CN101163492B - Method of Treating 2nd and 3rd Degree Burns with Oxidation Reduction Potential Aqueous Solution - Google Patents

Abstract

The present invention provides a method of treating burns, preferably 2nd and 3rd degree burns, by administering an aqueous oxidation reduction potential (ORP) solution that remains stable for at least 24 hours.

Description

Method of Treating 2nd and 3rd Degree Burns with Oxidation Reduction Potential Aqueous Solution

Cross-references to related patent applications

This patent application claims priority to the following U.S. provisional patent applications: 60/760,635 filed January 20, 2006, 60/760,567 filed January 20, 2006, 60/760,645 filed January 20, 2006 60/760,557 filed on January 20, 2005, 60/730,743 on October 27, 2005, 60/676,883 on May 2, 2005, 60/667,101 on March 31, 2005, and 2005 60/664,361, filed March 23, which is hereby incorporated by reference into this application in its entirety. the

field of invention

The present invention relates to a method of treating burns, preferably 2nd and 3rd degree burns, by administering an aqueous redox potential solution. the

Background of the invention

Oxidation-reduction potential (ORP) water (also known as super-oxidized water) can be used as a non-toxic disinfectant for cleaning in a variety of situations to destroy microorganisms including bacteria, viruses and spores. For example, ORP water can be used in healthcare and medical devices to sanitize surfaces and medical equipment. Advantageously, OPR water is environmentally safe, thus avoiding the need for costly disposal operations. ORP water can also be used in wound care, medical equipment sterilization, food sterilization, hospitals, user homes and anti-bioterrorism. the

Although ORP water is an effective sanitizer, it has a very limited shelf life, usually only a few hours. Due to this short life, the production of ORP water must be performed in close proximity to where the ORP water is used as a disinfectant. This means that healthcare facilities such as hospitals must purchase, locate and maintain the equipment necessary to produce ORP water. In addition, existing production techniques have not been able to produce ORP water in sufficient commercial scale quantities to permit its widespread use as a disinfectant in healthcare settings. the

Accordingly, there is a need for stable ORP water over extended periods of time and methods of using such ORP water. There is also a need for more economical methods of producing ORP water in commercial scale quantities. The present invention provides such ORP water and methods of making and using such ORP water. the

ORP water has also been used as a growth promoter for patient tissue cells as described in US Patent Application Publication 2002/0160053A1. Infection remains a problem in wound care, especially with the emergence of multi-antibiotic resistant bacteria. These infections include, for example, Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and the like. Accordingly, there is a need for ORP water-containing compositions for burn treatment and infection prevention. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein. the

Brief description of the invention

The present invention provides a method of treating burns in a patient by administering an oxidation-reduction potential (ORP) aqueous solution, wherein the solution remains stable for at least 24 hours. The present invention also relates to a method of treating burns in a patient by administering an aqueous redox potential solution, wherein the solution comprises anodic water and cathodic water. In one embodiment, the ORP water solution used in the methods of the present invention contains one or more chlorine species. the

The present invention also provides a method of treating damaged or damaged tissue comprising contacting the damaged or damaged tissue with a therapeutically effective amount of ORP water solution, wherein the solution remains stable for at least 24 hours. The method includes treating tissue that has been damaged or injured by surgery or by causes not necessarily related to surgery, such as burns, cuts, abrasions, scrapes, rashes, ulcers, Stabs, infections, etc. the

The invention also provides a method of disinfecting a surface comprising contacting the surface with an anti-infective amount of an ORP water solution, wherein the solution remains stable for at least 24 hours. Surfaces can be biological surfaces, inanimate surfaces, or a combination of these surfaces, which can be disinfected according to the present invention. Biological surfaces that may be disinfected according to the present invention include, for example, muscle tissue, bone tissue, organ tissue, mucosal tissue, and combinations thereof. Inanimate surfaces include, for example, surgically implantable devices, prosthetic devices, and medical instruments. the

Another aspect of the invention includes a formulation for topical application comprising an aqueous redox potential solution and a thickening agent, wherein the formulation remains stable for at least 24 hours. the

The present invention also relates to a pharmaceutical dosage form comprising (1) a formulation for topical application comprising an aqueous redox potential solution and a thickening agent and (2) a sealed container, wherein the formulation remains stable for at least 24 hours. the

Additionally, the present invention relates to methods for treating a condition in a patient comprising topically administering to the patient a therapeutically effective amount of a formulation comprising a redox potential solution and a thickening agent, wherein the formulation remains stable for at least about 24 hours. the

The present invention also provides a method of promoting wound healing in a patient comprising applying to the wound a formulation comprising an aqueous redox potential solution and a thickening agent, wherein the formulation is applied in an amount sufficient to promote wound healing, and wherein the formulation remains stable for at least about 24 Hour. the

The present invention also provides a method for preventing a condition in a patient comprising topically administering to the patient a therapeutically effective amount of a formulation comprising an aqueous redox potential solution and a thickening agent, wherein the formulation remains stable for at least about 24 hours. the

Another aspect of the invention comprises an apparatus for producing an aqueous redox potential solution comprising at least two electrolytic cells, wherein each electrolytic cell comprises an anode compartment, a cathode compartment and a salt solution compartment between the anode compartment and the cathode compartment, wherein The anode electrode and first membrane separate the anode chamber from the salt solution chamber, and the cathode electrode and second membrane separate the cathode chamber from the salt solution chamber. The device may include a recirculation system for the saline solution supplied to the saline solution chamber to allow control and maintenance of the salt ion concentration. the

The present invention also provides a method for producing an aqueous redox potential solution comprising providing at least two electrolytic cells, wherein each electrolytic cell comprises an anode compartment, a cathode compartment and a salt solution compartment between the anode compartment and the cathode compartment, wherein the anode An electrode and a first membrane separate the anode compartment from the salt solution compartment, and a cathode electrode and a second membrane separate the cathode compartment from the salt solution compartment; provide water flow through the anode and cathode compartments; provide flow of salt solution through the salt solution compartment ; simultaneously supplying current to the anode electrode and the cathode electrode with a flow of water flowing through the anode chamber and the cathode chamber and a flow of saline solution flowing through the salt solution chamber; and collecting an oxidation-reduction potential aqueous solution generated by the electrolytic cell. the

The invention also relates to a method for producing an aqueous redox potential solution, comprising providing at least one electrolytic cell, wherein the electrolytic cell comprises an anode compartment, a cathode compartment and a salt solution compartment between the anode compartment and the cathode compartment, wherein the anode electrode and the first The membrane separates the anode compartment from the salt solution compartment, and the cathode electrode and second membrane separate the cathode compartment from the salt solution compartment; provide water flow through the anode and cathode compartments; provide flow of salt solution through the salt solution compartment; The flow of water in the anode and cathode compartments and the flow of saline solution through the brine solution compartment simultaneously provide electrical current to the anode electrode and the cathode electrode; and collecting a redox potential aqueous solution produced by the electrolytic cell, wherein the solution includes anodic water and cathodic water. the

Brief description of the drawings

Figure 1 is a schematic diagram of a three-compartment electrolytic cell for producing the redox potential aqueous solution of the present invention. the

Figure 2 illustrates a three-compartment electrolytic cell and depicts the ion species generated therein. the

Figure 3 is a schematic flow diagram of a process for producing redox potential water of the present invention. the

4A-4C depict a graphical comparison of cell viability, apoptosis and necrosis of human dermal fibroblasts (HDF) treated with exemplified ORP water solution (MCN) and hydrogen peroxide (HP). the

Figure 5 is a graphical comparison of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct levels in exemplified ORP water solution (MCN) and 500 μM hydrogen peroxide (HP) treated HDF. the

Figures 6A-6B illustrate the expression of senescence-associated β-galactosidase in HDFs following chronic exposure to low concentrations of exemplary ORP water solution (MCN) and hydrogen peroxide (HP). the

Detailed description of the invention

The present invention provides a method of preventing or treating a condition in a patient, the method comprising administering to the patient a therapeutically effective amount of an oxidation-reduction potential (ORP) aqueous solution, wherein the solution remains stable for at least 24 hours. Conditions may include, for example, medical conditions, diseases, injuries, allergies, etc., which may be treated with the ORP water solution of the present invention. the

In the context of the present invention, a therapeutically effective amount administered to a patient such as an animal (particularly a human) should be sufficient to achieve a therapeutic or prophylactic response in the patient within a reasonable time frame. Dosages can be readily determined using methods well known in the art. Those skilled in the art will recognize that the particular dosage level for any particular patient will depend on a variety of factors. For example, dosages can be determined based on the strength of the particular ORP water solution employed, the severity of the condition, the patient's weight, the patient's age, the patient's physical and mental state, general health, sex, diet, and the like. The size of the dosage will also be determined by the occurrence, nature and extent of any adverse side effects that may be associated with the administration of a particular ORP water solution. Wherever possible it is desirable to keep adverse side effects to a minimum. the

Factors that may need to be considered in combination for a specific dosage may include, for example, bioavailability, metabolic profile, administration time, administration route, excretion rate, pharmacokinetics of a specific ORP water solution in a specific patient, and the like. Other factors can include, for example, the potency or effectiveness of the ORP water solution with respect to the particular condition being treated, the severity of symptoms occurring before or during the course of treatment, and the like. In some cases, the dose that constitutes a therapeutically effective amount may also be determined in part by the use of one or more assays, such as biological assays that reasonably predict the clinical efficacy of a particular ORP water solution for the treatment or prevention of a particular condition . the

The ORP water solution of the present invention may be administered therapeutically to a patient, eg, a human, alone or in combination with one or more other therapeutic agents, eg, to treat an existing condition. The ORP water solution of the present invention may also be administered prophylactically, alone or in combination with one or more other therapeutic agents, to a patient, such as a human, who has been exposed to one or more pathogenic factors associated with the disorder. For example, the ORP water solution of the present invention may be suitably administered prophylactically to a patient who has been exposed to one or more infection-causing microorganisms (e.g., viruses, bacteria, and/or fungi) to inhibit or reduce the likelihood of infection in the patient or reduce the severity of an infection resulting from such exposure. the

Those skilled in the art know that suitable methods of administering the ORP water solution of the present invention are available, and although more than one route of administration may be used, a particular route may provide a more rapid and effective response than another route. A therapeutically effective amount may be the dose necessary to achieve an "effective level" of the ORP water solution in an individual patient. A therapeutically effective amount can be defined, for example, as the amount administered to an individual patient required to obtain blood, tissue, and/or intracellular levels of the ORP water of the present invention to prevent or treat a condition in a patient. the

When effective levels are used as the preferred endpoint of administration, actual dosages and schedules may vary depending, for example, on interindividual differences in pharmacokinetics, distribution, metabolism, and the like. The effective level may also vary when the ORP water solution of the present invention is used in combination with one or more therapeutic agents other than the ORP water solution of the present invention, such as one or more anti-infective drugs, a One or more "palliatives", "modulators" or "neutralizers" (such as described in US Patent Nos. 5,334,383 and 5,622,848), one or more anti-inflammatory agents, etc. the

Appropriate indicators can be used to determine and/or monitor effective levels. Effective levels can be determined, for example, by direct analysis (eg, analytical chemistry) or indirect analysis (eg, clinical chemical indicators) of an appropriate patient sample (eg, blood and/or tissue). Efficacy can also be determined, for example, by direct or indirect observation of, for example, urinary metabolite concentrations, changes in disorder-related markers (e.g., viral counts in viral infections), histopathological and immunochemical analyses, relief of disorder-related symptoms, etc. level. the

The ORP water used in the present invention can be applied using any suitable method of application known in the art. The ORP water used in the present invention can be administered in combination with one or more pharmaceutically acceptable carriers, vehicles, adjuvants, excipients or diluents known in the art. Suitable formulations and methods of application for administering the ORP water of the present invention can be readily determined by those skilled in the art. Those skilled in the art can readily make any necessary dosage adjustments to better suit the nature or severity of the condition being treated, depending on other factors such as side effects, changes in the general condition of the patient, and the like. the

The ORP solution of the present invention may be administered to the upper airway in the form of a steam or spray. Additionally, the ORP water solution of the present invention may be administered by aerosolization, nebulization, or atomization. When the ORP water solution of the present invention is administered by aerosolization, nebulization or atomization, it is preferably administered in the form of droplets ranging in diameter from about 1 micron to about 10 microns. the

Methods and equipment for aerosolization, nebulization and atomization are well known in the art. For example, medical nebulizers are used to deliver metered doses of physiologically active liquids into the inspiratory stream for inhalation by a subject. See, eg, US Patent No. 6,598,602. A medical nebulizer can be manipulated to generate liquid droplets which, together with inhaled gas, form an aerosol. In other cases, medical nebulizers can be used to inject small water droplets into an inhalation gas stream, providing the recipient with gas with an appropriate water content when the inhalation gas stream is delivered by a mechanical breathing aid such as a ventilator, ventilator, or anesthesia This is especially useful when provided by the system. the

Exemplary nebulizers are described, for example, in WO95/01137, which describes a hand-held device operated to inject droplets of medical liquid into a passing air stream (inhalation air stream) generated by inhalation by the recipient through a mask . Another example can be seen in U.S. Patent No. 5,388,571, which describes a positive pressure ventilation system that provides control and augmentation of breathing to a patient with respiratory insufficiency, which includes delivery of liquid medication to the patient's airways and alveoli Atomizer for particles. US Patent No. 5,312,281 describes an ultrasonic nebulizer that can atomize water or liquids at low temperatures and is reported to be able to adjust the size of the mist. Additionally, US Patent No. 5,287,847 describes a pneumatic nebulizer with variable flow rate and output volume that can be used to deliver pharmaceutical aerosols to neonates, children, and adults. Additionally, US Patent No. 5,063,922 describes an ultrasonic nebulizer. the

The methods of the invention can also be used to prevent or treat infections that can be treated with the ORP water solution of the invention. An infection can be caused by one or more infectious agents, such as infectious microorganisms. These microorganisms may include, for example, viruses, bacteria and fungi. Viruses may include, for example, one or more viruses selected from the group consisting of adenovirus, HIV, rhinovirus, and influenza virus. The bacteria may include, for example, one or more bacteria selected from the group consisting of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium tuberculosis. The fungi may include, for example, one or more fungi selected from the group consisting of Candida albicans, Bacillus subtilis, and Bacillus athrophaeus. The methods of the invention can also be used to prevent or treat inflammatory conditions or allergic reactions, which can be treated with the ORP water solution of the invention. the

Additionally, organisms that may be controlled, reduced, killed or eliminated by treatment with the ORP water solution used in accordance with the present invention include, for example, Pseudomonas aeruginosa, Escherichia coli, Enterococcus helium, Acinetobacter baumannii, Acinetobacter Genus, Bacteroides fragilis, Enterobacter aerogenes, Enterococcus faecalis, Vancomycin-resistant Enterococcus faecium (VRE, MDR), Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Vine Yellow bacteria, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes, Salmonella choleraesuis, Shigella dysenteriae, and other susceptible bacteria, and yeasts such as Trichophyton mentagrophytes, Candida albicans, and Tropical species. ORP water solution can also be used according to the present invention to control, reduce, kill or eliminate viruses, including for example adenovirus, human immunodeficiency virus (HIV), rhinovirus, influenza virus (such as influenza virus A), hepatitis virus (such as hepatitis A virus) , coronavirus (causing, for example, severe acute respiratory syndrome (SARS)), rotavirus, avian influenza virus, respiratory syncytial virus, herpes simplex virus, varicella zoster virus, rubella virus, and other susceptible viruses. the

In another embodiment, the methods of the invention comprise parenteral administration of the ORP water solution of the invention. Parenteral administration can include intravenous, subcutaneous, intramuscular or intraperitoneal administration of the ORP water solution of the invention. In a preferred embodiment, according to the method of the present invention, the ORP water solution of the present invention is administered intravenously to prevent or treat a condition. Suitable conditions may include, for example, viral myocarditis, multiple sclerosis and AIDS. See, eg, US Patent Nos. 5,334,383 and 5,622,848, which describe intravenous administration of ORP water solution for the treatment of viral myocarditis, multiple sclerosis and AIDS. the

The invention also provides a method of treating damaged or damaged tissue comprising contacting the damaged or damaged tissue with a therapeutically effective amount of an ORP water solution of the invention. Damaged or damaged tissue may be contacted by any suitable method to treat damaged or damaged tissue in accordance with the present invention. For example, damaged or injured tissue may be treated in accordance with the present invention by irrigating the tissue with the ORP water solution of the present invention so that the damaged or injured tissue contacts the ORP water. Alternatively (and additionally), the ORP water solution of the present invention may be administered in the form of a steam or spray, or by aerosolization, nebulization or mist as described herein, such that damaged or injured tissue is contacted with the ORP water. the

The methods of the invention can be used to treat tissue that has been damaged or damaged by, for example, surgery. For example, the methods of the invention can be used to treat tissue that has been damaged or damaged by cutting. In addition, the methods of the invention can be used to treat tissue that has been damaged or damaged by oral surgery, graft surgery, implant surgery, transplant surgery, cauterization, amputation, radiation, chemotherapy, and combinations thereof. Oral surgery may include, for example, dental surgery such as root canal surgery, tooth extraction, gingival surgery, and the like. the

The methods of the present invention also include treating tissue that has been damaged or damaged by one or more of burns, cuts, abrasions, scrapes, rashes, sores, punctures, and combinations thereof, which damages or injuries do not necessarily result from surgery . The methods of the invention can also be used to treat infected damaged or damaged tissue or tissue damaged or damaged as a result of infection. These infections may be caused by one or more infectious pathogens, such as one or more microorganisms selected from the group consisting of viruses, bacteria and fungi, as described herein. the

The present invention also provides a method of disinfecting a surface comprising contacting the surface with an anti-infective amount of the ORP water solution of the present invention. According to the method of the present invention, any suitable method may be used to contact the surface. For example, a surface can be contacted to disinfect a surface in accordance with the present invention by rinsing the surface with an ORP water solution of the present invention. Additionally, the ORP water solution of the present invention may be applied to a surface in steam or spray form or contact the surface by aerosolization, spraying or atomization as described herein to disinfect the surface in accordance with the present invention. Additionally, the ORP water solution of the present invention may be applied to the surface with a cleaning wipe, as described herein. By disinfecting a surface according to the invention, the surface can be freed of infectious microorganisms. Alternatively (or in addition), the ORP water solution of the present invention may be applied to a surface in order to provide a barrier to infection, thereby disinfecting the surface according to the present invention. the

The methods of the invention can be used to disinfect surfaces that are biological, inanimate, or a combination thereof. A biological surface can include, for example, one or more tissues within a body cavity, such as the oral cavity, sinus cavity, cranial cavity, abdominal cavity, and thoracic cavity. Tissues within the oral cavity include, for example, oral tissue, gingival tissue, tongue tissue, and throat tissue. Biological tissue can also include muscle tissue, skeletal tissue, organ tissue, mucosal tissue, and combinations thereof. Inanimate surfaces may include, for example, surgically implanted devices, prosthetic devices, and medical instruments. According to the method of the present invention, for example, surfaces of internal organs, viscera, muscles, etc. that may be exposed during surgery can be sterilized to maintain the sterility of the surgical environment. the

The present invention also provides formulations for topical administration comprising an oxidation-reduction potential (ORP) aqueous solution and a thickening agent, said formulations being formulated to provide enhanced potency and stability. the

Water is generally present in the formulations of the invention in an amount from about 10% to about 95% by weight of the formulation. Preferably, water is present in an amount of from about 50% to about 90% by weight. the

The formulations of the present invention preferably include an ORP water solution comprising anodic water and cathodic water. Anode water is produced in the anode compartment of the electrolytic cell used in the present invention. Cathode water is produced in the cathode compartment of the electrolytic cell. the

Formulations for topical administration according to the invention also contain thickeners. Any suitable thickener can be used to produce a formulation of the desired viscosity, which is usually higher than that of the ORP water solution alone. The thickener used is preferably compatible with the ORP water solution as well as other optional components of the formulation. Suitable thickeners include, but are not limited to, polymers and hydroxyethylcellulose. Suitable polymers may be homopolymers or copolymers, and are optionally crosslinked. Other suitable thickeners are known in the art (see e.g. Handbook of Cosmetic and Personal Care Additives , 2nd ed., Ashe et al.eds. (2002), and Handbook of Pharmaceutical Excipients , 4th ed., Rowe et al.eds .(2003)).

Preferred thickeners are acrylic based polymers. More preferably, the thickener is a high molecular weight, cross-linked, acrylic-based polymer. These polymers have the following general structure:

出售。Carbopol

聚合物通常被作为流变学修饰剂，用作各种个人护理产品、药品、和家居清洁剂中的增稠剂、助悬剂和稳定剂。可以使用固体(例如粉末)或液体形式的Carbopol聚合物。  Such polymers are marketed by Noveon under the tradename Carbopol

sell. Carbopol

Polymers are commonly used as rheology modifiers and as thickeners, suspending agents, and stabilizers in a variety of personal care products, pharmaceuticals, and household cleaners. Carbopol can be used in solid (such as powder) or liquid form polymer.

Acrylic-based polymers suitable for use in the present invention may be homopolymers or copolymers. Suitable homopolymers may preferably be crosslinked with allyl sucrose or allyl pentaerythritol. Suitable acrylic copolymers are modified with long chain (C ₁₀ -C ₃₀ ) alkyl acrylates and may preferably be crosslinked with allyl pentaerythritol.

聚合物。所提供的Carbopol

聚合物是干的、紧密卷曲的酸性分子，通过氢键保持卷曲结构。一旦其被分散于水或另一种溶剂时，它们开始水化并部分解卷曲。通过Carbopol

聚合物实现最大增稠作用的最常用方式是将酸性聚合物转化成盐。通过常用碱例如氢氧化钠(NaOH)或三乙醇胺(TEA)的中和作用容易实现这一点。这种中和作用使得长链聚合物“解卷曲”，使分子膨胀成有效的增稠形式。  Neutralized Carbopol for maximum viscosity

polymer. Provided by Carbopol

Polymers are dry, tightly coiled acidic molecules that maintain the coiled structure through hydrogen bonds. Once they are dispersed in water or another solvent, they begin to hydrate and partially uncurl. by Carbopol

The most common way for polymers to achieve maximum thickening is by converting acidic polymers into salts. This is readily accomplished by neutralization with common bases such as sodium hydroxide (NaOH) or triethanolamine (TEA). This neutralization allows the long-chain polymers to "uncurl," allowing the molecules to swell into an effective thickening form.

934是优选的。 由于其有益的生物粘附性能，也可以使用Carbopol974P。  A suitable thickener will provide the formulation with the desired viscosity as well as other characteristics such as appearance, shear resistance, ion resistance and thermal stability. For example, for suspension or emulsion (rather than clear gel) formulations with viscosities greater than 3000 centipoise (cps), Carbopol

934 is preferred. Carbopol can also be used due to its beneficial bioadhesive properties 974P.

The formulations of the invention may contain any suitable amount of a thickening agent in order to produce the desired viscosity of the formulation. The amount of thickener is generally from about 0.1% to about 50% by weight of the formulation. Preferably, the amount of thickener is from about 0.1% to about 10% by weight. the

In other words, the amount of thickener is generally about 0.1% weight/volume (mg/mL) to about 50% weight/volume (mg/mL) based on the volume of the ORP water solution. Preferably, the amount of thickener is from about 0.1% w/v to about 10% w/v. the

The amount of thickener is generally from about 0.1 g/250 mL to 50 mg/250 mL ORP water solution. Preferably, the thickener is present in an amount of from about 1 mg/250 mL to about 20 mg/250 mL of the ORP water solution, and most preferably from about 3 mg/250 mL to about 15 mg/250 mL. the

The formulation tends to flow fairly smoothly when low concentrations of acrylic-based polymers are used. At higher concentrations, the formulations of the invention have high viscosity and are pseudoplastic and difficult to flow. When shear is applied by a mixer or pump, the apparent viscosity decreases and the formulation can be pumped. the

The formulations of the invention may optionally include a neutralizing agent. Any suitable neutralizing agent can be used to generate the desired pH of the formulation. Suitable neutralizing agents include, for example, sodium hydroxide, triethanolamine, ammonia, potassium hydroxide, L-arginine, AMP-95, Neutrol TE, Tris Amino, Ethomeen, diisopropanolamine, and triisopropanolamine . Other neutralizing agents are generally known in the art (see, e.g., Handbook of Cosmetic and Personal Care Additives , 2nd ed., Ashe et al.eds. (2002), and Handbook of Pharmaceutical Excipients , 4th ed., Rowe et al .eds.(2003)). Suitable neutralizing agents may be in liquid or solid form.

时，使用中和剂三乙醇胺。中和剂将制剂转化成了凝胶。  Preferably when the thickener is an acrylic based polymer such as Carbopol

When using neutralizer triethanolamine. The neutralizing agent converts the formulation into a gel.

The formulations of the invention may include any suitable amount of a neutralizing agent. Typically, the amount of neutralizing agent is from about 0.1% to about 50% by weight of the formulation. Preferably, the amount of neutralizing agent is from about 0.1% to about 10% by weight of the formulation. In terms of volume, the neutralizing agent is included in an amount of from about 1% to about 50% by volume, based on the volume of the ORP water solution. the

When adding the neutralizing agent in liquid form, the amount of neutralizing agent added can be from about 1 mL/250 mL to about 100 mL/250 mL ORP water solution. Preferably, the amount of neutralizing agent is from about 10 mL/250 mL to about 90 mg/250 mL ORP water solution. In addition, when the neutralizing agent is in solid form, a solid amount of the neutralizing agent corresponding to these liquid amounts may be added. the

The formulations may also contain additional components such as colorants, fragrances, buffers, physiologically acceptable carriers and/or excipients, and the like. Examples of suitable colorants include, but are not limited to, titanium dioxide, iron oxides, carbazole violet, chromium-cobalt-aluminum oxide, 4-bis[(2-hydroxyethyl)amino]-9,10-anthracendione bis (2-acrylate) ester copolymer, etc. Any suitable fragrance can be used. the

The formulations of the invention may be prepared by any suitable method. The components of the formulation, such as the ORP water solution and the thickener, may be mixed together in any manner to produce a homogeneous mixture. Preferably, the components are mixed together for several minutes using an electric mixer or other suitable equipment to ensure homogeneity. The components of the formulation are usually mixed from about 400 rpm to about 1000 rpm, preferably from about 500 rpm to about 800 rpm and more preferably from about 500 rpm to about 600 rpm. the

The formulation is mixed for a period of time sufficient to produce a homogeneous mixture, generally from about 1 minute to about 10 minutes after all components have been combined. the

When the thickener is in powder form, the thickener may first be sieved to break up large agglomerates to allow a uniform formulation to be prepared. the

 解卷曲，据此生成具有所需粘度的制剂。  A neutralizing agent such as triethanolamine can then be added to the formulation containing the ORP water solution and a thickening agent. As mentioned above, the addition of triethanolamine allows thickeners such as Carbopol

Uncurling, thereby resulting in a formulation with the desired viscosity.

溶解于ORP水之前或之后向混合物中加入着色剂或芳香剂，但是一定要在中和步骤之前。  It is also possible to add a thickener such as Carbopol

Add color or fragrance to the mixture either before or after dissolving in ORP water, but always before the neutralization step.

The physical properties of the formulations of the invention are generally the same as those of the ORP water solution present in the formulation. Even after the addition of thickeners and optional neutralizers, the properties of the ORP water solution are retained. For example, the stability and pH of the ORP water solution itself and formulations containing the ORP water solution are generally the same. Accordingly, all features of the ORP water solution described herein apply to the formulations of the present invention. the

For example, formulations of the invention generally remain stable for at least 24 hours, typically at least 2 days. More typically, the formulation remains stable for at least about 1 week (e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, etc.), preferably at least about 2 months. More preferably, the formulation is stable for at least 6 months after its manufacture. Even more preferably, the formulation remains stable for at least 1 year and most preferably for at least 3 years. the

The pH of the formulation is usually from about 6 to about 8. Preferably, the pH of the formulation is from about 6.2 to about 7.8, and most preferably from about 7.4 to about 7.6. the

The formulations of the present invention may be used in any form suitable for topical administration to a patient, suitable forms including, but not limited to, gels, lotions, creams, pastes, ointments, etc., such forms are known in the art (see e.g. Modern Pharmaceuticals, 3rd ed., Banker et al. ed. (1996)). Gels are generally semi-solid emulsions or suspensions with a three-dimensional structure. Preferably, the formulation is in gel form. the

Pastes are generally semisolid suspensions, often containing a majority of solids (eg, from about 20% to about 50%) dispersed in an aqueous or fatty vehicle. Lotions are typically liquid emulsions containing a water-based carrier and a volatile agent (over 50%), with a viscosity low enough to be poured (less than 30,000 cps). Ointments and creams are usually semisolid emulsions or suspensions which may contain hydrocarbons or polyethylene glycols as part of the carrier and other volatile ingredients. the

When the formulations of the present invention are in the form of a gel, the viscosity of the gel ranges from about 10,000 to about 100,000 centipoise (cps) (e.g., about 15,000 cps, about 20,000 cps, about 25,000cps, 30,000cps, 35,000cps, 40,000cps, 45,000cps, 50,000cps, 55,000cps, 60,000cps, 65,000cps, 70,000cps, 75,000cps, 80,000cps, 85,0 , about 90,000cps, about 95,000cps, or a range thereof). the

聚合物的粘度可以下降，导致不令人满意的局部用制剂。优选地，凝胶的pH值是从约6.4到约7.8，以及更优选地是从约7.4到约7.6。  The pH of the gel is generally from about 6.0 to about 8.0. Above this pH, thickeners such as Carbopol

The viscosity of the polymer can drop, resulting in unsatisfactory topical formulations. Preferably, the pH of the gel is from about 6.4 to about 7.8, and more preferably from about 7.4 to about 7.6.

The formulations of the present invention are suitable for topical administration to patients, including humans and/or animals, for the treatment of various conditions. In particular, formulations can be administered to animals (e.g., mice, rats, pigs, cows, horses, dogs, cats, rabbits, guinea pigs, hamsters, birds) and humans. Topical administration includes application to the skin as well as oral, intranasal, intrabronchial and rectal routes of administration. the

In another embodiment, the present invention is directed to a method of treating a condition in a patient by topically administering a formulation comprising an ORP water solution and a thickening agent. the

Conditions in patients that may be treated by the present invention include conditions such as the following: surgical/developmental wound cleansers, antiseptic skin pathogens (e.g. bacteria, mycoplasma, viruses, fungi, prions), antiseptic wounds (e.g. war wounds), promotion of wound healing , burn healing, treatment of fungal skin, psoriasis, athlete's foot, ear infections (eg swimmer's ear), traumatic wounds, acute, subchronic and chronic infections (eg diabetic foot infection is an example of the latter), pressure ulcers , skin abrasions, debrided wounds, laser resurfacing, donor sites/grafts, exuding partial and full thickness wounds, superficial injuries (lacerations, cuts, abrasions, minor skin irritations), and human or Other medical applications on or in animals. Ulcers treated according to the invention may or may not have abscesses or necrotic tissue present. the

Additionally, the present invention relates to methods of promoting wound healing in a patient by administering to the wound a formulation comprising an aqueous redox potential solution and a thickening agent. Wounds treated may result from any surgery, ulcer or otherwise. Ulcers that may be treated include, for example, diabetic foot ulcers. the

The present invention also relates to a method of preventing a condition in a patient by topically administering a formulation comprising an ORP water solution and a thickening agent. For example, formulations (eg, in gel form) can be used as barriers on open wounds to prevent infection. In particular, the formulation (eg, in gel form) may be applied to the surface of a wound, such as a diabetic foot ulcer, which is prone to neurological and vascular complications. The administered formulation can thus provide a barrier to infection, since these wounds are the main portal of infection in diabetic patients. the

The formulations can be used to prevent sexually transmitted diseases including, for example, infection in a patient. These infections that can be prevented include herpes, human immunodeficiency virus (HIV), and vaginal infections. When the formulation is in gel form it can be used as a spermicide. the

A therapeutically effective amount of a formulation of the invention may be used or administered so as to provide the desired therapeutic effect on bacteria, viruses and/or pathogens. A therapeutically effective amount herein means the amount of the formulation that results in an amelioration of the condition being treated or prevented. For example, when used to treat an infection, a therapeutically effective amount of the formulation reduces the extent of the infection and/or prevents further infection. Those skilled in the art understand that the efficacy of the formulations of the invention obtained by administering the formulations may be short-term (eg, days) and/or long-term (eg, months). the

The formulations can also be administered for a sufficient period of time, eg 1, 2, or several days, about 1 week or several weeks, until the desired effect is observed in the patient. the

The ORP water solution or formulation thereof may be administered by any suitable means. For example, an amount of formulation can be applied to the surface of the patient being treated, and the patient then spreads it evenly with his or her fingers. Alternatively, a healthcare practitioner can administer the formulation to a patient's tissue. The formulations may be applied with suitable devices such as disposable wipes or cloths. the

The ORP water of the present invention is produced by a redox process, which may be referred to as electrolysis or a redox reaction, in which electrical energy is used to create a chemical change in an aqueous solution. Electrical energy is introduced into and transmitted through water by conducting electrical charges in the form of electrical current from one point to another. In order for an electric current to occur and maintain, there must be charge carriers in the water, and there must be a force to move the carriers. For metals and semiconductors, the charge carriers can be electrons, or for solutions they can be positive and negative ions. the

In the method for preparing the ORP water solution of the present invention, a reduction reaction occurs at the cathode while an oxidation reaction occurs at the anode. The specific reduction and oxidation reactions that take place are described in International Application WO 03/048421A1. the

As used herein, water generated at the anode is referred to as anode water, and water generated at the cathode is referred to as cathode water. The anodic water contains oxidized species from the electrolysis reaction, while the cathodic water contains reduced species from the reaction. the

Anode water generally has a low pH, typically from about 1 to about 6.8. Anolyte water generally contains chlorine in various forms including, for example, chlorine gas, chloride ions, hydrochloric acid, and/or hypochlorous acid. Various forms of oxygen may also be present, optionally including, for example, oxygen, peroxide, and/or ozone. Cathodic water generally has a high pH, usually from about 7.2 to about 11. Cathodic water generally contains hydrogen gas, hydroxyl radicals, and/or sodium ions. the

The ORP water solution of the present invention can be acidic, neutral or basic, with a pH generally from about 1 to about 14. At this pH, an appropriate amount of the ORP water solution can be safely applied to a hard surface without damaging the surface or harming objects in contact with the ORP water solution, such as human skin. The pH of the ORP water solution is typically from about 3 to about 8. More preferably, the pH of the ORP water solution is from about 6.4 to about 7.8, and most preferably, the pH is from about 7.4 to about 7.6. the

The ORP water solution of the present invention typically has an oxidation-reduction potential of from about -1000 millivolts (mV) to about +1350 millivolts (mV). This potential is a measure of the tendency (ie potential) of a solution to accept or transfer electrons, which is sensed by a metal electrode and compared to a reference electrode in the same solution. This potential can be determined using standard techniques, including, for example, by measuring the millivolt potential of the ORP water solution relative to a standard reference silver/silver chloride electrode. The potential of ORP water is generally from about -400 mV to about +1300 mV or about +1150 mV. Preferably, the potential of the ORP water solution is from about 0 mV to about +1250 mV, more preferably from about +500 mV to about +1250 mV. Even more preferably, the ORP water of the present invention has a potential of from about +800 mV to about +1100 mV, and most preferably from about +800 mV to about +1000 mV. the

A variety of different ionic and other species can be present in the ORP water solution of the present invention. For example, the ORP water solution may contain chlorine (eg, free chlorine and combined chlorine), and optionally ozone and peroxides (eg, hydrogen peroxide). It is believed that the presence of one or more of these species gives the ORP water solution its sanitizing ability to kill a variety of microorganisms such as bacteria, fungi and viruses. the

Free chlorine generally includes but is not limited to hypochlorous acid (HClO), hypochlorite ion (ClO ^- ), sodium hypochlorite (NaOCl), chloride ion (Cl ^- ), chlorite ion (ClO ₂ ^- ), dissolved chlorine gas (Cl ₂ ) and other free radical chlorine species. The ratio of hypochlorous acid to hypochlorite ions is pH dependent. At a pH of 7.4, the hypochlorous acid level is from about 25 ppm to about 75 ppm. Temperature also affects the proportion of free chlorine components.

Bound chlorine is chlorine in chemical combination with ammonia or organic amines such as chloramine. The combined chlorine content is usually up to about 20 ppm. the

Any suitable amount of chlorine and optionally ozone and hydrogen peroxide may be present in the ORP water solution of the present invention. The levels of these components can be determined by methods known in the art. the

The total chlorine content (including free and combined chlorine) is typically from about 50 parts per million (ppm) to about 200 ppm. Preferably, the total chlorine content is from about 80 ppm to about 150 ppm. the

Chlorine content can be determined by methods known in the art, such as the DPD colorimetric method (Lamotte Company, Chestertown, Maryland) or other known methods established by the Environmental Protection Agency. In the DPD colorimetric method, free chlorine reacts with N,N-diethyl-p-phenylenediamine (DPD) to produce a yellow color, the intensity of which is measured with a calibrated colorimeter, which provides parts per million. Output the result. Further addition of potassium iodide turns the solution pink to provide a total chlorine value. The combined chlorine content can then be determined by subtracting free chlorine from total chlorine. the

The amount of ozone optionally present is from about 0.03 ppm to about 0.2 ppm, preferably from about 0.10 ppm to about 0.16 ppm. the

The level of hydrogen peroxide optionally present in the ORP water solution ranges from about 0.01 ppm to about 200 ppm, preferably from about 0.05 ppm to about 100 ppm. More preferably, hydrogen peroxide is included in an amount of from 0.1 ppm to about 40 ppm, most preferably from about 1 ppm to 4 ppm. Peroxides (eg, _H2O2 , _H2O2- and _{HO2- )} are optionally present ^at concentrations of ^less than 0.12 millimolar ( _mM ).

The ORP water solution contains a total amount of oxidizing chemical species in the range of about 2 millimolar (mM), which includes the aforementioned chlorine species, oxygen species, and other species that may be difficult to measure such as Cl ⁻ , ClO ₃ , Cl ₂ ⁻ , and _ClOx . The levels of oxidized chemical species contained can also be determined by ESR spectroscopy (using TemponeH as a spin-trap molecule).

The ORP water solution of the present invention generally remains stable for at least about 24 hours, usually at least about 2 days. More typically, the ORP water solution remains stable for at least about 1 week (eg, 1 week, 2 weeks, 3 weeks, 4 weeks, etc.), and preferably at least about 2 months. More preferably, the ORP water solution remains stable for at least about 6 months after its preparation. Even more preferably, the ORP water solution remains stable for at least about 1 year, and most preferably for at least about 3 years. the

As used herein, the term stable generally refers to the ability of the ORP water solution to remain suitable for its intended use, such as decontamination, disinfection, sterilization, Antimicrobial cleansing and wound cleansing. the

The ORP water solution of the present invention is also stable for at least about 90 days, and preferably about 180 days when stored under accelerated conditions (typically from about 30°C to about 60°C). the

The concentrations of ionic species and other species contained in the solution are generally maintained during storage of the ORP water solution. Typically, the concentration of free chlorine and optionally ozone and hydrogen peroxide is maintained at about 70% or higher of its initial concentration for at least about 2 months after the ORP water solution is prepared. Preferably, these concentrations are maintained at about 80% or greater of their initial concentration for at least about 2 months after the ORP water solution is prepared. More preferably, these concentrations are about 90% or higher of their initial concentration for at least about 2 months after preparation of the ORP water solution, most preferably about 95% or higher. the

The stability of the ORP water solution of the present invention can also be determined in terms of the reduction in the amount of organisms contained in the sample after exposure to the ORP water solution. Determination of reduction in the concentration of an organism can be performed using any suitable organism, including bacteria, fungi, yeast, or viruses. Suitable organisms include, but are not limited to: Escherichia coli, Staphylococcus aureus, Candida albicans, and Bacillus athrophaeus (formerly known as Bacillus subtilis). ORP water solution can be used as both a low-level disinfectant capable of reducing the concentration of living microorganisms by about 4 logs (10 ⁴ ), and as a high-level disinfectant capable of reducing the concentration of living microorganisms by about 6 logs (10 ⁶ ) disinfectant.

In one aspect of the invention, the ORP water solution is capable of causing at least about a 4 log (10 ⁴ ) reduction in total organism concentration after 1 minute of exposure when measured at least 2 months after preparation of the solution. Preferably, the ORP water solution is also capable of achieving this level of reduction in organism concentration when measured at least 6 months after preparation of the solution. More preferably, the ORP water solution is also capable of achieving this level of reduction in organism concentration when measured at least about 1 year after preparation of the ORP water solution, most preferably when measured at least about 3 years after preparation of the solution ORP water solution was also able to achieve this level of reduction in the concentration of organisms when used.

In another aspect of the invention, the ORP water solution is capable of reducing the concentration of a living microbial sample by at least about 6 logs (10 ⁶ ) within 1 minute of exposure when measured at least 2 months after preparation of the ORP water solution, so The microorganisms are selected from the group consisting of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Preferably, the ORP water solution is capable of achieving such a reduction in Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans when measured at least 6 months after preparation, and more preferably at least 1 year after preparation . Preferably, the ORP water solution is capable of reducing the concentration of such living microorganisms by at least about 7 logs (10 ⁷ ) within 1 minute of exposure when measured at least 2 months after preparation.

The ORP water solution of the present invention is generally capable of reducing a viable microbial sample from an initial concentration of about 1 x ¹⁰⁶ to about 1 x ¹⁰⁸ microorganisms/ml within 1 minute of exposure when measured at least 2 months after preparation of the ORP water solution. The final concentration was about 0 microorganisms/ml, including but not limited to Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. The reduction in microbial concentration is between about 6 logs (10 ⁶ ) to about 8 logs (10 ⁸ ). Preferably, the ORP water solution is capable of achieving this for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, or Candida albicans organisms when measured at least 6 months after preparation, and more preferably at least 1 year after preparation. level of reduction.

Alternatively, the ORP water solution of the present invention is capable of reducing the concentration of a spore suspension of Bacillus athrophaeus spores by about 6 logs (10 ⁶ ) within about 5 minutes of exposure when measured at least 2 months after preparation of the ORP water solution . Preferably, the ORP water solution is capable of achieving such a reduction in the concentration of Bacillus athrophaeus spores when measured at least about 6 months after preparation, and more preferably when measured at least 1 year after preparation.

The ORP water solution was also capable of reducing the concentration of the spore suspension of Bacillus athrophaeus spores by about 4 logs ( ¹⁰⁴ ) within about 30 seconds of exposure when measured at least 2 months after preparation of the ORP water solution. Preferably, the ORP water solution is capable of achieving this level of reduction in Bacillus athrophaeus spore concentration when measured at least about 6 months after preparation, and more preferably when measured at least 1 year after preparation.

The ORP water solution is also capable of reducing the concentration of fungal spores, such as Aspergillus niger spores, by about 6 logs ( ¹⁰⁶ ) within about 5 to 10 minutes of exposure when measured at least about 2 months after preparation of the ORP water solution. Preferably, the ORP water solution is capable of achieving this level of reduction in fungal spore concentration when measured at least 6 months after preparation, and more preferably when measured at least 1 year after preparation.

In one embodiment, the ORP water solution of the present invention optionally comprises hydrogen peroxide ( _H2O2 ) and one or more chlorine species _. The chlorine species contained are preferably free chlorine species. Free chlorine species can be selected from hypochlorous acid (HOCl), hypochlorite ion (OCl ⁻ ), sodium hypochlorite (NaOCl), chlorite ion (ClO ₂ ⁻ ), chloride ion (Cl ⁻ ), dissolved chlorine gas ( Cl ₂ ) and mixtures thereof.

The ORP water solution optionally contains hydrogen peroxide generally from about 0.01 ppm to about 200 ppm, preferably from about 0.05 ppm to about 100 ppm. More preferably, hydrogen peroxide is included in an amount of from about 0.1 ppm to about 40 ppm, and most preferably from about 1 ppm to about 4 ppm. the

The total amount of free chlorine species is generally from about 10 ppm to about 400 ppm, preferably from about 50 ppm to about 200 ppm, and most preferably from about 50 ppm to about 80 ppm. The amount of hypochlorous acid is generally from about 15 ppm to about 35 ppm. The amount of sodium hypochlorite generally ranges from about 25 ppm to about 50 ppm. Chlorine dioxide levels are generally less than about 5 ppm. the

The ORP water solution is generally stable for at least about 1 week. Preferably, the ORP water solution is stable for at least about 2 months, more preferably the ORP water solution is stable for at least about 6 months after its preparation. Even more preferably, the ORP water solution remains stable for at least about 1 year and most preferably remains stable for at least about 3 years. the

In this embodiment, the pH of the ORP water solution is generally from about 6 to about 8. Preferably, the pH of the ORP water solution is from about 6.2 to about 7.8, and most preferably from about 7.4 to about 7.6. the

While not wishing to limit the invention, it is believed that controlling the pH allows for the formation of a stable ORP water solution in which chlorine species such as hypochlorous acid and hypochlorite ions coexist. the

After preparation, the ORP water solution or formulation of the present invention can be transferred to a sealed container for distribution and sale to end users such as healthcare settings including hospitals, nursing homes, physician's offices, ambulatory surgery centers, dental offices, and the like. A pharmaceutical dosage form according to the invention comprises a formulation for topical administration as described herein and a sealed container into which the formulation is placed. the

Any suitable sealed container that maintains the sterility and stability of the ORP water solution or formulation it contains can be used. The container can be made of any material that is compatible with the ORP water solution or formulation components (eg, ORP water solution or thickener). The container should generally be non-reactive so that the ions contained in the ORP water solution do not react with the container to any appreciable extent. the

Preferably, the container is made of plastic or glass. The plastic can be rigid so that the container can be stored on a shelf. Alternatively, the container may be flexible, such as a flexible bag. the

Suitable plastics include polypropylene, polyethylene terephthalate (PET), polyolefins, cycloolefins, polycarbonate, ABS resins, polyethylene, polyvinyl chloride, and mixtures thereof. Preferably, the container comprises polyethylene selected from the group consisting of high density polyethylene (HDPE), low density polyethylene (LDPE) and linear low density polyethylene (LLDPE). Most preferably, the container is made of high density polyethylene. the

The container preferably has an opening to allow dispensing of the ORP water solution or formulation for administration to a patient. The container opening can be sealed in any suitable manner. For example, the container can be sealed with a twist cap or stopper. Optionally, the opening can also be sealed with a foil. the

The top gas of the sealed container may be air or other suitable gas that does not react with the ORP water solution or other components of the formulation containing the ORP water solution. Suitable top gases include nitrogen, oxygen and mixtures thereof. the

The present invention also provides an ORP water solution comprising anode water and cathode water. Anode water is produced in the anode compartment of the electrolytic cell used in the present invention. Cathode water is produced in the cathode compartment of the electrolytic cell. the

The ORP water solution of the present invention generally contains cathode water in an amount of from about 10% solution volume to about 90% solution volume. Preferably, the ORP water solution contains cathode water in an amount of from about 10% by volume to about 50% by volume, more preferably from about 20% by volume of the solution to about 40% by volume of the solution, and most preferably from about 20% by volume Solution volume to about 30% solution volume. In addition, the ORP water solution contains anode water in an amount from about 50% solution volume to about 90% solution volume. the

As noted, the ORP water solution containing anode water and cathode water may be acidic, neutral or basic, generally having a pH of from about 1 to about 14. The pH of the ORP water solution is typically from about 3 to about 8. Preferably, the pH is from about 6.4 to about 7.8, more preferably from about 7.4 to about 7.6. the

The ORP water solution of the present invention has a wide range of uses as a disinfectant, cleaning agent, cleaning agent, bactericidal preservative, etc. to control the activity of unwanted or harmful substances present in the environment. Substances that can be treated with an ORP water solution include, for example, organisms and allergens. the

The ORP water solution can be used as a disinfectant, sterilizer, detergent, antiseptic and/or cleaning agent. The ORP water solution of the present invention is suitable for the following representative applications: medical, dental and/or veterinary equipment and devices, food industry (e.g. hard surfaces, fruits, vegetables, meat), hospitals/health care units (e.g. hard surfaces) , the cosmetic industry (eg skin cleansers), household goods (eg floors, counters, hard surfaces), electronics industry (eg cleaning lines, hard drives), and bioterrorism (eg anthrax, infectious microorganisms). the

The ORP water solution can also be administered to humans and/or animals to treat a variety of conditions including, for example, surgical/open wound cleansing, skin pathogen disinfection (e.g. against bacteria, mycoplasma, viruses, fungi, prions), Disinfecting war wounds, promoting wound healing, promoting burn healing, treating gastric ulcers, wound irrigation, dermatophytes, psoriasis, athlete's foot, pink eye and other eye infections, ear infections (e.g. swimmer's ear), lung/nose/sinus infections , and other medical applications on or in the human or animal body. The use of ORP water solution as a tissue cell growth promoter is also described in US Patent Application Publication 2002/0160053A1. the

While not limiting the invention in any way, it is believed that the ORP water solution removes bacteria in contact with it and destroys the bacterial cellular components including proteins and DNA. the

For example, the ORP water solution is capable of reducing, within 30 seconds of exposure, the concentration of a sample of living microorganisms by at least about 5 logs (10 ⁵ ) when measured at least 2 months after preparation of the ORP water solution Free Pseudomonas aeruginosa, Escherichia coli, Enterococcus helium, Acinetobacter baumannii, Acinetobacter spp, Bacteroides fragilis, Enterobacter aerogenes, Enterococcus faecalis, Vancomycin-resistant Enterococcus faecium (VRE, MDR), Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Bacillus luteus, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Grape hemolyticus coccus, Staphylococcus hominis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes, Candida albicans, and Candida tropicalis.

In one embodiment, the ORP water solution administered in accordance with the present invention is capable of reducing a live microbial sample from about 1×10 ⁶ to about 1× The initial concentration of ¹⁰⁸ organisms/ml was reduced to a final concentration of about 0 organisms/ml, said living microorganisms including but not limited to Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. This corresponds to about a 6 log (10 ⁶ ) to about 8 log (10 ⁸ ) reduction in organism concentration. Preferably, the ORP water solution is capable of achieving Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, or Organisms such as Candida albicans were reduced by about 10 ⁶ to about 10 ⁸ .

Alternatively, the ORP water solution administered in accordance with the present invention is capable of reducing the concentration of the spore suspension of Bacillus athrophaeus spores by about 6 logs within about 5 minutes of exposure when measured at least about 2 months after the ORP water solution was prepared ( 10 ⁶ ). Preferably, the ORP water solution administered in accordance with the present invention is capable of achieving a reduction in the concentration of Bacillus athrophaeus spores of about ¹⁰ when measured at least about 6 months after preparation, and more preferably when measured at about 1 year after preparation . The ORP water solution is also capable of reducing the concentration of a spore suspension of Bacillus athrophaeus spores by about 4 logs (10 ⁴ ) within about 30 seconds of exposure when measured at least about 2 months after preparation of the ORP water solution. Preferably, the ORP water solution is capable of achieving this level of reduction in Bacillus athrophaeus spore concentration when measured at least about 6 months after preparation, and more preferably when measured at about 1 year after preparation.

The ORP water solution is also capable of reducing the concentration of fungal spores, such as Aspergillus niger spores, by about 6 logs ( ¹⁰⁶ ) within about 5 to 10 minutes of exposure when measured at least about 2 months after preparation of the ORP water solution. Preferably, the ORP water solution is capable of achieving this level of reduction in fungal spore concentration when measured at least 6 months after preparation, and more preferably when measured at least 1 year after preparation.

ORP water solution administered in accordance with the present invention is also capable of reducing the concentration of viruses such as human immunodeficiency virus (HIV) and adenovirus by more than 3 logarithmic levels (10 ³ ). Preferably, the ORP water solution is capable of achieving a > ¹⁰³ reduction in virus concentration when assayed at least about 6 months after preparation, and more preferably when assayed at least about 1 year after manufacture.

The ORP water solution administered in accordance with the present invention is also capable of completely inhibiting the growth of M. bovis within about 5 minutes of exposure when measured at least about 2 months after preparation of the ORP water solution. Preferably, the ORP water solution is capable of achieving complete inhibition of mycobacteria concentrations when assayed at least about 6 months after preparation, and more preferably when assayed at least about 1 year after preparation. the

Thus, organisms that can be controlled, reduced, killed, or eliminated by treatment with the ORP water solution include, but are not limited to, bacteria, fungi, yeasts, and viruses. Susceptible bacteria include, but are not limited to, Escherichia coli, Staphylococcus aureus, Bacillus athrophaeus, Streptococcus pyogenes, Salmonella choleraesuis, Pseudomonas aeruginosa, Shigella dysenteriae, and other susceptible bacteria. Fungi and yeasts that can be treated with the ORP water solution include, for example, Candida albicans and Trichophyton mentagrophytes. ORP water solution can also be administered to viruses, including, for example, adenoviruses, human immunodeficiency virus (HIV), rhinoviruses, influenza viruses (such as influenza A virus), hepatitis viruses (such as hepatitis A virus), coronaviruses (causing severe acute Respiratory syndrome (SARS)), rotavirus, respiratory syncytial virus, herpes simplex virus, varicella zoster virus, rubella virus, and other susceptible viruses. the

In a preferred embodiment, the ORP water solution of the present invention may be administered to treat patients suffering from 1st, 2nd or 3rd degree burns. Patients with combined burns, such as a combination of 2nd and 3rd degree burns, can also be treated with the ORP water solution. 1st degree burns involve the epidermis or the surface of the skin. 2nd degree burns involve the epidermis and underlying dermis. 3rd degree burns involve the epidermis, dermis, and subdermis. More preferably, the ORP water solution is administered to treat patients suffering from 2nd or 3rd degree burns. Burns suitable for treatment by the present invention may result from a variety of injuries including, for example, exposure to fire, boiling liquid (eg, water, milk, etc.), or electrical contact, and typically extend from about 0% to about 69% of the patient's tissue. the

The ORP water solution may be administered to a burn patient in any suitable manner. The ORP water solution can be applied topically by spraying, bathing, soaking, wiping, or otherwise moistening the burn. ORP water solution is administered in an amount sufficient to treat the burn. The ORP water solution is administered to the burn at least once a day and preferably more than once a day. More preferably, the ORP water solution is administered to the burn 3 times a day. the

The ORP water solution can be applied directly to the burned area, for example by pouring from a container or spraying from a reservoir. Burns may be sprayed with any suitable device. Preferably, the ORP water solution is sprayed onto the burn with a high pressure irrigation device. the

Burns can be soaked by partially or completely submerging them in the ORP water solution. The burn may be soaked for any suitable period of time. Generally, the burn is soaked in the ORP water solution for at least about 1 minute. Preferably, the burn is soaked for about 5 minutes to about 15 minutes. the

Alternatively, the ORP water solution may be applied to the burn using a substrate such as gauze that has been saturated with ORP water. Preferably, the ORP water solution is applied by a variety of methods including spraying, spraying and immersing the burn. the

Optionally the burn can be dressed by applying a moist wound dressing saturated with ORP water solution. In addition to wet wound dressings, burns can optionally be covered with dry gauze and adhesive coverings. Following application of the ORP water solution, any suitable suave, cream, gel and/or ointment may also be applied to the burn surface. the

In one embodiment, a patient with a burn in need of treatment is subjected to a washing step with the ORP water solution of the present invention. The ORP water solution is first sprayed onto the burn using a high-pressure irrigation device. Next, soak the burn in the ORP water solution for a suitable period of time. After soaking, then spray the burn with ORP water solution. Then, allow the burn to remain moist for at least about 5 minutes. This treatment step is performed on the patient's burn at least once a day, preferably twice a day, more preferably three times a day. In this embodiment, the burned surface is preferably not dressed between applications of the ORP water solution. the

Prior to application of the ORP water solution, burns are preferably treated with debridement to remove hyperkeratotic, necrotic, and other unhealthy tissue until healthy-appearing tissue is exposed. In debridement burns, the wound edges are excised up to healthy bleeding tissue. Following debridement, debris from the burn can be removed. The ORP water solution administered according to the present invention may also be used as an irrigation solution for hydrosurgery equipment for debridement of skin ulcers. Suitable hydrosurgical devices may include, for example, the VersaJet device sold in the US by Smith and Nephew, the Debritom sold in Europe by Medaxis, the JetOx sold in the US and Europe by DeRoyal, or the PulsaVac in Italy. It is believed that the ORP water solution can act synergistically with the device by reducing the microbial load at the wound site and avoiding the formation of infectious mist during debridement. Thus, according to the invention, it is possible to carry out burn debridement with continuous irrigation with said device, reducing the infection process and avoiding the formation of an infectious fog. the

和V.A.C.Instill^TM。相信ORP水溶液可以与所述设备协同作用，通过控制炎症-过敏过程，同时减少微生物负荷。因此，根据本发明，可以在间断或连续冲洗下，给开放性烧伤施用所述设备，以便治疗或预防组织感染或坏死。  ORP water solution administered according to the present invention may also be used as a flushing solution for negative pressure devices used to relieve water and increase blood flow. Suitable negative pressure devices may include, for example, one or more vacuum assisted wound closure devices such as the VAC sold by Kinetic Concepts in the U.S.

and VAC Instill ^™ . It is believed that the ORP water solution may act synergistically with the device by controlling the inflammatory-allergic process while reducing the microbial load. Thus, according to the present invention, the device can be administered to open burns with intermittent or continuous irrigation in order to treat or prevent tissue infection or necrosis.

Optionally, a number of adjuvant treatments may also be utilized in accordance with the present invention, including bioengineered skin (Apligraf, Organogenesis, Inc., Canton), acellular skin substitutes (Oasis Wound Matrix, Healthpoint), ultrasonically administered ORP water, and topical Oxygen replacement or hyperbaric oxygen therapy (eg, hyperbaric chamber, Vent-Ox system). 

The ORP water solution may be administered in conjunction with skin grafts, if desired, to promote healing of the burn. the

Administration of the ORP solution may optionally be combined with administration of topical and/or systemic antibiotics. Suitable antibiotics may include, but are not limited to, penicillins, cephalosporins or other beta-lactams, macrolides (such as erythromycin, 6-O-methylerythromycin, and azithromycin), fluoroquinolones, sulfa Classes, tetracyclines, aminoglycosides, clindamycin, quinolones, metronidazole, vancomycin, chloramphenicol, their antibacterial effective derivatives and combinations thereof. Suitable anti-infective agents may also include antifungal agents such as amphotericin B, fluconazole, flucytosine, ketoconazole, miconazole, derivatives thereof, and combinations thereof. Suitable anti-inflammatory agents may include, for example, one or more anti-inflammatory drugs, such as one or more anti-inflammatory steroids or one or more non-steroidal anti-inflammatory drugs (NSAIDs). Exemplary anti-inflammatory drugs may include, for example, cyclophilins, FK binding proteins, anti-cytokine antibodies (eg, anti-TNF), steroids, and NSAIDs. the

In another embodiment of the present invention, the patient's 2nd and/or 3rd degree burns are debrided first, and then the ORP water solution is sprayed with a high-pressure flushing device. The amount of ORP water solution used to wash the burn is preferably sufficient to remove debris. The burn is then soaked in the ORP water solution for a suitable period of time. Next, spray the patient's burn with the ORP water solution and allow the solution to moisten the burn for a suitable period of time, preferably from about 5 minutes to about 15 minutes. Repeat misting and wetting about 3 times a day. The burned surface was left undressed between ORP water solution applications. the

The process of high pressure spraying, optionally soaking, spraying and wetting the burn may be repeated at appropriate intervals. Preferably, the procedure of high pressure spraying, optionally soaking, spraying and wetting the burn is repeated about once a week, and more preferably about once a day. Treatment of burns with ORP water solution can be continued until the burn is fully healed, which usually requires repeating the procedure over several days. Generally, the ORP water solution is administered daily for at least about 3 days. Typically, the ORP water solution is administered daily for at least about 5 days, preferably at least about 7 days and more preferably at least about 10 days. Burn healing is usually measured by the rate of scar contracture and epidermisization. the

The ORP water of the present invention is also suitable for controlling the activity of allergens present in the environment. As used herein, an allergen includes any substance other than bacteria, fungi, yeast or viruses that is capable of eliciting an adverse immune response or allergy in a susceptible human or animal. Asthma is a common physiological response following exposure to one or more allergens. Allergens may be living (ie from living or dead organisms) or inanimate (eg non-living such as textiles) and may be present in the environment such as the home and/or workplace. the

Protein-based household allergens that can be treated with ORP water include, for example, animal hair, dander and feces, household dust, ragweed, grass, trees, mites and pollen. Animal allergens include, for example, cat epithelium, dog epithelium, horse dander, cow dander, dog dander, guinea pig epithelium, goose feathers, mouse epithelium, mouse urine, rat epithelium, and rat epithelium. Rat urine. the

Occupational allergens include, for example, high molecular weight substances such as natural proteins, often derived from vegetable or animal proteins, and low molecular weight chemical substances such as diisocyanates and other materials found in some textiles. Other chemical allergens that may be present in the workplace include, for example, anhydrides, antibiotics, wood dust, and dyes. A variety of proteins can be occupational allergens including vegetable gums, enzymes, animal proteins, insects, vegetable proteins, and soy. the

Other allergens suitable for treatment with ORP water solutions are described in Korenblat and Wedner, Allergy Theory and Practice (1992) and Middleton, Jr., Allergy Principles and Practice (1993). the

It has been found that the ORP water solution administered according to the present invention is virtually non-toxic to normal tissues and normal mammalian cells. The ORP water solution administered according to the present invention does not cause a significant decrease in eukaryotic cell viability, a significant increase in apoptosis, a significant acceleration of cellular senescence and/or significant oxidative DNA damage in mammalian cells. The lack of toxicity is particularly beneficial, perhaps even surprising, since the ORP water solution administered according to the present invention has about the same disinfecting power as hydrogen peroxide, yet is significantly toxic to normal tissues and normal mammalian cells less than hydrogen peroxide. These findings demonstrate that the ORP water solution administered according to the present invention can be safely applied to eg mammals including humans. the

For the ORP water solution administered in accordance with the present invention, the cell viability rate is preferably at least about 65%, more preferably at least about 70%, still more preferably at least about 75% after about 30 minutes of exposure to the ORP water solution. In addition, the ORP water solution applied in accordance with the present invention preferably only causes a maximum of about 10 % of cells, more preferably at most only about 5% of cells and still more preferably at most about 3% of cells, have Annexin V exposed on their cell surface. Furthermore, the ORP water solution administered in accordance with the present invention preferably results in less than about 15% of the cells, more preferably less than about 10% of the cells, and still more preferably less than 5% of the cells expressing SA-beta-galactostasis after chronic exposure to the ORP water solution Glycosidase. The ORP water solution administered according to the invention preferably causes the same fraction of oxidized DNA adduct formation as that caused by saline solution, for example hydrogen peroxide normally causes oxidized DNA in cells treated under equivalent conditions About 20% or less of the adduct is formed, about 10% or less, or about 5% or less. the

ORP water solution administered according to the present invention does not cause significant RNA degradation. Thus, RNA extracted from human cell cultures analyzed by denaturing gel electrophoresis after about 30 minutes of exposure to ORP water solution or 3 hours after about 30 minutes of exposure generally does not show significant RNA degradation, typically The presence of two discrete bands corresponding to ribosomal eukaryotic RNA (ie, 28S and 18S) demonstrates that the ORP water solution administered according to the invention leaves the RNA substantially intact. Likewise, RNA extracted from human cell cultures exposed to ORP water solution for 30 minutes or after approximately 3 hours of exposure can be reverse-transcribed and amplified (RT-PCR) for constitutive human GAPDH (glyceraldehyde-3-phosphate dehydrogenase) gene, a strong GAPDH band was formed on the gel electrophoresis of the RT-PCR product. In contrast, cells treated with HP for the same period of time showed significant RNA degradation and little, if any, GAPDH RT-PCR product. the

Any suitable amount of the ORP water solution of the present invention may be used or administered in order to provide the desired bactericidal, virucidal, bactericidal and/or antiallergenic effect. the

The ORP water solution may be applied in any suitable manner for disinfection and sterilization. For example, to sanitize and sterilize medical and dental equipment, the equipment is kept in contact with the ORP water solution for a period of time long enough to reduce the level of organisms present on the equipment to a desired level. the

For disinfection and sterilization of hard surfaces, the ORP water solution can be applied directly to the hard surface from the container in which the ORP water solution is stored. For example, the ORP water solution can be poured, sprayed, or otherwise applied directly onto hard surfaces. The ORP water solution can then be distributed over the entire hard surface with a suitable substrate such as cloth, fabric or paper towels. In hospital administration, the substrate is preferably sterile. Alternatively, the ORP water solution may be first applied to a substrate such as cloth, fabric or tissue. The wetted substrate is then brought into contact with the hard surface. Alternatively, the ORP water solution can be applied to hard surfaces by dispersing the solution into the air as described herein. The ORP water solution can be administered to humans and animals in a similar manner. the

The present invention also provides a cleaning wipe comprising a water-insoluble substrate and an ORP water solution as described herein, wherein the ORP water solution is formulated onto the substrate. The ORP water solution can be soaked, coated, covered or otherwise applied to the substrate. Preferably, the substrate is pretreated with the ORP water solution prior to distributing the cleaning wipe to end users. the

The substrate of the cleaning wipe can be any suitable water-insoluble absorbent or absorbent material. A variety of materials can be used as substrates. It should have sufficient wet strength, washout, loft, and porosity, and the substrate should not adversely affect the stability of the ORP water solution. Examples include nonwoven substrates, woven substrates, hydroentangled substrates, and sponges. the

The substrate can have one or more layers. Each layer can have the same or different texture construction and abrasiveness. Different texture configurations may result from using different combinations of materials or from using different production processes or combinations thereof. The substrate should not dissolve or disintegrate in water. The substrate provides a vehicle for delivering the ORP water solution to the substrate to be treated. the

The substrate can be a single nonwoven sheet or a plurality of nonwoven sheets. Nonwoven sheets can be made from wood pulp, synthetic fibers, natural fibers, and blends thereof. Suitable synthetic fibers for the substrate include, but are not limited to, polyester, rayon, nylon, polypropylene, polyethylene, other cellulosic polymers, and blends of these fibers. Nonwoven materials may include nonwoven fibrous sheet materials including meltblown, coform, airlaid, spunbond, wet laid, bonded-carded web materials, hydroentangled (also known as spunlaced) materials, and combinations thereof . These materials may include synthetic or natural fibers or combinations thereof. The substrate may optionally contain a binder. the

Examples of suitable nonwoven, water-insoluble substrates include 100% cellulose Wadding Grade 1804, 100% polypropylene needlepunch material NB 701-2.8-W/R, Hydraspun 8579, a blend of cellulose and synthetic fibers, and 70 %Viscose/30%PES Code9881. Other examples of nonwoven substrates suitable for cleaning wipes are described in US Pat. the

The substrate can also be made of textile materials such as cotton fibers, cotton/nylon blends, or other textiles. Regenerated cellulose, polyurethane foam, etc. used for making sponges are also suitable. the

The liquid loading capacity of the substrate should be at least about 50% to 1000% of its dry weight, preferably at least about 200% to 800%. This is expressed as a loading of about 1/2 to 10 times the weight of the substrate. The weight of the substrate can vary from, but is not limited to, about 0.01 to about 1000 grams per square meter, and is most preferably from about 25 to about 120 grams per square ^meter (referred to as "basis weight"), usually made In sheets or webs, which can be cut, die cut, or otherwise formed into suitable shapes and sizes. The cleaning wipe preferably has a certain wet tensile strength, which is preferably from about 25 to about 250 Newton/m, more preferably about 75-170 Newton/m.

The ORP water solution can be dispensed, soaked, coated, covered, or otherwise applied to the substrate by any suitable method. For example, individual portions of the substrate can be treated with varying amounts of the ORP water solution. Preferably, intensive treatment of the continuous web of substrate material with the ORP water solution is performed. The entire web of substrate material can be soaked in the ORP water solution. Alternatively, the ORP water solution can be sprayed or metered onto the web as the shafts string the substrate web, or even during creation of the nonwoven substrate. Manufacturers can soak or coat a stack of individually cut and sized substrate portions in their container with the ORP water solution. the

The cleaning wipe may optionally contain additional components to enhance the performance of the cleaning wipe. For example, cleaning wipes can also include polymers, surfactants, polysaccharides, polycarboxylates, polyvinyl alcohols, solvents, chelating agents, buffers, thickeners, dyes, colorants, fragrances, and mixtures thereof to enhance The performance of the cleaning wipe. These optional components should not adversely affect the stability of the ORP water solution. Examples of various components that the cleaning wipe may optionally contain are described in US Patent Nos. 6,340,663, 6,649,584, and 6,624,135. the

The cleaning wipes of the present invention may be individually sealed with an insulating or adhesive thermoplastic overwrap (eg, polyethylene, Mylar, etc.). For more economical dispensing, the cleaning wipes may be packaged in many individual pieces. Cleaning wipes can be prepared by first placing sheets of substrate in a dispenser and then contacting the sheets of substrate with the ORP water solution of the present invention. Alternatively, the cleaning wipe in the form of a continuous web can be formed by applying an ORP water solution to the substrate during production and then loading the wetted substrate into a dispenser. the

Dispensers include, but are not limited to, having a closed tank or having a closed basin. The closure on the dispenser is to isolate the moist wipes from the external environment and to avoid premature volatilization of the liquid components. the

The dispenser can be made of any suitable material that is compatible with both the substrate and the ORP water solution. For example, the dispenser may be made of plastic such as high density polyethylene, polypropylene, polycarbonate, polyethylene terephthalate (PET), polyvinyl chloride (PVC), or other hard plastics. the

The continuous web of wipes can be passed through a narrow opening above the dispenser, most preferably through a closure. Tools are then required to cut the desired length or size of the wipe from the web. Above the dispenser there may be provided a knife edge, a serrated knife edge or other means to cut the web to the desired size, without limitation the narrow opening actually does double duty as a knife edge. Alternatively, the rubbed continuous web can be creased, folded, segmented, perforated, or partially cut to uniform or non-uniform sizes or lengths, which eliminates the need for sharp knife edges. Additionally, the wipes can be staggered so that removing one directly reveals the next. the

The ORP water solution of the present invention can be dispersed into the environment through a gaseous medium such as air. The ORP water solution can be dispersed into the air by any suitable means. For example, ORP water solution can be formed into small droplets of any suitable size and dispersed into a room. the

For small-scale applications, the ORP water solution can be applied from a spray bottle including a reservoir and pump. Alternatively, the ORP water solution can be packaged into an aerosol container. Aerosol containers generally include the product to be administered, propellant, container and valve. Valve includes actuator and dip tube. The contents of the container can be administered by depressing the actuator. The various components in the aerosol container are compatible with the ORP water solution. Suitable propellants may include liquefied halocarbons, hydrocarbons, or halocarbon-hydrocarbon blends, or compressed gases such as carbon dioxide, nitrogen, or nitrous oxide. Aerosol systems typically generate droplets ranging in size from about 0.15 μm to about 5 μm. the

The ORP water solution may be dispensed in aerosol form as part of an inhalation system for the treatment of lung and/or airway infections or for wound healing on such parts of the body. the

For larger scale applications, the ORP can be dispersed into the air with any suitable device, including but not limited to humidifiers, mist generators, fog formers, nebulizers, atomizers, sprinklers, and other misting devices. These devices allow continuous application of the ORP water solution. Sprayers that mix gas and water directly at the nozzle can be used. The ORP water solution can be converted into steam, such as low pressure steam, and released into an air jet. Different types of humidifiers can be used such as ultrasonic humidifiers, steam humidifiers or nebulizers, and evaporative humidifiers. the

Special equipment for dispersing the ORP water solution can be integrated into the ventilation system in order to provide a wide application of the ORP water solution throughout the house or in a health care unit (eg hospital, nursing home, etc.). the

The present invention also provides a method for producing an ORP water solution using at least one electrolytic cell comprising an anode chamber, a cathode chamber and a salt solution chamber between the anode chamber and the cathode chamber, wherein the ORP water solution comprises anode water and cathode water. Figure 1 shows a schematic diagram of a classic three-compartment electrolytic cell used in the present invention. the

The electrolytic cell 100 has an anode compartment 102 , a cathode compartment 104 and a salt solution compartment 106 . The salt solution chamber is located between the anode chamber 102 and the cathode chamber 104 . The anode chamber 102 has an inlet 108 and an outlet 110 to allow water to flow through the anode chamber 102 . The cathode chamber 104 also has an inlet 112 and an outlet 114 to allow water to flow through the cathode chamber 104 . Saline solution chamber 106 has an inlet 116 and an outlet 118 . Electrolytic cell 100 preferably includes a tank that holds all components together. the

The anode compartment 102 is separated from the saline solution compartment by an anode electrode 120 and an anion exchange membrane 122 . An anode electrode 120 may be adjacent to the anode chamber 102 with a membrane 122 positioned between the anode electrode 120 and the saline solution chamber 106 . Alternatively, the membrane 122 may be adjacent to the anode chamber 102 with the anode electrode 120 positioned between the membrane 122 and the saline solution chamber 106 . the

The cathode chamber 104 is separated from the saline solution chamber by a cathode electrode 124 and a cathode ion exchange membrane 126 . Cathode electrode 124 may be adjacent to cathode chamber 104 with membrane 126 positioned between cathode electrode 124 and saline solution chamber 106 . Alternatively, membrane 126 may be adjacent to cathode chamber 104 with cathode electrode 124 positioned between membrane 122 and saline solution chamber 106 . the

The electrodes, usually constructed of metal, allow a voltage potential to be applied between the anode and cathode compartments. Metal electrodes are usually planar and have similar dimensions and cross-sectional surface area to ion exchange membranes. The electrodes are configured such that a majority of the surface of the ion exchange membrane is exposed to water in their respective anode and cathode compartments. This allows ion species to move between the saline solution chamber, the anode chamber and the cathode chamber. Preferably, the electrode has a plurality of channels or pores evenly distributed over the surface of the electrode. the

A potential source is connected to the anode electrode 120 and the cathode electrode 124 such that an oxidation reaction in the anode compartment 102 and a reduction reaction in the cathode compartment 104 can be induced. the

The ion exchange membranes 122 and 126 used in the electrolytic cell 100 can be constructed of any suitable material to allow the exchange of ions (e.g., chloride ions C1−) between the salt solution chamber 106 and the anode chamber 102 and between the salt solution chamber 106 and the cathode chamber 104 Ion exchange between (such as Na+). Anode ion exchange membrane 122 and cathode ion exchange membrane 126 may be made of the same or different materials. Preferably, the anodic ion exchange membrane comprises a fluorinated polymer. Suitable fluorinated polymers include, for example, perfluorosulfonic acid polymers and copolymers such as perfluorosulfonic acid/PTFE copolymers and perfluorosulfonic acid/TFE copolymers. Ion exchange membranes can be made from single layer materials or multilayer materials. the

The water source for the anode compartment 102 and cathode compartment 104 of the electrolytic cell 100 may be any suitable water supply system. The water can come from the municipal water supply or can be pretreated before being used in the electrolytic cells. Preferably, the water is pretreated and selected from the group consisting of demineralized water, purified water, distilled water, and deionized water. More preferably, the pretreated water source is ultrapure water obtained through reverse osmosis and UV line purification devices. the

The brine solution used in the brine solution chamber 106 can be any aqueous brine solution that contains suitable ionic species to produce the ORP water solution. Preferably, the brine solution is an aqueous sodium chloride (NaCl) salt solution, also commonly referred to as brine solution. Other suitable salt solutions include other chloride salts such as potassium chloride, ammonium chloride and magnesium chloride and other halide salts such as potassium and bromide. The saline solution may comprise a mixture of salts. the

The saline solution can have any suitable concentration. Saline solutions can be saturated or concentrated. Preferably, the saline solution is a saturated sodium chloride solution. the

Figure 2 shows the various ion species believed to be generated in the three compartment electrolytic cell used in the present invention. Three-compartment electrolytic cell 200 includes an anode compartment 202 , a cathode compartment 204 and a salt solution compartment 206 . After applying a suitable current to the anode 208 and cathode 210, the ions contained in the salt solution flowing through the salt solution chamber 206 migrate through the anode ion exchange membrane 212 and the cathode ion exchange membrane 214 into the anode chamber 202 and cathode chamber 204, respectively. of water. the

Positive ions migrate from the salt solution 216 flowing through the salt solution chamber 206 into the cathode water 218 flowing through the cathode chamber 204 . Negative ions migrate from the brine 216 flowing through the brine chamber 206 into the anode water 220 flowing through the anode chamber 202 . the

Preferably, salt solution 216 is an aqueous sodium chloride (NaCl) solution containing sodium ions (Na+) and chloride (Cl-) ions. Positive Na+ ions migrate from the brine solution 216 into the cathode water 218 . Negative Cl- ions migrate from the brine solution 216 into the anode water 220 . the

The sodium ions and chloride ions may also undergo further reactions in the anode compartment 202 and cathode compartment 204 . For example, chloride ions can react with various oxygen-containing ions and other species (e.g., oxygen radicals, O2, O3) contained in the anode water 220 to form ClOn- and ClO-. Other reactions may also occur in the anode chamber 202, including the formation of oxygen radicals, hydrogen ions (H+), oxygen (O2) and optionally ozone (O3), and peroxides (eg, hydrogen peroxide). In the cathode chamber 204, hydrogen gas (H2), hydroxide ions (OH-), sodium hydroxide (NaOH), and other radicals may be formed. the

The present invention also provides a method and device for producing ORP water solution using at least two three-chamber electrolytic cells. Figure 3 shows a schematic diagram of a method for producing an ORP water solution using two electrolytic cells of the present invention. the

Method 300 includes two three-compartment electrolytic cells, specifically a first electrolytic cell 302 and a second electrolytic cell 304 . Water is transferred, pumped, or otherwise distributed from water source 305 into anode compartment 306 and cathode compartment 308 of first electrolysis cell 302 and anode compartment 310 and cathode compartment 312 of second electrolysis cell 304 . The process of the present invention can generally produce from about 1 liter/minute to about 50 liters/minute of ORP water solution. Production capacity can be increased by utilizing additional electrolytic cells. For example, 3, 4, 5, 6, 7, 8, 9, 10 or more three-compartment electrolytic cells can be used to increase the output of the ORP water solution of the present invention. the

The anode water produced by the anode chamber 306 and the anode chamber 310 is collected in the mixing tank 314 . A portion of the cathode water produced by the cathode chamber 308 and the cathode chamber 312 is collected in the mixing tank 314 and mixed with the anode water. The remainder of the cathode water produced by the method is discarded. The cathode water may optionally be treated by gas separator 316 and/or gas separator 318 before being added to mixing tank 314 . The gas separator removes gases such as hydrogen formed in the cathode water during the production process. the

A mixing tank 314 may optionally be connected to a circulation pump 315 to allow uniform mixing of the anode water and part of the cathode water from the electrolytic cells 302 and 304 . Additionally, mixing tank 314 may optionally include suitable equipment for monitoring the level and pH of the ORP water solution. The ORP water solution may be transferred from mixing tank 314 via pump 317 for application at or near the mixing tank location for disinfection or sterilization. Alternatively, the ORP water solution can be dispensed into suitable containers for delivery to remote locations (eg, warehouses, hospitals, etc.). the

The method 300 also includes a saline solution circulation system to provide saline solution to the saline solution chamber 322 of the first electrolytic cell 302 and the saline solution chamber 324 of the second electrolytic cell 304 . A salt solution is prepared in the salt tank 320. The saline solution is transferred via pump 321 into saline solution chambers 322 and 324 . Preferably, the saline solution flows first through the saline solution chamber 322 followed by the saline solution chamber 324 in sequence. Alternatively, saline solution can be pumped into both saline solution chambers simultaneously. the

The brine solution may flow through a heat exchanger 326 in the mixing tank 314 before being returned to the brine tank 320 to control the temperature of the ORP water solution as desired. the

Ions in the salt solution in the first electrolytic cell 302 and the second electrolytic cell 304 are depleted over time. Additional ion sources can be periodically added to the mixing tank 320 to replace the ions being transferred to the anode and cathode waters. An additional source of ions can be used to maintain a constant pH of the salt solution, which tends to drop (ie become acidic) over time. The source of additional ions may be any suitable compound including, for example, a salt such as sodium chloride. Preferably, sodium chloride is added to the mixing tank 320 to replace sodium ions (Na+) that are transferred to the anode and cathode waters. the

In another embodiment, the present invention provides an apparatus for generating an aqueous redox potential solution comprising at least two three-compartment electrolytic cells. Each electrolytic cell includes an anode chamber, cathode water, and a salt solution chamber separating the anode chamber from the cathode chamber. The apparatus includes a mixing tank for collecting anolyte water produced by the electrolytic cells and a portion of cathodic water produced by one or more electrolytic cells. Preferably, the apparatus further comprises a salt circulation system allowing recirculation of the salt solution supplied to the salt solution chamber of the electrolytic cell. the

The following examples further describe and illustrate the invention, which of course should not be construed as constituting any limitation on the scope of the invention. the

Example 1-3

These examples demonstrate the unique characteristics of the ORP water solution of the present invention. The ORP water solution samples of Examples 1-3 were analyzed according to the methods described herein to determine the physical properties and levels of ionic species and other chemical species present in each sample. The results obtained for chlorine dioxide, ozone, and hydrogen peroxide are based on the standard test methods used to determine these species; however, the results may indicate a different species that may also produce a positive test result. Furthermore, it has been reported that chlorine dioxide, ozone and hydrogen peroxide can react with hypochlorite, causing their consumption and the production of other species such as HCl and _O2 . Table 1 shows the pH, oxidation-reduction potential (ORP) and ionic species present for each ORP water solution sample.

Table 1: Physical characteristics and ion species contained in ORP water solution samples

The ORP water solution has suitable physical characteristics for disinfection, sterilization and/or cleaning. the

Example 4-10

These examples demonstrate the addition of varying amounts of bleach to the ORP water solution of the present invention. In particular, these examples demonstrate the antimicrobial activity and fabric bleaching capabilities of the compositions. the

漂白溶液。然后用10％漂白溶液制备出下面的溶液：80％ORP水溶液/20％漂白剂(实施例4)；60％ORP水溶液/40％漂白剂(实施例5)；40％ORP水溶液/60％漂白剂(实施例6)；20％ORP水溶液/80％漂白剂(实施例7)；和0％ORP水溶液/100％漂白剂(实施例8)。也用两种对照溶液进行比较，包括100％ORP水溶液/0％漂白剂(实施例9)和含0.01％Tween20去污剂的ORP水溶液(实施例10)。确定出这些样品的物理特征，特别是pH值、氧化还原电位(ORP)、总氯(Cl^-)含量、次氯酸(HClO^-)含量、二氧化氯含量和过氧化物含量，表2显示了这些数据。  Prepare 10% Clorox with distilled water

bleach solution. The following solutions were then prepared with 10% bleach solution: 80% ORP water solution/20% bleach (Example 4); 60% ORP water solution/40% bleach (Example 5); 40% ORP water solution/60% bleach 20% ORP water solution/80% bleach (Example 7); and 0% ORP water solution/100% bleach (Example 8). Two control solutions were also used for comparison, including 100% ORP water solution/0% bleach (Example 9) and ORP water solution with 0.01% Tween 20 detergent (Example 10). The physical characteristics of these samples, especially pH, oxidation-reduction potential (ORP), total chlorine (Cl ^- ) content, hypochlorous acid (HClO ^- ) content, chlorine dioxide content and peroxide content were determined, as shown in Table 2 these data.

Table 2: Physical Characteristics of ORP Water Solution/Bleach Compositions

[0215] Addition of large amounts of fluoride ions as part of the bleach prevents accurate determination of chlorine dioxide and peroxide levels, as indicated by nd. The results obtained for chlorine dioxide and peroxide are also based on the standard test methods used to determine these species; however, the results may indicate a different species that may also produce a positive test result. Furthermore, it has been reported that chlorine dioxide, ozone and hydrogen peroxide can react with hypochlorite, causing their consumption and the production of other species such as HCl and _O2 . As shown in these examples, the levels of hypochlorous acid in ORP water solutions with or without added bleach were similar.

The samples of Examples 4-10 were assayed for high spore count using Bacillus subtilis var. niger spores (ATCC #9372 obtained from SPS Medical of Rush, New York). The spore suspension was concentrated (by evaporation in a sterile hood) to 4 x ¹⁰⁶ spores per 100 µl. A 100 microliter sample of the spore suspension was mixed with 900 microliter of each sample from Examples 4-10. As indicated in Table 3, samples were incubated at room temperature for periods of 1 to 5 minutes. At the times indicated, 100 microliters of incubated samples were plated onto individual TSA plates and incubated at 35°C ± 2°C for 24 hours, after which the number of colonies formed on each plate was determined. The control plate confirmed the initial spore concentration >1×10 ⁶ spores/100 μl. Table 3 shows the concentration of Bacillus spores (average of two determinations) for different samples at different incubation times.

Table 3: Bacillus spore concentration (spores/100 microliters)

These results indicate that with increasing bleach concentration (10% aqueous bleach solution), the number of killed bacillus spores decreased in samples incubated for 2-3 minutes. However, for samples incubated for 5 minutes, the bleach concentration did not affect the killing effect on Bacillus spores. In addition, the results indicated that adding 0.01% detergent to the OPR water solution did not reduce spore kill. the

Fabric bleaching tests were performed using the samples of Examples 4-10. The fabric used for sample testing was a 100% rayon children's t-shirt with dark blue dye spots. A 2 inch square piece of dyed fabric was placed into a 50 mL plastic tube. Each piece of fabric was covered with a sample of the solution in Examples 4-10. Table 4 shows the time taken until complete bleaching was achieved (determined by fabric whitening). the

Table 4: Time taken to fully bleach fabric samples

These examples show that as the concentration of ORP water solution in the composition is increased, the time it takes to achieve complete bleaching increases. the

Example 11

This example relates to the toxicological characteristics of the ORP water solution of the present invention. Microcyn 60 (or M60) - an exemplary ORP water solution of the present invention - was used in these studies. the

In terms of safety, M60 has no irritation to the skin or conjunctiva of rabbits as tested according to international standards (AAMI 1997, NV SOP 16G-44, PFEUM 2000). In addition, acute inhalation toxicity studies in rats confirmed the safety of Microcyn 60 administered by this route. the

The irritation potential of Microcyn 60 was evaluated in a primary eye irritation study in rabbits. Microcyn 60 in a volume of 0.1 mL was instilled into the right eyes of 3 New Zealand white rabbits. The left eye of each animal was left untreated as a control. Eyes were observed and scored for corneal ulceration or opacity, iris inflammation, conjunctival redness, or conjunctival edema at 1, 24, 48, and 72 hours. All animals were also observed once daily for signs of mortality and ill health. the

No signs of eye irritation were observed in any treated or control eyes at any time throughout the study. All animals appeared to be in clinical health for the duration of the study. These findings suggest that Microcyn 60 does not elicit a positive irritant response. the

Acute inhalation toxicity studies were also performed in rats to determine the potential inhalation toxicity of Microcyn 60. Ten Sprauge-Dawley albino rats were exposed to an aerosol of undiluted Microcyn 60 for 4 hours. The concentration of Microcyn 60 was determined to be 2.16mg/L. Animals were observed frequently on the day of exposure and daily for 14 days thereafter for mortality and clinical/behavioral signs of toxicity in all animals. All animals were euthanized on day 14 and gross necropsy was performed. the

All animals exhibited very slight to slight piloerection and very slight decreased activity at 4 1/2 and 6 hours after the start of exposure, but were asymptomatic by the next day and all appeared clinically normal for the duration of the study. One male rat did not gain body weight between days 0 and 7. There were no fatalities and gross autopsy revealed no visible abnormalities. The estimated acute inhalation LD50 from this study was greater than 2.16 mg/L. the

Additional toxicology studies were performed in rabbits. Aerosol superoxide water (1 mL) was delivered into the right nostril of 20 New Zealand rabbits through a positive pressure device three times a day for 15, 30, 45 and 60 days. The left control nostril was left untreated. Nasal mucosal biopsies of untreated and M60-treated nares were obtained from 5 animals at each time point. These tissues were then observed under light and electron microscopes. A complete medical examination was performed on each animal on alternate days, and nasal congestion, facial neuralgia, compression, mucopurulent rhinorrhea, and malaise were noted. Side effects were reported as rare, mild and transient. the

Changes in the nasal mucosa occurred after 60 days of intranasal M60 administration. At day 60, slight disruption of the epithelium, discrete inflammatory infiltrates in the subepithelial area, and hyperplasia of glands and blood vessels were present in all samples. Under ultrastructural observation, we found a variety of cystic changes in epithelial cells, mitochondrial aggregation and deformation, and partial membrane dissolution. Some epithelial cells detach, epithelial cilia are nearly lost, their membranes dissolve and intracellular spaces widen. Some cells detach from the basement membrane. The lamina propria is mildly edematous. the

This study demonstrated that M60 slightly irritated the nasal mucosa after 60 days of intranasal administration. However, this damage is minimal and reversible, so the intranasal route of M60 can be considered safe. This is based on the fact that although the nasal mucosa can be severely damaged years after the administration of vasoconstrictors, it returns to normal after discontinuation of these drugs. This is possible because the process of nasal mucosal regeneration depends on whether the basal cells and basement membrane remain intact after injury. Adjacent basal cells can migrate along the basement membrane to cover the lesion. Thus, even in the presence of slight detachment of epithelial cells in some areas after M60 treatment, the basement membrane survived and the surviving epithelial cells adjacent to the lesion area grew toward areas lacking epithelium. In addition, topical steroids may also be administered to promote restoration of nasal mucosal structure and function. the

In conclusion, intranasal administration of M60 for 5 days was safe in this cohort. Pathological mucosal changes are mild and reversible. Therefore, intranasal administration of M60 can be widely used. the

Example 12

This example describes the activity, stability and lack of toxicity of exemplary ORP water solutions. the

One such ORP water solution used in this study is called "Microcyn", which was recently introduced to the Mexican market as an antimicrobial preservative. Microcyn is a super-oxidized solution with neutral pH, which has bactericidal, antiseptic and wound antiseptic activity according to the certificate obtained from the Mexican Health Agency. Microcyn is prepared from pure water and salt (NaCl), which has a low concentration of sodium (<55ppm) and chlorine (<80ppm), a pH range from 7.2 to 7.8, and a redox potential range from 840mV to 960mV. Only one concentration of Microcyn is prepared and requires no activation or dilution. the

The solution is prepared with water obtained by reverse osmosis and then treated with high voltage and an electrochemical gradient generated by sodium chloride. In this way, the reactive species formed in the multiple chambers in which the electrochemical gradient is generated are selected in a controlled manner to generate Microcyn. The result is a solution with a controlled content of free radicals giving a high redox potential (+840 mV to +960 mV) and thus a high antimicrobial activity. the

Hypochlorous acid and sodium hypochlorite are the most abundant components in Microcyn, and Microcyn also contains other components in lower concentrations such as hydrogen peroxide, ozone, chloride ion, hydride and sodium hydroxide. While applicants do not wish to be bound by a particular theory, it is believed that the sanitizing effect is not necessarily dependent on the amount of chlorine, but rather on the level of free radicals, since the levels of sodium and chlorine in Microcyn are less than 50 and 60 ppm, respectively. In addition, compared with other superoxidized solutions that have been reported in the literature, Microcyn has a neutral pH (6.4-7.8), is non-corrosive, and can be stored stably for up to 2 years. All of these features allow the generation of super-oxidized solutions that are effective as high-level disinfectants and suitable for inanimate surfaces and tissues. the

Accelerated stability tests have demonstrated that Microcyn can be stored under widely varying temperature conditions (from 4 to 65°C) without losing its disinfecting activity within 2 years. This extended shelf stability is also different from previously reported superoxidized solutions, which were only effective when used immediately after preparation. In other words, Microcyn can be stored and dispensed even under extreme conditions without losing its antimicrobial activity, but other solutions must be generated by specialized and expensive machines in each hospital that wants to use the solution. Nevertheless, the manufacturer recommends that once a container of Microcyn is opened, it should be used within 30 days in order to ensure its uniform activity and constant effect. the

Because only one concentration of Microcyn is produced, the dosage of Microcyn can only be varied by varying the volume applied per unit area of skin. In toxicology studies, the dose of Microcyn topically applied to intact skin was between 0.05 and 0.07mL/ ^cm2 , and in acute skin toxicity studies and skin irritation studies, the dose was up to 8.0mL/ ^cm2 . In the study of deep wound application, the dose of Microcyn administered was 0.09 mL/cm ² .

Toxicology studies were performed in which Microcyn was topically applied to intact skin, in a single application, with an exposure of 4 to 24 h. Multiple applications of Microcyn to deep wounds in rats were evaluated once or twice daily for 7 days. the

Two studies were performed on intact rabbit skin to evaluate the acute irritation and skin toxicity of Microcyn. There were no clinical signs, skin irritation, or skin abnormalities at necropsy in any of the animals exposed to Microcyn. the

The characteristics of local and systemic toxicity induced by topical application of Microcyn to deep wounds were evaluated in rats. No abnormal, significant differences in blood biochemical or hematological parameters were observed, nor were abnormalities observed at autopsy. Neither the skin irritation grading nor the histopathology of the tissue surrounding the wound and application site showed any difference between Microcyn-treated wounds and saline solution-treated control wounds. the

Systemic toxicity of Microcyn was also evaluated by intraperitoneal injection in mice. For this, 5 mice were injected with a single dose (50 mL/kg) of Microcyn via the intraperitoneal route. Five control mice were injected with a single dose (50 mL/kg) of saline solution (0.9% sodium chloride) in the same manner. In this study, no mortality or any evidence of systemic toxicity was observed in any animal receiving a single intraperitoneal dose of Microcyn with an LD50 greater than ₅₀ mL/kg.

Microcyn was administered to rats by the oral route in order to allow absorption and to characterize any inherent toxic effects of the product. For this, a single dose (4.98 mL/kg) was administered to 3 albino rats of the Sprague-Dawley line via esophageal tube. There was no mortality, clinical signs or abnormalities in necropsy in any of the animals exposed to a single oral dose of Microcyn. the

The potential of topical Microcyn to cause eye irritation was also evaluated in rabbits. Ocular irritation and no other clinical signs were observed in any of the animals exposed to Microcyn topically administered by the ocular route. the

Microcyn was administered to rats by the inhalation route to determine possible acute toxicity by inhalation. Following exposure, all animals showed very slight or slight decreased activity and piloerection, but they were all asymptomatic the following day. No mortality or autopsy abnormalities were observed in animals exposed to Microcyn by inhalation. the

The potential for Microcyn to sensitize the skin was evaluated in guinea pigs using a modified occlusion patch method (Buehler). No irritation was observed in animals in the control group after a single treatment challenge, nor in animals evaluated (induced treatment) after a treatment challenge. Therefore, Microcyn does not cause sensitization. the

Therefore, Microcyn showed no product-related adverse effects when administered to intact skin, deep open skin wounds, conjunctival sacs by oral and inhalation routes or by intraperitoneal injection. Also has experience in treating more than 500 patients with cutaneous and mucous membrane wounds of very different nature, with excellent antiseptic and cosmetic results. Therefore, topical Microcyn should be effective and well tolerated in this clinical trial. the

Microcyn is packaged in clear 240mL PET bottles. Store this product at room temperature and it is shelf stable for up to 2 years if the bottle is not opened. Once the bottle has been opened, it is recommended that all product should be used within 90 days. Due to its high biosafety, Microcyn can be poured into sinks without risk of contamination or corrosion. the

Several microbiological trials of Microcyn have been conducted in the United States and Mexico. More than 90% of bacteria can be eliminated in the first few seconds of exposure. Table 5 summarizes the antibacterial and antifungal activity exhibited by Microcyn according to this criterion. the

Table 5. Antibacterial and antifungal activities of Microcyn

The sporicidal activity test was performed according to the PAHO [National American Health Organization]/WHO protocol. the

Regarding virucidal activity, Microcyn was found to reduce the viral load of human immunodeficiency virus (SF33 strain) by more than 3 logs within 5 minutes. This was confirmed by the cytopathic effect and absence of the antigen Agp24 in the Microcyn-treated virus assay. These tests were conducted in accordance with the US Environmental Protection Agency's Virucides Protocol (DIS/TSS-7/November 12, 1981). the

The virucidal activity of Microcyn has been demonstrated in recent US studies against HIV and polioviruses, as well as its activity against Listeria monocytogenes, MRSA and Mycobacterium tuberculosis. Thus, Microcyn has been shown to clear bacteria, fungi, viruses and spores after 1 to 15 minutes of exposure when administered as recommended. the

Example 13

This example demonstrates the use of the exemplary ORP water solution Microcyn as an effective antimicrobial solution. the

In vitro time-kill evaluations were performed with Microcyn redox potential water. The ability of Microcyn was evaluated against challenge suspensions of 50 different strains of microorganisms, 25 of which were strains from the American Standard Colony (ATCC) and 25 clinical isolates of these same species, as in Tentative Final Monograph, Federal Register, 17 June 1994 , vol. 59:116, pg.31444. Percentage reduction from the initial population of each challenge strain was determined after exposure to Microcyn for 30 seconds, 1 minute, 3 minutes, 5 minutes, 7 minutes, 9 minutes, 11 minutes, 13 minutes, 15 minutes and 20 minutes and Log10 reduction. All agar platings were performed in duplicate and the Microcyn concentration evaluated was 99% (v/v). All tests were performed in accordance with Good Laboratory Practices (as described in 21C.F.R Part 58). the

The table below summarizes the results of the above in vitro time-kill evaluations for all test populations with reductions greater than 5.0 Log ₁₀ at the 30 second exposure mark.

Table 6: In vitro 30-second sterilization

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For the remaining 3 strains not included in Table 6, Microcyn also showed antimicrobial activity against these 3 strains despite measuring a microbial reduction of less than 5.0 Log ₁₀ . More specifically, a 30 second exposure to Microcyn reduced the number of Streptococcus pneumoniae (clinical isolate; BSLI #072605Spnl) by more than 4.5 Log ₁₀ , which is the limit of detection for this species. In addition, when challenged with C. tropicalis (ATCC #750), Microcyn resulted in a microbial reduction exceeding 3.0 Log ₁₀ after 30 seconds of exposure. Additionally, when challenged with C. Minutes later resulted in a microbial reduction exceeding 3.0 Log ₁₀ .

The exemplary results of this in vitro time-kill evaluation demonstrate that Microcyn redox potential water has rapid (ie less than 30 seconds in most cases) antimicrobial activity against a broad spectrum of aggressive microorganisms. Within 30 seconds of exposure to the product, 47 of the 50 Gram-positive, Gram-negative and yeast species evaluated had a reduction in microbial load of greater than 5.0 Log ₁₀ .

Example 14

This example demonstrates the example ORP water solution of Microcyn with HIBICLENS Comparison of antimicrobial activity of chlorhexidine gluconate solution 4.0% (w/v) and 0.9% sodium chloride rinse (USP).

葡萄糖酸洗必泰溶液4.0％(w/v)和无菌的0.9％氯化钠冲洗液(USP)作为参照产物，如实施例13所述的进行体外时间-杀伤评价。用在Tentative Final Monograph特别指定的10种美国标准菌库(ATCC)菌株的悬浮液评价每种参照产物。然后分析所收集的数据，并与实施例13所记录的Microcyn的降低微生物的活性进行比较。  Utilize HIBICLENS

Chlorhexidine gluconate solution 4.0% (w/v) and sterile 0.9% sodium chloride rinse (USP) were used as reference products for in vitro time-kill evaluation as described in Example 13. Each reference product was evaluated with suspensions of 10 American Type Culture Collection (ATCC) strains specified in the Tentative Final Monograph. The collected data was then analyzed and compared to the Microcyn's microbial reducing activity reported in Example 13.

在下面的菌种暴露30秒钟之后都使得其微生物减少5.0Log₁₀以上：大肠杆菌(ATCC#11229和ATCC#25922)、铜绿假单胞菌(ATCC#15442和ATCC#27853)、和粘质沙雷菌(ATCC#14756)。此外，如上面表5所示，Microcyn显示出极好的抗藤黄微球菌(ATCC#7468)的抗微生物活性，在30秒暴露后减少了5.8420Log₁₀，但是，直接比较HIBICLENS

的抗藤黄微球菌(ATCC#7468)活性是不可能的，因为在暴露30秒钟后，HIBICLENS

使得菌株数量的减少达到了测试的检出限(在这个具体实例中是超过了4.8Log₁₀)。值得注意的是，无菌的0.9％氯化钠冲洗溶液在充分暴露20分钟后只使得上面所讨论的6种攻击菌株每一种的微生物数量减少小于0.3Log₁₀。  Microcyn redox potential water resulted in a reduction in the number of 5 challenge strains at levels comparable to HIBICLENS Comparable levels were observed with chlorhexidine gluconate solution. Microcyn and HIBICLENS

5.0 Log ₁₀ or more microbial reductions after 30 seconds of exposure to the following species: Escherichia coli (ATCC #11229 and ATCC #25922), Pseudomonas aeruginosa (ATCC #15442 and ATCC #27853), and slime Serratia (ATCC #14756). Furthermore, as shown in Table 5 above, Microcyn showed excellent antimicrobial activity against Micrococcus luteus (ATCC #7468), with a reduction of 5.8420 Log ₁₀ after 30 seconds of exposure, however, direct comparison with HIBICLENS

Activity against Micrococcus luteus (ATCC #7468) was unlikely because after 30 seconds of exposure, HIBICLENS

This resulted in a reduction in the number of strains that reached the limit of detection of the assay (in this particular example, exceeding 4.8 Log ₁₀ ). Notably, the sterile 0.9% sodium chloride rinse solution produced only less than 0.3 Log ₁₀ reduction in microbial counts for each of the 6 challenge strains discussed above after 20 minutes of full exposure.

和氯化钠冲洗更高的抗微生物活性。下面的表总结了这4种菌种的体外时间-杀伤评价的微生物减少的结果：  For the 4 test challenge strains: Enterococcus faecalis (ATCC #29212), Staphylococcus aureus (ATCC #6538 and ATCC #29213), and Staphylococcus epidermidis (ATCC #12228), Microcyn redox potential water provided more than HIBICLENS

and sodium chloride rinse for higher antimicrobial activity. The following table summarizes the microbial reduction results of the in vitro time-kill evaluation for these 4 strains:

Table 7: Comparative sterilization results

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相当的抗大肠杆菌(ATCC#11229和ATCC#25922)、铜绿假单胞菌(ATCC#15442和ATCC#27853)、粘质沙雷菌(ATCC#14756)和藤黄微球菌(ATCC#7468)的抗微生物活性，而且还提供了更为有效地抗粪肠球菌(ATCC#29212)、金黄色葡萄球菌(ATCC#6538和ATCC#29213)、和表皮葡萄球菌(ATCC#12228)的治疗。如表7所示，Microcyn在一些菌种中表现出了更为快速的抗微生物效应(即小于30秒钟)。此外，Microcyn暴露造成了表7所列所有菌种的更大的总体微生物的减少。  The results of this comparative in vitro time-kill evaluation confirmed that Microcyn redox potential water not only exhibited the same

Comparable resistance to Escherichia coli (ATCC #11229 and ATCC #25922), Pseudomonas aeruginosa (ATCC #15442 and ATCC #27853), Serratia marcescens (ATCC #14756) and Micrococcus luteus (ATCC #7468) It also provides more effective treatment against Enterococcus faecalis (ATCC #29212), Staphylococcus aureus (ATCC #6538 and ATCC #29213), and Staphylococcus epidermidis (ATCC #12228). As shown in Table 7, Microcyn showed a more rapid antimicrobial effect (ie less than 30 seconds) in some strains. In addition, Microcyn exposure resulted in greater overall microbial reductions for all species listed in Table 7.

Example 15

This example provides formulations of the invention suitable for topical administration to a patient. The preparation contains the following components:

Number of components

ORP water solution 250mL

聚合物粉(增稠剂)     15g  Carbopol

Polymer powder (thickener) 15g

Triethanolamine (neutralizer) 80mL

Example 16

This example provides formulations of the invention suitable for topical administration to a patient. The preparation contains the following components:

Number of components

ORP water solution 1000mL

Carbopol Polymer powder (thickener) 15g

Triethanolamine (neutralizer) 80mL

Example 17

This example provides formulations of the invention suitable for topical administration to a patient. The preparation contains the following components:

Number of components

ORP water solution 250mL

聚合物粉(增稠剂)   7g  Carbopol

Polymer powder (thickener) 7g

Triethanolamine (neutralizer) 12mL

Example 18

This example describes the production of a formulation of the invention comprising an ORP water solution and a thickener. the

974P聚合物经粗筛(或滤网)，其容许快速筛选，同时能打碎所有大的凝结块。然后加入聚合物Carbopol974P作为增稠剂。缓慢加入Carbopol

聚合物，以避免凝块的形成，并因此避免过长的混合周期。  Pour the ORP water solution into a suitable container such as a glass beaker or bottle. Carbopol

The 974P polymer is passed through a coarse screen (or screen) which allows for rapid screening while breaking up any large clots. Then add the polymer Carbopol 974P acts as a thickener. Slowly add Carbopol

polymer to avoid clot formation and thus avoid excessively long mixing cycles.

聚合物期间快速地混合溶液，使得粉末在室温下溶解。然后向溶液中加入中和剂三乙醇胺，并用电动混合器或其他合适的设备混合，直到获得均匀的凝胶。向Carbopol聚合物组合物中加入中和剂使得制剂变成了凝胶。  After joining Carbopol

The solution was mixed rapidly during polymerisation, allowing the powder to dissolve at room temperature. The neutralizing agent triethanolamine is then added to the solution and mixed with an electric mixer or other suitable equipment until a homogeneous gel is obtained. to Carbopol The addition of a neutralizing agent to the polymer composition turns the formulation into a gel.

Example 19

This example describes the use of the ORP water solution of the present invention for treating burns in children with burns, especially 2nd and 3rd degree burns. the

A total of 64 pediatric burn patients were treated with ORP water solution. The study group was compared with a control group of 64 patients who also received conventional burn treatment. The study group included the following patients: 1 patient with 1st degree burns, 6 patients with combined 1st and 2nd degree burns, 38 patients with 2nd degree burns, 4 patients with 3rd degree burns, 15 patients with combined 2nd and 3rd degree burns . In addition, the study group consisted of patients with the following burn percentages (i.e. burn extent): 10 patients with 0 to 9% burn extent, 27 patients with 10 to 19% burn extent, 11 patients with 20 to 29% burn extent 8 patients with 30 to 39% burn extent, 4 patients with 40 to 49% burn extent, 1 patient with 50 to 59% burn extent, and 3 patients with 60 to 69% burn extent of patients. Initial debridement was performed on each burn. The solution is applied by spraying through high-pressure washing equipment. Next, apply the solution by spray and allow the burn to moisten for 5 to 15 minutes, repeating the process 3 times a day. Do not dress the burn between applications of the solution. the

Of the cultures taken to determine the presence of microorganisms on the burn surface, only six ORP water-treated patients had positive cultures after 7-15 days of hospitalization, compared with 22 in the control group. The remaining patients in the study group (58 cases) and control group (42 cases) had negative cultures. the

Table 8 lists the microorganisms present in the positive cultures in the study and control groups. the

Table 8: Microorganisms in burn injuries

The frequency of administering ORP water solution varies according to the nature of each patient's burn. The mean hospitalization days were tabulated by burn grade for the study and control groups. For first-degree burns, the mean hospital stay was 4.6 days in the study group (6 patients) and 19.2 days in the control group (45 patients). For 2nd degree burns, the mean hospital stay was 10.6 days in the study group (44 patients) and 26.9 days in the control group (9 patients). For third-degree burns, the mean hospital stay was 29.5 days in the study group (14 patients) and 39.8 days in the control group (10 patients). Overall, administration of the ORP water solution of the present invention to pediatric burn patients resulted in a 48% reduction in the average length of hospital stay from 28.6 days to 14.9 days. Table 9 lists the mean length of hospital stay for the control group versus the study group based on the extent of burn injury. the

Table 9: Length of hospital stay

It can be seen from this example that the ORP water solution of the present invention can be beneficially administered to children with burns, resulting in a decrease in hospitalization days. the

Example 20

This example describes the administration of the ORP water solution of the present invention without administration of antibiotics to a pediatric burn patient. the

None of the 58 patients in the study group described in Example 19 above who had negative microbial cultures after 7-15 days of hospitalization were treated with antibiotics. The mean hospital stay for this group of patients was 12.3 days. In the control group, 46 patients received antibiotics in addition to ORP water solution. Positive microbial cultures were observed in 22 of these patients, and the mean hospital stay for these patients on antibiotics was 28.6 days. the

As shown in this example, the ORP water solution of the present invention can be beneficially administered to pediatric burn patients without the routine use of antibiotics. the

Example 21

This example shows the effect of exemplary ORP water solution and hydrogen peroxide (HP) on the viability of human diploid fibroblasts (HDF). To investigate this potential toxicity, HDFs were exposed in vitro to ORP water solution and hydrogen peroxide (HP). HP is known to be toxic to eukaryotic cells, increasing apoptosis and necrosis and reducing cell viability. In this example, cell viability, apoptosis and necrosis were determined in HDF exposed to pure ORP water solution and 880 mM HP (the concentration used for the antibacterial use of HP) for 5 minutes and 30 minutes. the

HDF cultures were obtained from 3 different foreskins, pooled and frozen together for use in this study. All experiments used only diploid cells. In cell cycle analysis, DNA diploidy was defined as the presence of a single G0-G1 peak with a corresponding G2/M peak at a CV ≤ 7% of at least 20,000 total events collected. Figures 4A-4C depict the results, with white and black bars depicting the results for exposure times of 5 and 30 minutes, respectively. Simultaneous analysis of these parameters was performed on the same cell population by flow cytometry using: A) 7-aminoactinomycin D (7AAD), B) Annexin V-FITC and C) propidium iodide. Figures 4A-4C depict percentage values expressed as mean ± SD (n=3). the

Cell viability after 5 min exposure to ORP water solution and HP was 75% and 55%, respectively (Fig. 4A). If the exposure was extended to 30 min, the cell viability was further reduced to 60% and 5%, respectively. ORP water solution apparently induced cell death by necrosis, as 15% of cells incorporated propidium iodide in flow cytometric analysis at both time points (Fig. 4C). While not wishing to be bound by any particular theory, this result may be due to Microcyn's hypotonicity (13 mOsm) induced osmosis, as cells were maintained with ORP water only, with no added growth factors or ions. Apoptosis does not appear to be the mechanism by which ORP water solution induces cell death, as only 3% of ORP water solution-treated cells exposed annexin V, a marker of apoptosis, on their cell surface (Fig. 4B). This percentage is in fact similar to that determined in the control group. In contrast, HP induced necrosis in 20% and 75% of treated cells and apoptosis in 15% and 20% after 5 and 30 min of exposure, respectively. These results together indicate that the (undiluted) ORP water solution is much less toxic to HDF than HP at antimicrobial concentrations. the

Example 22

This example describes the effect of exemplary ORP water solutions relative to hydrogen peroxide (HP) on oxidative DNA damage and formation of the DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) in HDF. Intracellular 8-OHdG adduct formation is known to be a marker of oxidative damage at specific residues of DNA. Additionally, high intracellular levels of this adduct have been associated with mutagenesis, carcinogenesis, and cellular senescence. the

Figure 5 shows the levels of 8-OHdG adducts contained in DNA samples from HDFs after control treatment, ORP water solution treatment and HP treatment for 30 minutes. DNA was extracted immediately after exposure (T0, white bars) or 3 hours after the challenge period (T3, black bars). DNA was digested and 8-OHdG adducts were assayed with an ELISA kit according to the manufacturer's instructions. Values (ng/mL) are represented by mean±SD (n=3). ORP water solution exposure for 30 minutes did not increase adduct formation in treated cells compared to control cells after 30 minutes of incubation. In contrast, treatment with highly diluted HP (low to a sublethal and non-therapeutic HP concentration (500 μM HP)) (500 μM HP for 30 min) resulted in an increase in the amount of 8-OHdG adduct compared to control-treated or ORP water solution The number in treated cells increased about 25-fold. the

ORP water-treated cells were able to reduce the level of 8-OHdG adducts if the cells were left in supplemented DMEM for 3 hours after exposure to ORP water solution. Despite allowing the same 3 hour recovery period, HP-treated cells had approximately 5-fold higher adducts than control-treated or ORP water solution-treated cells. Taken together, these results confirm that acute exposure to ORP water solution does not induce significant DNA oxidative damage. These results also suggest that ORP water solution is unlikely to induce mutagenesis or carcinogenesis either in vitro or in vivo. the

Example 23

This example describes the effect on HDF of chronic exposure to low concentrations of exemplary ORP water solutions and HP. Chronic oxidative stress is known to induce premature senescence of cells. To mimic prolonged oxidative stress, primary HDF cultures were chronically exposed to low concentrations of ORP water solution (10%) or nonlethal HP concentrations (5 μM) during 20 population doublings. SA-β-galactosidase expression and activity have previously been found to correlate with the aging process in vivo and in vitro. In this example, the expression of SA-β-galactosidase was analyzed after 1 month of continuous exposure of HDFs to ORP water solution or HP. Figure 6 shows the results. Expression of SA-β-galactosidase was analyzed by counting the number of blue cells in 20 microscopic fields (see panel A for exemplary staining patterns). Panel B shows that only HP treatment accelerated cell senescence, as indicated by the number of cells overexpressing SA-β-galactosidase (n=3). Chronic treatment with low doses of HP increased the expression of SA-β-Gal in 86% of the cells, whereas treatment with ORP water solution did not induce overexpression of this protein. From this example it can be concluded that ORP water solution is not an inducer of premature cellular senescence. the

Example 24

This example describes the results of toxicity studies using exemplary ORP water solutions. the

Acute systemic toxicity studies were performed in mice to determine the possible systemic toxicity of the exemplary ORP water solution Microcyn 60. A single dose (50 mL/kg) of Microcyn 60 was injected intraperitoneally into 5 mice. Five control mice were injected with a single dose (50 mL/kg) of saline (0.9% sodium chloride). The mortality and adverse reactions of all animals were observed immediately and 4 hours after injection, and then observed once a day for 7 days. All animals were also weighed prior to injection and again on day 7. There were no mortality rates during the study period. All animals were clinically normal throughout the study period. All animals gained body weight. The estimated acute intraperitoneal LD50 of Microcyn 60 from this study is greater than 50 mL/kg. This example demonstrates that Microcyn 60 lacks significant toxicity and should be safe for therapeutic applications of the present invention. the

Example 25

This example describes studies performed to determine the potential cytogenetic toxicity of exemplary ORP water solutions. the

A micronucleus assay was performed using an exemplary ORP water solution (Microcyn 10%) to evaluate the mutagenic potential of the ORP water solution administered intraperitoneally to mice. The mammalian in vivo micronucleus assay has been used to identify agents that cause damage to the chromosomes or mitotic apparatus in polychromatic erythrocytes of mice. This damage results in the formation of "micronuclei," intracellular structures that contain fragments of lagging chromosomes or isolated whole chromosomes. The ORP water solution study included 3 groups, 10 mice (5 males/5 females) in each group: test group (administration of ORP water solution), negative control group (administration of 0.9% NaCl solution) and positive control group (administration of inducible changed cyclophosphamide solution). The test group and the negative control group received intraperitoneal injection (12.5 mL/kg) of ORP water solution or 0.9% NaCl solution, respectively, for 2 consecutive days (Day 1 and Day 2). Positive control mice received a single intraperitoneal injection of cyclophosphamide (8 mg/mL, 12.5 mL/kg) on day 2. All mice were observed for any adverse reactions immediately after injection. All animals appeared clinically normal throughout the study period and no signs of toxicity were noted in either group. On day 3, all animals were weighed and sacrificed. the

Femurs were excised from sacrificed mice, bone marrow was removed, and duplicate bone marrow smears were prepared from each mouse. The bone marrow slides of each animal were read under 40X magnification. The ratio of polychromatic erythrocytes (PCE) to normal chromatin erythrocytes (NCE), an indicator of myelotoxicity, was determined for each mouse by counting a total of at least 200 erythrocytes. Then a minimum of 2000 scoreable PCEs were evaluated for each mouse, and the incidence of polychromatic erythrocytes with micronuclei was calculated. Statistical analysis of the data was performed with the Mann and Whitney test (5% hazard threshold) in the statistical software package (Statview 5.0, SAS Institute Inc., USA). the

Positive control mice had statistically significantly lower PCE/NCE ratios (male: 0.77 vs. 0.90, female: 0.73 vs. 1.02) when compared to their corresponding negative controls, demonstrating the effect of cyclophosphamide on treated bone marrow toxicity. However, there was no statistically significant difference between the PCE/NCE ratios of ORP water solution treated mice and negative controls. Likewise, the positive control mice were statistically significantly better than the ORP water-treated mice (male: 11.0 vs. 1.4, female: 12.6 vs. 0.8) and negative controls (male: 11.0 vs. 0.6, female: 12.6 vs. 1.0). Significantly higher numbers of polychromatic erythrocytes with micronuclei. There was no statistically significant difference between the number of polychromatic erythrocytes with micronuclei in ORP water solution treated mice and negative control mice. the

This example demonstrates that Microcyn 10% does not induce toxicity or mutagenesis after intraperitoneal injection into mice. the

Example 26

This study confirmed the lack of toxicity of the exemplary ORP water solution Dermacyn. the

This study was performed according to the ISO 10993-5:1999 standard to determine the potential of the exemplary ORP water solution Dermacyn to cause cytotoxicity. A filter paper disc containing 0.1 mL of Dermacyn was placed on the surface of the agarose, directly on top of the monolayer of mouse fibroblasts (L-929). The prepared samples were observed for cytotoxic damage after incubation for 24 hours at 37°C in the presence of 5% CO ₂ . Compare the observations with the positive and negative control samples. Samples containing Dermacyn did not show any evidence of cell lysis or toxicity, while positive and negative controls behaved as expected.

From this study, it was concluded that Dermacyn does not exert cytotoxic effects on mouse fibroblasts. the

Example 27

This study was performed with 16 rats to evaluate the local tolerance of Dermacyn, an exemplary ORP water solution, and its effect on the histopathology of the wound bed in a full-thickness skin wound healing model. Wounds were made on both sides of the subject rats. During the healing process, left or right skin sections (eg, Dermacyn-treated and saline-treated, respectively) are removed. the

A board-certified veterinary pathologist evaluated Masson's trichrome-stained sections and type II collagen-stained sections of Dermacyn- and saline-treated surgical wound sites. The sections were evaluated for the amount of collagen type 2 expression, fibroblast morphology and collagen formation, appearance of neo-epithelium, inflammation and degree of skin ulceration in transverse sections as evidence of desmoplasia. the

The results indicated that Dermacyn was well tolerated by rats. There were no treatment-related histopathological lesions in skin sections from either side of the wound (Dermacyn-treated and saline-treated, respectively). There were no relevant histopathological differences between saline-treated and Dermacyn-treated wound sites, indicating that Dermacyn treatment was well tolerated. There were no significant differences in type 2 collagen expression between saline-treated and Dermacyn-treated wound sites, suggesting that Dermacyn has no adverse effects on fibroblasts or on collagen production processing during wound healing. the

Example 28

This study can be used to demonstrate the safety and efficacy of Dermacyn, an exemplary ORP water solution used in the present invention, as a replacement solution for the Versajet ^™ (Smith & Nephew) spray irrigation system for the treatment of necrotic tissue (ulcers) in the distal ankle, and compared to standard protocols. Compare.

This is a prospective, randomized controlled, double-blind study. About 30 patients were enrolled in the study (about 20 in the Dermacyn group and about 10 in the control group). The study population was patients with lower extremity ulcers (eg diabetic foot ulcers, venous stasis ulcers). At Day 0, all patients eligible for study inclusion must meet all study inclusion and exclusion criteria. Inclusion criteria were: patients aged ≥18 years; patients with lower extremity ulcers showing necrotic tissue and candidates for mechanical debridement via irrigation systems; patients with ulcers located distal to the ankle; patients with ulcer surface areas greater than or Equal to 1.0 cm ² ; patient's ulcer extends through dermis into subcutaneous tissue (granulation tissue may be present), and may expose muscle or tendon, but no bone and/or joint capsule involvement; patient's ankle-arm Index (ABI) greater than or equal to 0.8, or the patient's toe pressure greater than or equal to 40mmHg.

Exclusion criteria were: clinical evidence of gangrene in any part of the patient's treated limb; patient's ulcer expected to require excision or amputation during the study; patient with the following signs of systemic inflammatory response syndrome (SIRS); patient's ulcer Total surface area less than 1 cm ² ; patient has one or more medical conditions (including renal, hepatic, hematological, neurological or immune disease) that make the investigator consider the patient unsuitable for this study; patient is known to have active alcohol or drug abuse ; the patient is receiving oral or parenteral glucocorticoids, immunosuppressants, or cytotoxic agents, or is expected to need these drugs during the study; the patient is known to be allergic to chlorine; the patient has osteomyelitis associated with the ulcer; and the patient has Any medical condition that would seriously impede the patient's ability to complete this study.

After signing informed consent and meeting inclusion and exclusion criteria, patients were randomized (2:1 randomization) to one of the following treatments: Treatment group: Dermacyn application with a spray irrigation system, plus application of a hydrogel wound dressing Protocol; control group: saline (standard treatment with spray irrigation system), plus application of a hydrogel wound dressing protocol. the

Each patient randomized to Dermacyn will receive the investigational product, Dermacyn, administered via the Versajet Spray System during mechanical debridement of the patient's wound. The standard compression device on the Versajet will be used for diabetic foot ulcers located distal to the ankle. Following debridement, apply Dermacyn to the wound in an amount sufficient to wash away all debris from the wound bed. Cover the wound with a hydrogel dressing. At each dressing change, rinse the wound with Dermacyn and cover the wound with a new hydrogel dressing. Dressings were changed every 3 days unless otherwise specified by the investigator. Clinical response factors (CFR) ((1) reduction in wound bacteria; (2) reduction in wound area; and (3) development of granulation tissue) were determined during weekly visits. the

Each control patient will receive a control product (saline solution) administered via the Versajet Spray System during mechanical debridement of the patient's wound. Following debridement, saline is applied to the wound in an amount sufficient to wash away all debris from the wound bed. Cover the wound with a hydrogel dressing. At each dressing change, the wound was rinsed with saline and covered with a new hydrogel dressing. Dressings were changed every 3 days unless otherwise specified by the investigator. Clinical response factors were determined during weekly visits. the

Wound debridement may be performed at weekly visits. Prior to wound evaluation, any necrotic tissue was removed with the irrigation system. Dermacyn or saline (depending on randomization) was used to wash away debris from the ulcer. Between visits, patients will irrigate the wound with Dermacyn or saline (depending on randomization) at each dressing change. After debridement at each visit, pictures of the wound were taken. the

The primary efficacy endpoints were: (1) reduction in wound bacteria; (2) reduction in wound area; and (3) development of granulation tissue. Safety was evaluated for all randomized patients in the study. Treatment of urgent and serious adverse events was documented. the

Example 29

This study will demonstrate the safety and efficacy of an exemplary ORP water solution, Dermacyn, as an alternative to the Jet-Ox ND Irrigation System for the treatment of necrotic tissue in leg ulcers and compare it with the standard protocol used with the Jet-Ox ND System. the

The Jet-Ox ND system removes necrotic tissue in chronic wounds through controlled irrigation of sterile saline without damaging underlying healthy tissue. This study will replace saline with Dermacyn, which is expected to provide the same spray washing effect and also reduce the bacterial load in the wound which may inhibit wound closure. the

Twenty patients were studied (randomized into 10 Dermacyn patients and 10 control patients). Inclusion criteria were: patient age greater than 18 years; patient had a below-knee lower extremity ulcer with necrotic tissue and was a candidate for mechanical debridement with the Jet-Ox ND irrigation system; >30 days present; ulcer surface area >1 cm ² ; extension of ulcer through dermis into subcutaneous tissue (granulation tissue may be present), and possible exposure of muscle or tendon, but not exposed bone and/or joint capsule; patients measured by Doppler Ankle/arm index > 0.8 and/or patient's toe pressure >40mmHg; palpable dorsalis pedis and/or posterior tibial artery pulse.

The exclusion criteria are as follows: patients with impaired kidney, liver, blood, nerve or immune function, including human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS); the investigator believes that the patient is not suitable for participating in this study; Wounds with the following clinical signs of infection; gangrene in any part of the treated limb; ulcers showing bone (palpable bone) or other evidence of underlying osteomyelitis at the site of the ulcer; infected ulcers expected to be amputated during treatment or resection; severe malnutrition as indicated by albumin <2.0; known alcohol or drug abuse; patient is receiving oral or parenteral corticosteroids, immunosuppressant or cytotoxic drugs, coumarins, heparin, or The need for these drugs is anticipated during treatment; and the patient is known to be allergic to chlorine. the

Each individual was randomized to one of two treatment groups: Dermacyn or saline. Target ulcers will undergo mechanical debridement, followed by irrigation of the wound with Dermacyn or saline, and dressing of the wound with a hydrogel dressing. Central wound biopsies were taken for quantitative cultures, as well as laboratory studies (hematology, serum chemistry, and pregnancy tests where appropriate), noninvasive peripheral vascular studies, history and physical examination, ulcer tracking, and ulcer photographs. the

The Jet-Ox ND Irrigation System can be administered with Dermacyn or saline, hydrogels, and wraps. Instructions for home administration are provided. Visits include screening, enrollment (day 0) and randomization, weekly visits for debridement, photography and evaluation. Efficacy was assessed by (1) reduction in wound bacteria; (2) reduction in wound area; and (3) development of granulation tissue during the study period. Safety was evaluated for all randomized patients in the study. Treatment of urgent and serious adverse events was documented. the

All references, including publications, patent applications, and patents, cited herein are incorporated by reference into this application to the same extent as if each reference were individually and specifically indicated to be incorporated by reference into this application and herein. Listed in full. the

The use of the terms "a" and "the" and similar references in the context of describing the present invention (especially in the context of the following claims) should be understood to encompass both the singular and the plural, unless otherwise specified herein Explanation or explicit negation. The terms "including", "having", "comprising" and "containing" are to be construed as open-ended terms (ie meaning "including but not limited to"), unless stated otherwise differently. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were are stated here individually. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (eg, "such as") provided herein, is intended merely to better illustrate the invention and is not intended to limit the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. the

Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend that the invention may be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, the invention encompasses any combination of the above-described elements in all possible variations unless otherwise stated otherwise herein or otherwise clearly contradicted by the context. the

Claims (38)

1. Use of an oxidation-reduction potential aqueous solution for the preparation of a medicament for treating 2nd or 3rd degree burns in a patient, wherein the pH of the solution is 6.4 to 7.8, and it remains stable for at least 2 months, wherein the oxidative The reduction potential aqueous solution is produced by equipment comprising the following: A three-compartment electrolysis cell having an anode compartment, a cathode compartment, and a brine solution compartment between the anode and cathode compartments, wherein the anode compartment is separated from the brine solution compartment by a metal anode electrode and an anion exchange membrane, and wherein separating the cathode compartment from the brine solution compartment by a metal cathode electrode and a cathode ion exchange membrane; wherein the anode chamber has an inlet and an outlet for water to flow through the anode chamber; wherein the cathode chamber has an inlet and an outlet for water to flow through the cathode chamber; wherein the saline solution chamber has an inlet and an outlet; Water sources for the anode and cathode chambers; a saline solution recirculation system providing saline solution to the saline solution chamber; at least one liquid supply system for circulating liquid through the saline solution chamber; an anode inlet pipe connecting the water supply system to the anode chamber; a cathode inlet pipe connecting the water supply system to the cathode chamber; an intermediate inlet pipe connecting the saline solution chamber to the liquid supply system; a source of electrical potential connected to said anode electrode and said cathode electrode; an anode outlet pipe for transporting anode water out of said anode chamber; a cathode outlet pipe for transporting cathode water out of said cathode chamber; and At least one mixing vessel for collecting anode water and cathode water transported from said electrolysis unit. 2. The use of claim 1, wherein the solution remains stable for at least 1 year. 3. Use according to claim 2, wherein the pH is from 7.4 to 7.6. 4. Use according to claim 1, wherein the solution comprises anolyte water and catholyte water. 5. The use according to claim 4, wherein the amount of cathode water contained is 10% by volume to 50% by volume of the solution. 6. The use according to claim 5, wherein the amount of cathode water contained is 20% by volume to 40% by volume of the solution. 7. The use according to claim 5, wherein the anode water is contained in an amount ranging from 50% by volume to 90% by volume of the solution. 8. The use of claim 4, wherein the solution is administered to the patient by spraying the solution on the burn. 9. Use according to claim 8, wherein the solution is administered to the patient by spraying said solution on the burn with a high pressure irrigation device. 10. The use of claim 8, wherein the burn is moistened with the solution for at least 5 minutes. 11. The use of claim 10, wherein the burn is moistened with the solution for at least 15 minutes. 12. The use of claim 4, wherein the solution is administered to the patient at least daily. 13. The use of claim 12, wherein the solution is administered to the patient 3 times per day. 14. The use of claim 1, wherein said solution comprises at least 1 free chlorine species. 15. The use of claim 14, wherein the free chlorine species is selected from the group consisting of hypochlorous acid, hypochlorite ions, chlorite ions, chloride ions, dissolved chlorine gas, and mixtures thereof. 16. Use according to claim 14, wherein the amount of free chlorine species is from 10 ppm to 400 ppm. 17. Use according to claim 16, wherein the free chlorine species is hypochlorous acid in an amount from 15 ppm to 35 ppm. 18. The use of claim 16, wherein the free chlorine species is hypochlorite ion, wherein said hypochlorite ion is provided by sodium hypochlorite in an amount from 25 ppm to 50 ppm. 19. The use of claim 14, wherein the solution is administered to the patient by spraying the solution on the burn. 20. The use of claim 19, wherein the solution is administered to the patient by spraying the solution on the burn with a high pressure irrigation device. 21. The use of claim 19, wherein the burn is moistened with the solution for at least 5 minutes. 22. The use of claim 21, wherein the burn is moistened with the solution for at least 15 minutes. 23. The use of claim 14, wherein the solution is administered to the patient at least daily. 24. The use of claim 23, wherein the solution is administered to the patient 3 times per day. 25. The use of claim 1, wherein the solution comprises hypochlorous acid in an amount from 15 ppm to 35 ppm and sodium hypochlorite in an amount from 25 ppm to 50 ppm. 26. The use of claim 25, wherein the solution is administered to the patient by spraying the solution on the burn. 27. The use of claim 26, wherein the solution is administered to the patient by spraying the solution on the burn with a high pressure irrigation device. 28. The use of claim 26, wherein the burn is moistened with the solution for at least 5 minutes. 29. The use of claim 28, wherein the burn is moistened with the solution for at least 15 minutes. 30. The use of claim 25, wherein the solution is administered to the patient at least daily. 31. The use of claim 30, wherein the solution is administered to the patient 3 times per day. 32. The purposes of claim 1, wherein said treatment comprises (1) spray oxidation-reduction potential (ORP) aqueous solution to burn with high pressure; (2) soak burn with ORP aqueous solution optionally; (3) spray ORP aqueous solution to burn; and (4) moistening the burn with the ORP water solution. 33. The use of claim 32, wherein the burn is treated with debridement prior to spraying. 34. The use of claim 32, wherein no antibiotics are administered to the patient during the treatment of the burn. 35. The use of claim 32, further comprising applying a skin graft to the patient. 36. The use of claim 32, wherein steps (3)-(4) are repeated 3 times per day. 37. The use of claim 32, wherein steps (1)-(4) are repeated until the burn is fully healed. 38. The use of claim 32, further comprising administering an antibiotic to the patient.

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