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Kafe 바로가기국가/구분 | United States(US) Patent 등록 |
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국제특허분류(IPC7판) |
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출원번호 | US-0144227 (2013-12-30) |
등록번호 | US-9402803 (2016-08-02) |
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 (e.g., 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 cond
Provided are electrokinetically-altered fluids (e.g., 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 a wound to a surface tissue or a symptom thereof. The electrokinetically-altered fluids or therapeutic 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 inflammatory 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 a wound to a surface tissue or a symptom thereof, comprising administering to a subject in need thereof a therapeutically effective amount of an oxygenated ionic aqueous solution of charge-stabilized oxygen nanobubbles having an average diameter of less than 100 nanometers s
1. A method for treating a wound to a surface tissue or a symptom thereof, comprising administering to a subject in need thereof a therapeutically effective amount of an oxygenated ionic aqueous solution of charge-stabilized oxygen nanobubbles having an average diameter of less than 100 nanometers sufficient to promote treating a wound to a surface tissue or a symptom thereof. 2. The method of claim 1, wherein the charge-stabilized oxygen nanobubbles are stably configured in the ionic aqueous solution in an amount sufficient to provide, upon contact of a living cell by the solution, modulation of at least one of cellular membrane potential and cellular membrane conductivity. 3. The method of claim 1, wherein treating the wound comprises treating to decrease scarring in the wound to the surface tissue, wherein scarring is reduced. 4. The method of claim 3, wherein the oxygenated ionic aqueous solution further increases the level of chemokines at the wound. 5. The method of claim 1, wherein treating the wound comprises treating to increase or decrease nitric oxide production or degradation in the wound to the surface tissue, wherein an increased or decreased level of nitric oxide is afforded. 6. The method of claim 1, wherein the oxygenated ionic aqueous solution is contacted to the wound by means of a wound dressing. 7. The method of claim 1, wherein the oxygenated ionic aqueous solution accelerates epidermal or dermal layering. 8. The method of claim 1, wherein the oxygenated ionic aqueous solution increases cellular migration of at least one type of cell to the wound. 9. The method of claim 8, wherein the type of cellular migration or proliferation comprises at least one cell selected from the group consisting of: keratinocytes, fibroblasts, epidermal cells, dermal cells, epithelial cells, mast cells, neutrophils, lymphocytes, and macrophages. 10. The method of claim 1, wherein the oxygenated ionic aqueous solution accelerates neoangiogenesis of blood vessels or lymphatic vessels. 11. The method of claim 1, wherein the oxygenated ionic aqueous solution increases collagen deposition at the wound. 12. The method of claim 1, wherein the oxygenated ionic aqueous solution reduces growth of at least one microbe in the wound. 13. The method of claim 12, wherein the microbe comprises Pseudomonas. 14. The method of claim 1, wherein the charge-stabilized oxygen nanobubbles are the major charge-stabilized gas-containing nanobubble species in the fluid. 15. The method of claim 1, wherein the percentage of dissolved oxygen molecules present in the oxygenated ionic aqueous solution as the charge-stabilized oxygen nanobubbles 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%. 16. The method of claim 1, wherein the total dissolved oxygen is substantially present in the charge-stabilized oxygen nanobubbles. 17. The method of claim 1, wherein the charge-stabilized oxygen nanobubbles 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. 18. The method of claim 1, wherein the oxygenated ionic aqueous solution comprises a saline solution. 19. The method of claim 1, wherein the oxygenated ionic aqueous solution is superoxygenated. 20. The method of claim 1, wherein the oxygenated ionic aqueous solution comprises a form of solvated electrons. 21. The method of claim 1, wherein the wound to a surface tissue or the symptom thereof comprises at least one wound type selected from the group consisting of lacerations, abrasions, rupture, puncture wounds, chemical, thermal, or radiation-induced burns, cuts, scrapes, incisions, blisters, diabetic ulcers, bedsores or pressure ulcers, skin grafts, and surgical wounds. 22. The method of claim 21, wherein the wound to a surface tissue or the symptom thereof comprises at least one of diabetic ulcers, bedsores or pressure ulcers, skin grafts, and surgical wounds. 23. The method of claim 22, wherein the wound to a surface tissue or the symptom thereof comprises diabetic ulcers, and bedsores or pressure ulcers. 24. The method of claim 1, wherein the symptom is related to at least one condition selected from the group consisting of epidmeral or dermal layering, cellular migration, collagen deposition at the wound, neoangiogenesis at the wound, elastin deposition at the wound, inflammation at the wound, expression of proteoglycans or glycosaminoglycans, cellular proliferation, and hyaluronic acid concentration at the wound. 25. The method of claim 1, wherein the oxygenated ionic aqueous solution modulates localized or cellular levels of nitric oxide. 26. The method of claim 1, wherein the oxygenated ionic aqueous solution 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. 27. 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. 28. The method of claim 27, wherein said other anti-inflammatory agent comprises a steroid or glucocorticoid steroid. 29. The method of claim 28, wherein said steroid comprises a glucocorticoid steroid. 30. The method of claim 1, further comprising combination therapy, wherein at least one additional therapeutic agent is administered to the patient. 31. The method of claim 30, wherein the one additional therapeutic agent is selected from the group consisting of anti-microbial agents, antifungal agents, and antibiotic agents. 32. The method of claim 30, wherein, the at least one additional therapeutic agent is selected from the group consisting of: ciclosporin, hyaluronic acid, carmellose, macrogol(s), dextran and hyprolose, sodium and calcium, sodium and povidone, hypromellose, carbomer, amikacin, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin, paromomycin, geldanamycin, herimycin, loracarbef, ertapenem, imipenem/cilastatin, meropenem, cefadroxil, cefazolin, cefalotin/cefalothin, cephalexin, cefaclor, cefamandole, cefoxitin, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefeprime, teicoplanin, vancomycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, spectinomycin, aztreonam, amoxicillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, nafcillin, penicillin, peperacillin, ticarcillin, bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, trovafloxacin, mafenide, protosil, sulfacetamide, sulfamethizole, sulfanilamide, sulfasalazine, sulfisoxazole, trimethoprim, trimethoprim-sulfamethoxazole, demeclocycline, doxycycline, minocycline, oxytetracycline, tetracycline, arsphenamine, chloramphenicol, clindamycin, lincoamycin, ethambutol, fosfomycin, fusidic acid, furazolidone, isoniazid, linezolid, metronidazole, mupirocin, nitrofurantoin, platensimycin, pyrazinamide, quinupristin/dalfopristin, rifampin/rifampicin, tinidazole, miconazole, ketoconazole, clotrimazole, econazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, fluconazole, itraconazole, isavuconazole, ravuconazole, posaconazole, voriconazole, teronazole, terbinafine, amorolfine, naftifine, butenafine, anidulafungin, caspofungin, micafungin, ciclopirox, flucytosine, griseofulvin, Gentian violet, haloprogin, tolnaftate, undecylenic acid, and combinations thereof. 33. The method of claim 30, wherein the at least one additional therapeutic agent is a thymic stromal lymphopoietin (TSLP) and/or thymic stromal lymphopoietin receptor (TSLPR) antagonist. 34. The method of claim 33, 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. 35. The method of claim 2, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises altering of a conformation, ligand binding activity, or a catalytic activity of a membrane associated protein. 36. The method of claim 35, 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. 37. The method of claim 36, wherein the transmembrane receptor comprises a G-Protein Coupled Receptor (GPCR). 38. The method of claim 37, wherein the G-Protein Coupled Receptor (GPCR) interacts with a G protein a subunit. 39. The method of claim 38, wherein the G protein a subunit comprises at least one selected from the group consisting of Gαs, Gαi, Gαq, and Gα12. 40. The method of claim 39, wherein the at least one G protein a subunit is Gαq. 41. The method of claim 2, wherein modulating cellular membrane conductivity, comprises modulating whole-cell conductance. 42. The method of claim 41, wherein modulating whole-cell conductance, comprises modulating at least one of linear and non-linear voltage-dependent contribution of the whole-cell conductance. 43. The method of claim 2, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of a calcium dependent cellular messaging pathway or system. 44. The method of claim 2, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of phospholipase C activity. 45. The method of claim 2, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of adenylate cyclase (AC) activity. 46. The method of claim 2, wherein modulation of at least one of cellular membrane potential and cellular membrane conductivity comprises modulation of intracellular signal transduction associated with at least one condition or symptom selected from the group consisting of epidmeral or dermal layering, cellular migration, collagen deposition at the wound, neoangiogenesis at the wound, elastin deposition at the wound, inflammation at the wound, expression of proteoglycans or glycosaminoglycans, cellular proliferation, and hyaluronic acid concentration at the wound. 47. The method of claim 1, comprising administration to a cell network or layer, and further comprising modulation of an intercellular junction therein. 48. The method of claim 47, wherein the intracellular junction comprises at least one selected from the group consisting of tight junctions, gap junctions, zona adherins and desmasomes. 49. The method of claim 47, wherein the cell network or layers comprises at least one selected from the group consisting of epithelial cell layer or network. 50. The method of claim 1, wherein the oxygen in the oxygenated ionic aqueous solution 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. 51. The method of claim 1, wherein the oxygenated ionic aqueous solution comprises at least one of a form of solvated electrons and electrokinetically modified or charged oxygen species. 52. The method of claim 51, wherein the form of 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. 53. The method of claim 51, wherein the oxygenated ionic aqueous solution comprises a form of solvated electrons stabilized, at least in part, by molecular oxygen. 54. The method of claim 2, wherein the ability to modulate at least one of cellular membrane potential and cellular membrane conductivity 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.
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