Alterations in endothelin receptors following hemorrhage and resuscitation by centhaquin
Inventors
Gulati, Anil • Lavhale, Manish • KATIA, BHAWNA • Singh, Abhishek Kumar
Assignees
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Publication Number
US-12629406-B2
Publication Date
2026-05-19
Expiration Date
Abstract
The present disclosure is related to methods and compositions for treating or preventing kidney injury or failure, comprising administering an endothelin B (ETB) receptor agonist and/or an α2 adrenergic agent.
Core Innovation
The invention describes a method of treating or preventing acute kidney injury or failure, including acute kidney function decline associated with hemorrhage, by administering a therapeutically effective amount of a composition comprising centhaquin or a salt thereof. The composition is optionally administered in combination with an endothelin B receptor agonist such as IRL-1620. In addition, centhaquin may be coadministered with resuscitation fluids.
In hemorrhagic-shock studies in rats, centhaquin improves renal medullary blood perfusion, attenuates shock-associated decrease in renal endothelin B receptors, and reduces endothelin A receptor expression. Centhaquin also attenuates endothelin A elevation and increases endothelin B expression in the abdominal aorta. Interim phase II results report a larger decrease in serum creatinine and a larger increase in glomerular filtration rate with centhaquin than with control.
Claims Coverage
The claims identify 1 inventive feature directed to the treatment of acute kidney function decline using a composition comprising centhaquin or a salt thereof.
Treatment of acute kidney function decline
The independent claim covers administering to an individual suffering acute kidney function decline a therapeutically effective amount of a composition comprising centhaquin or a salt thereof. Dependent claims specify associated causes and conditions, citrate, pyruvate, or lactate salt forms, dose ranges, and coadministration with a resuscitation fluid or selected agents.
The claim coverage centers on treating acute kidney function decline with centhaquin or a salt thereof, with dependent claims specifying associated conditions, salt forms, dose ranges, and coadministration with resuscitation fluids or selected agents.
Stated Advantages
In rat hemorrhagic-shock studies, centhaquin improves renal medullary blood perfusion, attenuates shock-associated endothelin A elevation, and alters renal endothelin receptor expression.
Interim phase II results report larger decreases in serum creatinine and larger increases in glomerular filtration rate with centhaquin than with control.
Documented Applications
Treating or preventing acute kidney injury or failure, including acute kidney function decline associated with hemorrhage, illnesses, injuries, conditions, procedures, exposures, and causes of dehydration.
Treating acute kidney function decline by administering centhaquin or a salt thereof, including coadministration with resuscitation fluids.
Use of centhaquin with an endothelin B (ETB) receptor agonist such as IRL-1620 for acute kidney injury or failure.
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