMI using CGRP family receptor activation, with a coronary-selective effect characterized by a higher CGRP potency in the coronary artery than in the mesenteric artery.
The document describes administration by subcutaneous, intraperitoneal, and intravenous routes, and local delivery in connection with percutaneous coronary intervention (PCI). Repeated dosing of the α- and β-CGRP analogue peptides, including Compound I/II and derivatives, salts, and conservative variants, improves myocardial perfusion defect recovery after rat permanent LAD occlusion.
Claims Coverage
The disclosed claim set contains one independent claim. The independent claim centers on administering a specified β-CGRP-analogue, with pharmaceutically acceptable salts and solvates, for a defined immediate post-incident consecutive-day regimen with at least once-daily administration.
Treatment of acute myocardial infarction by administering a CGRP compound
Administering a calcitonin gene-related peptide (CGRP) compound as a method for the treatment of acute myocardial infarction (AMI).
Specific β-CGRP analogue peptide as the CGRP compound
Wherein the CGRP compound is N-alpha-[2-(2-{2-[(S)]-4-carboxy-4-(17-carboxyheptadecanoylamino)-butyryl-amino]-ethoxy}ethoxy)acetyl][Ser1]beta-human CGRP peptide (β-CGRP-analogue), and pharmaceutically acceptable salts and solvates thereof.
At least once per day consecutive post-incident administration
Wherein the CGRP compound is administered at least once per day, and wherein the CGRP is administered for one to thirty consecutive days immediately after incident.
Overall, the independent claim defines treatment of AMI via administration of a specific β-CGRP-analogue peptide, with salts and solvates, given at least once per day for one to thirty consecutive days immediately after the incident.
Stated Advantages
Increased myocardial perfusion recovery in connection with acute myocardial infarction (AMI).
Coronary-selective CGRP effects characterized by higher CGRP potency in coronary artery than in mesenteric artery and coronary-selective receptor sensitization.
Endothelial protection.
Documented Applications
Treatment of acute myocardial infarction (AMI) by inducing myocardial perfusion recovery using CGRP family receptor activation.
Use of the described CGRP compounds in connection with percutaneous coronary intervention (PCI), including local delivery.
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