Claims for Patent: 8,980,325

Summary for Patent: 8,980,325

Title:	Compositions and methods for treating digestive disorders
Abstract:	Provided are electrokinetically-altered fluids (e.g., gas-enriched (e.g., oxygen-enriched) electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide, upon contact with a cell, modulation of at least one of cellular membrane potential and cellular membrane conductivity, and therapeutic compositions and methods for using same in treating digestive disorders or at least one symptom thereof. The electrokinetically-altered fluid compositions and methods include electrokinetically-altered ioinic aqueous fluids optionally in combination with other therapeutic agents. Particular aspects provide for regulating or modulating intracellular signal transduction associated with said digestive disorders by modulation of at least one of cellular membranes, membrane potential, membrane proteins such as membrane receptors, including but not limited to G-Protein Coupled Receptors (GPCR), and intercellular junctions (e.g., tight junctions, gap junctions, zona adherins and desmasomes). Other embodiments include particular routes of administration or formulations for the electrokinetically-altered fluids and therapeutic compositions.
Inventor(s):	Watson; Richard L. (McPherson, KS), Wood; Anthony B. (Dallas, TX), Archambeau; Gregory J. (Puyallap, WA)
Assignee:	Revalesio Corporation (Tacoma, WA)
Application Number:	12/432,571
Patent Claims:	1. A method for treating a digestive disorder or digestive disease, or at least one symptom thereof, comprising administering to a subject in need thereof a therapeutically effective amount of an electrokinetically-altered aqueous fluid comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanobubbles having an average diameter of less than 100 nanometers and stably configured in the ionic aqueous fluid in an amount to provide for treating a digestive disorder or digestive disease, or at least one symptom thereof, wherein a method for treating a digestive disorder or digestive disease, or at least one symptom thereof is thereby afforded, and wherein the digestive disorder or digestive disease, or at least one symptom thereof is at least one selected from the group consisting of acid reflux including heartburn, gastroesophageal reflux disease (GERD), and eosinophilic esophagitis. 2. The method of claim 1, wherein the charge-stabilized oxygen-containing nanaobubbles are the major charge-stabilized gas-containing nanostructure species in the fluid. 3. The method of claim 1, wherein the percentage of dissolved oxygen molecules present in the fluid as the charge-stabilized oxygen-containing nanobubbles is a percentage greater than 0.01%. 4. The method of claim 1, wherein the total dissolved oxygen is substantially present in the charge-stabilized oxygen-containing nanobubbles. 5. The method of claim 1, wherein the charge-stabilized oxygen-containing nanobubbles have an average diameter of less than 90 nm. 6. The method of claim 1, wherein the ionic aqueous solution comprises a saline solution. 7. The method of claim 1, wherein the fluid is superoxygenated. 8. The method of claim 1, wherein the fluid comprises a form of solvated electrons. 9. The method of claim 1, wherein alteration of the electrokinetically altered aqueous fluid comprises exposure of the fluid to hydrodynamically-induced, localized electrokinetic effects. 10. The method of claim 9, wherein, exposure to the localized electrokinetic effects comprises exposure to at least one of voltage pulses and current pulses. 11. The method of claim 9, wherein the exposure of the fluid to hydrodynamically-induced, localized electrokinetic effects, comprises exposure of the fluid to electrokinetic effect-inducing structural features of a device used to generate the fluid. 12. The method of claim 1, wherein the digestive disorder or disease, or the at least one symptom thereof comprises at least one selected from the group consisting of acid reflux including gastroesophageal reflux disease (GERD), and eosinophilic esophagitis. 13. The method of claim 1, wherein the digestive disorder or disease, or the at least one symptom thereof comprises at least one of acid reflux including gastroesophageal reflux disease (GERD) and eosinophilic esophagitis. 14. The method of claim 1, further comprising combination therapy, wherein at least one additional therapeutic agent is administered to the patient. 15. The method of claim 14, wherein the at least one additional therapeutic agent is selected from the group consisting proton pump inhibitors, including omeprazole, pantoprazole, lansoprazole, esomeprazole, tenatoprazole, and rabeprazole; histamine H2 receptor blockers, including ranitidine, famotidine, cimetidine, and nizatidine; antacids, including aluminum hydroxide, magnesium hydroxide, aluminum carbonate, magnesium carbonate, calcium carbonate, sodium bicarbonate, hydrotalcite, and magaldrate-simethicone; prokinetics, including itopride, domperidone, metoclopramide, erythromycin, prucalopride, and cisapride; antidiarrheal agents, including bismuth subsalicyte, loperamide, and diphenocylate; corticosteroids, including hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methyprednisolone, and prednisone; antispasmodics including dicyclomine, atropine, atropine methonitrate, mebeverine, scopolamine, and pirenzepine; immunomodulators including azathioprine, mercaptopurine, and methotrexate; antibiotics, including amoxicillin (penicillins), clarithromycin, levofloxacin, metronidazole; biologics including infliximab, etanercept, adalimumab, certolizumab, and natalizumab; anti-inflammatory agents, including 4-Aminosalicylic acid and 5-Aminosalicylic acid; laxatives including lubiprostone and tegaserod; alginic acid; sucralfate; misoprostol; and mosapride and combinations thereof. 16. The method of claim 14, wherein the at least one additional therapeutic agent is selected from the group consisting of proton pump inhibitors, histamine H2 receptor blockers, antacids, prokinetics, anticholinergics, corticosteroids (inhaled or otherwise), systemic corticosteroids, glucocorticoids, antispasmodics, immunomodulators, antibiotics, biologics, anti-inflammatory agents, laxatives, and combinations thereof. 17. The method of claim 14, wherein the at least one additional therapeutic agent is selected from the group consisting of albuterol, budesonide, esomeprazole (Nexium) and omeprazole (Prilosec), and active derivatives thereof. 18. The method of claim 14, wherein the at least one additional therapeutic agent is selected from the group consisting of TSLP antagonists, TSLPR antagonists and combinations thereof. 19. The method of claim 18, wherein the antagonist is selected from the group consisting of neutralizing antibodies specific for TSLP or the TSLP receptor, soluble TSLP receptor molecules, TSLP receptor fusion proteins, TSLPR-immunoglobulin Fc molecules and combinations thereof. 20. The method of claim 1, wherein the electrokinetically-altered aqueous fluid modulates localized or cellular levels of nitric oxide. 21. The method of claim 1, wherein the electrokinetically-altered aqueous fluid promotes a localized decrease at the site of administration of at least one cytokine selected from the group consisting of: IL-1beta, IL-8, TNF-alpha, and TNF-beta. 22. The method of claim 1, further comprising a synergistic or non-synergistic inhibition or reduction in inflammation by simultaneously or adjunctively treating the subject with another anti-inflammatory agent. 23. The method of claim 1, wherein the charge-stabilized oxygen-containing nanobubbles are stably configured in the ionic aqueous fluid in an amount sufficient to provide, upon contact of a living cell by the fluid, modulation of at least one of cellular membrane potential and cellular membrane conductivity. 24. The method of claim 23, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of cellular membrane structure or function by altering of a conformation, ligand binding activity, or a catalytic activity of a membrane associated protein or component. 25. The method of claim 24, wherein the membrane associated protein comprises at least one selected from the group consisting of receptors, transmembrane receptors, ion channel proteins, intracellular attachment proteins, cellular adhesion proteins, and integrins. 26. The method of claim 25, wherein the transmembrane receptor comprises a G-Protein Coupled Receptor (GPCR). 27. The method of claim 26, wherein the G-Protein Coupled Receptor (GPCR) interacts with a G protein .alpha. subunit. 28. The method of claim 27, wherein the G protein .alpha. subunit comprises at least one selected from the group consisting of G.alpha..sub.s, G.alpha..sub.i, G.alpha..sub.q, and G.alpha..sub.12. 29. The method of claim 28, wherein the at least one G protein .alpha. subunit is G.alpha..sub.q. 30. The method of claim 23, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of intracellular signal transduction comprising modulation of a calcium dependent cellular messaging pathway or system. 31. The method of claim 30, wherein modulation of intracellular signal transduction comprises modulation of phospholipase C activity. 32. The method of claim 30, wherein modulation of intracellular signal transduction comprises modulation of adenylate cyclase (AC) activity. 33. The method of claim 23, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of intracellular signal transduction. 34. The method of claim 23, wherein modulating whole-cell conductance, comprises modulating at least one of a linear or non-linear voltage-dependent contribution of the whole-cell conductance. 35. The method of claim 1, comprising administration to a cell network or layer, and further comprising modulation of an intercellular junction therein. 36. The method of claim 35, wherein the intracellular junction comprises at least one selected from the group consisting of tight junctions, gap junctions, zona adherins and desmasomes. 37. The method of claim 35, wherein the cell network or layers comprises at least one selected from the group consisting of esophageal epithelium, gastric epithelium, large intestinal epithelium including epithelium of the cecum and colon regions thereof, small intestinal epithelium, including the epithelium or the duodenum, jejunum, and ileum regions thereof. 38. The method of claim 1, wherein the electrokinetically altered aqueous fluid is oxygenated, and wherein the oxygen in the fluid is present in an amount of at least 8 ppm oxygen at atmospheric pressure. 39. The method of claim 1, wherein the electrokinetically altered aqueous fluid comprises at least one of a form of solvated electrons, and electrokinetically modified or charged oxygen species. 40. The method of claim 39, wherein the form of solvated electrons or electrokinetically modified or charged oxygen species are present in an amount of at least 0.01 ppm. 41. The method of claim 39, wherein the electrokinetically altered oxygenated aqueous fluid comprises solvated electrons stabilized by molecular oxygen. 42. The method of claim 1, wherein administration is by oral, sublingual, buccal, parenteral, rectal, topical, or injection route. 43. The method of claim 42, wherein the administration route is by transdermal, intravaginal, intraoccular, intraotical, intranasal, inhalation, injection or insertion of implantable devices or materials. 44. The method of claim 42, wherein the injection route is subcutaneous, intramuscular, intra-arterial, intraperitoneally, intracisternally, intravesically, intrathecally, or intravenous. 45. The method of claim 1, wherein the electrokinetically-altered aqueous fluid comprises oxygen-enriched water.

Details for Patent 8,980,325

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2039-02-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2039-02-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2039-02-26
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2039-02-26
Immunex Corporation	ENBREL	etanercept	Injection	103795	02/01/2007		2039-02-26
Immunex Corporation	ENBREL MINI	etanercept	Injection	103795	09/14/2017		2039-02-26
Immunex Corporation	ENBREL	etanercept	Injection	103795			2039-02-26