CN-121987637-A - Use of Olorinab in preparing medicine for treating and/or preventing ischemic cardiomyopathy

Abstract

The invention belongs to the field of new application of medicines, and in particular relates to an application of Olorinab in preparing medicines for treating and/or preventing ischemic cardiomyopathy. Animal experiments prove that Olorinab can obviously improve the left ventricular ejection fraction and the left ventricular short axis shortening rate of a myocardial infarction model mouse, improve cardiac function and reduce cardiac fibrosis area, and has the effect of improving myocardial reconstruction and contraction dysfunction. The discovery provides a new treatment strategy for ischemic cardiomyopathy and has important clinical application prospect.

Inventors

• LIN ZHUOFENG
• LI YULIN
• LI SHUAI
• GAN JING
• PENG YUE

Assignees

• 广东医科大学

Dates

Publication Date

20260508

Application Date

20260318

Claims (9)

1. Application of Olorinanb in preparing medicament for treating and/or preventing ischemic cardiomyopathy.
2. 2. The use according to claim 1, wherein the ischemic cardiomyopathy comprises myocardial infarction-induced contractile dysfunction.
3. 3. The use of claim 2, wherein the medicament is for increasing left ventricular ejection fraction and left ventricular short axis shortening rate.
4. 4. The use according to claim 1, wherein the medicament is made of the Olorinab together with pharmaceutically acceptable carriers and/or excipients.
5. 5. A pharmaceutical composition for the treatment and/or prophylaxis of ischemic cardiomyopathy, comprising Olorinab or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and/or excipients.
6. 6. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition further comprises one or more other drugs for treating and/or preventing ischemic cardiomyopathy.
7. 7. The pharmaceutical composition according to claim 4, wherein the content of Olorinab in the pharmaceutical composition is 0.1wt% to 99wt%.
8. 8. The pharmaceutical composition of claim 4, wherein the pharmaceutical composition is administered orally or by injection.
9. 9. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is in the form of a tablet, capsule, granule, dispersion, oral liquid, injection, spray or drop.

Description

Use of Olorinab in preparing medicine for treating and/or preventing ischemic cardiomyopathy Technical Field The invention belongs to the field of new application of medicines, and in particular relates to an application of Olorinab in preparing medicines for treating and/or preventing ischemic cardiomyopathy. Background Ischemic cardiomyopathy (Ischemic Cardiomyopathy, ICM) is a special type or advanced stage of coronary heart disease, and the core is defined as a series of clinical syndromes of clinical manifestations such as coronary insufficiency caused by coronary atherosclerosis, long-term myocardial ischemia and hypoxia, myocardial limitation or diffuse fibrosis, and finally cardiac contraction and/or relaxation function impairment, and cardiac enlargement or stiffness, chronic heart failure, arrhythmia and the like. According to global disease burden study (GBD) data, ischemic heart disease patients have exceeded 2.4 million people worldwide, and have become one of the major causes of heart failure. The pathophysiology mechanism of ischemic cardiomyopathy is complicated, coronary atherosclerosis is taken as an initiating link, and the interaction among multiple links of myocardial cell injury, myocardial reconstruction, nerve fluid disorder and electrophysiological abnormality is involved, so that the structure and the function of the heart are finally irreversibly damaged. Thus, it has been a treatment difficulty in ischemic cardiomyopathy. Because of the complexity of pathophysiological mechanisms of ischemic cardiomyopathy, clinical treatment takes 'improving myocardial blood supply, controlling myocardial reconstruction, preventing and treating heart failure and arrhythmia and reducing the risk of cardiovascular events' as a core target, and adopts a comprehensive treatment scheme to take the individuation difference into consideration. The clinical drug therapy for ischemic cardiomyopathy mainly comprises beta receptor blocker, angiotensin Converting Enzyme Inhibitor (ACEI)/angiotensin II receptor Antagonist (ARB), aldosterone receptor antagonist and the like. Wherein, the beta receptor blocker is used as one of core drugs for treating ischemic cardiomyopathy, and has the dual functions of improving myocardial ischemia and inhibiting myocardial reconstruction. However, beta blocker therapy is beneficial to only a fraction of patients, and clinical application requires strict management of indications, contraindications and medication details. Both angiotensin converting enzyme inhibitors and angiotensin II receptor Antagonists (ARBs) are centered on blocking the renin-angiotensin-aldosterone system (RAAS), inhibiting the production or binding of angiotensin II (ang II), reducing ang II-mediated vasoconstriction, sodium retention, and reducing cardiac preload. However, the long-term use may cause adverse reactions and side effects such as hypotension, deterioration of renal function, hyperkalemia, etc. Aldosterone receptor antagonists often constitute "golden triangle" treatment regimens for heart failure with ACEI/ARB, beta blockers, but they rely on combination therapy and have a high risk of adverse reactions, which can cause arrhythmias, cardiac arrest, and the like in severe cases. Therefore, it is important to explore safer and more effective drugs capable of preventing and alleviating ischemic cardiomyopathy. Disclosure of Invention The invention aims at providing the application of Olorinab in preparing a medicament for treating and/or preventing ischemic cardiomyopathy. The invention provides an application of Olorinab in preparing a medicament for treating and/or preventing ischemic cardiomyopathy. The energy metabolism in normal cardiac muscle keeps dynamic balance, and the synergistic effect of beta oxidation of fatty acid, glucose oxidation and glycolysis provides stable energy supply for myocardial contraction. After myocardial infarction occurs, the ischemia and hypoxia environment breaks energy metabolism steady state, myocardial cell fatty acid oxidation is inhibited, glycolysis is abnormally activated, and the myocardial cell is accompanied with proliferation and differentiation disorder of cardiac progenitor cells and myocardial repair disorder. ABI3BP is used as an extracellular matrix protein critical to the cardiovascular system and is a core molecule playing a protective role in the pathological process of myocardial infarction. The method can stabilize the energy metabolism of myocardial cells by regulating and controlling MAPK/ERK and PI3K/Akt signal paths, and can promote the repair of damaged cardiac muscle by regulating and controlling the proliferation and differentiation balance of cardiac progenitor cells by regulating and controlling the expression of cyclin D1 and Src kinase activity. ABI3BP can promote the combination of cells and extracellular matrix, lighten inflammatory reaction and apoptosis after myocardial ischemia, maintain myocardial structural integrity