Compositions for the treatment of inflammation of the gastrointestinal tract

Abstract

Provided herein are methods for preventing or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract, for example, those involving the esophagus. Also provided herein are pharmaceutical compositions useful for the methods of the present invention.

1 . A method of treating, preventing or alleviating inflammation of the gastrointestinal tract comprising orally administering to an individual in need thereof a composition comprising a corticosteroid, a preservative, a chelating agent, an isotonic agent, a surfactant, and an excipient that increases the interaction of the composition with a surface of the gastrointestinal tract. 
   
   
       2 . The method of  claim 1 , wherein the corticosteroid is budesonide. 
   
   
       3 . The method of  claim 1 , wherein the corticosteroid is present in the composition in an amount of about 0.01 mg to about 1.0 mg of corticosteroid per gram of composition. 
   
   
       4 . The method of  claim 1 , wherein the corticosteroid is present in the composition in an amount of about 0.01 mg to about 1.0 mg of corticosteroid per mL of composition. 
   
   
       5 . A method of  claim 4 , wherein the method comprises administering about 5 mL to about 50 mL of the composition to the individual. 
   
   
       6 . The method of  claim 1 , wherein the preservative is potassium sorbate. 
   
   
       7 . The method of either of  claims 1  or  6 , wherein the preservative is present in the composition in an amount of about 0.0002% to about 0.5% w/w of the composition. 
   
   
       8 . The method of  claim 1 , wherein the chelating agent is edetate. 
   
   
       9 . The method of  claim 1 , wherein the chelating agent is present in the composition in an amount of about 0.0005% to about 0.1% w/w of the composition. 
   
   
       10 . The method of  claim 1 , wherein the isotonic agent is dextrose. 
   
   
       11 . The method of  claim 1 , wherein the surfactant is polysorbate 80. 
   
   
       12 . The method of  claim 1 , wherein the surfactant is present in the composition in an amount of about 0.0005% to about 2% w/w of the composition. 
   
   
       13 . The method of  claim 1 , wherein the excipient that increases the interaction of the composition with a surface of the gastrointestinal tract is a viscosity enhancing agent. 
   
   
       14 . The method of  claim 13 , wherein the viscosity enhancing agent is selected from microcrystalline cellulose, carboxymethyl cellulose sodium and a combination thereof. 
   
   
       15 . The method of  claim 14 , wherein the viscosity enhancing agent is a combination of microcrystalline cellulose and carboxymethyl cellulose sodium. 
   
   
       16 . The method of  claim 13 , wherein the viscosity enhancing agent is present in the composition in about 0.01% to about 3.0% w/w of the composition. 
   
   
       17 . The method of  claim 15 , wherein the viscosity enhancing agent is a combination of a CMC and MCC. 
   
   
       18 . The method of  claim 1 , wherein the composition is formulated as a micronized suspension of the corticosteroid in an aqueous vehicle. 
   
   
       19 . The method of  claim 1 , wherein the composition has a target pH of about 4.5. 
   
   
       20 . The method of  claim 19 , wherein the target pH of the composition is attained by adding a pH adjusting agent to the composition. 
   
   
       21 . The method of  claim 20 , wherein the pH adjusting agent is hydrochloric acid. 
   
   
       22 . The method of  claim 1 , wherein the composition further comprising a sweetener, a flavoring agent or a combination thereof. 
   
   
       23 . The method of  claim 1 , wherein the composition comprises:
 a. about 0.01 mg to about 1.0 mg of budesonide per mL of composition;   b. about 0.0002% to about 0.5% w/w of potassium sorbate;   c. about 0.0005% to about 0.1% w/w of disodium edetate;   d. about 0.0005% to about 2% w/w of polysorbate 80; and   e. about 0.01% to about 3.0% w/w of a combination of microcrystalline cellulose and carboxymethyl cellulose sodium.   
   
   
       24 . The method of  claim 1 , comprising administering about 0.1 mg to about 20 mg of corticosteroid per day. 
   
   
       25 . The method of  claim 1 , wherein the inflammation of the gastrointestinal tract is inflammation of the esophagus. 
   
   
       26 . The method of  claim 1 , wherein the inflammation of the gastrointestinal tract is eosinophilic esophagitis, an inflammatory bowel disease involving the esophagus, Crohn's disease, celiac disease, intermediate esophagitis, epithelial hyperplasia, basal cell hyperplasia, elongated papillae, dilated vessels in papillae, fungal esophagitis, viral esophagitis, bacterial esophagitis, corrosive esophagitis, radiation esophagitis, chemotherapy esophagitis, graft vs. host disease, a skin disease with esophageal involvement, bullous pemphigoid, pemphigus vulgaris, epidermolysis bollosa, Stevens-Johnson syndrome, Behcet's disease, sarcoidosis, idiopathic esophagitis, eosinophilic gastritis, Ménétrier's disease, parasitic gastritis, lymphocytic esophagitis, inflammatory bowel disease-associated esophagitis, parasitic gastritis, lymphocytic esophagitis, inflammatory bowel disease-associated esophagitis, eosinophilic duodenitis, functional dyspepsia, esophageal inflammation secondary to caustic/irritant ingestion, persistent/recurrent esophageal strictures of any cause and including caustic/irritant ingestion, pill-induced esophagitis, systemic diseases, congenital diseases or post-surgery inflammation. 
   
   
       27 . The method of  claim 25 , wherein the individual has eosinophilic esophagitis. 
   
   
       28 . The method of  claim 25 , wherein the individual has been diagnosed with gastroesophageal reflux disease (GERD), nonerosive reflux disease (NERD), or erosive esophagitis.