アンジオテンシン変換酵素２（ＡＣＥ２）の活性な低分子量変異体

• Format: Patent
• Language: Japanese
• Published: 05.03.2020
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

ＡＣＥ２の変異体、ＡＣＥ２の変異体を含む医薬組成物、及びそれを必要とする対象におけるアンジオテンシンＩＩ（１〜８）血漿レベルを低下させる及び／又はアンジオテンシン（１〜７）血漿レベルを上昇させる治療方法が開示される。ＡＣＥ２の開示された変異体は、ＡｎｇＩＩ（１−８）をＡｎｇ（１−７）に変換するためのＡＣＥ２活性を有するＡＣＥ２のポリペプチド断片を含み得る。開示された治療方法に適した適切な対象には、糖尿病及び非糖尿病の慢性腎疾患、急性腎不全及びその予防、慢性腎臓病、重度の高血圧、強皮症及びその皮膚、肺、腎臓及び高血圧性合併症、悪性高血圧、腎動脈狭窄に続発する腎血管性高血圧、特発性肺線維症、肝硬変患者などの肝線維症、大動脈瘤、心臓線維症及びリモデリング、左心室肥大、及び急性脳卒中を有するか又はそれを発症するリスクを有する対象を含み得る。 Disclosed are variants of ACE2, pharmaceutical compositions comprising the variants of ACE2, and treatment methods for reducing Angiotensin II(1-8) plasma levels and/or increasing Angiotensin (1-7) plasma levels in a subject in need thereof. The disclosed variants of ACE2 may include polypeptide fragments of ACE2 having ACE2 activity for converting AngII(1-8) to Ang(1-7). Suitable subjects suitable for the disclosed methods of treatment may include subjects having or at risk for developing diabetic and non-diabetic chronic kidney disease, acute renal failure and its prevention, chronic kidney disease, severe hypertension, scleroderma and its skin, pulmonary, kidney and hypertensive complications, malignant hypertension, renovascular hypertension secondary to renal artery stenosis, idiopathic pulmonary fibrosis, liver fibrosis such as in liver cirrhosis patients, an aortic aneurysm, cardiac fibrosis and remodeling, left ventricular hypertrophy, and an acute stroke.