Compositions comprising bile acid sequestrants for treating esophageal disorders

Abstract

Disclosed herein are novel compositions and methods for treating or preventing upper GI tract disorders and protecting stratified squamous epithelium against injury by a noxious substance. The methods generally include administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising at least one bile acid sequestrant, alone or in combination with at least one proton pump inhibitor, and optionally one or more agent chosen from antacids, histamine H 2 -receptor antagonists, γ-aminobutyricacid-b (GABA-B) agonists, prodrugs of GABA-B agonists, and protease inhibitors.

1 . A composition for treating or preventing an upper GI tract disorder comprising 0.1 g to 3 g of bile acid sequestrant or pharmaceutically acceptable salt thereof. 
     
     
         2 . A composition according to  claim 1  further comprising a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         3 . A composition according to  claim 1 , wherein the bile acid sequestrant is chosen from one or more of cholestyramine, colesevelam, ursodeoxycholic acid, colestipol, sevelamer, a dialkylaminoalkyl derivatives of a cross-linked dextran, and N-(cycloalkyl)alkylamine, or a pharmaceutically acceptable salt thereof. 
     
     
         4 - 5 . (canceled) 
     
     
         6 . A composition according to  claim 3 , wherein the bile acid sequestrant is colesevelam hydrochloride. 
     
     
         7 - 8 . (canceled) 
     
     
         9 . A composition according to  claim 1  further comprising a therapeutically effective amount of at least one proton pump inhibitor. 
     
     
         10 . A composition according to  claim 9 , wherein the at least one proton pump inhibitor is chosen from omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, tenatoprazole, leminoprazole, dontoprazole, and ransoprazole. 
     
     
         11 - 33 . (canceled) 
     
     
         34 . A composition according to  claim 1 , wherein the upper GI tract disorder is chosen from dyspepsia, heartburn, erosive esophagitis, GERD, peptic ulcer, esophagitis, Barrett's esophagus, esophageal adenocarcinoma, pharyngitis, and GERD-related pulmonary dysfunctions. 
     
     
         35 - 108 . (canceled) 
     
     
         109 . A composition according to  claim 1 , wherein said composition further comprises a gastric-retention vehicle composition comprising one or more hydrogels, wherein said dosage form expands upon contact with gastric fluid. 
     
     
         110 . A composition according to  claim 1 , wherein said composition comprises at least 0.4 g of bile acid sequestrant or pharmaceutically acceptable salt thereof. 
     
     
         111 . A composition according to  claim 1 , wherein said composition comprises from 0.1 g to 1.0 g of bile acid sequestrant or pharmaceutically acceptable salt thereof. 
     
     
         112 . A dosing regimen comprising directing one, two, three, or four oral dosage units of 0.1 g to 3 g of bile acid sequestrant, or pharmaceutically acceptable salt thereof, to be administered per day to a patient having or at risk of developing an upper GI tract disorder. 
     
     
         113 . A dosing regimen according to  claim 112 , wherein said oral dosage unit comprises 400 to 600 mg of bile acid sequestrant, or pharmaceutically acceptable salt thereof. 
     
     
         114 . A dosing regimen according to  claim 112 , wherein the bile acid sequestrant is chosen from one or more of cholestyramine, colesevelam, ursodeoxycholic acid, colestipol, sevelamer, a dialkylaminoalkyl derivative of a cross-linked dextran, and N-(cycloalkyl)alkylamine, or a pharmaceutically acceptable salt thereof. 
     
     
         115 . A dosing regimen according to  claim 114 , wherein the bile acid sequestrant is colesevelam hydrochloride. 
     
     
         116 . A dosing regimen according to  claim 112 , wherein said oral dosage unit further comprises a gastric-retention vehicle composition comprising one or more hydrogels, wherein said dosage unit expands upon contact with gastric fluid. 
     
     
         117 . A dosing regimen according to  claim 113 , wherein said oral dosage unit further comprises a gastric-retention vehicle composition comprising one or more hydrogels, wherein said dosage unit expands upon contact with gastric fluid. 
     
     
         118 . A method of treating a patient having or at risk of developing an upper GI tract disorder, said method comprising directing a dosing regimen comprising one, two, three, or four oral dosage units of 0.1 g to 3 g of bile acid sequestrant, or pharmaceutically acceptable salt thereof, to be administered per day to a patient in need thereof. 
     
     
         119 . A method according to  claim 118 , wherein the bile acid sequestrant is chosen from one or more of cholestyramine, colesevelam, ursodeoxycholic acid, colestipol, sevelamer, a dialkylaminoalkyl derivative of a cross-linked dextran, and N-(cycloalkyl)alkylamine, or a pharmaceutically acceptable salt thereof. 
     
     
         120 . A method according to  claim 119 , wherein the bile acid sequestrant is colesevelam hydrochloride. 
     
     
         121 . A method according to  claim 118 , wherein said oral dosage unit further comprises a gastric-retention vehicle composition comprising one or more hydrogels, wherein said dosage form expands upon contact with gastric fluid. 
     
     
         122 . A method according to  claim 118 , wherein said oral dosage unit comprises 400 to 600 mg of bile acid sequestrant, or pharmaceutically acceptable salt thereof.