PROBLEM TO BE SOLVED : To provide compositions comprising modified angiotensin converting enzyme 2 (ACE2) polypeptides. SOLUTION : Disclosed herein is a pharmaceutical composition comprising a population of Zn2+ depleted-, Zn2+ free-, mixed metal and metal ion-substituted angiotensin-converting enzyme 2 (ACE2) polypeptides and a pharmaceutically acceptable carrier or excipient. Also disclosed are methods for producing the pharmaceutical composition and medical application thereof to hypertension, congestive heart failure, chronic heart failure, acute heart failure, contractile heart failure, myocardial infarction, arteriosclerosis, kidney failure, renal failure and lung diseases, renal fibrosis, chronic renal failure, acute renal failure, chronic renal failure, acute kidney injury and multi-organ dysfunction syndrome, etc. SELECTED DRAWING : None COPYRIGHT : (C)2019, JPO&INPIT