Methods of wound care and treatment

Abstract

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 ionic 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 ionic aqueous solution of charge-stabilized oxygen-containing nanostructures having an average diameter of less than 100 nanometers persisting in the ionic aqueous fluid in an amount sufficient for treating a wound to a surface tissue or a symptom thereof. 
     
     
         2 . 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. 
     
     
         3 . The method of  claim 2 , wherein the ionic aqueous solution further increases the level of chemokines at the wound. 
     
     
         4 . 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. 
     
     
         5 . The method of  claim 1 , wherein the ionic aqueous solution is contacted to the wound by means of a wound dressing. 
     
     
         6 . The method of  claim 1 , wherein the ionic aqueous solution accelerates epidermal or dermal layering. 
     
     
         7 . The method of  claim 1 , wherein the ionic aqueous solution increases cellular migration of at least one type of cell to the wound. 
     
     
         8 . The method of  claim 7 , 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. 
     
     
         9 . The method of  claim 1 , wherein the ionic aqueous solution accelerates neoangiogenesis of blood vessels or lymphatic vessels. 
     
     
         10 . The method of  claim 1 , wherein the ionic aqueous solution increases collagen deposition at the wound. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the charge-stabilized oxygen-containing nanostructures are the major charge-stabilized gas-containing nanostructure species in the ionic aqueous solution. 
     
     
         14 . The method of  claim 1 , wherein the percentage of dissolved oxygen molecules present in the fluid as the charge-stabilized oxygen-containing nanostructures is greater than 0.01%. 
     
     
         15 . The method of  claim 1 , wherein the percentage of dissolved oxygen molecules present in the fluid as the charge-stabilized oxygen-containing nanostructures is greater than 1%. 
     
     
         16 . 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. 
     
     
         17 . The method of  claim 1 , wherein the ionic aqueous solution comprises a saline solution. 
     
     
         18 . The method of  claim 1 , wherein the fluid is superoxygenated. 
     
     
         19 . The method of  claim 1 , wherein the fluid comprises a form of solvated electrons, or electrokinectically modified or charged oxygen species. 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . 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. 
     
     
         24 . The method of  claim 23 , 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. 
     
     
         25 . The method of  claim 24 , wherein the wound to a surface tissue or the symptom thereof comprises diabetic ulcers, and bedsores or pressure ulcers. 
     
     
         26 . The method of  claim 1 , wherein the at least one symptom is related to at least one condition selected from the group consisting of epidermal or dermal layering, cellular migration, collagen deposition at the wound, neoangiogenesis at the wound, elastin deposition at the wound, expression of proteoglycans or glycosaminoglycans, cellular proliferation, and hyaluronic acid concentration at the wound. 
     
     
         27 . The method of  claim 4 , wherein the ionic aqueous solution modulates localized or cellular levels of nitric oxide. 
     
     
         28 . The method of  claim 1  wherein the 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. 
     
     
         29 . The method of  claim 1 , further comprising a inhibition or reduction in inflammation by simultaneously or adjunctively treating the subject with another anti-inflammatory agent. 
     
     
         30 . The method of  claim 29 , wherein said other anti-inflammatory agent comprises a steroid or glucocorticoid steroid. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 1 , further comprising combination therapy, wherein at least one additional therapeutic agent is administered to the patient. 
     
     
         33 . The method of  claim 32 , wherein the one additional therapeutic agent is selected from the group consisting of anti-microbial agents, antifungal agents, and antibiotic agents. 
     
     
         34 . The method of  claim 32 , 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, timidazole, 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. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 1 , wherein the charge-stabilized oxygen-containing nanostructures are stably configured in the ionic aqueous solution in an amount sufficient to provide, upon contact of a living cell by the ionic aqueous solution, modulation of at least one of cellular membrane potential or cellular membrane conductivity. 
     
     
         38 . The method of  claim 37 , 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. 
     
     
         39 . The method of  claim 38 , 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. 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 37 , wherein modulating cellular membrane conductivity, comprises modulating linear or non-linear voltage-dependent contributions of whole-cell conductance. 
     
     
         45 . (canceled) 
     
     
         46 . The method of  claim 37 , 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, modulation of phospholipase C activity or modulation of adenylate cyclase (AC) activity. 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . The method of  claim 37 , 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 epidermal or dermal layering, cellular migration, collagen deposition at the wound, neoangiogenesis at the wound, elastin deposition at the wound, expression of proteoglycans or glycosaminoglycans, cellular proliferation, and hyaluronic acid concentration at the wound. 
     
     
         50 . The method of  claim 1 , comprising administration to a cell network or layer, and further comprising modulation of an intercellular junction therein. 
     
     
         51 . (canceled) 
     
     
         52 . (canceled) 
     
     
         53 . The method of  claim 1 , wherein the ionic aqueous solution 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. 
     
     
         54 . (canceled) 
     
     
         55 . (canceled) 
     
     
         56 . (canceled) 
     
     
         57 . The method of  claim 37 , wherein the ability to modulation of 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. 
     
     
         58 . The method of  claim 38 , wherein the membrane associated protein comprises CCR3. 
     
     
         59 . The method of  claim 1 , wherein treating a wound to a surface tissue or a symptom thereof, comprises modulation of intracellular NF-κB expression and/or activity. 
     
     
         60 . (canceled) 
     
     
         61 . (canceled) 
     
     
         62 . (canceled) 
     
     
         63 . (canceled) 
     
     
         64 . The method of  claim 1 , wherein treating comprises administration by at least one of topical, inhalation, intranasal, oral and intravenous. 
     
     
         65 . The method of  claim 1 , wherein, the charge-stabilized oxygen-containing nanostructures of the electrokinetically-altered fluid comprise at least one salt or ion from Tables 1 and 2 disclosed herein.