HK1116340B

HK1116340B - Method of treating second and third degree burns using oxidative reductive potential water solution

Info

Publication number: HK1116340B
Application number: HK08106681.3A
Authority: HK
Inventors: H．阿里米
Original assignee: 奥古露丝创新科学公司
Priority date: 2005-03-23
Filing date: 2006-03-23
Publication date: 2013-10-11

Description

Method for treating 2 degree and 3 degree burn using oxidation-reduction potential water solution

Cross reference to related patent applications

This patent application claims priority from the following U.S. provisional patent applications: 60/760,635 filed on month 1 and 20 of 2006, 60/760,567 filed on month 1 and 20 of 2006, 60/760,645 filed on month 1 and 20 of 2006, 60/760,557 filed on month 1 and 20 of 2006, 60/730,743 filed on month 10 and 27 of 2005, 60/676,883 filed on month 5 and 2 of 2005, 60/667,101 filed on month 3 and 31 of 2005, and 60/664,361 filed on month 3 and 23 of 2005, the entire contents of which are incorporated herein by reference.

Technical Field

The present invention relates to a method of treating burns, preferably 2 and 3 degree burns, by administering an oxidative reductive potential water solution.

Background

Oxidation Reduction Potential (ORP) water (also known as super oxidized water) can be used as a non-toxic disinfectant to eliminate microorganisms including bacteria, viruses, and spores in a variety of contexts. For example, ORP water may find application in the field of health care and medical instruments for disinfecting surfaces and medical equipment. Advantageously, the OPR water is environmentally safe, thus avoiding the need for expensive disposal operations. ORP water may also find application in wound care, medical device sterilization, food sterilization, hospitals, consumer homes, and in anti-bioterrorism applications.

Although ORP water is an effective disinfectant, it has a very limited shelf life, usually only a few hours. Because of this short lifetime, ORP water production must be performed in close proximity to the site where ORP water is used as a disinfectant. This means that a health care unit such as a hospital must purchase, place and maintain the equipment necessary to produce ORP water. In addition, existing production technologies have not been able to produce ORP water in sufficient commercial scale quantities to allow it to be widely used as a disinfectant for health care units.

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

ORP water has also been used as a growth promoter for patient tissue cells, as described in U.S. patent application publication 2002/0160053A 1. Infection remains a problem in wound care, particularly with the emergence of multiple antibiotic-resistant bacteria. Such infections include, for example, Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and the like. Thus, there is a need for ORP water-containing compositions for use in the treatment of burns to prevent infection. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.

Brief description of the invention

The present invention provides a method of treating burns in a patient by administering an Oxidative Reduction Potential (ORP) water solution, wherein the solution remains stable for at least 24 hours. The invention also relates to a method of treating a burn in a patient by administering an oxidative reductive potential water solution, wherein the solution comprises anodic water and cathodic water. In one embodiment, the ORP water solution used in the method of the invention comprises one or more chlorine species.

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

The invention also provides a method of disinfecting a surface, the method comprising contacting the surface with an anti-infective amount of the ORP water solution, wherein the solution remains stable for at least 24 hours. The surface may be a biological surface, an inanimate surface, or a combination of these surfaces, which may 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 devices.

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

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

In addition, the present invention relates to a method 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 invention also provides a method of promoting wound healing in a patient comprising applying to a wound a formulation comprising an oxidative reductive potential water solution and a thickening agent, wherein the amount of the formulation applied is sufficient to promote wound healing, and wherein the formulation remains stable for at least about 24 hours.

The 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 oxidative reductive potential water solution and a thickening agent, wherein the formulation remains stable for at least about 24 hours.

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

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

The invention also relates to a process for producing an oxidative reductive potential water solution comprising providing at least one electrolytic cell, wherein the electrolytic cell comprises an anode compartment, a cathode compartment and a brine compartment located between the anode compartment and the cathode compartment, wherein an anode electrode and a first membrane separate the anode compartment from the brine compartment and a cathode electrode and a second membrane separate the cathode compartment from the brine compartment; providing a flow of water through the anode chamber and the cathode chamber; providing a flow of saline solution through a saline solution chamber; simultaneously supplying current to the anode electrode and the cathode electrode with a flow of water through the anode chamber and the cathode chamber and a flow of brine through the brine chamber; and collecting the oxidative reductive potential water solution produced by the electrolytic cell, wherein the solution comprises anode water and cathode water.

Brief description of the drawings

FIG. 1 is a schematic of a three-compartment electrolytic cell for producing an oxidative reductive potential water solution of the present invention.

FIG. 2 illustrates a three-compartment electrolytic cell and depicts ionic species generated therein.

FIG. 3 is a schematic flow diagram of a process for producing oxidation-reduction potential water of the present invention.

FIGS. 4A-4C depict graphical comparisons of cell viability, apoptosis, and necrosis of human skin fibroblasts (HDF) treated with an exemplary ORP water solution (MCN) and Hydrogen Peroxide (HP).

FIG. 5 is a graphical comparison of 8-hydroxy-2' -deoxyguanosine (8-OHdG) adduct levels in HDF treated with an exemplary ORP water solution (MCN) and 500 μ M Hydrogen Peroxide (HP).

FIGS. 6A-6B illustrate the expression of senescence-associated β -galactosidase in HDF after chronic exposure to low concentrations of an exemplary ORP aqueous solution (MCN) and Hydrogen Peroxide (HP).

Detailed Description

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 Oxidative Reductive Potential (ORP) water 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 invention.

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. One skilled in the art will recognize that the specific dosage level for any particular patient will depend upon a variety of factors. For example, the dosage may be determined based on the strength of the particular ORP water solution employed, the severity of the condition, the weight of the patient, the age of the patient, the physical and mental status of the patient, general health, sex, diet, and the like. The size of the dose may also be determined by the occurrence, nature and extent of any adverse side effects that may accompany the administration of a particular ORP water solution. It is desirable to keep adverse side effects to a minimum whenever possible.

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

The ORP water solution of the invention may be administered therapeutically to a patient, such as a human, alone or in combination with one or more other therapeutic agents, for example, to treat an existing condition. The ORP water solution of the invention may also be administered prophylactically to a patient, such as a human, who has been exposed to one or more disease causing factors associated with a condition, either alone or in combination with one or more other therapeutic agents. For example, an ORP water solution of the invention may suitably be 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 to reduce the severity of infection caused by such exposure.

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

When an effective level is used as a preferred endpoint for administration, the actual dosage and schedule may vary depending, for example, on the differences in pharmacokinetics, distribution, metabolism, etc., between individuals. Effective levels may also vary when the ORP water solution of the invention is used in combination with one or more therapeutic agents other than the ORP water solution of the invention, such as one or more anti-infective agents, one or more "demulcents", "regulators" or "neutralizers" (such as described in U.S. Pat. Nos.5,334,383 and 5,622,848), one or more anti-inflammatory agents, and the like.

Appropriate indications may be used to determine and/or monitor the effective level. For example, an effective level can be determined by direct analysis (e.g., analytical chemistry) or indirect analysis (e.g., clinical chemistry indicators) of a suitable patient sample (e.g., blood and/or tissue). Effective levels can also be determined, for example, by direct or indirect observation of, for example, urine metabolite concentrations, changes in condition-associated markers (e.g., viral counts in viral infections), histopathological and immunochemical analyses, alleviation of condition-associated symptoms, and the like.

The ORP water used in the present invention may be administered using any suitable administration method known in the art. The ORP water used in the present invention may be administered in combination with one or more pharmaceutically acceptable carriers, vehicles, adjuvants, excipients, or diluents known in the art. One skilled in the art can readily determine suitable formulations and methods of administration for administering ORP water of the present invention. Depending on other factors such as side effects, changes in the overall condition of the patient, etc., any necessary dosage adjustments can be readily made by those skilled in the art to more closely match the nature or severity of the condition being treated.

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

Methods and apparatus for aerosolization, spraying, and atomization are well known in the art. For example, medical nebulizers are used to deliver metered doses of physiologically active liquids to an inspiratory airflow for inhalation by a subject. See, for example, U.S. patent No.6,598,602. A medical vaporizer can be operated to generate liquid droplets that, together with an inhalation gas, form an aerosol. In other cases, medical nebulizers may be used to inject small droplets of water into an inspiratory gas stream, providing the subject with gas having a suitable moisture content, which is particularly useful when the inspiratory gas stream is provided by a mechanical respiratory assistance such as a ventilator, or anesthesia delivery system.

An exemplary nebulizer is described, for example, in WO95/01137, which describes a handheld device that operates to project droplets of a medical liquid into a passing stream of air (inhalation stream) generated by the inhalation of a subject through a mask. Another example can be seen in us patent No.5,388,571, which describes a positive airway pressure system that provides respiratory control and augmentation to patients with respiratory insufficiency, which includes a nebulizer that delivers liquid drug particles to the airways and alveoli of the patient. Us patent No.5,312,281 describes an ultrasonic atomizer which can atomize water or liquid at low temperatures and reportedly can adjust the size of the mist. In addition, U.S. patent No.5,287,847 describes a pneumatic nebulizer with variable flow rate and output volume that can be used to deliver drug aerosols to newborns, children, and adults. In addition, U.S. patent No.5,063,922 describes an ultrasonic nebulizer.

The methods of the invention may also be used to prevent or treat infections that may be treated with the ORP water solution of the invention. The infection may be caused by one or more infectious pathogens, such as infectious microorganisms. These microorganisms may include, for example, viruses, bacteria, and fungi. The virus may comprise, 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 atrophaeus. The methods of the invention may also be used to prevent or treat inflammatory conditions or allergic reactions, which may be treated with the ORP water solution of the invention.

In addition, organisms that can be controlled, reduced, killed or eliminated by treatment with the ORP aqueous solution used according to the invention include, for example, Pseudomonas aeruginosa, Escherichia coli, enterococcus Hirshi, Acinetobacter baumannii, Acinetobacter, Bacteroides fragilis, Enterobacter aerogenes, enterococcus faecalis, vancomycin-resistant enterococcus faecium (VRE, MDR), Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Micrococcus luteus, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus human, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes, Salmonella choleraesuis, Shigella dysenteriae, and other susceptible bacteria, as well as yeasts such as Trichophyton mentagrophytes, Candida albicans, and Candida tropicalis. ORP water solutions may also be used in accordance with the present invention to control, reduce, kill or eliminate viruses including, for example, adenovirus, Human Immunodeficiency Virus (HIV), rhinovirus, influenza virus (e.g., influenza A), hepatitis virus (e.g., hepatitis A), 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.

In another embodiment, the method of the invention comprises parenteral administration of the ORP water solution of the invention. Parenteral administration may include intravenous, subcutaneous, intramuscular or intraperitoneal administration of the ORP water solution of the invention. In a preferred embodiment, the ORP water solution of the invention is administered intravenously, according to the method of the invention, to prevent or treat a disorder. Suitable conditions may include, for example, viral myocarditis, multiple sclerosis, and AIDS. See, e.g., U.S. Pat. Nos.5,334,383 and 5,622,848, which describe methods of treating viral myocarditis, multiple sclerosis, and AIDS by administering ORP water solutions intravenously.

The invention also provides a method of treating damaged or injured tissue, the method comprising contacting the damaged or injured tissue with a therapeutically effective amount of the ORP water solution of the invention. Damaged or injured tissue may be contacted by any suitable method for treating damaged or injured tissue according to the present invention. For example, damaged or injured tissue may be treated according to the invention by flushing the tissue with the ORP water solution of the invention so that the damaged or injured tissue comes into contact with the ORP water. Alternatively (and additionally), the ORP water solution of the invention may be administered in the form of a vapour or spray or by aerosol, spray or nebulisation as described herein, such that damaged or injured tissue comes into contact with the ORP water.

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

The methods of the present invention also include treating tissue that has been damaged or injured by one or more burns, cuts, abrasions, scrapes, rashes, ulcers, punctures, combinations thereof, and the like, which damage or injury is not necessarily caused by surgery. The methods of the invention may also be used to treat infected damaged or injured tissue or tissue damaged or injured by infection. These infections may be caused by one or more infectious pathogens, for example one or more microorganisms selected from the group consisting of viruses, bacteria and fungi, as described herein.

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

The method of the present invention may be used to disinfect a surface that is biological, inanimate, or a combination thereof. The biological surface may 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 may also include muscle tissue, bone 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, muscles, etc. that may be exposed during surgery may be sterilized to maintain sterility of the surgical environment.

The invention also provides a formulation for topical administration comprising an Oxidative Reduction Potential (ORP) aqueous solution and a thickening agent, the formulation being formulated to provide enhanced efficacy and stability.

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

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

The formulations for topical administration according to the invention also comprise a thickening agent. Any suitable thickener can be used to produce a formulation having the desired viscosity, which is generally higher than 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 hydroxyethyl cellulose. Suitable polymers may be homopolymers or copolymers, and are optionally crosslinked. Other suitable thickeners are well known in the art (see, e.g.Handbook of Cosmetic and Personal CareAdditives2nd ed., Ashe et al. eds. (2002), andHandbook ofPharmaceutical Excipients，4th ed.，Rowe et al.eds.(2003))。

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

such polymers are sold under the trade name Carbopol by NoveonAnd (5) selling. CarbopolPolymers are commonly used as rheology modifiers for a variety of applicationsThickeners, suspending agents and stabilizers in personal care products, pharmaceuticals, and household cleaners. Carbopol may be used in solid (e.g. powder) or liquid formA polymer.

The acrylic-based polymer suitable for use in the present invention may be a homopolymer or a copolymer. Suitable homopolymers may preferably be crosslinked with allyl sucrose or allyl pentaerythritol. Suitable acrylic copolymers are long-chained (C)₁₀-C₃₀) Alkyl acrylates, and may preferably be cross-linked with allyl pentaerythritol.

Neutralization of Carbopol to achieve maximum viscosityA polymer. Carbopol is providedPolymers are dry, tightly curled acidic molecules that retain the curled structure through hydrogen bonding. Once they are dispersed in water or another solvent, they begin to hydrate and partially unwrap. By CarbopolThe most common way of achieving maximum thickening of the polymer is to convert the acidic polymer into a salt. This is readily achieved by neutralization with a common base such as sodium hydroxide (NaOH) or Triethanolamine (TEA). This neutralization causes the long chain polymer to "unwind," swelling the molecule into an effective thickened form.

Suitable thickeners will provide the desired viscosity to the formulation as well as other characteristics such as appearance, shear resistance, ionic resistance and thermal stability. For example, for suspension or emulsion (rather than clear gel) formulations having a viscosity greater than 3000 centipoise (cps), Carbopol934 is preferred. Carbopol may also be used due to its beneficial bioadhesive properties974P。

The formulations of the present invention may contain any suitable amount of thickener 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.

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

When a low concentration of acrylic acid-based polymer is used, the formulation flows fairly smoothly. 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 formulations of the present invention may optionally include a neutralizing agent. Any suitable neutralizing agent may 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., seeHandbook of Cosmetic and Personal Care Additives2nd ed., Ashe et al. eds. (2002), andHandbook of PharmaceuticalExcipients, 4th ed., Rowe et al. eds. (2003)). Suitable neutralizing agents may be in liquid or solid form.

Preferably, when the thickener is an acrylic acid-based polymer such as CarbopolWhen in use, neutralizing agent triethanolamine is used. The neutralizing agent converts the formulation into a gel.

The formulations of the present invention may include any suitable amount of 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. 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, by volume.

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

The formulation 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-anthracenedione bis (2-propenoic acid) ester copolymer, and the like. Any suitable fragrance may be used.

The formulations of the invention may be prepared by any suitable method. The components of the formulation, for example 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 using an electric mixer or other suitable device for several minutes to ensure uniformity. The components of the formulation are typically mixed from about 400rpm to about 1000rpm, preferably from about 500rpm to about 800rpm and more preferably from about 500rpm to about 600 rpm.

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

When the thickener is in powder form, the thickener may be sieved first, breaking up large agglomerates, to allow for the preparation of a uniform formulation.

A neutralizing agent such as triethanolamine can then be added to the formulation containing the ORP water solution and the thickener. As mentioned above, the addition of triethanolamine may allow for the addition of thickeners such as CarbopolUncrimped, thereby producing a formulation having a desired viscosity.

Thickening agents such as Carbopol may also be usedThe colorant or fragrance is added to the mixture before or after dissolution in the ORP water, but must be 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. The performance of the ORP water solution is retained even after the addition of the thickener and optional neutralizing agent. For example, the stability and pH of the ORP water solution itself and the formulation containing the ORP water solution are generally the same. Thus, all of the features of the ORP water solution described herein are applicable to the formulations of the present invention.

For example, the formulations of the present 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 remains stable for at least 6 months after its preparation. Even more preferably, the formulation remains stable for at least 1 year and most preferably for at least 3 years.

The pH of the formulation is typically 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 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 and the like, all of which are known in the art (see, e.g., Modern pharmaceuticals, 3rd ed., Banker et al, 1996). Gels are generally semisolid emulsions or suspensions having a three-dimensional structure. Preferably, the formulation is in the form of a gel.

Pastes are generally semi-solid suspensions, often containing a majority of solids (e.g., from about 20% to about 50%) dispersed in an aqueous or fatty carrier. Lotions are typically liquid emulsions containing a water-based carrier and a propellant (over 50%) with a sufficiently low viscosity (less than 30,000cps) to be poured. Ointments and creams are generally semisolid emulsions or suspensions that may contain, as part of a carrier, a hydrocarbon or polyethylene glycol, as well as other volatile components.

When the formulation of the present invention is 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 15,000cps, about 20,000cps, about 25,000cps, about 30,000cps, about 35,000cps, about 40,000cps, about 45,000cps, about 50,000 cps, about 55,000cps, about 60,000cps, about 65,000cps, about 70,000cps, about 75,000cps, about 80,000cps, about 85,000cps, about 90,000cps, about 95,000cps, or a range thereof) at about room temperature (e.g., about 25 ℃).

The pH of the gel is typically from about 6.0 to about 8.0. Above this pH, thickeners such as CarbopolThe viscosity of the polymer may decrease, resulting in an unsatisfactory topical formulation. 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, in order to treat a variety of conditions. In particular, the 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 routes of administration to the skin as well as oral, intranasal, intrabronchial and rectal.

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

Conditions that may be treated by the present invention include, for example, the following: surgical/developmental wound cleansers, skin pathogen disinfection (e.g., bacteria, mycoplasma, viruses, fungi, prions), wound disinfection (e.g., war wounds), wound healing promotion, burn healing promotion, treatment of dermatophytes, psoriasis, athlete's foot, ear infections (e.g., swimmer's ear), traumatic wounds, acute, sub-chronic and chronic infections (e.g., diabetic foot infection is an example of the latter), pressure ulcers, skin abrasion, debrided wounds, laser resurfacing, donor site/graft, exuding partial and full-thickness wounds, superficial injuries (lacerations, cuts, abrasions, small skin irritations), and other medical applications on or within the human or animal body. The ulcers treated according to the present invention may or may not have abscess or necrotic tissue present.

In addition, the present invention relates to a method of promoting wound healing in a patient by applying to the wound a formulation comprising an oxidative reductive potential water solution and a thickening agent. The wound to be treated may be caused by any surgery, ulcer or other means. Ulcers that may be treated include, for example, diabetic foot ulcers.

The 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, the formulation (e.g., in gel form) may be used as a barrier against infection over an open wound. In particular, the formulation (e.g., in gel form) may be applied to the surface of wounds such as diabetic foot ulcers, which are prone to neurological and vascular complications. The applied formulation can thus provide a barrier to infection, as these wounds are the major portals of infection for diabetic patients.

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

A therapeutically effective amount of a formulation of the present invention may be used or administered to provide the desired therapeutic effect on bacteria, viruses and/or pathogens. A therapeutically effective amount herein means an amount of the agent that results in an improvement in 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. One skilled in the art understands that the efficacy of the formulation of the invention obtained by administration of the formulation can be short-term (e.g., days) and/or long-term (e.g., months).

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

The ORP water solution or formulation thereof may be administered by any suitable means. For example, a quantity of the formulation may be applied to the surface of the patient being treated and then the patient applies it evenly with his or her fingers. Alternatively, the medical practitioner can apply the formulation to the tissue of the patient. The formulation may be applied with a suitable device, such as a disposable wipe or cloth.

The ORP water of the present invention is produced by a redox process, which may be referred to as an electrolysis or redox reaction, in which chemical changes in an aqueous solution are produced with electrical energy. Electrical energy is introduced into and transported through water by conducting electrical charge in the form of an electrical current from one point to another. In order for the current to occur and be maintained, the water must have charge carriers and must have a force that causes the carriers to move. The charge carriers may be electrons for metals and semiconductors or positive and negative ions for solutions.

In the method for producing 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 WO03/048421A 1.

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

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

The ORP water solution of the present invention may be acidic, neutral or basic, and the pH is generally from about 1 to about 14. At this pH, a suitable amount of ORP water solution can be safely applied to a hard surface without damaging the surface or injuring 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 oxidation-reduction potential of the ORP water solution of the present invention is generally from about-1000 millivolts (mV) to about +1350 millivolts (mV). This potential is a measure of the tendency (i.e., potential) of a solution to accept or transfer electrons, as sensed by a metal electrode and compared to a reference electrode in the same solution. This potential can be determined by standard techniques, including, for example, by measuring the millivolt potential of the ORP aqueous solution relative to a standard reference silver/silver chloride electrode. The potential of ORP water is generally from about-400 mV to about +1300mV or about +1150 mV. Preferably, the potential of the ORP water solution is from about 0mV to about +1250mV, more preferably from about +500mV to about +1250 mV. Even more preferably, the potential of the ORP water of the present invention is from about +800mV to about +1100mV, and most preferably from about +800mV to about +1000 mV.

A variety of different ionic and other species may be present in the ORP water solution of the present invention. For example, the ORP water solution can contain chlorine (e.g., free chlorine and bound chlorine), and optionally ozone and peroxides (e.g., hydrogen peroxide). It is believed that the presence of one or more of these species provides the ORP water solution with a disinfectant capacity that kills a variety of microorganisms, such as bacteria, fungi, and viruses.

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 depends on the pH. At a pH of 7.4, the hypochlorous acid level is from about 25ppm to about 75 ppm. The temperature also affects the proportion of the free chlorine component.

Bound chlorine is chlorine in chemical combination with ammonia or an organic amine (e.g., chloramine). The level of bound chlorine is generally up to about 20 ppm.

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

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

Chlorine content can be determined by methods known in the art, such as DPD colorimetric (Lamotte Company, Chestertown, Maryland) or other known methods established by the environmental protection agency. In DPD colorimetry, free chlorine reacts with N, N-diethyl-p-phenylenediamine (DPD) to produce a yellow color, and the intensity is measured with a calibrated colorimeter, which provides an output in parts per million. Further addition of potassium iodide converted the solution to a pink color to provide a total chlorine number. The bound chlorine content can then be determined by subtracting the free chlorine from the total chlorine.

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

The level of hydrogen peroxide optionally present in the ORP water solution ranges from about 0.01ppm to about 200ppm, preferably from about 0.05ppm to about 100 ppm. More preferably, the hydrogen peroxide is present in an amount of from 0.1ppm to about 40ppm, most preferably from about 1ppm to 4 ppm. Optionally in the presence of a peroxide (e.g. H)₂O₂，H₂O₂ ^-And HO₂ ^-) At a concentration of less than 0.12 millimolar (mM).

The ORP water solution contains oxidizing chemical species in a total amount ranging from about 2 millimolar concentrations (mM) that include the aforementioned chlorine species, oxygen species, and other species that may be difficult to measure, such as Cl^-、ClO₃、Cl₂ ^-And ClO_x. The level of the contained oxidizing chemical species can also be measured 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 (e.g., 1 week, 2 weeks, 3 weeks, 4 weeks, etc.), and preferably for 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.

As used herein, the term stable generally refers to the ability of the ORP water solution, after its preparation, to remain under normal storage conditions (i.e., room temperature) for a specified period of time suitable for its intended use, such as decontamination, disinfection, sterilization, antimicrobial cleansing, and wound cleansing.

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

The concentration of ionic species and other species contained in the solution is 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 more of its initial concentration, at least until about 2 months after the ORP water solution is prepared. Preferably, these concentrations are maintained at about 80% or greater of their initial concentrations, at least until about 2 months after the ORP water solution is prepared. More preferably, these concentrations are about 90% or more of their initial concentrations, at least up to about 2 months after the ORP water solution is prepared, most preferably about 95% or more.

The stability of the ORP water solution of the invention can also be determined from the reduction in the amount of organisms contained in the sample after exposure to the ORP water solution. The determination of the reduction in the concentration of the organism may 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 (previously known as Bacillus subtilis). ORP water solution can be used as a solution capable of reducing the concentration of living microorganisms by about 4 logarithmic orders (10)⁴) Can also be used as a disinfectant capable of reducing the concentration of viable microorganisms by about 6 logs (10)⁶) High levels of disinfectants.

In one aspect of the invention, the ORP water solution is capable of causing a reduction in the total concentration of organisms by at least about 4 log (10) after 1 minute of exposure when measured at least 2 months after the solution is prepared⁴). Preferably, the ORP water solution is also capable of achieving this level of reduction in organism concentration when measured at least 6 months after the solution is prepared. More preferably, the ORP water solution is also capable of achieving this level of reduction in the concentration of organisms when measured at least about 1 year after the ORP water solution is prepared, and most preferably, the ORP water solution is also capable of being measured at least about 3 years after the ORP water solution is preparedA reduction in the concentration of organisms to this level is achieved.

In another aspect of the invention, the ORP water solution is capable of reducing the concentration of a viable microorganism sample by at least about 6 log (10) within 1 minute of exposure when measured at least 2 months after preparation of the ORP water solution⁶) The microorganism is 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 and more preferably at least 1 year after preparation. Preferably, the ORP water solution is capable of reducing the concentration of these living microorganisms by at least about 7 log (10) within 1 minute of exposure, as measured at least 2 months after preparation⁷)。

ORP water solutions of the present invention are generally capable of providing a viable microorganism sample at about 1X 10 from an initial concentration within 1 minute of exposure when measured at least 2 months after preparation of the ORP water solution⁶To about 1X 10⁸Individual microorganisms/ml were reduced to a final concentration of about 0 microorganisms/ml, including but not limited to escherichia coli, pseudomonas aeruginosa, staphylococcus aureus, and candida albicans. The reduction in microbial concentration is on the order of about 6 log (10)⁶) To about 8 logarithmic stages (10)⁸) In the meantime. Preferably, the ORP water solution is capable of achieving such a reduction in levels of escherichia coli, pseudomonas aeruginosa, staphylococcus aureus or candida albicans organisms when measured at least 6 months and more preferably at least 1 year after preparation.

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 log steps (10) within about 5 minutes of exposure when measured at least 2 months after preparation of the ORP water solution⁶). Preferably, the ORP water solution is capable of effecting Bacillus athrophaeus spores when measured at least about 6 months after preparation, and more preferably when measured at least 1 year after preparationThis reduction in concentration.

The ORP water solution is also capable of reducing the concentration of a spore suspension of Bacillus athrophaeus spores by about 4 log (10) within about 30 seconds of exposure when measured at least 2 months after preparation of the ORP water solution⁴). Preferably, the ORP water solution is capable of achieving this level of 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 is also capable of reducing the concentration of fungal spores, such as Aspergillus niger spores, by about 6 log order (10) within about 5 to 10 minutes of exposure when measured at least about 2 months after preparation of the ORP water solution⁶). 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 invention optionally comprises hydrogen peroxide (H)₂O₂) And one or more chlorine species. The chlorine species contained is preferably a free chlorine species. The free chlorine species may be selected from the group consisting of 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 0.01ppm to about 200ppm, preferably from about 0.05ppm to about 100 ppm. More preferably, the hydrogen peroxide is present in an amount of from about 0.1ppm to about 40ppm, and most preferably from about 1ppm to about 4 ppm.

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

The ORP water solution is generally stable for at least about 1 week. Preferably, the ORP water solution remains stable for 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 is stable for at least about 1 year and most preferably stable for at least about 3 years.

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.

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

After preparation, the ORP water solution or formulation of the invention can be transferred to a sealed container for distribution and sale to end-users such as healthcare facilities including hospitals, nursing homes, doctor's offices, outpatient surgery centers, dental clinics, and the like. The 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.

Any suitable sealed container that maintains the sterility and stability of the ORP water solution or formulation contained within the container may be used. The container may be made of any material that is compatible with the ORP water solution or a component of the formulation (e.g. ORP water solution or thickener). The vessel should generally be non-reactive so that the ions contained in the ORP water solution do not react with the vessel to any significant extent.

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

Suitable plastics include polypropylene, polyester terephthalate (PET), polyolefins, cycloolefins, polycarbonate, ABS resin, 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 container preferably has an opening that allows the ORP water solution or formulation to be dispensed for administration to a patient. The container opening may be sealed in any suitable manner. For example, the container may be sealed with a twist cap or stopper. Optionally, the opening may also be sealed with a foil.

The top gas of the sealed vessel may be air or another suitable gas which will 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 invention also provides an ORP water solution comprising anode water and cathode water. Anode water is generated in the anode chamber of the electrolytic cell used in the present invention. Cathode water is produced in the cathode chamber of the cell.

The ORP water solution of the present invention typically 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 from about 10% by volume to about 50% by volume, more preferably from about 20% by volume to about 40% by volume of the solution, and most preferably from about 20% by volume to about 30% by volume of the solution. Additionally, the ORP water solution contains an amount of anode water that is from about 50% solution volume to about 90% solution volume.

As described herein, the ORP water solution containing the anode water and cathode water can be acidic, neutral or basic, with a pH generally 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 ORP water solution of the present invention has a wide range of uses as disinfectants, cleaning agents, detergents, antimicrobial preservatives, etc. for controlling the activity of unwanted or harmful substances present in the environment. Substances that can be treated with the ORP water solution include, for example, organisms and allergens.

The ORP water solution may be used as a disinfectant, sterilant, detergent, antiseptic preservative 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), hospital/health care units (e.g., hard surfaces), cosmetic industry (e.g., skin cleansers), household items (e.g., floors, counters, hard surfaces), electronics industry (e.g., washing lines, hard disks), and bioterrorism (e.g., anthrax, infectious microorganisms).

The ORP water solution may also be administered to humans and/or animals to treat various conditions including, for example, the following: surgical/open wound cleansers, skin pathogen disinfection (e.g., against bacteria, mycoplasma, viruses, fungi, prions), war wound disinfection, wound healing promotion, burn healing promotion, treatment of gastric ulcers, wound irrigation, dermatophytes, psoriasis, athlete's foot, pinkeye and other eye infections, ear infections (e.g., swimmer ears), lung/nose/sinus infections, and other medical applications on or within the human or animal body. The use of ORP water solution as a tissue cell growth promoter is also described in U.S. patent application publication 2002/0160053A 1.

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

For example, when measured at least 2 months after preparation of the ORP water solution, the ORP water solution is capable of reducing the concentration of a viable microorganism sample by at least about 5log (10) within 30 seconds of exposure⁵) The living microorganism is selected from the group consisting of Pseudomonas aeruginosa, Escherichia coli, enterococcus Hibisci, Acinetobacter baumannii, Acinetobacter, Bacteroides fragilis, Enterobacter aerogenes, enterococcus faecalis, vancomycin-resistant enterococcus faecium (VRE, MDR), Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniaeBacteria, Micrococcus luteus, Proteus mirabilis, Serratia marcescens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes, Candida albicans, and Candida tropicalis.

In one embodiment, an ORP water solution administered in accordance with the present invention is capable of providing a viable microorganism sample from about 1X 10 within about 1 minute of exposure when measured at least about 2 months after preparation of the ORP water solution⁶To about 1X 10⁸The initial concentration of organisms per ml is reduced to a final concentration of about 0 organisms per ml, including but not limited to E.coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. This corresponds to a reduction in the concentration of organisms by about 6 log-orders (10)⁶) To about 8 logarithmic stages (10)⁸). Preferably, the ORP water solution is capable of achieving about a 10 reduction in organisms such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus or Candida albicans, when assayed at least about 6 months after preparation, and more preferably when assayed about 1 year after preparation⁶To about 10⁸。

Alternatively, an ORP water solution administered in accordance with the present invention is capable of reducing the concentration of a spore suspension of Bacillus athrophaeus spores by about 6 log steps (10) within about 5 minutes of exposure when measured at least about 2 months after preparation of the ORP water solution⁶). Preferably, the ORP water solution administered according to the 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 about 1 year after preparation⁶. The ORP water solution is also capable of reducing the concentration of a spore suspension of Bacillus athrophaeus spores by about 4 log (10) within about 30 seconds of exposure when measured at least about 2 months after preparation of the ORP water solution⁴). Preferably, the ORP water solution is capable of achieving this level of reduction in the concentration of Bacillus athrophaeus spores when measured at least about 6 months after preparation, and more preferably when measured about 1 year after preparation.

ORP water solutions administered according to the invention are also capable of reducing the concentration of viruses, such as Human Immunodeficiency Virus (HIV) and adenovirus, by more than 3log (10) after about 5 to 10 minutes of exposure when measured at least about 2 months after preparation of the ORP water solution³). Preferably, the ORP water solution is capable of achieving a > 10 reduction in virus concentration when measured at least about 6 months after preparation, and more preferably when measured at least about 1 year after preparation³。

ORP water solutions administered according to the present invention are also capable of completely inhibiting the growth of mycobacterium 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 mycobacterial concentration when measured at least about 6 months after preparation, and more preferably when measured at least about 1 year after preparation.

Thus, organisms that may 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. The ORP water solution can also be administered to viruses including, for example, adenovirus, Human Immunodeficiency Virus (HIV), rhinovirus, influenza virus (e.g., influenza A), hepatitis virus (e.g., hepatitis A), coronavirus (causing Severe Acute Respiratory Syndrome (SARS)), rotavirus, respiratory syncytial virus, herpes simplex virus, varicella zoster virus, rubella virus, and other susceptible viruses.

In a preferred embodiment, the ORP water solution of the invention may be administered to treat a patient suffering from 1 degree, 2 degrees or 3 degrees burns. Patients with combination burns, such as a combination of 2 degree and 3 degree burns, can also be treated with the ORP water solution. 1 degree burns involve the epidermis or skin surface. A 2 degree burn affects the epidermis and underlying dermis. 3 degree burns involve the epidermis, dermis and hypodermis. More preferably, the ORP water solution is administered to treat a patient suffering from a 2 degree or 3 degree burn. Burns suitable for treatment by the present invention may be caused by a variety of injuries including, for example, electrical contact with fire, boiling liquids (e.g., water, milk, etc.), or generally extend to about 0% to about 69% of the patient's tissue.

The ORP water solution may be administered to the burn patient in any suitable manner. The ORP water solution may be administered topically by spraying, bathing, soaking, wiping, or otherwise wetting the burn site. The ORP water solution is administered in an amount sufficient to treat the burn. The ORP water solution is administered to the burn at least 1 time per day and preferably more than 1 time per day. More preferably, the ORP water solution is administered to the burn 3 times per day.

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

The burn can be soaked by partially or completely immersing the burn in 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.

Alternatively, the ORP water solution can be applied to a 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 soaking the burn.

The burn may optionally be bandaged by applying a wet wound dressing saturated with ORP water solution. In addition to wet wound dressings, the burn may optionally be bandaged with dry gauze and adhesive coverings. Any suitable suave, cream, gel and/or ointment may also be administered to the burn surface after administration of the ORP water solution.

In one embodiment, a patient suffering from a burn in need of treatment is subjected to a washing step with an ORP water solution of the invention. The ORP water solution is first sprayed onto the burn using a high pressure irrigation device. Next, the burn is soaked in ORP water solution for a suitable period of time. After soaking, the burn was then sprayed with ORP water solution. The burn is then allowed to remain moist for at least about 5 minutes. The treatment step is performed on the patient's burn at least 1 time per day, preferably 2 times per day, more preferably 3 times per day. In this embodiment, it is preferred that the burn surface is not coated between applications of ORP water solution.

Prior to administration of the ORP water solution, the burn is preferably debrided to remove hyperkeratotic, necrotic and other unhealthy tissue until a healthy appearance of the tissue is exposed. In debridement burns, the wound margins are cut to healthy bleeding tissue. After debridement, the burn site may be cleared of debris. The ORP water solution administered according to the present invention may also be used as a rinsing solution for hydro surgery (hydroturbery) devices for skin ulcer debridement. Suitable hydrotherapy devices may include, for example, the VersaJet device sold by Smith and Nephew in the United states, Debritom sold by Mediaxis in Europe, Jetox sold by DeRoyal in the United states and Europe, or PulsaVac in Italy. It is believed that the ORP water solution may act synergistically with the device by reducing the microbial load at the wound and avoiding the formation of infectious mist during debridement. Thus, according to the invention, burn debridement can be performed with the device under continuous irrigation, reducing the infection process and avoiding the formation of infectious mist.

ORP water solutions administered according to the present invention may also be used as a feed forIrrigation solution for negative pressure devices 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 v.a.c. sold by Kinetic hubs in the united states.And v.a.c.Instill^TM. It is believed that the ORP water solution may act synergistically with the device to reduce microbial load by controlling the inflammation-allergy process. Thus, according to the present invention, the device can be applied to open burns with intermittent or continuous irrigation in order to treat or prevent tissue infection or necrosis.

Optionally, some adjunctive therapies may also be utilized in accordance with the present invention, including bioengineered skin (Apligraf, Organogenesis, inc., Canton), acellular skin substitutes (Oasis Wound Matrix, health point), ultrasound administration of ORP water solutions, and topical oxygen replacement or hyperbaric oxygen therapy (e.g., hyperbaric chamber, Vent-Ox system).

If desired, the ORP water solution can be administered in conjunction with a skin graft to promote healing of the burn.

Administration of the ORP solution optionally may be in conjunction with administration of local and/or systemic antibiotics. Suitable antibiotics may include, but are not limited to, penicillins, cephalosporins or other beta-lactams, macrolides (e.g., erythromycin, 6-0-methylerythromycin, and azithromycin), fluoroquinolones, sulfonamides, tetracyclines, aminoglycosides, clindamycin, quinolones, metronidazole, vancomycin, chloramphenicol, antibacterial effective derivatives thereof, 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 (e.g., anti-TNF), steroids, and NSAIDs.

In another embodiment of the invention, the patient is first debrided of a 2 degree and/or 3 degree burn and then sprayed with the ORP water solution using a high pressure irrigation device. The amount of ORP water solution used to clean the burn is preferably sufficient to remove debris. The burn is then soaked in ORP water solution for a suitable period of time. Next, the patient's burn is sprayed with the ORP water solution, allowing the solution to wet the burn for a suitable period of time, preferably from about 5 minutes to about 15 minutes. Spraying and wetting were repeated about 3 times per day. Between ORP water solution applications, the burn surface is not coated.

The process of high pressure spraying, optionally soaking, spraying and moistening the burn may be repeated at suitable intervals. Preferably, the high pressure spraying, optionally soaking, spraying and moistening of the burn is repeated about 1 time per week, and more preferably about 1 time per day. Treatment of burns with ORP water solution can continue until the burn has healed sufficiently, which typically requires repeating the procedure within 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. Healing of a burn is usually measured by the rate of scar contracture and epidermization.

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, yeasts 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 (i.e. from living or dead organisms) or non-living (e.g. non-living such as textiles), and may be present in an environment such as a home and/or workplace.

Protein-based household allergens that can be treated with ORP water include, for example, animal hair, dander and manure, 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 hair, mouse epithelium, mouse urine, rat epithelium, and rat urine.

Occupational allergens include, for example, high molecular weight substances such as natural proteins, which are typically derived from plant or animal proteins, and low molecular weight chemicals such as diisocyanates and other materials found in some textiles. Other chemical allergens that may be present at the workplace include, for example, anhydrides, antibiotics, wood dust, and dyes. The various proteins may be occupational allergens including plant gums, enzymes, animal proteins, insects, plant proteins, and legumes.

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

It has been found that the ORP water solution administered according to the 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 of mammalian cells. Non-toxicity is particularly beneficial and may even be surprising, since the ORP water solution administered according to the invention has a disinfection capacity which is about the same as that of hydrogen peroxide, but which is significantly less toxic to normal tissues and normal mammalian cells than hydrogen peroxide. These findings demonstrate that ORP water solutions administered according to the invention can be safely applied to, for example, mammals including humans.

For ORP water solutions administered in accordance with the present invention, the cell viability is preferably at least about 65%, more preferably at least about 70%, still more preferably at least about 75% after exposure to the ORP water solution for about 30 minutes. In addition, when contacted with the ORP water solution for up to about 30 minutes or less (e.g., after about 30 minutes of contact or after about 5 minutes of contact with the ORP water solution), the ORP water solution administered according to the invention preferably results in at most only about 10% cells, more preferably at most about 5% cells and still more preferably at most about 3% cells exposing annexin V on the cell surface thereof. Furthermore, the ORP water solution administered according to the invention preferably results in less than about 15% cells, more preferably less than about 10% cells, and still more preferably less than 5% cells expressing SA- β -galactosidase after chronic exposure to the ORP water solution. The ORP water solution administered according to the present invention preferably causes the same fraction of oxidized DNA adduct formation as the saline solution, e.g., less than about 20%, less than about 10%, or about 5% or less of the oxidized DNA adduct formation normally caused by hydrogen peroxide in cells treated under equivalent conditions.

The ORP water solution administered according to the present invention does not cause significant RNA degradation. Thus, RNA extracted from human cell cultures exposed to the ORP water solution about 30 minutes later or about 30 minutes 3 hours after exposure and analyzed by denaturing gel electrophoresis will generally not exhibit significant RNA degradation, and will generally exhibit two discrete bands corresponding to ribosomal eukaryotic RNA (i.e., 28S and 18S), indicating that the ORP water solution administered according to the invention leaves the RNA substantially intact. Also, RNA extracted from human cell cultures after exposure to the ORP water solution for 30 minutes or after about 3 hours of exposure can be reverse transcribed and amplify (RT-PCR) the constitutive human GAPDH (glyceraldehyde-3-phosphate dehydrogenase) gene, forming a strong GAPDH band on gel electrophoresis of the RT-PCR product. In contrast, cells treated for the same time with HP showed significant RNA degradation and few, if any, GAPDH RT-PCR products.

Any suitable amount of the ORP water solution of the invention may be used or applied in order to provide the desired bactericidal, virucidal, bactericidal and/or anti-allergenic effect.

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

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

The 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 substrate may be soaked, coated, covered or otherwise applied with the ORP water solution. Preferably, the substrate is pretreated with the ORP water solution prior to dispensing the cleaning wipe to the end user.

The substrate of the cleaning wipe can be any suitable water-insoluble absorbent or absorbent material. A variety of materials may be used as the substrate. 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 substrate may have one or more layers. Each layer may have the same or different texture and abrasiveness. Different texture configurations may result from the application of different material combinations or from the application of different production processes or combinations thereof. The substrate should not dissolve or disintegrate in water. The substrate provides a carrier for delivering the ORP water solution to the substrate to be treated.

The substrate may be a single nonwoven sheet or a plurality of nonwoven sheets. The nonwoven sheet may 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 mixtures of these fibers. Nonwoven materials may include nonwoven fibrous sheet materials including meltblown, coform, airlaid, spunbond, wet laid, bonded-carded web materials, hydroentangled (also called spunlace) materials, and combinations thereof. These materials may include synthetic or natural fibers or combinations thereof. The substrate may optionally contain a binder.

Examples of suitable non-woven, water-insoluble substrates include 100% cellulose wadding grade 1804, 100% polypropylene needlepunch material NB 701-2.8-W/R, blend of cellulose and synthetic fibers Hydraspun 8579, and 70% Viscose/30% PES Code 9881. Other examples of nonwoven substrates suitable for use in cleaning wipes are described in U.S. Pat. Nos. 4,781,974, 615,937, 4,666,621, and 5,908,707, and International patent application publications WO98/03713, WO97/40814, and WO 96/14835.

The substrate may also be made of a textile material, such as cotton fibers, cotton/nylon blends, or other textiles. Regenerated cellulose, polyurethane foam, and the like for preparing the sponge are also suitable.

The liquid loading capacity of the substrate should be at least about 50% to 1000%, preferably at least about 200% to 800% of its dry weight. This is expressed as a load capacity of about 1/2 to 10 times the weight of the substrate. The weight of the substrate may vary from about 0.01 to about 1000 grams per square meter, but is not so limited, and most preferably is from about 25 to about 120 grams/m²(referred to as "basis weight") is typically made as a sheet or web that can be cut, die cut, or otherwise formed into a suitable shape and size. The cleaning wipe preferably has a defined wet tensile strength which is preferably from about 25 to about 250 newtons/m, more preferably about 75-170 newtons/m.

The ORP water solution may be dispensed, soaked, coated, draped or otherwise applied to the substrate by any suitable means. For example, a single portion of the substrate may be treated with different amounts of ORP water solution. Preferably, the centralized treatment of the continuous web of substrate material with the ORP water solution is performed. The entire web of substrate material can be immersed in the ORP water solution. Alternatively, the ORP water solution can be sprayed or metered onto the web when the web is in-line with the shaft or even during the creation of the nonwoven substrate. The manufacturer may soak or coat a stack of separately cut and sized substrate portions with the ORP water solution in its container.

The cleaning wipe may optionally contain additional components to enhance the performance of the cleaning wipe. For example, the cleaning wipe may 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 U.S. patents 6,340,663, 6,649,584, and 6,624,135.

The cleaning wipe of the present invention can be individually sealed with a thermally insulating or bondable thermoplastic overwrap (e.g., polyethylene, Mylar, etc.). The cleaning wipe may be packaged in a number of individual sheets for more economical deployment. The cleaning wipe can be prepared by first placing a plurality of substrates in a dispenser and then contacting the substrate sheets with the ORP water solution of the invention. Alternatively, the cleaning wipe can be formed as a continuous web by applying the ORP water solution to the substrate during manufacture and then loading the wetted substrate into a dispenser.

Dispensers include, but are not limited to, cans with closures or basins with closures. The closure on the dispenser is to isolate the moist wipe from the external environment and to avoid premature evaporation of the liquid component.

The dispenser may 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 a plastic such as high density polyethylene, polypropylene, polycarbonate, polyethylene terephthalate (PET), polyvinyl chloride (PVC), or other hard plastic.

The continuous web of wipes may pass through a narrow opening above the dispenser, most preferably through a closure. A wipe tool of the desired length or size then needs to be cut from the web. A knife edge, serrated knife edge, or other tool may be provided above the dispenser to cut the web to the desired size, a non-limiting example being a narrow opening that actually has the dual function of a knife edge. Alternatively, the wiped continuous web may be indented, folded, segmented, perforated or partially cut to uniform or non-uniform sizes or lengths, which eliminates the need for sharp edges. In addition, the wipes may be staggered so that removal of one sheet directly reveals the next.

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 may be dispersed into the air by any suitable means. For example, the ORP water solution may be formed into small droplets of any suitable size and dispersed into a room.

For small scale applications, the ORP water solution may be administered by a spray bottle including a reservoir and a pump. Alternatively, the ORP water solution may be packaged into an aerosol container. Aerosol containers typically include the product to be administered, a propellant, a container, and a valve. The valve includes an actuator and a dip tube. The contents of the container may 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 ORP water solution may be dispensed in the form of an aerosol as part of an inhalation system for the treatment of lung and/or airway infections or for wound healing of such parts of the body.

For larger scale applications, the ORP may be dispersed into the air using any suitable device, including but not limited to humidifiers, mist formers, fog formers, nebulizers, atomizers, water jets, and other spray devices. These devices allow continuous administration of the ORP water solution. A sprayer that mixes gas and water directly at the nozzle may be used. The ORP water solution can be converted to steam, e.g. low pressure steam, and released as an air jet. Different types of humidifiers may be used such as ultrasonic humidifiers, steam humidifiers or nebulizers, and evaporative humidifiers.

A special device for dispersing ORP water solution may be integrated into the aeration system in order to provide a wide application of ORP water solution throughout the house or health care unit (e.g. hospital, nursing home, etc.).

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

The cell 100 has an anode compartment 102, a cathode compartment 104 and a saline solution compartment 106. The saline 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 flow through the anode chamber 102. The cathode chamber 104 also has an inlet 112 and an outlet 114 to allow water flow through the cathode chamber 104. The saline solution chamber 106 has an inlet 116 and an outlet 118. The electrolytic cell 100 preferably includes a tank that holds all of the components together.

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

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

The electrodes are typically made of metal, allowing a voltage potential to be applied between the anode and cathode compartments. The metal electrodes are generally planar, having similar dimensions and cross-sectional surface area as the ion exchange membrane. The electrodes are configured such that most of the surface of the ion exchange membranes are exposed to the water in their respective anode and cathode compartments. This allows the ionic 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 uniformly distributed over the surface of the electrode.

A potential source is connected to the anode electrode 120 and the cathode electrode 124 to induce an oxidation reaction in the anode compartment 102 and a reduction reaction in the cathode compartment 104.

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

The water supply to the anode and cathode chambers 102, 104 of the cell 100 may be any suitable water supply. The water may come from a municipal water supply or may be pre-treated prior to use in the electrolytic cell. Preferably, the water is pretreated and selected from the group consisting of demineralized water, purified water, distilled water, and deionized water. More preferably, the pre-treated water source is ultra pure water obtained by reverse osmosis and UV line purification apparatus.

The brine solution used in the brine solution compartment 106 may be any aqueous salt solution containing the appropriate 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 a 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 bromine salts. The salt solution may comprise a mixture of salts.

The salt solution may have any suitable concentration. The salt solution may be saturated or concentrated. Preferably, the salt solution is a saturated sodium chloride solution.

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

Positive ions travel from the saline solution 216 flowing through the saline solution chamber 206 to the cathode water 218 flowing through the cathode chamber 204. The negative ions travel from the saline solution 216 flowing through the saline solution chamber 206 to the anode water 220 flowing through the anode chamber 202.

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

Sodium and chloride ions may also undergo further reactions in the anode and cathode chambers 202 and 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 (e.g., hydrogen peroxide). In cathode chamber 204, hydrogen gas (H2), hydroxide ions (OH-), sodium hydroxide (NaOH), and other radicals may be formed.

The invention also provides a method and apparatus for producing ORP water solution using at least two three-compartment electrolysis cells. FIG. 3 shows a schematic of a process for producing ORP water solution using two electrolytic cells of the invention.

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

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

The mixing tank 314 may optionally be connected to a circulation pump 315 to allow for uniform mixing of the anode water and a portion of the cathode water from the electrolytic cells 302 and 304. In addition, the 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 the mixing tank 314 via pump 317 for application to disinfection or sterilization at or near the mixing tank location. Alternatively, the ORP water solution may be dispensed into a suitable container for transport to a remote location (e.g., warehouse, hospital, etc.).

The method 300 further 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 to the saline solution chambers 322 and 324 via the pump 321. Preferably, the saline solution flows sequentially first through the saline solution chamber 322, followed by the saline solution chamber 324. Alternatively, the saline solution may be pumped into both saline solution chambers simultaneously.

Before returning to salt tank 320, the salt solution may flow through heat exchanger 326 in mixing tank 314 to control the temperature of the ORP water solution as desired.

Over time, ions in the salt solution in the first electrolytic cell 302 and the second electrolytic cell 304 are consumed. Additional ion sources may be periodically added to the mixing tank 320 to replace the ions transferred to the anode and cathode waters. Additional sources of ions may be used to maintain a constant pH of the salt solution, which may tend to decrease over time (i.e., become acidic). The additional source of 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 +) transferred to the anode and cathode waters.

In another embodiment, the invention provides an apparatus for generating an oxidative reductive potential water solution, the apparatus comprising at least two three-compartment electrolytic cells. Each cell includes an anode chamber, cathode water, and a saline solution chamber separating the anode and cathode chambers. The apparatus includes a mixing tank for collecting anode water produced by the electrolytic cells and a portion of cathode water produced by one or more of the 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 following examples further illustrate the invention and, of course, should not be construed as in any way limiting its scope.

Examples 1 to 3

These examples demonstrate the unique characteristics of the ORP water solution of the invention. Root of herbaceous plantThe 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 all based on standard test methods for determining these species; however, the results may indicate different categories that may also produce positive test results. In addition, it has been reported that chlorine dioxide, ozone and hydrogen peroxide can react with hypochlorite, causing their consumption and other species (e.g., HCl and O)₂) And (4) generating. Table 1 shows the pH, oxidation-reduction potential (ORP) and the ionic species present for each ORP water solution sample.

Table 1: physical characteristics of ORP aqueous solution samples and ionic species contained therein

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

Examples 4 to 10

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

Preparation of 10% Clorox with distilled WaterA bleaching solution. The following solutions were then prepared with a 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 (example 6); 20% ORP water solution/80% bleach (example 7); and 0% ORP water solution/100% bleach (example 8). The ratio was also made with two control solutionsIn comparison, ORP water solution (example 10) comprising 100% ORP water solution/0% bleach (example 9) and 0.01% Tween20 detergent. The physical characteristics of these samples, in particular the pH, the oxidation-reduction potential (ORP), the total chlorine (Cl) were determined^-) Content, hypochlorous acid (HClO)^-) Content, chlorine dioxide content and peroxide content, these data are shown in table 2.

Table 2: physical characteristics of ORP aqueous solution/bleach compositions

[0215] The addition of a large amount of fluoride ions as part of the bleach prevents accurate determination of chlorine dioxide and peroxide levels, as indicated by the designation n.d. The results obtained for chlorine dioxide and peroxide are also based on standard test methods for determining these species; however, the results may indicate different categories that may also produce positive test results. In addition, it has been reported that chlorine dioxide, ozone and hydrogen peroxide can react with hypochlorite, causing their consumption and other species (e.g., HCl and O)₂) And (4) generating. As shown in these examples, the hypochlorous acid level in the ORP water solution with or without added bleach is similar.

The samples of examples 4-10 were subjected to high spore count assays 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 4X 10 per 100. mu.l⁶And (4) spores. A100 microliter sample of the spore suspension was mixed with 900 microliter of each of the samples of examples 4-10. As shown in table 3, the samples were incubated at room temperature for a period of 1 to 5 minutes. At the times indicated, 100 microliters of incubated samples were plated onto individual TSA plates and incubated at 35 ℃. + -. 2 ℃ for 24 hours, after which the number of colonies formed on each plate was determined. Control plates confirmed initial spore concentrations > 1X 10⁶Spore/100 microliter. Table 3 shows the concentration of Bacillus spores (average of two determinations) for different samples at different incubation times.

Table 3: bacillus spore concentration (spore/100 microliter)

These results show that the number of killed bacillus spores in samples incubated for 2-3 minutes decreases with increasing bleach concentration (10% aqueous bleach solution). However, for the 5 minute incubated samples, the bleach concentration did not affect the killing effect on the bacillus spores. Furthermore, the results show that the addition of 0.01% detergent to an aqueous OPR solution does not reduce spore killing.

The fabric bleaching tests were performed with the samples of examples 4-10. The fabric used for the sample testing was a 100% rayon child T-shirt with dark blue dye spots. The 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 of examples 4-10. Table 4 shows the time (as determined by fabric whitening) taken until complete bleaching action was achieved.

Table 4: time spent in fully bleaching the fabric sample

These examples show that when the concentration of ORP water solution in a composition is increased, the time taken to achieve complete bleaching increases.

Example 11

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

In terms of safety, M60 had no irritating effect on rabbit skin or conjunctiva as tested according to the international standards (AAMI 1997, NV SOP 16G-44, PFEUM 2000). In addition, acute inhalation toxicity studies in rats confirmed that administration of Microcyn 60 by this route is safe.

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

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

Acute inhalation toxicity studies were also conducted in rats to determine the potential inhalation toxicity of Microcyn 60. 10 Sprauge-Dawley albino rats were exposed to an aerosol formed from undiluted Microcyn 60 for 4 hours. The concentration of Microcyn 60 was determined to be 2.16 mg/L. Animals were observed frequently on the day of exposure and all animals were observed once daily for 14 days thereafter for clinical/behavioral signs of mortality and toxicity. All animals were euthanized on day 14 and subjected to gross necropsy.

All animals showed very slight to mild piloerection and very slight reduction in activity at 41/2 and 6 hours after the start of exposure, but had no symptoms by the next day and were clinically normal for the duration of the study. 1 male mouse did not gain weight between day 0 and day 7. No mortality and no visible abnormalities were found at gross necropsy. The acute inhalation LD50 estimated from this study was greater than 2.16 mg/L.

Additional toxicology studies were performed in rabbits. Aerosol super oxygenated water (1mL) was delivered by a positive pressure device into the right nostrils of 20 New Zealand rabbits 3 times daily for 15, 30, 45 and 60 days. The left control nostril was not treated. Nasal mucosal biopsies of untreated and M60-treated nostrils were obtained from 5 animals at each time point. These tissues were then observed under light and electron microscopy. Every other day, each animal was subjected to a comprehensive medical examination and recorded for nasal congestion, facial neuralgia, pressure, mucopurulent rhinorrhea, and discomfort. Side effects are reported to be rare, mild and transient.

Changes in nasal mucosa occurred after 60 days of intranasal M6060 administration. At day 60, mild destruction of the epithelium, discrete inflammatory infiltrates of the subepithelial region, and hyperplasia of glands and vessels occurred in all samples. Under the observation of ultrastructure, we found that in epithelial cells, a variety of different vesicle-like changes occurred, mitochondria cohered and deformed, and part of the membrane was dissolved. Some epithelial cells segregate, epithelial cilia are nearly eliminated, their membranes dissolve and the intracellular space widens. Some cells are separated from the basement membrane. The lamina propria is mildly edematous.

This study demonstrated that M60 slightly irritated the nasal mucosa 60 days after intranasal administration. However, this injury is small and reversible, and therefore the M60 route of intranasal administration may be considered safe. This is based on the fact that although the nasal mucosa can be severely damaged after years of administration of the vasoconstrictor, it returns to normal after the withdrawal 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. The adjacent basal cells can move along the basement membrane to the lesion and cover the lesion. Thus, even in the presence of slight separation of epithelial cells in some areas after M60 treatment, the basement membrane survives and viable epithelial cells adjacent to the diseased area grow to areas lacking epithelium. In addition, topical steroids may also be administered to promote restoration of nasal mucosal structure and function.

In summary, intranasal administration of M605 was safe in this group for days. Pathological mucosal changes are mild and reversible. Therefore, intranasal administration of M60 can be widely used.

Example 12

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

One such ORP water solution used in this study is called "Microcyn" which has recently been introduced to the mexico market as an antimicrobial preservative. Microcyn is a super-oxygenated solution with a neutral pH that has bactericidal, bactericidal and wound antiseptic activity according to the certificate obtained from the mexico health agency. Microcyn is prepared from pure water and salt (NaCl) with low concentrations of sodium (< 55ppm) and chlorine (< 80ppm), a pH ranging from 7.2 to 7.8, and an oxidation-reduction potential ranging from 840mV to 960 mV. Only one concentration of Microcyn was prepared without activation or dilution.

The solution is prepared with water obtained by reverse osmosis and then treated with a high voltage and an electrochemical gradient generated by sodium chloride. In this manner, the reactive species formed in the plurality of 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 which provide a high redox potential (+840mV to +960mV), the solution thus having a high antimicrobial activity.

Hypochlorous acid and sodium hypochlorite are the most abundant components contained in Microcyn, which also contains other components at lower concentrations such as hydrogen peroxide, ozone, chloride ions, hydrides, sodium hydroxide, and the like. Although applicants do not wish to be bound by a particular theory, it is believed that the disinfecting action does not necessarily depend on the amount of chlorine, but rather on the free radical content, since the sodium and chlorine levels in Microcyn are less than 50 and 60ppm, respectively. In addition, Microcyn has a neutral pH (6.4-7.8) compared to other superoxygenated solutions that have been reported in the literature, is non-corrosive, and is stable for up to 2 years of storage. All of these features allow for the generation of superoxygenated solutions that are effective as high level disinfectants and suitable for inanimate surfaces and tissues.

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

Since only one concentration of Microcyn is produced, the dose of Microcyn can only be varied by the change in the volume applied per unit area of skin. In toxicology studies, the dose of Microcyn administered topically to intact skin was between 0.05 and 0.07mL/cm²In the acute skin toxicity study and the skin irritation study, the dose is up to 8.0mL/cm²In studies investigating the use thereof in deep wounds, the dose of Microcyn administered was 0.09mL/cm²。

Toxicology studies were performed in which Microcyn was topically applied to intact skin in a single application, exposure 4 to 24 h. Multiple applications of Microcyn in deep wounds of rats were evaluated, 1 or 2 times daily for 7 days.

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

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

Systemic toxicity of Microcyn was also assessed by intraperitoneal injection in mice. For this, 5 mice were injected with a single dose (50mL/kg) of Microcyn by the intraperitoneal route. 5 control mice were injected in the same manner with a single dose (50mL/kg) of saline solution (0.9% sodium chloride). In this study, no evidence of mortality or any systemic toxicity, LD, was observed in any animals receiving a single intraperitoneal dose of Microcyn₅₀More than 50 mL/kg.

Microcyn was administered to rats by the oral route in order to allow their absorption and to characterize any intrinsic toxic effects of the product. To this end, 3 Sprague-Dawley albino rats were administered a single dose (4.98mL/kg) via the oesophagus. There was no mortality, no clinical signs, or autopsy abnormalities in all animals exposed to a single oral dose of Microcyn.

Rabbits were also evaluated for the possibility of eye irritation caused by topical administration of Microcyn. No eye irritation and any other clinical signs were observed in all animals exposed to Microcyn administered topically via the ocular route.

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

Evaluation of the possibility of Microcyn sensitization of the skin was carried out in guinea pigs using the modified occlusion patch method (Buehler). No irritation was observed in the animals of the control group after a single treatment challenge, as well as in the animals evaluated after the treatment challenge (induced treatment). Thus, Microcyn does not trigger a sensitization reaction.

Thus, Microcyn showed no product-related adverse effects when administered to intact skin, deep open skin wounds, conjunctival sac by oral and inhalation routes or by intraperitoneal injection. There is also experience in treating over 500 patients with skin and mucosal wounds of very different nature, with excellent antiseptic and cosmetic results. Thus, topical application of Microcyn should be effective and well tolerated in this clinical trial.

Microcyn were packaged in clear 240mL PET bottles. The product is stored at room temperature and can remain stable on the shelf for up to 2 years if the bottle is not opened. Once the bottle has been opened, it is recommended that all products should be used up within 90 days. Due to its high biological safety, Microcyn can be poured into a sink without risk of contamination or corrosion.

Several microbiological tests of Microcyn have been carried out in the United states and Mexico. Over 90% of the bacteria can be removed during the first few seconds of exposure. Table 5 summarizes the antibacterial and antifungal activity exhibited by Microcyn according to this standard.

TABLE 5 antibacterial and antifungal Activity of Microcyn

The sporicidal activity test was performed according to the PAHO [ all American health organization ]/WHO protocol.

Regarding virucidal activity, Microcyn was found to reduce the viral load of human immunodeficiency virus (strain SF 33) by more than 3log steps within 5 minutes. This was confirmed by the cytopathogenic effect and the absence of the antigen Agp24 in the Microcyn-treated virus assay. These experiments were performed according to the virucidal protocol of the U.S. environmental protection agency (DIS/TSS-7/1981, 11/12).

Recent studies in the united states against HIV and poliovirus have demonstrated the virucidal activity of Microcyn, as well as its activity against listeria monocytogenes, MRSA and mycobacterium tuberculosis. Thus, it has been demonstrated that Microcyn is capable of eliminating bacteria, fungi, viruses and spores after 1 to 15 minutes of exposure when applied as recommended.

Example 13

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

In vitro time-kill evaluation was performed with Microcyn redox potential water. The ability of Microcyn to challenge suspensions of 50 different microbial strains was evaluated, 25 strains of the american standard pool (ATCC), 25 clinical isolates of these same species, such as the Tentative Final Monograph, Federal Register, 17 June 1994, vol. 59: 116, pg.31444. The percentage reduction and Log10 reduction from the initial population of flora was determined for each challenge strain after 30 seconds, 1 minute, 3 minutes, 5 minutes, 7 minutes, 9 minutes, 11 minutes, 13 minutes, 15 minutes, and 20 minutes of exposure to Microcyn. All agar plates were run in duplicate and the Microcyn concentration evaluated was 99% (v/v). All tests were performed according to Good Laboratory Practices (as described in section 58 of 21 c.f.r.).

The following table summarizes the reduction of over 5.0Log at the 30 second exposure mark₁₀Results of the above in vitro time-kill evaluation of all test populations.

Table 6: sterilizing in vitro for 30 seconds

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For the remaining 3 strains not contained in Table 6, the microbial reduction was determined to be less than 5.0Log₁₀However, Microcyn also showed antimicrobial activity against these 3 strains. More specifically, 30 seconds exposure to Microcyn reduced the number of Streptococcus pneumoniae (clinical isolate; BSLI #072605Spnl) by more than 4.5Log₁₀This is the detection limit for this species. In addition, Microcyn reduced microorganisms by more than 3.0Log after 30 seconds of exposure when challenged with Candida tropicalis (ATCC #750)₁₀In addition, Microcyn reduced microorganisms by more than 3.0Log after 20 minutes of exposure when challenged with Candida tropicalis (BSLI #042905Ct)₁₀。

This in vitro time-kill evaluation example result indicates that Microcyn oxidation-reduction potential water has rapid (i.e., less than 30 seconds in most cases) antimicrobial activity against a broad spectrum of aggressive microorganisms. Microbial biomass was evaluated as a 5.0Log reduction in 47 of 50 gram positive, gram negative and yeast species within 30 seconds of exposure to the product₁₀The above.

Example 14

This example demonstrates exemplary ORP aqueous solution Microcyn and HIBICLENSComparison of antimicrobial Activity of chlorhexidine gluconate solution 4.0% (w/v) and 0.9% sodium chloride rinse (USP).

Using HIBICLENSChlorhexidine 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 a suspension of 10 U.S. Standard library (ATCC) strains specifically designated at the tent Final Monograph. The data collected were then analyzed and compared to the microbial reduction activity of Microcyn recorded in example 13.

Microcyn redox potential water reduces the number of 5 challenge strains to HIBICLENSComparable levels were observed for chlorhexidine gluconate solutions. Microcyn and HIBICLENSThe microbial reduction of 5.0Log was achieved after 30 seconds of exposure of the following species₁₀The method comprises the following steps: escherichia coli (ATCC #11229 and ATCC #25922), Pseudomonas aeruginosa (ATCC #15442 and ATCC #27853), and Serratia marcescens (ATCC # 14756). Furthermore, as shown in Table 5 above, Microcyn showed excellent antimicrobial activity against Micrococcus luteus (ATCC #7468), a reduction of 5.8420Log after 30 seconds exposure₁₀However, direct comparison of HIBICLENSActivity against Micrococcus luteus (ATCC #7468) was not possible because HIBICLENS was present after 30 seconds of exposureThe reduction in the number of strains reached the detection limit of the test (in this particular example, it exceeded 4.8 Log)₁₀). Value ofNotably, a sterile 0.9% sodium chloride rinse solution reduced the microbial count of each of the 6 challenge strains discussed above by less than 0.3Log after sufficient exposure for 20 minutes₁₀。

For the 4 test challenge strains: microcyn redox potential water provides specific HIBICLENS for enterococcus faecalis (ATCC #29212), Staphylococcus aureus (ATCC #6538 and ATCC #29213), and Staphylococcus epidermidis (ATCC #12228)And sodium chloride rinse greater antimicrobial activity. The following table summarizes the results of the microbial reduction of the in vitro time-kill evaluation of these 4 species:

table 7: comparing results of sterilization

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This comparison of in vitro time-kill evaluation results confirmed that Microcyn redox potential water not only exhibited with HIBICLENSComparable antimicrobial activity against Escherichia coli (ATCC #11229 and ATCC #25922), Pseudomonas aeruginosa (ATCC #15442 and ATCC #27853), Serratia marcescens (ATCC #14756) and Micrococcus luteus (ATCC #7468), and 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 (i.e., less than 30 seconds) in some species. In addition, Microcyn exposure resulted in all of the species listed in Table 7Greater reduction of total microorganisms.

Example 15

This example provides a formulation of the invention suitable for topical administration to a patient. The formulation comprised the following components:

components Number of

ORP aqueous solution 250mL

CarbopolPolymer powder (thickener) 15g

Triethanolamine (neutralizer) 80mL

Example 16

components Number of

ORP aqueous solution 1000mL

CarbopolPolymer powder (thickener) 15g

Triethanolamine (neutralizer) 80mL

Example 17

components Number of

ORP aqueous solution 250mL

CarbopolPolymer powder (thickener) 7g

12mL triethanolamine (neutralizer)

Example 18

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

The ORP water solution is poured into a suitable container such as a glass beaker or bottle. Mixing CarbopolThe 974P polymer is coarse screened, which allows for rapid screening while breaking up all large agglomerates. Then the polymer Carbopol was added974P as a thickener. Slowly add CarbopolPolymer to avoid the formation of coagulum and thus avoid lengthy mixing cycles.

Adding CarbopolThe solution is mixed rapidly during the polymerization so that the powder dissolves at room temperature. The neutralizing agent triethanolamine is then added to the solution and mixed with an electric mixer or other suitable device until a homogeneous gel is obtained. To CarbopolThe addition of a neutralizing agent to the polymer composition causes the formulation to become a gel.

Example 19

This example describes the use of the ORP water solution of the invention to treat burns, particularly 2 and 3 degree burns, in children's burn patients.

A total of 64 children burn patients received ORP water solution treatment. The study group was compared with a control group also consisting of 64 patients receiving traditional burn treatment. The study groups included the following patients: 1 patient with 1 degree burn, 6 patients with a combination of 1 degree and 2 degree burns, 38 patients with 2 degree burn, 4 patients with 3 degree burn, 15 patients with a combination of 2 degree and 3 degree burn. Furthermore, the study group consisted of patients with the following burn percentage (i.e. burn range): 10 patients with a burn range of 0 to 9%, 27 patients with a burn range of 10 to 19%, 11 patients with a burn range of 20 to 29%, 8 patients with a burn range of 30 to 39%, 4 patients with a burn range of 40 to 49%, 1 patient with a burn range of 50 to 59%, and 3 patients with a burn range of 60 to 69%. Each burn was initially debrided. The solution is applied by spraying through a high pressure rinsing device. Next, the solution was applied by spraying and allowed to wet the burn for 5 to 15 minutes, repeating the process 3 times per day. No burn was applied between applications of the solutions.

Of the cultures taken to determine the presence of microorganisms on the burned surfaces, only 6 patients treated with ORP water solution developed positive cultures 7-15 days after hospitalization, while 22 controls were present. The remaining patients in both the study group (58) and the control group (42) were negative cultures.

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

Table 8: microorganism for burn

The frequency of administration of ORP water solution will vary depending on the nature of the burn in each patient. Average hospital days were tabulated for the study and control groups by burn grade. For 1 degree burns, the average day of hospitalization was 4.6 days for the study group (6 patients) and 19.2 days for the control group (45 patients). For 2 degree burns, the average day of hospitalization was 10.6 days for the study group (44 patients) and 26.9 days for the control group (9 patients). For 3 degree burns, the average day of hospitalization was 29.5 days for the study group (14 patients) and 39.8 days for the control group (10 patients). In summary, administration of ORP water solution of the invention to children burn patients reduced the average length of hospitalization from 28.6 days to 14.9 days, a 48% reduction. Table 9 lists the average days of hospitalization of the control versus the study based on burn range.

Table 9: time of stay

As can be seen from this example, the ORP water solution of the present invention can be beneficially administered to children burn patients, resulting in a reduction in the number of hospitalizations.

Example 20

This example describes administration of the ORP water solution of the invention to children burn patients without administration of antibiotics.

None of the 58 patients in the study group described in example 19 above who were negative for microbial cultures after 7-15 days of hospitalization were treated with antibiotics. The average hospitalization day for this group of patients was 12.3 days. In the control group, 46 patients used antibiotics in addition to the administration of ORP water solution. Positive microbial cultures were observed in 22 of these patients, and the average hospitalization day for these antibiotic-administered patients was 28.6 days.

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

Example 21

This example shows the effect of an 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 decreasing cell viability. In this example, cell viability, apoptosis and necrosis of HDFs exposed to neat ORP water solution and 880mM HP (the concentration employed for antimicrobial use of HP) for 5 minutes and 30 minutes were determined.

HDF cultures were obtained from 3 different foreskins, pooled and cryopreserved together for use in this study. All experiments used only diploid cells. In cell cycle analysis, DNA diploidy is defined as the presence of a single G0-G1 peak with a CV of 7% or less and the corresponding G2/M peak in at least 20,000 total events collected. The results are depicted in fig. 4A-4C, where the results for exposure times of 5 and 30 minutes are depicted in white and black bars, respectively. The following steps are utilized: A) simultaneous analysis of these parameters was performed on the same cell population by flow cytometry using 7-amino actinomycin D (7AAD), B) annexin V-FITC and C) propidium iodide. Fig. 4A-4C depict percentage values, expressed as mean ± SD (n ═ 3).

Cell viability was 75% and 55% after exposure to ORP water solution and HP5 minutes, respectively (fig. 4A). If the exposure is extended to 30 minutes, cell viability is further reduced to 60% and 5%, respectively. The ORP water solution apparently induced cell death by necrosis, since 15% of the cells were spiked with propidium iodide in flow cytometry analysis at both time points (fig. 4C). While not wanting to be bound by any particular theory, this result may be due to hypotonic (13mOsm) induced osmosis of Microcyn, since cells are maintained only with ORP water solution, without the addition of growth factors or ions. Apoptosis does not appear to be the mechanism by which ORP water solution induces cell death, as only 3% of cells treated with ORP water solution expose annexin V (a marker of apoptosis) on their cell surface (fig. 4B). This percentage is in fact similar to the results measured in the control group. In contrast, HP induced necrosis and apoptosis in 20% and 75% of treated cells and 15% and 20% after 5 minutes and 30 minutes of exposure, respectively. Together, these results indicate that the toxicity of the (undiluted) ORP water solution to HDF is much lower than that of HP at antibacterial concentrations.

Example 22

This example describes the effect of an exemplary ORP water solution versus Hydrogen Peroxide (HP) on oxidative DNA damage and DNA adduct 8-hydroxy-2' -deoxyguanosine (8-OHdG) formation in HDF. Intracellular 8-OHdG adduct formation is known to be a marker of oxidative damage at specific residues of DNA. In addition, high intracellular levels of this adduct are associated with mutagenesis, carcinogenesis and cellular senescence.

FIG. 5 shows the levels of 8-OHdG adduct contained in the DNA samples from HDF after control treatment, ORP aqueous solution treatment and HP treatment for 30 minutes. DNA was extracted either immediately after exposure (T0, white bars) or 3 hours after challenge (T3, black bars). The DNA was digested and the 8-OHdG adduct was determined by ELISA kit according to the commercial instructions. The values (ng/mL) are expressed as mean ± SD (n ═ 3). Exposure of the ORP water solution for 30 minutes did not increase adduct formation within the treated cells compared to control cells after 30 minutes of incubation. In contrast, treatment with highly diluted HP (low to sub-lethal and non-therapeutic HP concentration (500 μ M HP)) for 30 minutes with 500 μ M HP increased the amount of 8-OHdG adduct by about 25-fold over the amount in control-treated or ORP water solution-treated cells.

Cells treated with ORP water solution are able to reduce the levels of 8-OHdG adducts if the cells are left in supplemented DMEM for 3 hours after exposure to ORP water solution. Despite allowing the same 3 hours recovery period, HP treated cells still had approximately 5 times more adduct than control treated or ORP water solution treated cells. Taken together, these results demonstrate that acute exposure to ORP water solution does not induce significant DNA oxidative damage. These results also indicate that the ORP water solution is less likely to induce mutagenesis or carcinogenesis, neither in vitro nor in vivo.

Example 23

This example describes the effect of chronic exposure to low concentrations of exemplary ORP water solution and HP on HDF. Chronic oxidative stress is known to induce premature senescence of cells. To simulate prolonged oxidative stress, primary HDF cultures were chronically exposed to low concentrations of ORP water solution (10%) or non-lethal HP concentrations (5 μ M) during 20 population doublings. It has previously been found that the expression and activity of SA- β -galactosidase is associated with the aging process both in vivo and in vitro. In this example, SA- β -galactosidase expression was analyzed after consecutive exposure of HDF to ORP water solution or HP1 months. The results are shown in FIG. 6. SA- β -galactosidase expression was analyzed by counting the number of blue cells in 20 microscopic fields (exemplary staining pattern see panel a). Panel B shows that only HP treatment accelerated cellular 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 cell senescence.

Example 24

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

Acute systemic toxicity studies were performed in mice to determine the possible systemic toxicity of the exemplified ORP water solution Microcyn 60. 5 mice were injected intraperitoneally with a single dose (50mL/kg) of Microcyn 60. 5 control mice were injected with a single dose (50mL/kg) of saline (0.9% sodium chloride). All animals were observed for mortality and adverse reactions immediately after injection, 4 hours after injection, and then 1 time per day for 7 days. All animals were also weighed before injection, once again on day 7. There was no mortality during the study. All animals had normal clinical performance throughout the study period. All animals gained weight. Microcyn 60 estimated from this study had an acute intraperitoneal LD50 of greater than 50 mL/kg. This example demonstrates that Microcyn 60 lacks significant toxicity and should be safe for therapeutic use in the present invention.

Example 25

This example describes a study conducted to determine the potential cytogenetic toxicity of an exemplary ORP water solution.

Micronucleus experiments were performed using an exemplary ORP water solution (Microcyn 10%) to evaluate the mutagenic potential of intraperitoneal injection of ORP water solution into mice. Mammalian in vivo micronucleus assays are used to identify agents that cause damage to the chromosome or mitotic apparatus of murine polychromatic erythrocytes. This damage results in the formation of "micronuclei," an intracellular structure containing lagging chromosome segments or isolated whole chromosomes. The ORP water solution study included 3 groups of 10 mice per group (5 males/5 females): test group (administration of ORP water solution), negative control group (administration of 0.9% NaCl solution) and positive control group (administration of mutagenic cyclophosphamide solution). The test group and the negative control group received intraperitoneal injections (12.5mL/kg) of ORP water solution or 0.9% NaCl solution for 2 consecutive days (days 1 and 2), respectively. Positive control mice received a single intraperitoneal injection of cyclophosphamide (8mg/mL, 12.5mL/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 found in either group. On day 3, all animals were weighed and sacrificed.

Femurs were cut from sacrificed mice, bone marrow was removed, and duplicate bone marrow smears were prepared for each mouse. The bone marrow slices of each animal were read under 40X magnification. The ratio of polychromatic erythrocytes (PCE) to orthochromatic erythrocytes (NCE) per mouse was determined by counting a total of at least 200 erythrocytes, an indicator of bone marrow toxicity. A minimum of 2000 scorable PCEs were then evaluated per mouse and the incidence of micronucleated, pleochroic erythrocytes was calculated. Data were statistically analyzed using the Mann and Whitney test (5% risk 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 mice: 0.77 vs. 0.90, female mice: 0.73 vs. 1.02) when compared to their corresponding negative controls, showing the toxicity of cyclophosphamide to the treated bone marrow. However, there was no statistically significant difference between the PCE/NCE ratios of the ORP water solution treated mice and the negative control. Likewise, the positive control mice had a statistically significantly higher number of polychromatic erythrocytes with micronuclei than the ORP water solution-treated mice (male: 11.0 vs. 1.4, female: 12.6 vs. 0.8) and the negative controls (male: 11.0 vs. 0.6, female: 12.6 vs. 1.0). There was no statistically significant difference between the number of polychromatic erythrocytes with micronuclei in ORP water solution-treated mice and negative control mice.

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

Example 26

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

According to ISO 10993-5: 1999 standards this study was conducted to determine the possibility of an exemplary ORP water solution Dermacyn causing cytotoxicity. A filter paper containing 0.1mL Dermacyn was placed on the agarose surface and pressed directly onto a monolayer of mouse fibroblasts (L-929). In the presence of 5% CO₂After incubation at 37 ℃ for 24 hours, the prepared samples were observed for cytotoxic damage. The observations were compared to positive and negative control samples. The Dermacyn-containing samples did not show any evidence of cell lysis or toxicity, whereas the positive and negative controls had the expected performance.

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

Example 27

The study was conducted with 16 rats to evaluate the local tolerance of the exemplified ORP water solution Dermacyn and its effect on the histopathology of the wound bed in the 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 are removed (e.g., Dermacyn and saline treatments, respectively).

The Dermacyn and saline treated surgical wound sites were evaluated by a committee-certified veterinary pathologist on Masson trichrome stained sections and collagen II stained sections. The sections were evaluated for the amount of type 2 collagen expression as a manifestation of connective tissue hyperplasia, fibroblast morphology and collagen formation, the appearance of neogenetic epidermis in the cross section, inflammation and extent of skin ulceration.

The results indicate that rats are well tolerant to Dermacyn. No treatment-related histopathological lesions were found in skin sections from either side of the wound (Dermacyn-treated and saline-treated, respectively). There were no histopathological differences associated between the saline treatment and the Dermacyn treated wound sites, indicating that the Dermacyn treatment was well tolerated. There was no significant difference in collagen 2 expression between the saline-treated and Dermacyn-treated wound sites, indicating that Dermacyn had no adverse effects on fibroblasts or on collagen production processing during wound healing.

Example 28

This study can be used to demonstrate that an exemplary ORP aqueous solution Dermacyl used in the present invention is Versajet^TM(Smith&Nephew) replacement solution for the spray system was used to treat the safety and efficacy of necrotic tissue (ulcers) distal to the ankle and compared to standard protocols.

This is a prospective, random control, double blind study. Approximately 30 patients were enrolled in the study (approximately 20 in the Dermacyn group and approximately 10 in the control group). The population studied was patients with lower limb ulcers (e.g. diabetic foot ulcers, venous stasis ulcers). On day 0, all patients eligible for inclusion studies must meet all study inclusion and exclusion criteria. The inclusion criteria were: the patient is 18 years old or older; lower limb ulcers in patients show necrotic tissue and are candidates for mechanical debridement via jet-wash systems; the ulcer of the patient is located distal to the ankle; the ulcer surface area of the patient is greater than or equal to 1.0cm²(ii) a The patient's ulcers extend through the dermis into the subcutaneous tissue (granulation tissue may be present), and may expose muscles or tendons, but not the bones and/or joint capsules; an ankle-arm index (ABI) of the patient greater than or equal to 0.8 as measured by Doppler, or a toe pressure of the patient greater than or equal to 40 mmHg.

The exclusion criteria were: clinical evidence of gangrene in any part of the patient's treated limb; the patient's ulcers are expected to require amputation or amputation during the study; the patient had the following signs of Systemic Inflammatory Response Syndrome (SIRS); the total surface area of the ulcer of the patient is less than 1cm²(ii) a Patients had one or more medical conditions (including kidney, liver, blood, neurological or immunological disease) that led researchers to believe that patients were not suitable for the study; the patient is known to have active alcoholism orDrug abuse; patients are receiving oral or parenteral glucocorticoids, immunosuppressive or cytotoxic agents, or are expected to require these drugs during the study; patients are known to be allergic to chlorine; the patient's ulcer is accompanied by osteomyelitis; and patients suffering from any condition that would seriously hamper the ability of the patient to complete the study.

After signing the informed consent and meeting the inclusion and exclusion criteria, patients were randomized (2: 1 randomized) to one of the following treatments: treatment groups: dermacyn was applied with a spray system, plus the use of a hydrogel wound dressing protocol; control group: saline (standard treatment with spray systems), plus a protocol for applying hydrogel wound dressings.

Each patient randomized to Dermacyn will receive study product Dermacyn via a Versajet spray system during mechanical debridement of the patient's wound. The standard pressure device on Versajet will be used for diabetic foot ulcers located distal to the ankle. After debridement, Dermacyn is applied to the wound in an amount sufficient to rinse off all debris from the wound bed. The wound was covered with a hydrogel dressing. At each dressing change, the wound was irrigated with Dermacyn and covered with a new hydrogel dressing. The dressing was changed every 3 days unless the investigator had other different instructions. Clinical response factors (CFR) were determined during each week visit (1) reduction of wound bacteria, (2) reduction of wound area, and (3) development of granulation tissue).

Each control patient will receive a control product (saline solution) applied via the Versajet spray system during mechanical debridement of the patient's wound. After debridement, saline is applied to the wound in an amount sufficient to rinse off all debris from the wound bed. The wound was covered with a hydrogel dressing. At each dressing change, the wound was rinsed with saline and covered with a new hydrogel dressing. The dressing was changed every 3 days unless the investigator had other different instructions. Clinical response factors were determined during the weekly visit.

Wound debridement may be performed at weekly visits. Prior to wound evaluation, any necrotic tissue was removed with a spray system. Debris on the ulcers was rinsed away with Dermacyn or saline (depending on the random groupings). Between visits, patients will irrigate the wound with Dermacyn or saline (depending on the random groupings) at each dressing change. After debridement at each visit, photographs of the wounds were taken.

The main efficacy endpoints are: (1) reduction of wound bacteria; (2) the area of the wound is reduced; and (3) the development of granulation tissue. Safety was assessed for all patients in the study that were randomly grouped. Treatment for emergency and serious adverse events were recorded.

Example 29

This study will demonstrate the safety and efficacy of an exemplary ORP water solution derman as a replacement solution for Jet-Ox ND irrigation system for the treatment of necrotic tissue in lower limb ulcers, and compare it to the standard protocol used for Jet-Ox ND systems.

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

20 patients (randomized into 10 Dermacyn patients and 10 control patients) were studied. The inclusion criteria were: the patient is older than 18 years; patients have ulcers below the lower limb knee that present necrotic tissue and are candidates for mechanical debridement with Jet-Ox ND irrigation system; prior to the screening visit, the patient had ulcers present for > 30 days; ulcer surface area > 1cm²(ii) a The ulcer extends through the dermis into the subcutaneous tissue (granulation tissue may be present), and may expose a muscle or tendon, but not the exposed bone and/or joint capsule; an ankle/arm index of > 0.8 for the patient and/or a toe pressure of > 40mmHg as determined by Doppler; the pulse of the dorsalis pedis artery and/or the posterior tibial artery of the patient can be touched.

Exclusion criteria were as follows: patients with impaired kidney, liver, blood, nerve or immune function, including Human Immunodeficiency Virus (HIV) or acquired immunodeficiency syndrome (AIDS); wherein the investigator deems the patient unsuitable for participation in the study; wounds with the following clinical signs of infection; treating gangrene of any part of the limb; ulcers reveal bone (accessible) or other evidence of potential osteomyelitis at the site of the ulcer; the affected ulcer is expected to be amputated or excised during treatment; severe malnutrition, as indicated by albumin < 2.0; known alcoholism or drug abuse; the patient is receiving oral or parenteral glucocorticoids, immunosuppressive or cytotoxic drugs, coumarins, heparin or is expected to require these drugs during treatment; and patients are known to be allergic to chlorine.

Each individual was randomly grouped into one of two treatment groups: dermacyn or saline. The target ulcer will receive mechanical debridement, after which the wound is irrigated with Dermacyn or saline and bandaged with a hydrogel dressing. Central wound biopsies were taken for quantitative culture, as well as laboratory studies (appropriate hematology, serum chemistry, and pregnancy tests), non-invasive peripheral vascular studies, medical history and physical examination, ulcer tracking, and photographs of ulcers.

Jet-Ox ND irrigation system may be applied with derman or saline, hydrogel and dressing wrap. Providing guidance for home administration. Visits included screening, grouping (day 0) and random grouping, debridement per week visit, photography and evaluation. By study period (1) reduction of wound bacteria; (2) the area of the wound is reduced; and (3) evaluation of the efficacy of the development of granulation tissue. Safety was assessed for all patients in the study that were randomly grouped. Treatment for emergency and serious adverse events were recorded.

All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. 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 individually recited herein. 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 (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on 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.

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 may 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 for the invention to 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, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

Claims

1. Use of an aqueous redox potential solution in the manufacture of a medicament for treating a 2 or 3 degree burn in a patient, wherein the solution has a pH of 6.4 to 7.8 and is stable for at least 2 months, wherein the aqueous redox potential solution is produced by an apparatus comprising:

a three-compartment electrolysis cell having an anode compartment, a cathode compartment, and a brine solution compartment located 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 the cathode compartment is separated 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 flowing water 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 of the anode chamber and the cathode chamber;

a saline solution recirculation system for 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 and the anode chamber;

a cathode inlet tube connecting the water supply to the cathode chamber;

an intermediate inlet tube connecting the brine solution chamber with the liquid supply system;

a potential source connected to the anode electrode and the cathode electrode;

an anode outlet pipe for carrying anode water out of the anode chamber;

a cathode outlet pipe for carrying cathode water out of the cathode chamber; and

at least one mixing vessel for collecting anode water and cathode water transported out of the electrolysis cell.

2. The use of claim 1, wherein the solution remains stable for at least 1 year.

3. The use of claim 2, wherein the pH is from 7.4 to 7.6.

4. Use according to claim 1, wherein the solution comprises anode water and cathode water.

5. Use according to claim 4, wherein the cathode water is present in an amount of from 10% by volume to 50% by volume of the solution.

6. Use according to claim 5, wherein the cathode water is present in an amount of from 20% by volume to 40% by volume of the solution.

7. Use according to claim 5, wherein the anode water is present in an amount of 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 burn with the solution.

9. The use of claim 8, wherein the solution is administered to the patient by spraying the burn with the solution in 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 the 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. The use of claim 14, wherein the amount of free chlorine species is from 10ppm to 400 ppm.

17. The use of claim 16, wherein the free chlorine species is hypochlorous acid in an amount of from 15ppm to 35 ppm.

18. The use of claim 16, wherein the free chlorine species is hypochlorite ion, wherein the hypochlorite ion is provided by sodium hypochlorite in an amount of from 25ppm to 50 ppm.

19. The use of claim 14, wherein the solution is administered to the patient by spraying the burn with the solution.

20. The use of claim 19, wherein the solution is administered to the patient by spraying the burn with the solution in 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. Use according to claim 1, wherein the solution comprises hypochlorous acid in an amount from 15 to 35ppm and sodium hypochlorite in an amount from 25 to 50 ppm.

26. The use of claim 25, wherein the solution is administered to the patient by spraying the burn with the solution.

27. The use of claim 26, wherein the solution is administered to the patient by spraying the burn with the solution in 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 use of claim 1, wherein the treatment comprises (1) spraying the burn with an Oxidative Reductive Potential (ORP) water solution at high pressure; (2) optionally soaking the burn with ORP water solution; (3) spraying ORP water solution on the burn; and (4) wetting the burn with ORP water solution.

33. The use of claim 32, wherein the burn is debrided 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 sufficiently healed.

38. The use of claim 32, further comprising administering an antibiotic to the patient.