Use of alginate compositions in preventing or reducing liver damage caused by a hepatotoxic agent

Abstract

Disclosed herein are compositions, methods and uses utilizing alginate compositions, for treating, preventing and/or reducing liver damage induced by a hepatotoxic agent, and for treating a medical condition treatable by a hepatotoxic agent, in which an alginate composition is administered prior to, concomitant with, or shortly after exposure to a hepatotoxic agent. Also disclosed are pharmaceutical compositions comprising a hepatotoxic agent and an alginate composition and uses thereof for treating medical conditions treatable by the hepatotoxic agent.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising a therapeutically effective amount of a hepatotoxic agent and a therapeutically effective amount of an alginate composition, said alginate composition comprising a pharmaceutically acceptable carrier, wherein said alginate composition comprises alginate characterized by a molecular weight in a range of from 10 to 75 kDa. 
     
     
         2 . The composition of  claim 1 , being a unit dosage form. 
     
     
         3 . The composition of  claim 1 , wherein said carrier is an aqueous carrier. 
     
     
         4 . The composition of  claim 1 , wherein said alginate composition comprises alginate at a concentration in a range of from 0.4% to 10% (w/v). 
     
     
         5 . The composition of  claim 1 , wherein said alginate composition comprises alginate in a form of a sodium salt. 
     
     
         6 . The composition of  claim 1 , being formulated for systemic administration. 
     
     
         7 . The composition of  claim 1 , being formulated for oral administration and/or intraperitoneal administration. 
     
     
         8 . The composition of  claim 1 , wherein said hepatotoxic agent is selected from the group consisting of ethanol, paracetamol, acarbose, amiodarone, bosentan, bromfenac, dantrolene, diclofenac, dihydralazine, disulfiram, felbamate, fluoxetine, halothane, isoniazid, kava, ketoconazole, labetalol, leflunomide, methotrexate, methyldopa, nefazodone, nicotinic acid, paroxetine, pemoline, propylthiouracil, pyrazinamide, rifampin, ritonavir, sertraline, statins, tacrine, tetracycline antibiotics, tolcapone, troglitazone, trovafloxacin, valproic acid, ximelagatran, zafirlukast, zileuton, anabolic steroids, azathioprine, azithromycin, captopril, cimetidine, ciprofloxacin, clopidogrel, dicloxacillin, erythromycin, estrogens, flucloxacillin, naproxen, phenobarbital, phenothiazine antipsychotics, phenytoin, sulindac, terbinafine, tricyclic antidepressants, amoxicillin-clavulanic acid, carbamazepine, cyclosporine, enalapril, flutamide, methimazole, nitrofurantoin, sulfonamides, trazodone, trimethoprim, verapamil, allopurinol, aspirin, betahistine, busulfan, cephalosporins, chlorpheniramine, clarithromycin, codeine, corticosteroids, cyclophosphamide, cytarabine, danazol, dihydrocodeine, fluconazole, hydralazine, indinavir, ma-huang, mebeverine, metoclopramide, oxycodone, penicillamine, phenylbutazone, procainamide, quinidine, retinol, reverse transcriptase inhibitors, sulpiride, tamoxifen and telithromycin. 
     
     
         9 . A method of reducing a liver damage caused by paracetamol, the method comprising administering to a subject exposed to paracetamol a therapeutically effective amount of an alginate composition, said administering being effected prior to, concomitant with, or shortly after exposure to paracetamol, thereby reducing liver damage, wherein administration of said alginate composition is effected by oral administration. 
     
     
         10 . The method of  claim 9 , wherein said administering is effected up to 50 minutes after said exposure to paracetamol. 
     
     
         11 . The method of  claim 9 , wherein said administering is effected during a time period ranging from 100 minutes prior to said exposure to paracetamol to 50 minutes subsequent to said exposure to paracetamol. 
     
     
         12 . The method of  claim 9 , wherein said alginate composition comprises an aqueous carrier. 
     
     
         13 . The method of  claim 12 , wherein said alginate composition is characterized by a solution viscosity in a range of from 3 to 50 mPa*seconds, at a shear rate of 1 second −1  and at a concentration of 2% (w/v) alginate in said aqueous carrier. 
     
     
         14 . The method of  claim 9 , wherein said alginate composition comprises alginate is in a form of a sodium salt. 
     
     
         15 . The method of  claim 9 , wherein said alginate composition and said paracetamol are co-formulated within the same composition. 
     
     
         16 . A method of treating a medical condition treatable by paracetamol in a subject in need thereof, the method comprising co-administering to the subject a therapeutically effective amount of paracetamol and a therapeutically effective amount of an alginate composition, said co-administering being effected such that said alginate composition is administered to the subject during a time period ranging from 100 minutes prior to administration of paracetamol to 50 minutes subsequent to administration of paracetamol, thereby treating the medical condition. 
     
     
         17 . The method of  claim 16 , wherein said medical condition is selected from the group consisting of fever and pain. 
     
     
         18 . The method of  claim 16 , wherein said alginate composition comprises alginate characterized by a molecular weight in a range of from 10 to 75 kDa. 
     
     
         19 . The method of  claim 16 , wherein said alginate composition comprises alginate is in a form of a sodium salt. 
     
     
         20 . The method of  claim 16 , wherein said alginate composition and said paracetamol are co-formulated within the same composition.