Treatment of esophagitis

Abstract

A method for treatment of esophagitis is disclosed in which a therapeutic composition is introduced into the esophagus to contact a mucosal surface within the esophagus. The pharmaceutical composition comprises a reverse-thermal gelation polyoxyalkylene block copolymer, a pharmaceutical substance and a pharmaceutical substance selected from the group consisting of glutathione and a precursor for glutathione biosynthesis.

1 . A method for treatment of esophagitis in the esophagus of a human host the method comprising: 
 introducing a therapeutic composition into the host directed to the esophagus of the host, the therapeutic composition comprising: 
 (i) a carrier liquid;  
 (ii) a reverse-thermal gelation biocompatible polymer that is a polyoxyalkylene block copolymer, comprising at least one block of a first polyoxyalkylene and at least one block of a second polyoxyalkylene that is different than the first polyoxyalkylene; and  
 (iii) a pharmaceutical substance selected from the group consisting of glutathione and a precursor for glutathione biosynthesis, the pharmaceutical substance, as formulated in the therapeutic composition, being effective for treatment of esophagitis at a mucosal site within the esophagus; and  
   wherein, after the introducing, at least a portion of the biocompatible polymer and at least a portion of the pharmaceutical substance adhere to a mucosal surface at the mucosal site.    
   
   
       2 . The method of  claim 1 , wherein the pharmaceutical substance comprises a thiol-containing compound.  
   
   
       3 . The method of  claim 1 , wherein the pharmaceutical substance comprises a sulfur-containing antioxidant.  
   
   
       4 . The method of  claim 3 , wherein the sulfur-containing antioxidant is selected from the group consisting of S-carboxymethylcysteine, procysteine, lipoic acid, s-allyl cysteine, and methylmethionine sulfonium chloride.  
   
   
       5 . The method of  claim 3 , wherein the sulfur-containing antioxidant includes sulfur in at least one functional group selected from the group consisting of thiol, thioether, thioester, thiourea, thiocarbamate, disulfide, and sulfonium salt.  
   
   
       6 . The method of  claim 1 , wherein the pharmaceutical substance comprises a precursor for glutathione biosynthesis.  
   
   
       7 . The method of  claim 6 , wherein the precursor is selected from the group consisting of procysteine, lipoic acid, s-allyl cysteine, S-carboxymethylcysteine, and methylmethionine sulfonium chloride.  
   
   
       8 . The method of  claim 1 , wherein the pharmaceutical substance comprises N-acetylcysteine.  
   
   
       9 . The method of  claim 1 , wherein the liquid vehicle and the biocompatible polymer interact to impart reverse-thermal viscosity behavior to the therapeutic composition, with the therapeutic composition exhibiting the reverse-thermal viscosity behavior over at least some range of temperatures between 1 ° C. and the physiological temperature of the host.  
   
   
       10 . The method of  claim 9 , wherein the therapeutic composition exhibits an increase in viscosity from no larger than about 60 cP to at least about 70 cP when a temperature of the therapeutic composition is increased over at least some range of temperatures between 1 ° C. and the physiological temperature of the host.  
   
   
       11 . The method of  claim 1 , wherein the therapeutic composition exhibits an increase in viscosity from no larger than about 50 cP to at least about 70 cP when a temperature of the therapeutic composition is increased over at least some range of temperatures between 1 ° C. and the physiological temperature of the host.  
   
   
       12 . The method of  claim 1 , wherein the therapeutic composition has reverse-thermal gelation properties and a reverse-thermal liquid-gel transition temperature in a range of from 1 ° C. and the physiological temperature of the host.  
   
   
       13 . The method of  claim 12 , wherein during the introducing, the therapeutic composition is at an administration temperature within a range of from 1 ° C. to 10° C.  
   
   
       14 . The method of  claim 1 , wherein the therapeutic composition comprises a bioadhesive agent other than the biocompatible polymer.  
   
   
       15 . The method of  claim 1 , wherein the therapeutic composition comprises from 0.001 to 25 weight percent of the pharmaceutical substance and from 1 to 70 weight percent of the biocompatible polymer.  
   
   
       16 . The method of  claim 15 , wherein the first polyoxyalkylene is a polyoxyethylene and the second polyoxyalkylene is a polyoxypropylene, and the biocompatible polymer comprises two of the block of the first polyoxyalkylene and one of the block of the second polyoxyalkylene.  
   
   
       17 . The method of  claim 16 , wherein the therapeutic composition comprises from 5 to 20 weight percent of the biocompatible polymer.  
   
   
       18 . The method of  claim 17 , wherein the pharmaceutical substance is N-acetylcysteine.  
   
   
       19 . The method of  claim 1 , wherein the esophagitis is a side effect of the host undergoing cancer therapy treatment comprising one or both of chemotherapy and radiation therapy.  
   
   
       20 . The method of  claim 19 , wherein the introducing occurs prior to the cancer therapy treatment.  
   
   
       21 . The method of  claim 19 , wherein the introducing occurs multiple times, a first said introducing occurring prior to the cancer therapy treatment a second said introducing occurring after the cancer therapy treatment.  
   
   
       22 . The method of  claim 1 , wherein when introduced into the host, the therapeutic composition is in the form of a flowable medium.  
   
   
       23 . The method of  claim 1 , wherein when introduced into the host, the therapeutic composition is in the form of a gel.  
   
   
       24 . The method of  claim 1 , wherein when introduced into the host, the therapeutic composition has a viscosity of at least 70 cP.  
   
   
       25 . A method for treatment of esophagitis in the esophagus of a human host the method comprising: 
 introducing a therapeutic composition into the host directed to the esophagus of the host, the therapeutic composition comprising: 
 (i) an amount of from 0.001 to 25 weight percent of N-acetylcysteine effective as formulated in the therapeutic composition for treatment of esophagitis at a mucosal site within the esophagus;  
 (i) from 1 to 70 weight percent of a reverse-thermal gelation biocompatible polymer that is a polyoxyalkylene block copolymer, comprising at least two blocks of polyoxyethylene and at least one block of polyoxypropylene; and  
 (iii) an aqueous carrier liquid interacting with the biocompatible polymer to impart reverse-thermal viscosity behavior to the therapeutic composition;  
   wherein, the therapeutic composition exhibits the reverse-thermal viscosity behavior over at least some range of temperatures between 1° C. and the physiological temperature of the host.    
   
   
       26 . The method of  claim 25 , wherein during the introducing, the therapeutic composition is in the form of a flowable medium at an administration temperature that is at least 1° C. and that is lower than the physiological temperature of the host, and the therapeutic composition exhibits the reverse-thermal viscosity behavior over at least some range of temperatures between the administration temperature and the physiological temperature of the host.  
   
   
       27 . The method of  claim 26 , wherein the flowable medium is a solution comprising the N-acetylcysteine and the biocompatible polymer dissolved in the carrier liquid.  
   
   
       28 . The method of  claim 27 , wherein the therapeutic composition has a reverse-thermal liquid-gel transition temperature in a range of from the administration temperature to the physiological temperature of the host.  
   
   
       29 . The method of  claim 28 , wherein the biocompatible polymer is poloxamer 407 .  
   
   
       30 . The method of  claim 29 , wherein during the introducing, the therapeutic composition is in the form of a gel.  
   
   
       31 . The method of  claim 30 , wherein the biocompatible polymer is poloxamer 407.  
   
   
       32 . The method of  claim 25 , wherein the therapeutic composition comprises from 5 weight percent to 20 weight percent of the biocompatible polymer.  
   
   
       33 . The method of  claim 25 , wherein the therapeutic composition comprises from 10 weight percent to 20 weight percent of the biocompatible polymer.