Pharmaceutical composition and use thereof for relieving progression of chronic kidney disease or preventing thereof

Abstract

The current invention is in the field of molecular biology/pharmacology and provides methods of using a pharmaceutical composition of 5-(2′,4′-difluorophenyl)-salicylanilide derivatives and their ring-fused analogs for preventing, inhibiting, reducing, or treating chronic kidney disease, conditions leading to or arising from it, and/or negative effects of each thereof.

What is claimed is: 
     
         1 . A pharmaceutical composition for relieving progression of or preventing chronic kidney disease in a subject in need thereof, comprising administering a therapeutically effective amount of the pharmaceutical composition comprising a 5-(2′,4′-difluorophenyl)-salicylanilide derivatives and their ring-fused analogs. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the 5-(2′,4′-difluorophenyl)-salicylanilide derivatives comprise an 2-hydroxy-N-I3-(trifluoroinethyl)phenylibenzamide, N-(4-chloro-2-f1uorophertyl)-2-hydroxybenzamide, N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide, and 6(2,4-difluorophenyl)-3-(3-(trifiuoromethyl)phenyl)-2H-benzo[e][1,3]oxazine -2,4(3H )-dione. 
     
     
         3 . The pharmaceutical composition according to  claim 2 , wherein the chronic kidney disease comprises glomerulonephritis, renal fibrosis, and renal inflammation. 
     
     
         4 . The pharmaceutical composition according to  claim 3 , wherein the glomerulonephritis is selected from primary glomerulonephritis, and secondary glomerulonephritis. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein the primary glomerulonephritis is selected from IgA nephropathy. 
     
     
         6 . The pharmaceutical composition according to  claim 4 , wherein the secondary glomerulonephritis is selected from lupus nephritis. 
     
     
         7 . The pharmaceutical composition according to  claim 3 , wherein the renal fibrosis is selected from renal tubulointerstitial lesions. 
     
     
         8  The pharmaceutical composition according to  claim 3 . wherein the pharmaceutical composition attenuates glomerular cell proliferation about 15˜35%, attenuates sclerosis and fibrosis, attenuates neutrophil infiltration about 15˜50%, attenuates mononuclear leukocyte infiltration about 30˜60%, attenuates crescent formation about 40˜90%, attenuates fibrinoid necrosis about 40-90%, downregulate the expression of NLRP3 or/and IL-1β in a kidney of the subject. 
     
     
         9 . The pharmaceutical composition according to  claim 3 , wherein the pharmaceutical composition can regulate renal function and albuminuria, downregulate serum levels of blood urea nitrogen (serum levels of BUN) about 50˜60%, serum levels of creatinine serum levels of Cr) about 30˜40% and serum levels of IgG anti-dsDNA about 60˜70% of the subject. 
     
     
         10 . The pharmaceutical composition according to  claim 3 , wherein the therapeutically effective amount of the pharmaceutical composition is from about 5 mg/kg to about 30 mg/kg body weight per dose, wherein the subject is selected from mammals, wherein the mammals are selected from cat, dog, rabbit, cattle, horse, sheep, goat, monkey, mouse, rat, gerbil, guinea pig, pig and the human.