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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0467821 (2014-08-25) |
등록번호 | US-9011922 (2015-04-21) |
발명자 / 주소 |
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출원인 / 주소 |
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대리인 / 주소 |
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인용정보 | 피인용 횟수 : 0 인용 특허 : 334 |
Provided are electrokinetically-altered fluids (gas-enriched electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide modulation of at least one of cellular membrane potential and cellular membrane conductivi
Provided are electrokinetically-altered fluids (gas-enriched electrokinetic fluids) comprising an ionic aqueous solution of charge-stabilized oxygen-containing nanostructures in an amount sufficient to provide modulation of at least one of cellular membrane potential and cellular membrane conductivity, and therapeutic compositions and methods for use in treating diabetes and diabetes-associated conditions or disorders (e.g., insulin resistance), or symptoms thereof. Provided are electrokinetically-altered ionic aqueous fluids optionally in combination with other therapeutic agents. Particular aspects provide for regulating or modulating intracellular signal transduction associated with said responses 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 (e.g., electrokinetically-altered gas-enriched fluids and solutions) and therapeutic compositions.
1. A method for treating diabetes or a diabetes-associated condition or disorder, or symptoms thereof, comprising administering to a subject in need thereof a therapeutically effective amount of an ionic aqueous solution of charge-stabilized oxygen-containing nanobubbles having an average diameter o
1. A method for treating diabetes or a diabetes-associated condition or disorder, or symptoms thereof, comprising administering to a subject in need thereof a therapeutically effective amount of an ionic aqueous solution of charge-stabilized oxygen-containing nanobubbles having an average diameter of less than 100 nanometers persisting in the ionic aqueous solution in an amount sufficient for treating diabetes or a diabetes-associated condition or disorder, or at least one symptom thereof. 2. The method of claim 1, wherein the charge-stabilized oxygen-containing nanostructures 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 nanostructures is a percentage selected from the group consisting of greater than: 0.01%, 0.1%, 1%, 5%; 10%; 15%; 20%; 25%; 30%; 35%; 40%; 45%; 50%; 55%; 60%; 65%; 70%; 75%; 80%; 85%; 90%; and 95%. 4. The method of claim 1, wherein the percentage of dissolved oxygen molecules present in the fluid as the charge-stabilized oxygen gas-containing nanostructures is a percentage greater than 50%. 5. The method of claim 1, wherein the charge-stabilized oxygen-containing nanostructures have an average diameter of less than a size selected from the group consisting of: 90 nm; 80 nm; 70 nm; 60 nm; 50 nm; 40 nm; 30 nm; 20 nm; 10 nm; and less than 5 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 diabetes-associated condition or disorder comprises at least one selected from the group consisting of: diabetes; insulin-dependent diabetes mellitus or IDDM (Type 1); non-insulin dependent diabetes mellitus or NIDDM (Type 2); insulin resistance; and diabetic retinopathy. 13. The method of claim 12, wherein the diabetes-associated condition or disorder comprises at least one of diabetes and insulin resistance. 14. The method of claim 13, wherein the diabetes-associated condition or disorder comprises diabetes. 15. The method of claim 1, wherein the at least one symptom of the diabetes-associated condition or disorder is related to at least one condition selected from the group consisting of: chronic inflammation, acute inflammation, insulin resistance. 16. The method of claim 1, wherein the electrokinetically altered aqueous fluid modulates localized or cellular levels of nitric oxide. 17. 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. 18. 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. 19. The method of claim 18, wherein said other anti-inflammatory agent comprises a steroid or glucocorticoid steroid. 20. The method of claim 19, wherein the glucocorticoid steroid comprises Budesonide or an active derivative thereof. 21. The method of claim 1, further comprising combination therapy, wherein at least one additional therapeutic agent is administered to the patient. 22. The method of claim 21, wherein the at least one additional therapeutic agent is selected from the group consisting of: Biguanides including metformin, buformin, and phenformin, insulin, alpha-glucosidase inhibitors, biguanides, DPP-4 inhibitors, meglitinides, sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors including, acarbose and miglitol, DPP-4 inhibitors including vildagliptin, sitagliptin, saxagliptin, linagliptin, and alogliptin, sulfonylureas including acetohexamide, chlorpropamide, tolbutamide, tolazamide, glipizide, gliclazide, glibenclamide (glyburide), gliquidone, glyclopyramide, and glimepiride, meglitinides including nateglinide, mitiglinide, and repaglinide. thiazolidinediones including troglitazone, pioglitazone, and rosiglitazone, inhibitors of MMPs including inhibitor of MMP-9 and MMP-2, short-acting β2-agonists, long-acting β2-agonists, anticholinergics, corticosteroids, systemic corticosteroids, mast cell stabilizers, leukotriene modifiers, methylxanthines, β2-agonists, albuterol, levalbuterol, pirbuterol, artformoterol, formoterol, salmeterol, anticholinergics including ipratropium and tiotropium; corticosteroids including beclomethasone, budesonide, flunisolide, fluticasone, mometasone, triamcinolone, methyprednisolone, prednisolone, prednisone; leukotriene modifiers including montelukast, zafirlukast, and zileuton; mast cell stabilizers including cromolyn and nedocromil; methylxanthines including theophylline; combination drugs including ipratropium and albuterol, fluticasone and salmeterol, budesonide and formoterol; antihistamines including hydroxyzine, diphenhydramine, loratadine, cetirizine, and hydrocortisone; immune system modulating drugs including tacrolimus and pimecrolimus; cyclosporine; azathioprine; mycophenolatemofetil; and combinations thereof. 23. The method of claim 21, wherein the at least one additional therapeutic agent is a thymic stromal lymphopoietin (TSLP) and/or thymic, stromal lymphopoietin receptor (TSLPR) antagonist. 24. The method of claim 23, wherein the TSLP and/or TSLPR antagonist is selected from the group consisting of neutralizing antibodies specific for TSLP and the TSLP receptor, soluble TSLP receptor molecules, and TSLP receptor fusion proteins, including TSLPR-immunoglobulin Fc molecules or polypeptides that encode components of more than one receptor chain. 25. The method of claim 1, wherein treating comprises altering at least one of cellular membrane structure or function comprising altering at least one of a conformation, ligand binding activity, or a catalytic activity of a membrane associated protein. 26. The method of claim 25, 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. 27. The method of claim 26, wherein the transmembrane receptor comprises a G-Protein Coupled Receptor (GPCR). 28. The method of claim 27, wherein the G-Protein Coupled Receptor (GPCR) interacts with a G protein α subunit. 29. The method of claim 28, wherein the G protein α subunit comprises at least one selected from the group consisting of Gαs, Gαi, Gαq, and Gα12. 30. The method of claim 29, wherein the at least one G protein α subunit is Gαq. 31. The method of claim 1, wherein the charge-stabilized oxygen-containing nanostructures are 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. 32. The method of claim 31, wherein modulating cellular membrane conductivity, comprises modulating whole-cell conductance. 33. The method of claim 32, wherein modulating whole-cell conductance, comprises modulating at least one voltage-dependent contribution of the whole-cell conductance. 34. The method of claim 31, comprising modulation of a calcium dependent cellular messaging pathway or system. 35. The method of claim 31, comprising modulation of phospholipase C activity. 36. The method of claim 31, comprising modulation of adenylate cyclase (AC) activity. 37. The method of claim 31, comprising modulation of intracellular signal transduction associated with at least one condition or symptom selected from the group consisting of: chronic inflammation, acute inflammation, insulin resistance. 38. The method of claim 1, comprising administration to a cell network or layer, and further comprising modulation of an intercellular junction therein. 39. The method of claim 38, wherein the intracellular junction comprises at least one selected from the group consisting of tight junctions, gap junctions, zona adherins and desmasomes. 40. The method of claim 38, wherein the cell network or layers comprises at least one selected from the group consisting of endothelial cells, endothelial-astrocyte tight junctions in CNS vessels, blood-cerebrospinal fluid tight junctions or barrier, pulmonary epithelium-type junctions, bronchial epithelium-type junctions, and intestinal epithelium-type junctions. 41. 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 selected from the group consisting of at least 8 ppm, at least 15, ppm, at least 25 ppm, at least 30 ppm, at least 40 ppm, at least 50 ppm, and at least 60 ppm oxygen at atmospheric pressure. 42. 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. 43. The method of claim 42, wherein the solvated electrons or electrokinetically modified or charged oxygen species are present in an amount selected from the group consisting of at least 0.01 ppm, at least 0.1 ppm, at least 0.5 ppm, at least 1 ppm, at least 3 ppm, at least 5 ppm, at least 7 ppm, at least 10 ppm, at least 15 ppm, and at least 20 ppm. 44. The method of claim 43, wherein the electrokinetically altered oxygenated aqueous fluid comprises solvated electrons stabilized, at least in part, by molecular oxygen. 45. The method of claim 1, wherein the ability to alter cellular membrane structure or function sufficient to provide for modulation of intracellular signal transduction persists for a time period selected from the group consisting of at least two, at least three, at least four, at least five, at least 6, and at least 12 months in a closed gas-tight container at atmospheric pressure. 46. The method of claim 1, wherein the amount of oxygen present in charge-stabilized oxygen-containing nanostructures of the electrokinetically-altered fluid is selected from the group consisting at least 8 ppm, at least 15, ppm, at least 20 ppm, at least 25 ppm, at least 30 ppm, at least 40 ppm, at least 50 ppm, and at least 60 ppm oxygen at atmospheric pressure. 47. The method of claim 1, wherein treating comprises administration by at least one of topical, inhalation, intranasal, oral and intravenous routes. 48. The method of claim 25, wherein the membrane associated protein comprises CCR3. 49. The method of claim 1, wherein treating comprises modulation of intracellular NF-κB expression and/or activity.
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