Use of low-dose erythropoietin for the treatment of acute or chronic renal insufficiency and for the treatment of wounds

摘要

The use of erythropoietin (and/or its derivatives) (I) at a low dose of 0.001-90 IU/kg per week for stimulating endothelial precursor cells (EPS's), combating EPS dysfunction, treating or preventing associated diseases (e.g. cardiovascular or inflammatory diseases), cosmetic treatment and regenerating organs and tissues is new. The use of erythropoietin (and/or its derivatives) (I), at a weekly dose of 0.001-90 (preferably 0.05-50) IU/kg, is claimed in the production of pharmaceutical (including veterinary) compositions for: (a) prophylaxis or treatment in patients with endothelial precursor cell (EPS) dysfunction, cardiovascular risk factors and internal organ damage; (b) cosmetic treatment; (c) regeneration of tissue and blood vessels (where (I) is optionally used together with a mixture of EPS's with cell populations suitable for cell therapy, (I) being contacted with the mixture in vitro before use or used before, after or simultaneously with the mixture); or (d) use in a combined composition or kit together with at least one chemical, thermal, mechanical or biological agent (where the agent is used sequentially, successively or simultaneously with (I)). Independent claims are included for: (1) the use of erythropoietin (I') for: (a) production of a transplantable endothelial cell preparation (specifically by culturing EPS's in vitro in presence of 0.001-90 IU/kg per week of (I')); (b) pretreatment an/or further treatment of tissue or organs for transplantation, at a dose of 0.001-90 IU/kg per week; (c) production of implantable or transplantable cell-containing in vitro organ or tissue systems, pretreated with (I') before transplantation or implantation for induction of vasculogenesis and/or EPS formation; or (d) production of (I')-coated vascular prostheses or heart valves; (2) various (I)-containing compositions for use as above; (3) kits containing (I'), EPS's and at least one cell population useful for cell therapy; and (4) kits containing (I') at a dose of a dose of 0.001-90 IU/kg per week, an endoprosthesis and optionally a cell therapy agent (especially EPS's or a similar cell population). ACTIVITY : Hypotensive; Antilipemic; Cardiant; Antidiabetic; Antiinflammatory; Vasotropic; Antiarteriosclerotic; Gynecological; Hepatotropic; Cardiovascular-Gen.; Gastrointestinal-Gen.; Osteopathic; Antiulcer; Nephrotropic; Vulnerary; Dermatological. When FVB/N mice with surgically induced skin wounds on the flanks were treated with the recombinant human erythropoietin analog Aranesp by a single subcutaneous injection at 0.1 mu g/kg per week (starting 7 days before infliction of the wounds), the wounds were completely closed after ca. 7 days, compared with ca. 13 days in saline-treated controls. MECHANISM OF ACTION : Erythropoietin agonist; Cell therapy.