Melatonin for Preventing and Treating Radiation Cystitis

Abstract

Compositions comprising melatonin and/or derivatives thereof are provided for topical administration to the epithelium of the urinary bladder by instillation into the bladder to protect against or treat bladder injury due to irradiation and/or cytotoxic agents.

1 . A method for the prevention and/or treatment of a urinary bladder injury induced by irradiation and/or the use of one or more cytotoxic agents, comprising administering a composition comprising melatonin and/or an antioxidant metabolite, derivative or analogue thereof into the urinary bladder. 
     
     
         2 . The method of  claim 1 , additionally comprising administering a pharmaceutically acceptable form or derivative or analogue of one or more of the substances vitamin E, coenzyme Q, alpha-lipoic acid and vitamin C. 
     
     
         3 . The method of  claim 1 , wherein the urinary bladder injury is radiation cystitis due to pelvic external beam radiotherapy. 
     
     
         4 . The method of  claim 1 , wherein the urinary bladder injury is radiation cystitis due to pelvic brachyradiotherapy. 
     
     
         5 . The method of  claim 1 , wherein the urinary bladder injury is radiation cystitis due to a combination of pelvic external beam radiotherapy and brachyradiotherapy. 
     
     
         6 . The method of  claim 1 , wherein the urinary bladder injury is caused by one or more cytotoxic agents or radiation cystitis exacerbated by said cytotoxic agent or agents. 
     
     
         7 . The method of  claim 1 , wherein the melatonin and/or antioxidant metabolite, derivative or analogue thereof is formulated as a solution in dimethyl sulfoxide to be diluted in an aqueous medium prior to use. 
     
     
         8 . The method of  claim 1 , wherein the melatonin and/or antioxidant metabolite, derivative or analogue thereof is formulated for instillation into the urinary bladder as an aqueous solution or emulsion or suspension. 
     
     
         9 . The method of  claim 1 , wherein the composition is administered is 1, 2, 3, or 4 times per day. 
     
     
         10 . The method of  claim 1 , wherein the composition is administered over a period of up to 3 months or more, such as 4 months or more, such as 5 months or more, such as 6 months or more, such as 12 months. 
     
     
         11 . The method of  claim 1 , wherein the single standard adult dose of melatonin or an antioxidant metabolite, derivative or analogue thereof is 1 mg to 500 mg. 
     
     
         12 . The method of  claim 9 , wherein the method further comprises administering a pharmaceutically acceptable form or derivative or analogue of one or more of the substances vitamin E, coenzyme Q, alpha-lipoic acid and vitamin C, wherein the single standard adult dose of each of the one or more of the additional substances is in the range of 25% to 200% of the dose of melatonin or antioxidant metabolite, derivative or analogue thereof. 
     
     
         13 . The method of  claim 11 , wherein the daily dose of composition is from one to four times the single dose. 
     
     
         14 . The method of  claim 1 , wherein a single dose of the composition is administered within one hour, such as within 15 minutes to 30 minutes before an episode of irradiation.