# US 2014/0154339 A1 · Fast Acting Inhibitor of Gastric Acid Secretion > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154339 A1 - Document ID: US20140154339A1 - Status: Published application - Kind: A1 - Application number: 13/899,872 - Filed: 2013-05-22 - Published: 2014-06-05 - Earliest claimed: 2006-01-27 - Assignees: Yale University - Inventors: John P. Geibel; Phillipp Kirchhoff - Web page: https://patentgrep.com/patent/US20140154339A1 ## CPC - A61K 33/30: Zinc; Compounds thereof - A61K 31/315: Zinc compounds - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to the use of pharmaceutically acceptable zinc salts, in particular, zinc chloride and zinc acetate, alone or optionally, in combinations 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, including acid secretion in the fundus (by inhibiting vacuolar H+-ATPase or H+/K+-ATPase) and upper body region of the stomach (by inhibiting H+/K+-ATPase), thus raising the pH of gastric juices in rapid fashion and decreasing the duration of stomach acid release during a secretagogue phase. This method is also directed to 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. ## Claims ### Claim 1 A method of increasing the pH of the gastric juices of the stomach of a patient, said method comprising administering to said patient an effective amount of at least one pharmaceutically acceptable zinc salt. ### Claim 2 (depends on 1) The method according to claim 1 wherein a mixture of at least two zinc salts is administered to said patient. ### Claim 3 (depends on 1) The method according to claim 1 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 4 (depends on 2) The method according to claim 2 wherein said zinc salt is selected from at least two zinc salts selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 5 (depends on 1) The method according to claim 1 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate and mixtures thereof. ### Claim 6 (depends on 1) The method according to claim 1 wherein said zinc salt is selected from at least two zinc salts from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate and mixtures thereof. ### Claim 7 (depends on 1, 2, 3, 4, 5, 6) The method according to any of claims 1-6 wherein said zinc salt or at least one of said zinc salts is a zinc amino acid chelate. ### Claim 8 (depends on 7) The method according to claim 7 wherein said zinc amino acid chelate is selected from the group consisting of mono- and bis-chelates of L- or D-amino acids. ### Claim 9 (depends on 8, 9) The method according to claim 8 or 9 wherein said amino acid chelate is a chelate of zinc with an amino acid selected from the group consisting L-cysteine, L-cystine, L-N-acetylcysteine, L-histidine, D-histidine, L-taurine, L-glycinate, L-aspartate and L-methionine. ### Claim 10 (depends on 1, 2) The method according to claim 1 or 2 wherein said zinc salt is zinc chloride and optionally, at least one additional zinc salt selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc gluconate, zinc picolinate, zinc sulfate and a zinc amino acid chelate. ### Claim 11 (depends on 1) The method according to claim 1 wherein said zinc salt is zinc chloride. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) The method according to any of claims 1-11 wherein said zinc salt or said mixture of zinc salts is coadministered with at least one proton pump inhibitor. ### Claim 13 (depends on 12) The method according to claim 12 wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The method according to any of claims 1-13 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 of administering said zinc salt(s). ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The method according to any of claims 1-13 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 of administering said zinc salt(s). ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The method according to any of claims 1-13 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 of administering said zinc salt(s). ### Claim 17 A method of reducing the likelihood of an ulcer developing in a patient at risk for an ulcer because of elevated acid release in the stomach of said patient comprising administering to said patient at risk an effective amount at least one pharmaceutically acceptable zinc salt. ### Claim 18 (depends on 17) The method according to claim 17 wherein a mixture of at least two zinc salts is administered to said patient. ### Claim 19 (depends on 17) The method according to claim 17 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 20 (depends on 2) The method according to claim 2 wherein said zinc salt is selected from at least two zinc salts selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate (soluble in dilute acid at low pH of the stomach), zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undenylate, a zinc amino acid chelate or mixtures thereof. ### Claim 21 (depends on 17, 18, 19, 20) The method according to any of claims 17-20 wherein said zinc salt(s) is combined with an effective amount of at least one proton pump inhibitor. ### Claim 22 (depends on 21) The method according to claim 21 wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole and mixtures thereof. ### Claim 23 A method of treating a patient for a disease state or condition 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 administering to said patient an effective amount of at least one pharmaceutically acceptable zinc salt. ### Claim 24 (depends on 23) The method according to claim 23 wherein a mixture of at least two zinc salts is administered to said patient. ### Claim 25 (depends on 23) The method according to claim 23 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 26 (depends on 23) The method according to claim 23 wherein said zinc salt is selected from at least two zinc salts selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereo. ### Claim 27 (depends on 23) The method according to claim 23 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate or mixtures thereof. ### Claim 28 (depends on 23) The method according to claim 23 wherein said zinc salt is selected from at least two zinc salts from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate. ### Claim 29 (depends on 23, 24, 25, 26, 27, 28) The method according to any of claims 23-28 wherein said zinc salt or at least one of said zinc salts is a zinc amino acid chelate. ### Claim 30 (depends on 29) The method according to claim 29 wherein said zinc amino acid chelate is selected from the group consisting of mono- and bis-chelates of L- or D-amino acids. ### Claim 31 (depends on 29, 30) The method according to claim 29 or 30 wherein said amino acid chelate is a chelate of zinc with an amino acid selected from the group consisting L-cysteine, L-cystine, L-N-acetylcysteine, L-histidine, D-histidine, L-taurine, L-glycinate, L-aspartate and L-methionine. ### Claim 32 (depends on 23, 24) The method according to claim 23 or 24 wherein said zinc salt is zinc chloride and optionally, at least one additional zinc salt selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc gluconate, zinc picolinate, zinc sulfate and a zinc amino acid chelate. ### Claim 33 (depends on 23) The method according to claim 23 wherein said zinc salt is zinc chloride. ### Claim 34 (depends on 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33) The method according to any of claims 23-33 wherein said zinc salt or mixture of zinc salts 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. ### Claim 35 (depends on 34) The method according to claim 34 wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. ### Claim 36 (depends on 34) The method according to claim 34 wherein said H2 blocker is cimetidine, famotidine, nizatidine, ranitidine or mixtures thereof. ### Claim 37 (depends on 34) The method according to claim 34 wherein said cytoprotective agent is bismuth subsalicylate, sucralfate or mixtures thereof. ### Claim 38 (depends on 34) The method according to claim 34 wherein said mixture of agents is prevpac. ### Claim 39 (depends on 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38) The method according to any of claim 23-38 wherein said disease state or condition is GERD, NERD or ZE syndrome. ### Claim 40 (depends on 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38) The method according to any of claims 23-38 wherein said disease is ulcer disease and said zinc salt is further combined with at least one agent selected from the group consisting of an anti-H. pylori agent or helidac. ### Claim 41 A method of inhibiting vacuolar H+-ATPase, H+, K+-ATPase or both H+-ATPase and H+, K+-ATPase in the stomach of a patient comprising administering to said patient an effective amount of at least one pharmaceutically acceptable zinc salt. ### Claim 42 (depends on 41) The method according to claim 41 wherein a mixture of at least two zinc salts is administered to said patient. ### Claim 43 (depends on 41) The method according to claim 41 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 44 (depends on 42) The method according to claim 42 wherein said zinc salt is selected from at least two zinc salts selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 45 (depends on 41) The method according to claim 41 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate or mixtures thereof. ### Claim 46 (depends on 41) The method according to claim 41 wherein said zinc salt is selected from at least two zinc salts from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate. ### Claim 47 (depends on 41, 42, 43, 44, 45, 46) The method according to any of claims 41-46 wherein said zinc salt or at least one of said zinc salts is a zinc amino acid chelate. ### Claim 48 (depends on 47) The method according to claim 47 wherein said zinc amino acid chelate is selected from the group consisting of mono- and bis-chelates of L- or D-amino acids. ### Claim 49 (depends on 47, 48) The method according to claim 47 or 48 wherein said amino acid chelate is a chelate of zinc with an amino acid selected from the group consisting L-cysteine, L-cystine, L-N-acetylcysteine, L-histidine, D-histidine, L-taurine, L-glycinate, L-aspartate and L-methionine. ### Claim 50 (depends on 41, 42) The method according to claim 41 or 42 wherein said zinc salt is zinc chloride and optionally, at least one additional zinc salt selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc gluconate, zinc picolinate, zinc sulfate and a zinc amino acid chelate. ### Claim 51 (depends on 41) The method according to claim 41 wherein said zinc salt is zinc chloride. ### Claim 52 (depends on 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51) The method according to any of claims 41-51 wherein said zinc salt or said mixture of zinc salts is coadministered with at least one proton pump inhibitor. ### Claim 53 (depends on 52) The method according to claim 52 wherein said proton pump inhibitor is selected from the group consisting of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. ### Claim 54 (depends on 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53) The method according to any of claims 41-53 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 of administering said zinc salt(s). ### Claim 55 (depends on 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) The method according to any of claims 41-54 wherein said patient does not respond effectively to proton pump inhibitor therapy. ### Claim 56 A pharmaceutical composition comprising an effective amount of at least one pharmaceutically acceptable zinc salt in combination with an effective amount of a proton pump inhibitor, an H2 blocker, an anti-H. pylori agent, a cytoprotective agent, or mixtures thereof, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient. ### Claim 57 (depends on 56) The composition according to claim 56 wherein said proton pump inhibitor is esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole or mixtures thereof. ### Claim 58 (depends on 56) The composition according to claim 56 wherein said H2 blocker is cimetidine, famotidine, nizatidine, ranitidine or mixtures thereof. ### Claim 59 (depends on 56) The composition according to claim 56 wherein said anti-H. pylori agent is selected from the group consisting of amoxicillin, clarithromycin (biaxin), metronidazole (flagyl), tetracycline and mixtures thereof. ### Claim 60 (depends on 56) The composition according to claim 56 wherein said cytoprotective agent is bismuth subsalicylate or sucralfate. ### Claim 61 A method of treating an H. pylori infection in a patient comprising administering to said patient an effective amount of at least one pharmaceutically acceptable zinc salt, optionally in combination with an anti-H. pylori agent. ### Claim 62 (depends on 61) The method according to claim 61 wherein a mixture of at least two zinc salts is administered to said patient. ### Claim 63 (depends on 61, 62) The method according to claim 61 or 62 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 64 (depends on 61, 62, 63) The method according to any of claims 61-63 wherein said zinc salt is selected from at least two zinc salts selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 65 (depends on 61, 62) The method according to claim 61 or 62 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate or mixtures thereof. ### Claim 66 (depends on 61, 62) The method according to claim 61 or 62 wherein said zinc salt is selected from at least two zinc salts from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, a zinc amino acid chelate. ### Claim 67 (depends on 61, 62, 63, 64, 65, 66) The method according to any of claims 61-66 wherein said zinc salt or at least one of said zinc salts is a zinc amino acid chelate. ### Claim 68 (depends on 67) The method according to claim 67 wherein said zinc amino acid chelate is selected from the group consisting of mono- and bis-chelates of L- or D-amino acids. ### Claim 69 (depends on 67, 68) The method according to claim 67 or 68 wherein said amino acid chelate is a chelate of zinc with an amino acid selected from the group consisting L-cysteine, L-cystine, L-N-acetylcysteine, L-histidine, D-histidine, L-taurine, L-glycinate, L-aspartate and L-methionine. ### Claim 70 (depends on 67, 68) The method according to claim 67 or 68 wherein said zinc salt is zinc chloride and optionally, at least one additional zinc salt selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc gluconate, zinc picolinate, zinc sulfate and a zinc amino acid chelate. ### Claim 71 (depends on 61) The method according to claim 61 wherein said zinc salt is zinc chloride. ### Claim 72 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71) The method according to any of claims 61-71 wherein said zinc salt or mixture of zinc salts is coadministered with at least one anti-H. pylori agent. ### Claim 73 (depends on 72) The method according to claim 72 wherein said anti-H. pyroli agent is selected from the group consisting of amoxicillin, clarithromycin (biaxin), metronidazole (flagyl), tetracycline and mixtures thereof. ### Claim 74 Use of an effective amount of at least one pharmaceutically acceptable zinc salt in the manufacture of a medicament for increasing the pH of the gastric juices of the stomach of a patient. ### Claim 75 (depends on 74) The use according to claim 74 wherein said zinc salt is a mixture of at least two zinc salts. ### Claim 76 (depends on 74) The use according to claim 74 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc succinate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 77 Use of an effective amount of at least one pharmaceutically acceptable zinc salt in the manufacture of a medicament for treating a patient for a disease state or condition 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. ### Claim 78 (depends on 77) The use according to claim 77 wherein said zinc salt is a mixture of at least two zinc salts. ### Claim 79 (depends on 77) The use according to claim 77 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 80 Use of at least one pharmaceutically acceptable zinc salt, optionally in combination with an anti-H. pylori agent in the manufacture of a medicament for of treating an H. pylori infection in a patient. ### Claim 81 (depends on 80) The use according to claim 80 wherein said zinc salt is a mixture of at least two zinc salts. ### Claim 82 (depends on 80) The use according to claim 80 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc malate, zinc maleate, zinc picolinate, zinc salicylate, zinc stearate, zinc tartrate, zinc undecylenate, a zinc amino acid chelate and mixtures thereof. ### Claim 83 Use of at least one pharmaceutically acceptable zinc salt in the manufacture of a medicament for inhibiting vacuolar H+-ATPase, H+/K+-ATPase or both H+-ATPase and H+/K+-ATPase in the stomach of a patient. ### Claim 84 (depends on 83) The use according to claim 83 wherein said zinc salt is a mixture of at least two zinc salts. ### Claim 85 (depends on 83) The use according to claim 83 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc salicylate, zinc tartrate, zinc undenylate, a zinc amino acid chelate and mixtures thereof. ### Claim 86 A method of increasing the pH of the gastric juices of the stomach of a patient, said method comprising administering to said patient an effective amount of at least one pharmaceutically acceptable zinc salt selected from the group consisting of zinc acetate, zinc ascorbate, zinc benzoate, zinc bromide, zinc butyrate, zinc caprylate, zinc carbonate, zinc carnosine, zinc citrate, zinc chloride, zinc fluoride, zinc formate, zinc fumarate, zinc gallate, zinc gluconate, zinc glutarate, zinc glycerate, zinc glycerophosphate, zinc glycolate, zinc hydroxide, zinc iodide, zinc lactate, zinc malate, zinc maleate, zinc myristate, zinc nitrate, zinc oxide, zinc phenol sulfonate, zinc phosphate, zinc picolinate, zinc picrate, zinc propionate, zinc salicylate, zinc selenate, zinc succinate, zinc sulfate, zinc tartrate, zinc titanate, zinc undecylenate, zinc valerate, a zinc chelate and mixtures thereof. ### Claim 87 (depends on 86) The method according to claim 86 wherein a mixture of at least two zinc salts is administered to said patient. ### Claim 88 (depends on 86) The method according to claim 86 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc propionate, zinc salicylate, zinc malate, zinc maleate, zinc tartrate, zinc undecylunate, a zinc amino acid chelate and mixtures thereof. ### Claim 89 (depends on 87) The method according to claim 87 wherein said zinc salt is selected from at least two zinc salts selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc propionate, zinc salicylate, zinc malate, zinc maleate, zinc tartrate, zinc undecylunate, a zinc amino acid chelate and mixtures thereof. ### Claim 90 (depends on 88) The method according to claim 88 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, zinc succinate, zinc lactate, zinc malate, zinc propionate, zinc maleate, a zinc amino acid chelate or mixtures thereof. ### Claim 91 (depends on 89) The method according to claim 89 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc citrate, zinc chloride, zinc gluconate, zinc picolinate, zinc succinate, zinc lactate, zinc malate, zinc propionate, zinc maleate, a zinc amino acid chelate or mixtures thereof. ### Claim 92 A pharmaceutical composition comprising effective amounts at least one water soluble zinc salt in combination with at least one therapeutic agent which is favorably orally administered in combination with salt water soluble zinc salt, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient. ### Claim 93 (depends on 92) The composition according to claim 92 wherein said water soluble zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc benzoate, zinc bromide, zinc butyrate, zinc caprylate, zinc carbonate, zinc carnosine, zinc citrate, zinc chloride, zinc fluoride, zinc formate, zinc fumarate, zinc gallate, zinc gluconate, zinc glutarate, zinc glycerate, zinc glycerophosphate, zinc glycolate, zinc hydroxide, zinc iodide, zinc lactate, zinc malate, zinc maleate, zinc myristate, zinc nitrate, zinc oxide, zinc phosphate, zinc picolinate, zinc picrate, zinc propionate, zinc salicylate, zinc selenate, zinc succinate, zinc sulfate, zinc tartrate, zinc titanate, zinc undecylenate, zinc valerate, a zinc chelate and mixtures thereof. ### Claim 94 (depends on 92) The composition according to claim 92 wherein said at least one water soluble zinc salt comprises at least two water soluble zinc salts. ### Claim 95 (depends on 92) The composition according to claim 92 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc propionate, zinc salicylate, zinc succinate, zinc malate, zinc maleate, zinc tartrate, zinc undecylunate, a zinc amino acid chelate and mixtures thereof. ### Claim 96 (depends on 94) The composition according to claim 94 wherein said water soluble zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc benzoate, zinc bromide, zinc butyrate, zinc caprylate, zinc carbonate, zinc carnosine, zinc citrate, zinc chloride, zinc fluoride, zinc formate, zinc fumarate, zinc gallate, zinc gluconate, zinc glutarate, zinc glycerate, zinc glycerophosphate, zinc glycolate, zinc hydroxide, zinc iodide, zinc lactate, zinc malate, zinc maleate, zinc myristate, zinc nitrate, zinc oxide, zinc phenol sulfonate, zinc phosphate, zinc picolinate, zinc picrate, zinc propionate, zinc salicylate, zinc selenate, zinc succinate, zinc sulfate, zinc tartrate, zinc titanate, zinc undecylenate, zinc valerate, a zinc chelate and mixtures thereof. ### Claim 97 (depends on 94) The composition according to claim 94 wherein said zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc propionate, zinc salicylate, zinc succinate, zinc malate, zinc maleate, zinc tartrate, zinc undecylunate, a zinc amino acid chelate and mixtures thereof. ### Claim 98 (depends on 92) The composition according to claim 92 wherein said therapeutic agent is selected from the group consisting of 13-cis-Retinoic Acid; 2-Chlorodeoxyadenosine; 5-Azacitidine; 5-Fluorouracil; 6-Mercaptopurine; 6-Thioguanine; Abraxane; Isotretinoin; Actinomycin-D; Doxorubicin Hydrochloride; Anagrelide; Hydrocortisone; Aldesleukin; Alemtuzumab; Pemetrexed; Alitretinoin; Vinblastine; Melphalan; All-transretinoic Acid; AlphaInterferon; Altretamine; Amethopterin; Amifostine; Aminoglutethimide; Aminoglutethimide; Anagrelide; Asparaginase; Hydrocortone Phosphate; Leurocristine; Lenalidomide; Letrozole; Leucovorin; Leukeran; Sargramostim; Leuprolide; Cladribin; Liposomal Ara-C; Deltasone; Lomustine; L-phenylalanine mustard; L-Sarcolysin; Leuprolide Acetate; Procarbazine; Maxidex; Mechlorethamine; Mechlorethamine Hydrochloride; Methylprednisolone; Megestrol Acetate; Melphalan; Mercaptopurine; Mesna; Methotrexate; Nilutamide; Anastrozole; Arabinosylcytosine; Darbepoetin Alpha); Pamidronate; Exemestane); Nelarabine; Arsenic Trioxide; Atragen; Bevacizumab; Azacitidine; BCG (Bacillus Calmette Guerin); BCNU (Carmustine); Bexarotene; Tositumomab; Bicalutamide; Bleomycin; Bortezomib; Busulfan; Eribitux; Calcium Leucovorin; Alemtuzumab; Irinotecan hydrochloride; Camptothecin-11; Capecitabine; Carboplatin; Bicalutamide; CC-5013 (Revlimid); CCNU (lomustine); CDDP (Cisplatin); CeeNU; Daunorubicin; Cetuximab; Chlorambucil; Mitomycin; Mitomycin-C; Mitoxantrone; Mustine; Mitomycin; Hydroxyurea; Gemtuzumab Ozogamicin; Vinorelbine Tartrate; Nelarabine; Cyclophosphamide; Pegfilgrastim; Oprelvekin; Filgrastim; Sorafenib; Nilutamide); Pentostatin; Nitrogen Mustard; Genox; Mitoxantrone; Octreotide; Octreotide acetate; Pegylated asparaginase; Vincristine Sulfate); Denileukin Diftitox; Paclitaxel; Oprevelkin; Prednisolone Sodium Phosphate; Prednisone; Oxaliplatin; Paclitaxel; Paclitaxel Protein-bound; Pamidronate; Panitumumab; Paraplatin; Dactinomycin; Topotecan; Cyclophosphamide; Aminoglutethimide; Cytarabine; Cytarabine Liposomal; Dacarbazine; Dacogen; Dactinomycin; Dasatinib; Daunomycin; Daunorubicin; Daunorubicin Hydrochloride; Daunorubicin Liposomal; Decadron; Decitabine; Prednisolone; Prednisone; Denileukin diftitox; Cytarabine liposome; Dexamethasone; Dexamethasone acetate; Dexamethasone Sodium Phosphate; Dexasone; Dexrazoxane; Novantrone; Disseminated intravascular coagulation; Diodex; Docetaxel; Doxorubicin; Hydroxyurea; Dacarbazine; dacarbazine; PEG Interferon; Pegaspargase; Pegfilgrastim; Peginterferon alfa-2b; PEG-L-asparaginase; PEMETREXED; Pentostatin; Phenylalanine Mustard; Procarbazine; Epoetin Alfa; Aldesleukin; Prolifeprospan 20 with Carmustine; Implant; Mercaptopurine; Raloxifene; Lenalidomide; Trexall; Rituximab; (adriamycin); Rubidomycin hydrochloride; Octreotide Acetate; Sargramostim; Hydrocortisone Sodium Succinate; Methylprednisolone sodium succinate; Sorafenib; Dasatinib; Gleevec; Streptozocin; SU11248; Sunitinib; Sunitinib Malate; Tamoxifen; Erlotinib; Bexarotene; Paclitaxel; Epirubicin hydrochloride; Oxaliplatin; Estramustine; Epirubicin; Epoetin alfa; Cetuximab; Erlotinib; Erwinia L-asparaginase; Ethyol; Etoposide Phosphate; Etoposide; Flutamide; Raloxifene; Exemestane; Toremifene; Fulvestrant; Letrozole; Filgrastim; Floxuridine; Fludarabine; Fluoxymesterone; Flutamide; Folinic Acid; Floxuridine; Fulvestrant; Neupogen; Gefitinib; Gemcitabine; Gemtuzumab; ozogamicin; Gemcitabine); Carmustine Wafer; Goserelin; Granulocyte Colony Stimulating Factor; Docetaxel; Temozolomide; Teniposide; Thiotepa; Thalidomide; BCG (TheraCys strain); Thioguanine; Thiophosphamide; Thiotepa; Etoposide; Topotecan; Toremifene; Tositumomab; Trastuzumab; Tretinoin; Arsenic; VCR; Panitumumab; Vinblastine Sulfate Bortezomib; Azacitidine; Vinblastine; Vinblastine Sulfate; Vincristine; Vinorelbine; Vinorelbine tartrate; VM-26; Vorinostat; Teniposide; Capecitabine); Streptozocin; Fluoxymesterone; Trastuzumab; Hexadrol; Altretamin; Hexamethylmelamine; Hycamtin; Hydroxyurea; Ibritumomab; Ibritumomab Tiuxetan; Idarubicin; Idarubicin; Ifosfamide; IFN-alpha; IL-11; IL-2; Imatinib mesylate; Imidazole Carboxamide; Interferon alfa; Interferon Alfa-2b (PEG Conjugate); Interleukin-2; Interleukin-11; interferon alfa-2b; Getfitinib; Irinotecan; Isotretinoin; Dexrazoxane; Goserelin; Zoledronic acid; Zolinza and mixtures thereof. ### Claim 99 (depends on 92) The composition according to claim 92 wherein said therapeutic agent is a chemotherapeutic agent. ### Claim 100 (depends on 92) The composition according to claim 92 wherein said therapeutic agent is a non-steroidal antiinflammatory drug (NSAID). ### Claim 101 (depends on 92) The composition according to claim 92 wherein said therapeutic agent is an immunosuppressive agent. ### Claim 102 (depends on 92) The composition according to claim 92 wherein said therapeutic agent is an anti-asthma agent. ### Claim 103 (depends on 92) The composition according to claim 92 wherein said therapeutic agent is a statin. ### Claim 104 A method of increasing the bioavailability and/or reducing or alleviating the side effects of an orally administered therapeutic compound comprising coadministering with an effective amount of said compound an amount of at least one water soluble zinc salt effective to enhance the bioavailability and/or reduce or alleviate the side effects of said therapeutic compound. ### Claim 105 (depends on 104) The method according to claim 104 wherein said water soluble zinc salt is selected from the group consisting of zinc acetate, zinc ascorbate, zinc benzoate, zinc bromide, zinc butyrate, zinc caprylate, zinc carbonate, zinc carnosine, zinc citrate, zinc chloride, zinc fluoride, zinc formate, zinc fumarate, zinc gallate, zinc gluconate, zinc glutarate, zinc glycerate, zinc glycerophosphate, zinc glycolate, zinc hydroxide, zinc iodide, zinc lactate, zinc malate, zinc maleate, zinc myristate, zinc nitrate, zinc oxide, zinc phosphate, zinc picolinate, zinc picrate, zinc propionate, zinc salicylate, zinc selenate, zinc succinate, zinc sulfate, zinc tartrate, zinc titanate, zinc undecylenate, zinc valerate, a zinc chelate and mixtures thereof. ### Claim 106 (depends on 104) The method according to claim 104 wherein said at least one water soluble zinc salt comprises at least two water soluble zinc salts. ### Claim 107 (depends on 106) The method according to claim 106 wherein said zinc salts are selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc propionate, zinc salicylate, zinc succinate, zinc malate, zinc maleate, zinc tartrate, zinc undecylunate, a zinc amino acid chelate and mixtures thereof. ### Claim 108 (depends on 106) The method according to claim 106 wherein said water soluble zinc salts are selected from the group consisting of zinc acetate, zinc ascorbate, zinc benzoate, zinc bromide, zinc butyrate, zinc caprylate, zinc carbonate, zinc carnosine, zinc citrate, zinc chloride, zinc fluoride, zinc formate, zinc fumarate, zinc gallate, zinc gluconate, zinc glutarate, zinc glycerate, zinc glycerophosphate, zinc glycolate, zinc hydroxide, zinc iodide, zinc lactate, zinc malate, zinc maleate, zinc myristate, zinc nitrate, zinc oxide, zinc phenol sulfonate, zinc phosphate, zinc picolinate, zinc picrate, zinc propionate, zinc salicylate, zinc selenate, zinc succinate, zinc sulfate, zinc tartrate, zinc titanate, zinc undecylenate, zinc valerate, a zinc chelate and mixtures thereof. ### Claim 109 (depends on 108) The method according to claim 108 wherein said zinc salts are selected from the group consisting of zinc acetate, zinc ascorbate, zinc butryate, zinc carbonate, zinc citrate, zinc chloride, zinc iodide, zinc sulfate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc picolinate, zinc propionate, zinc salicylate, zinc succinate, zinc malate, zinc maleate, zinc tartrate, zinc undecylunate, a zinc amino acid chelate and mixtures thereof. ### Claim 110 (depends on 104) The method according to claim 104 wherein said therapeutic agent is selected from the group consisting of 13-cis-Retinoic Acid; 2-Chlorodeoxyadenosine; 5-Azacitidine; 5-Fluorouracil; 6-Mercaptopurine; 6-Thioguanine; Abraxane; Isotretinoin; Actinomycin-D; Doxorubicin Hydrochloride; Anagrelide; Hydrocortisone; Aldesleukin; Alemtuzumab; Pemetrexed; Alitretinoin; Vinblastine; Melphalan; All-transretinoic Acid; Alphalnterferon; Altretamine; Amethopterin; Amifostine; Aminoglutethimide; Aminoglutethimide; Anagrelide; Asparaginase; Hydrocortone Phosphate; Leurocristine; Lenalidomide; Letrozole; Leucovorin; Leukeran; Sargramostim; Leuprolide; Cladribin; Liposomal Ara-C; Deltasone; Lomustine; L-phenylalanine mustard; L-Sarcolysin; Leuprolide Acetate; Procarbazine; Maxidex; Mechlorethamine; Mechlorethamine Hydrochloride; Methylprednisolone; Megestrol Acetate; Melphalan; Mercaptopurine; Mesna; Methotrexate; Nilutamide; Anastrozole; Arabinosylcytosine; Darbepoetin Alpha); Pamidronate; Exemestane); Nelarabine; Arsenic Trioxide; Atragen; Bevacizumab; Azacitidine; BCG (Bacillus Calmette Guerin); BCNU (Carmustine); Bexarotene; Tositumomab; Bicalutamide; Bleomycin; Bortezomib; Busulfan; Eribitux; Calcium Leucovorin; Alemtuzumab; Irinotecan hydrochloride; Camptothecin-11; Capecitabine; Carboplatin; Bicalutamide; CC-5013 (Revlimid); CCNU (lomustine); CDDP (Cisplatin); CeeNU; Daunorubicin; Cetuximab; Chlorambucil; Mitomycin; Mitomycin-C; Mitoxantrone; Mustine; Mitomycin; Hydroxyurea; Gemtuzumab Ozogamicin; Vinorelbine Tartrate; Nelarabine; Cyclophosphamide; Pegfilgrastim; Oprelvekin; Filgrastim; Sorafenib; Nilutamide); Pentostatin; Nitrogen Mustard; Genox; Mitoxantrone; Octreotide; Octreotide acetate; Pegylated asparaginase; Vincristine Sulfate); Denileukin Diftitox; Paclitaxel; Oprevelkin; Prednisolone Sodium Phosphate; Prednisone; Oxaliplatin; Paclitaxel; Paclitaxel Protein-bound; Pamidronate; Panitumumab; Paraplatin; Dactinomycin; Topotecan; Cyclophosphamide; Aminoglutethimide; Cytarabine; Cytarabine Liposomal; Dacarbazine; Dacogen; Dactinomycin; Dasatinib; Daunomycin; Daunorubicin; Daunorubicin Hydrochloride; Daunorubicin Liposomal; Decadron; Decitabine; Prednisolone; Prednisone; Denileukin diftitox; Cytarabine liposome; Dexamethasone; Dexamethasone acetate; Dexamethasone Sodium Phosphate; Dexasone; Dexrazoxane; Novantrone; Disseminated intravascular coagulation; Diodex; Docetaxel; Doxorubicin; Hydroxyurea; Dacarbazine; dacarbazine; PEG Interferon; Pegaspargase; Pegfilgrastim; Peginterferon alfa-2b; PEG-L-asparaginase; PEMETREXED; Pentostatin; Phenylalanine Mustard; Procarbazine; Epoetin Alfa; Aldesleukin; Prolifeprospan 20 with Carmustine; Implant; Mercaptopurine; Raloxifene; Lenalidomide; Trexall; Rituximab; (adriamycin); Rubidomycin hydrochloride; Octreotide Acetate; Sargramostim; Hydrocortisone Sodium Succinate; Methylprednisolone sodium succinate; Sorafenib; Dasatinib; Gleevec; Streptozocin; SU11248; Sunitinib; Sunitinib Malate; Tamoxifen; Erlotinib; Bexarotene; Paclitaxel; Epirubicin hydrochloride; Oxaliplatin; Estramustine; Epirubicin; Epoetin alfa; Cetuximab; Erlotinib; Erwinia L-asparaginase; Ethyol; Etoposide Phosphate; Etoposide; Flutamide; Raloxifene; Exemestane; Toremifene; Fulvestrant; Letrozole; Filgrastim; Floxuridine; Fludarabine; Fluoxymesterone; Flutamide; Folinic Acid; Floxuridine; Fulvestrant; Neupogen; Gefitinib; Gemcitabine; Gemtuzumab; ozogamicin; Gemcitabine); Carmustine Wafer; Goserelin; Granulocyte Colony Stimulating Factor; Docetaxel; Temozolomide; Teniposide; Thiotepa; Thalidomide; BCG (TheraCys strain); Thioguanine; Thiophosphamide; Thiotepa; Etoposide; Topotecan; Toremifene; Tositumomab; Trastuzumab; Tretinoin; Arsenic; VCR; Panitumumab; Vinblastine Sulfate Bortezomib; Azacitidine; Vinblastine; Vinblastine Sulfate; Vincristine; Vinorelbine; Vinorelbine tartrate; VM-26; Vorinostat; Teniposide; Capecitabine); Streptozocin; Fluoxymesterone; Trastuzumab; Hexadrol; Altretamin; Hexamethylmelamine; Hycamtin; Hydroxyurea; Ibritumomab; Ibritumomab Tiuxetan; Idarubicin; Idarubicin; Ifosfamide; IFN-alpha; IL-11; IL-2; Imatinib mesylate; Imidazole Carboxamide; Interferon alfa; Interferon Alfa-2b (PEG Conjugate); Interleukin-2; Interleukin-11; interferon alfa-2b; Getfitinib; Irinotecan; Isotretinoin; Dexrazoxane; Goserelin; Zoledronic acid; Zolinza and mixtures thereof. ### Claim 110 (depends on 104) The method according to claim 104 wherein said therapeutic agent is a chemotherapeutic agent. ### Claim 111 (depends on 104) The method according to claim 104 wherein said therapeutic agent is a non-steroidal antiinflammatory drug (NSAID). ### Claim 112 (depends on 104) The method according to claim 104 wherein said therapeutic agent is an immunosuppressive agent. ### Claim 113 (depends on 104) The method according to claim 104 wherein said therapeutic agent is an anti-asthma agent. ### Claim 114 (depends on 104) The method according to claim 104 wherein said therapeutic agent is a statin.