Fast Acting Inhibitor of Gastric Acid Secretion

Abstract

The present invention relates to the use of pharmaceutically acceptable zinc salts, preferably water soluble zinc salts alone or optionally, in combination with one or more of a protein pump inhibitor (PPI), H2 blocker, anti- H. pylori antibiotic/antimicrobial, cytoprotective agent or a combination agent as otherwise described herein for providing fast action with optional long duration effect in reducing gastric acid secretion, raising the pH of the stomach during resting phase as well as decreasing the duration of stomach acid release during a secretagogue phase and for treating conditions including gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), Zollinger-Ellison syndrome (ZE disease), ulcer disease, and gastric cancer, as well as preventing or reducing the likelihood of ulcer disease. In addition, the present methods are useful for treating patients who are non-responsive to proton pump inhibitors (PPI) and as an alternative to traditional therapies or conditions which are caused by rapid and complete inhibition of secretagogue induced acid secretion. The present invention also relates to the use of one or more water soluble zinc salts, administered in combination with a therapeutic compound or agent (second therapeutic agent) which may be delivered orally with enhanced bioavailability (compared to compounds which are administered in the absence of water soluble zinc salts) or other favorable benefits. In addition, therapeutic agents which exhibit sensitivity to low pH may be advantageously orally administered in combination with an effective amount of at least one water soluble zinc salt. Compositions according to the present invention exhibit greater bioavailability of the active agent when formulated in combination with a water soluble zinc salt in oral dosage form than when administered with the water soluble zinc salt.

1 .- 114 . (canceled) 
     
     
         115 . A method of increasing the pH of the gastric juices of the stomach of a human patient in need of a rapid increase in stomach pH, said method comprising orally administering to said patient an effective amount of a composition consisting essentially of zinc camosine, wherein said pH of said gastric juices in said patient increases to at least about 3.0 within a period no greater than about one hour after administration of said composition. 
     
     
         116 . The method according to  claim 115  wherein said composition further includes at least one additional zinc salt selected from the group consisting of zinc acetate, zinc chloride, zinc lactate, zinc picolinate and zinc tartrate. 
     
     
         117 . The method according to  claim 115  wherein said pH of said gastric juices in said patient increases to at least about 3.5 within a period no greater than about 30 minutes after administration of said composition. 
     
     
         118 . The method according to  claim 116  wherein said pH of said gastric juices in said patient increases to at least about 3.5 within a period no greater than about 30 minutes after administration of said composition. 
     
     
         119 . The method according to  claim 115  wherein said pH of said gastric juices in said patient increases to at least 4.0 within a period no greater than about 20 minutes after administration of said composition. 
     
     
         120 . The method according to  claim 119  wherein said composition further includes at least one zinc salt selected from the group consisting of zinc acetate, zinc chloride, zinc lactate, zinc picolinate and zinc tartrate. 
     
     
         121 . The method according to  claim 115  wherein said zinc camosine is coadministered with at least one proton pump inhibitor. 
     
     
         122 . The method according to  claim 116  wherein said zinc camosine is coadministered with at least one proton pump inhibitor. 
     
     
         123 . The method according to  claim 121  wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. 
     
     
         124 . The method according to  claim 122  wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. 
     
     
         125 . A method of reducing the likelihood of an ulcer developing in a human patient at risk for an ulcer because of elevated acid release in the stomach of said patient by rapidly increasing pH of the gastric juices of the stomach in said patient in response to said acid release comprising orally administering to said patient at risk an effective amount of a composition consisting essentially of zinc camosine, wherein the administration of said composition increases the pH of gastric juices in the stomach of said patient to at least about 3.0 within a period no greater than about one hour after administration of said composition. 
     
     
         126 . The method according to  claim 125  wherein said pH of said gastric juices in said patient increases to at least about 3.5 within a period no greater than about 30 minutes after administration of said composition. 
     
     
         127 . The method according to  claim 125  wherein said pH of said gastric juices in said patient increases to at least 4.0 within a period no greater than about 20 minutes after administration of said composition. 
     
     
         128 . The method according to  claim 125  wherein said composition further includes at least one additional zinc salt selected from the group consisting of zinc acetate, zinc chloride, zinc lactate, zinc picolinate and zinc tartrate. 
     
     
         129 . The method according to  claim 125  wherein said zinc salt is combined with an effective amount of at least one proton pump inhibitor. 
     
     
         130 . The method according to  claim 129  wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole and mixtures thereof. 
     
     
         131 . The method according to  claim 128  wherein said zinc salt(s) is combined with an effective amount of at least one proton pump inhibitor. 
     
     
         132 . The method according to  claim 131  wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole and mixtures thereof. 
     
     
         133 . A method of treating a human patient in need for a disease state or condition in which elevated release of acid in the stomach of said patient occurs selected from the group consisting of gastroesophageal reflux disease, (GERD), non-erosive reflux disease (NERD), Zollinger-Ellison syndrome (ZE syndrome), ulcer disease and gastric cancer comprising orally administering to said patient an effective amount of a composition to rapidly increase pH of the gastric juices of the stomach in said patient in response to said release of acid consisting essentially of zinc carnosine, wherein the administration of said zinc camosine increases the pH of gastric juices in the stomach of said patient to at least about 3.0 within a period no greater than about one hour after administration of said composition. 
     
     
         134 . The method according to  claim 133  wherein said composition further includes at least one additional zinc salt selected from the group consisting of zinc acetate, zinc chloride, zinc lactate, zinc picolinate and zinc tartrate. 
     
     
         135 . The method according to  claim 133  wherein said zinc carnosine is coadministered with at least one agent selected from the group consisting of a proton pump inhibitor, an H2 blocker, a cytoprotective agent or a mixture of two or more of these agents. 
     
     
         136 . The method according to  claim 134  wherein said zinc camosine and said zinc salt(s) are coadministered with at least one agent selected from the group consisting of a proton pump inhibitor, an H2 blocker, a cytoprotective agent or a mixture of two or more of these agents. 
     
     
         137 . The method according to  claim 133  wherein said disease state or condition is GERD, NERD or ZE syndrome. 
     
     
         138 . The method according to  claim 134  wherein said disease state or condition is GERD, NERD or ZE syndrome. 
     
     
         139 . The method according to  claim 133  wherein said pH of said gastric juices in said patient increases to at least about 3.5 within a period no greater than about 30 minutes after administration of said zinc salt(s). 
     
     
         140 . The method according to  claim 136  wherein said H2 blocker is cimetidine, famotidine, nizatidine, ranitidine or mixtures thereof. 
     
     
         141 . The method according to  claim 136  wherein said cytoprotective agent is bismuth subsalicylate, sucralfate or a mixture thereof. 
     
     
         142 . The method according to  claim 136  wherein said mixture of agents is prevpac. 
     
     
         143 . A method of inhibiting vacuolar H + -ATPase, H + , K + -ATPase or both H + -ATPase and H + , K˜-ATPase in the stomach of a human patient in need in which elevated release of acid in the stomach of said patient occurs comprising administering to said patient an effective amount of a composition consisting essentially of zinc camosine to rapidly increase pH of the gastric juices of the stomach in said patient in response to said release of acid, wherein the administration of said composition increases the pH of gastric juices in the stomach of said patient to at least about 3.0 within a period no greater than about one hour after administration of said composition. 
     
     
         144 . The method according to  claim 143  wherein said composition further includes at least one additional zinc salt selected from the group consisting of zinc acetate, zinc chloride, zinc lactate, zinc picolinate and zinc tartrate. 
     
     
         145 . The method according to  claim 143  wherein said pH of said gastric juices in said patient increases to at least about 3.5 within a period no greater than about 30 minutes after administration of said zinc gluconate. 
     
     
         146 . The method according to  claim 143  wherein said zinc gluconate is coadministered with at least one proton pump inhibitor. 
     
     
         147 . The method according to  claim 143  wherein said patient does not effectively respond to proton pump inhibitor therapy.