Methods and treatment for allergies and inflammation associated with gastrointestinal diseases

Abstract

Methods of the prophylaxis of the development of allergy in a patient at risk of sensitization to an antigen(s) or allergen(s) due to impaired gastrointestinal functions include administering a mast cell inhibitor, e.g., ketotifen, e.g., ketotifen fumarate. Methods for prophylactically treating, reducing, delaying or controlling gastrointestinal disorders include administering a mast cell stabilizer, e.g., ketotifen to a patient in need thereof. Pharmaceutical preparation, composition for use in methods described, are also disclosed. Also disclosed are methods of prophylaxis or treating gastrointestinal and esophageal inflammation, and methods for the prophylaxis of the development of additional allergies to a newly introduced substance in a patient with a preexisting allergy. Such methods include delivery of a mast cell stabilizer, e.g., ketotifen. Oral and topical administration are contemplated within the scope of the methods.

1 . A method for the prophylaxis of the development of allergy in a patient at risk of sensitization to one or more antigen(s) or allergen(s) due to impaired gastrointestinal digestion and/or increased intestinal permeability if exposed to such antigen(s) or allergen(s), comprising administering an effective amount of mast cell stabilizer in free or pharmaceutically acceptable salt form. 
     
     
         2 . The method according to  claim 1 , wherein said patient suffers from one or more of the following: inflammatory bowel disease, irritable bowel syndrome (IBS), allergy, gastritis, enteritis, esophagitis and ulcers. 
     
     
         3 . The method according to  claim 1 , wherein said patient suffers from impaired gastrointestinal digestion. 
     
     
         4 . The method according  claim 1 , wherein said patient suffers from one or more disorders selected from the following: gastroesophageal reflux disease, dyspepsia, peptic ulcer, Zollinger-Ellison syndrome, Barrett's esophagus, gastrinomas, gastritis, eosinophilic gastritis, eosinophillic gastroenteritis, eosinophilic enteritis, and eosinophilic esophagitis. 
     
     
         5 . The method according to  claim 1 , wherein said patient is undergoing allergy desensitization. 
     
     
         6 . The method according to  claim 5 , further comprises administering, in conjunction with said mast cell stabilizer, one or more antigen(s) or allergen(s) to induce tolerance. 
     
     
         7 . The method according to  claim 6 , wherein the allergen is peanuts or hazelnuts. 
     
     
         8 . The method according to  claim 6 , wherein the mast cell stabilizer is administered prior to the commencement of each dose of allergen. 
     
     
         9 . The method according to  claim 6 , wherein the mast cell stabilizer is administered up to two weeks prior to commencement of each dose of allergen. 
     
     
         10 . The method according to  claim 1 , wherein said mast cell stabilizer is ketotifen in free or pharmaceutically acceptable salt form. 
     
     
         11 . The method according to  claim 10 , wherein the patient receives an oral dose of 0.5, 1 or 2 mg ketotifen twice daily. 
     
     
         12 . The method according to  claim 1 , said mast cell stabilizer is administered in conjunction with one or more agents selected from a group consisting of proton pump inhibitors, antacids, histamine H 2 -receptor antagonists, sucralfate, and M 1  muscarinic receptor antagonists, in free or pharmaceutically acceptable salt form. 
     
     
         13 . The method according to  claim 12 , wherein said agent is a proton pump inhibitor in free or pharmaceutically acceptable salt form. 
     
     
         14 . The method according to  claim 12 , wherein said agent is an antacid. 
     
     
         15 . The method according to  claim 12 , wherein said agent is a histamine H 2 -receptor antagonist in free or pharmaceutically acceptable salt form. 
     
     
         16 . A method for prophylactically treating, controlling, delaying or normalizing gastrointestinal disorders in a patient in need thereof comprising administering to said patient an effective amount of mast cell stabilizer in free or pharmaceutically acceptable salt form. 
     
     
         17 . The method according to  claim 16 , wherein said disorder is selected from one or more of the following: inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), allergy, gastritis, enteritis, esophagitis, and ulcers. 
     
     
         18 . The method according to  claim 16 , wherein said disorder is an acid peptic disease. 
     
     
         19 . The method according to  claim 16 , wherein said disorder is GERD. 
     
     
         20 . The method according to  claim 16 , wherein said mast cell stabilizer is ketotifen in free or pharmaceutically acceptable salt. 
     
     
         21 . The method according to  claim 16 , wherein said mast cell stabilizer is ketotifen fumarate. 
     
     
         22 . An enteric coated mast cell stabilizer comprising (i) a mast cell stabilizer in free or pharmaceutically acceptable salt form; and (ii) an enteric coating. 
     
     
         23 . A pharmaceutical composition comprising: a mast cell stabilizer in free or pharmaceutically acceptable salt form; or
 a) (i) one or more of a first agent(s) selected from a group consisting of proton pump inhibitors, antacids, histamine H 2 -receptor antagonists, sucralfate, prostaglandin analogs, sucrafate, M 1  muscarinic receptor antagonists, and prokinetic agents; and (ii) a mast cell stabilizer, in free or pharmaceutically acceptable salt form;   b) (i) one or more of a first agent(s) selected from a non-steroidal anti-inflammatory drug (NSAID) or an acetylsalicylate (ASA) drug; and (ii) a mast cell stabilizer, in free or pharmaceutically acceptable salt form;   c) an enteric coated mast cell stabilizer in free or pharmaceutically acceptable salt form,   
       in admixture with a pharmaceutically acceptable diluent or carrier. 
     
     
         24 . The pharmaceutical composition according to  claim 23 , wherein said mast cell stabilizer is ketotifen fumarate.