EP1959972A2 - Procede de traitement des blessures ouvertes par l'acide hypochloreux - Google Patents

Procede de traitement des blessures ouvertes par l'acide hypochloreux

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Publication number
EP1959972A2
EP1959972A2 EP06845416A EP06845416A EP1959972A2 EP 1959972 A2 EP1959972 A2 EP 1959972A2 EP 06845416 A EP06845416 A EP 06845416A EP 06845416 A EP06845416 A EP 06845416A EP 1959972 A2 EP1959972 A2 EP 1959972A2
Authority
EP
European Patent Office
Prior art keywords
saline solution
wound
electrolyzed saline
ulcer
electrolyzed
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP06845416A
Other languages
German (de)
English (en)
Other versions
EP1959972A4 (fr
Inventor
Joe B. Selkon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Puricore Inc
Original Assignee
Puricore Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Puricore Inc filed Critical Puricore Inc
Publication of EP1959972A2 publication Critical patent/EP1959972A2/fr
Publication of EP1959972A4 publication Critical patent/EP1959972A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/20—Elemental chlorine; Inorganic compounds releasing chlorine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/40—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing ingredients of undetermined constitution or reaction products thereof, e.g. plant or animal extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0076—Sprayable compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Definitions

  • This invention relates to methods of treating wounds and associated symptoms using an electrolyzed saline solution containing hypochlorous acid.
  • Treatment strategies include the use of topical treatments such as GRANUFLEX®, to aid granulation and skin repair, alginates to clean the wound of debris, dry inert dressings to protect the wound (but which do not promote healing), and bacteriostatic or bactericidal ointments to reduce the infection. While antibiotics have been used to reduce infection in the past, nowadays this is often not a treatment of choice due to the increased risk of antibiotic resistance.
  • potassium permanganate is an oxidant which has stood the test of time in the treatment of leg ulcers but still has the disadvantages of irritating and injuring newly grown sldn and causing skin discoloration.
  • other disinfectants such as EUSOL (Edinburgh University Solution of Lime) and Daikin's solution, rely on a high concentration of hypochlorite ions for their disinfectant properties and are also irritating and painful. In fact, these compounds are no longer recommended for use due to their irritant and painful effects and impairment of cell growth which outweigh their therapeutic value.
  • FIG. 1 is a schematic outline of the main processing stages of a method for producing an electrolyzes saline solution for application in certain embodiments of a method according to the present invention.
  • FIG. 2 is a flow diagram depicting a method of producing an electrolyzed saline solution for application according to certain embodiments of a method of the present invention.
  • FIG. 3 is a schematic illustration of an electrochemical cell that can be used to produce an eiectrolyzed saline solution for application in certain embodiments of a method of the present invention.
  • FIG. 4a is a bar graph illustrating the effect on dermal fibroblast proliferation, measured by absorption assay at 3 and 6 days, of various concentrations of an eiectrolyzed saline solution according to the present invention.
  • FIG. 4b is a bar jjraph similar to FIG. Ia, showing the results of the absorption assay at 6 days.
  • the present invention provides a method of treating a chronic, refractory open wound by applying to the wound an eiectrolyzed saline solution comprising hypochlorous acid having a pH of from about 4 to about 7 and an available free chlorine content of from about 50 to 1000 parts per million (ppm) when produced by an electrochemical cell system.
  • the present invention provides a method of reducing pain associated with an open wound by applying to the wound an eiectrolyzed saline solution comprising hypochlorous acid having a pH of from about 4 to about 7 and an available free chlorine content of from about 50 to about 1000 ppm when produced by an electrochemical cell system.
  • the present invention provides a method of treating an open wound comprising (i) applying a compression bandage to the wound and applying subsequently or concurrently to the wound an eiectrolyzed saline solution comprising hypochlorous acid having a pH of from about 4 to about 7 and an available free chlorine content of from about 50 to 1000 ppm when produced by an electrochemical cell system.
  • the present invention provides various methods of treating open wounds and associated symptoms in patients;.
  • An open wound as is generally known in the art, is a wound that breaks the skin or mucous membrane.
  • Non-limiting examples of open wounds include ulcers, pressure sores, burns, lacerations, surface wounds, and incisions.
  • Non-limiting examples of ulcers include diabetic ulcers and foot and leg ulcers (including arterial and venous leg ulcers).
  • patient includes human and animal patients.
  • treating as used herein refers to improving, preventing the occurrence or worsening of, or alleviating the symptoms or pathologic effects of an open wound.
  • treating can include decreasing the size of the open wound, decreasing the duration of the open wound, reducing the spread of infection, healing the open wound by facilitating cell growth and regeneration, decreasing the microbial count in the open wound, improving the clinical appearance of the open wound, and/or reducing the sensitivity of skin surrounding the open wound.
  • treating the open wound comprises healing the wound by reducing the microbial count in the wound and permitting cellular proliferation.
  • an electrolysed saline solution of the present invention has no adverse effect on fibroblasts and keratinocytes and thus acts as a microbiocide to aid in the healing process by not inhibiting normal cell growth and, in fact, allowing normal cell growth to occur.
  • the present invention provides a method of treating a chronic, refractory open wound in a patient by applying to the wound an electrolyzed saline solution.
  • the type of wounds that are classified as refractory open wounds are known in the art, in an embodiment, the type of refractory open wounds that are treated according to this aspect of the present invention is a wound that does not experience at least a 44% reduction in size after three weeks of standard treatment with compression bandaging.
  • the chronic, refractory wound is a wound that is over 5cm 2 in size and/or that is older than six months.
  • the open wound is a venous leg ulcer.
  • the present invention provides a method of reducing pain associated with an open wound in a patient by applying to the wound an electrolyzed saline solution.
  • One method of determining whether the patient has experienced a reduction in pain is by initially assessing the pain prior to treatment and then assessing the pain after treatment.
  • the patient can participate in a questionnaire, such as a McGiIl questionnaire, to determine the patient's level of pain.
  • a reduction in pain can be determined by comparing the patient'is level of pain after receiving treatment against another patient's level of pain who has not been treated with an electrolyzed saline solution of the present invention.
  • the present invention provides a method of treating an open wound by applying a compression bandage to the wound and then applying an electrolyzed saline solution to the wound.
  • the electrolyzed saline solution is applied to the wound in conjunction with a compression bandage.
  • the present invention provides a medicament for open wounds, which contains an electr ⁇ lyzed saline solution according to the embodiments describes herein, that is used for treating chronic refractory open wounds, reducing the pain associated with an open wound, and/or that is used subsequent to or concurrently with standard compression bandaging.
  • the medicament can be in any appropriate form, such as a solution, a gel, cream, ointment, paint, micronized spray or other form.
  • the present invention provides a kit for treating an open comprising an electrolyzed saline solution according to any of the embodiments described herein and a compression bandage.
  • an electrolyzed saline solution can be administered in combination with other treatments such as antibiotics, compression bandaging or other therapeutic agents;.
  • An electrolyzed saline solution of the present invention may be administered as frequently as necessary in order to obtain the desired therapeutic effect. Frequency of administration will depend, for example, on the stage of the open wound, the route of administration or associated symptom being treated. Suitable doses of an electrolyzed saline solution can be determined by a physician or qualified medical professional and depend on factors such as the nature of the open wound or symptom, the route of administration, the duration of treatment, and the condition of the patient.
  • An electrolyzed saline solution of the present invention can be applied in different forms such as a liquid or gas and in a number of ways such as by way of a gel, cream, ointment, or micronized spray. Alternatively or in addition, the open wound can be immersed in a bath, such as a hydrobath.
  • the pH of an electrolyzed saline solution of the present invention is between about 4 to 7, including all intermediate numbers therebetween. In a preferred embodiment, the pH is between about 5.4 to 5.8. In a more preferred embodiment, the pH is 5.4.
  • the available free chlorine (AFC) concentration of an electrolyzed saline solution of the present invention is between about 50-1000 parts per million (ppm). In a preferred embodiment, the AFC concentration is about 150-180 ppm.
  • the main active component in an electrolyzed saline solution of the present invention is hypochlorous acid and preferably the hypochlorous acid is present at 95%.
  • the electrolyzed saline solution has a biocide rate (D Value) of approximately 1 log unit reduction of bacillus subtilis spores in less than 1 minute with a 9:1 electrolyzed saline solution: innoculum mix.
  • D Value biocide rate
  • the biocide rate is about 3.4 seconds.
  • FIG. 1 provides a schematic outline of the main processing stages of a non-limiting, exemplary method for producing an electrolyzed saline solution of the present invention.
  • a method involves an input and pre-processing stage; a production stage; and a storage and dispensing stage.
  • water can be passed through a water softener zone where excess magnesium and calcium ions are removed.
  • the resultant softened water can be passed as process water to a brine generation zone where a salt (such as NaCl) can be added to produce a dilute salt solution.
  • a salt such as NaCl
  • the salt is vacuum dried crystalline salt which is commercially produced to a consistent standard.
  • the dilute salt solution can be a substantially constant concentration since a known quantity of salt is added to a known quantity of softened water to achieve a desired concentration of the dilute salt solution.
  • Another method may involve mixing a known amount of a salt, such as, for example, NaCl or KCl, with de-ionized or de-mineralized water. This water can be used as delivered by a deionizer or demineralizer or can be dosed with a known amount of a buffering agent, such as, for example, sodium bicarbonate. This electrolyte can then be introduced to the production stage.
  • a salt such as, for example, NaCl or KCl
  • the dilute saline solution or prepared electrolyte can be passed to one or more electrolytic cell systems, such as the electrolytic cell depicted in FIG. 2 (a preferred embodiment of which is described in more detail in FIG. 3).
  • the electrochemical cell includes a cathode and an anode chamber across which a substantially constant electric current is applied.
  • the applied electric current can be maintained constant via an energy control and monitoring zone.
  • Catholyte and anolyte are produced from the cathode and anode chambers respectively as a result of electrochemical treatment of the saline solution in the cells.
  • Catholyte and anolyte can be prevented from mixing using a separator.
  • a semi-permeable membrane can be used in the case of parallel plate technology (for example, NAFION® membrane) or a porous ceramic membrane.
  • the catholyte is not required for the final solution and is directed to drain.
  • all or part of the catholyte is re-introduced into the anode chamber (referred to in the art as catholyte recirculation).
  • Catholyte which is not recirculated can be directed to waste and anolyte, otherwise referred to as output solution, is passed to a buffer storage and quality subsystem.
  • the output solution can be tested in the buffer storage and quality subsystem, and, if it fails to meet the quality standards, can also be directed to waste. If the output solution falls within specification, the output solution can be permitted to pass to an output solution storage zone from where it can be subsequently dispensed for use.
  • FIG. 2 is a flow diagram or "hydraulic map" showing in more detail a non-limiting, exemplary method of producing an electrolyzed saline solution of the present invention.
  • Potable water can be passed through an external water softener containing a cation exchange resin (not shown) thereby exchanging hardness ions of calcium and magnesium onto the resin and releasing sodium ions into the water.
  • the softened water can be fed through a valve 16 into a softened water tank 14 which may include a plurality of level detectors for monitoring and controlling the softened water level in it.
  • tank 14 may include a level detector 20, which is a safety device which is activated only when the softened water in tank 14 reaches a predetermined extra high level to stop the charging of tank 14 with further softened water.
  • Tank 14 may also include a level detector 22 which ensures that tank 14 has a correct volume of softened water to prepare the appropriate concentration of saline solution.
  • Tank 14 may also include a level detector 26 and softened water will begin to re-charge tank 14 when the softened water drops below a predetermined low level determined by level detector 26 and at the end of production of one batch, of electrolyzed saline solution.
  • Tank 14 may also include a valve 28 which allows liquid to be drained.
  • a salt such as, for example, vacuum dried crystalline salt can be added to tank 14 via dispensing wheel 21.
  • Dispensing wheel 21 contains many tablets of known salt mass, a pre-determined number of which are dispensed through a hole in the top of tank 14 at the start of each electrolyzed saline solution production cycle.
  • the saline solution has a salt concentration range of 2.0 to 90.0 g/L.
  • Pump 59 can pump the saline solution towards an electrolytic cell pack 63.
  • the flow rate of the saline solution can be monitored by a sensor 10.
  • the sensor can ascertain whether the incoming saline solution is at a temperature within the range under which the process can reasonably operate, such as between 5 and 35°C.
  • Other parameters such as the incoming solution's pressure, softness, alkalinity, pH, conductivity, and microbial count can be monitored, modulated and/or controlled to establish that the solution falls within acceptable levels for the process or for desired characteristics of the resulting solution. For example, as the salt concentration of the solution is increased, the conductivity can be increased and other parameters, such as the current, would change.
  • the various parameters can be modified to correspond to the desired salt concentration of the solution.
  • incoming water is not suitable for processing according to the present invention. If sensor 10 detects that the properties of the incoming saline solution do not fall within acceptable limits, the solution can be diverted through a waste discharge manifold (not shown) to a drain via valve 12. On the other hand, if the incoming saline solution is acceptable, it can be allowed to flow into the cells through valve 13.
  • electrochemical cell pack 623 can include eight electrolytic cells, with two sets of four cells connected hydraulically in parallel. For simplicity, only one cell is illustrated. In general, the number of cells in the cell pack can be determined by the output volume required from the particular system.
  • Each cell has an anode chamber and a cathode chamber and the flow of saline solution can be split such that the greater portion is fed to the anode chamber and the lesser portion is fed to the cathode chamber. In certain embodiments, approximately 90% of the saline solution can be passed through the anode chamber and the remainder can be passed through the cathode chamber.
  • the flow rate of saline solution through the cathode chamber can be much lower than for the anode chamber and the pressure in the cathode chamber can also be lower.
  • the flow rate of saline solution into the cathode chamber which also has an influence on the pH of the output solution, can be controlled by a flow regulator 68.
  • Flow regulator 68 can be manually adjusted if there is a variation in input water quality.
  • the flow rate supplied to the anode is from 50% to 95%, inclusive of all intermi ⁇ diate values, of the solution applied to the electrolytic cell pack 63. In certain embodiments, the flow rate to the anode is from 85% to 95% of the solution supplied to the electrolytic cell.
  • the pH of the output solution may be at least partially controlled by dosing a portion of the catholyte to the inlet stream for the anode chambers.
  • the catholyte may be dosed to the inlet stream 58 by an adjustable pump and valve system 66 and the dosing rate is increased or decreased to achieve the target pH.
  • the remaining catholyte which is not dosed into the input stream 58 for the anode chambers can be directed, to waste, if necessary diluting it prior to disposal.
  • the: catholyte can be dosed into the anode stream 58 before this stream enters the anode.
  • the catholyte can also be dosed into the anode stream after it has been electrolyzed.
  • the electrolyte is prepared by mixing the various salts with de-ionized or de-mineralized water
  • mixing of the catholyte may not be performed, in which case all the catholyte is diverted to drain. If a proportion of the catholyte is used for pH control, then the catholyte can be dosed to the anode stream either before or after it enters the anode chamber.
  • the output solution can then be directed to tank 70.
  • the pH of such output solution can be measured by a meter 72. If the pH does not fall within the desired parameters, a valve 76 can be opened and the contents of tank 70 can be drained to waste.
  • Meter 72 can be linked to a pump and valve system 66 to adjust the level of catholyte dosed to the anode chambers thereby enabling the pH of the output solution to be adjusted to bring the output solution within the desired pH range. If the pH of the output solution is determined to fall within the desired parameters, valve 16 can be kept closed and the output solution can be allowed to fill tank 70.
  • Other properties of the output solution such as redox potential or AFC, could also form the basis of the measurement and control system consisting of meter 72 and adjustable pump and valve system 66.
  • Storage tank 7C ⁇ may include various level detectors for monitoring liquid levels in the tank.
  • a level detector 90 may be activated by an extra high level of output solution within the tank, raising; an alarm and stopping production.
  • Low level detector 94 may be activated when the level of the output solution falls to a low level, raising an alarm and preventing further dispensing to the appropriate receptacle.
  • the output solution As the output solution is dispensed and after a period of time below the level of detector 94, production of output solution may be re-commenced. From the storage tank, the output solution can be distributed in individual nebulizers, inhalers, or ampules.
  • the above-described processing steps of producing an electrolyzed saline solution are only exemplary and other electrochemical processes could be used to produce an electrolyzed saline solution of the present invention.
  • FIG. 3 shows an embodiment of an electrolytic cell 300 used in certain methods of producing an electrolyzed saline solution according to an embodiment of the present invention.
  • cell 300 comprises co-axial cylindrical and rod electrodes 302, 304 respectively, separated by a semi-permeable ceramic membrane 306 co-axially mounted between the electrodes thus splitting the space between the electrodes to form two chambers 308 and 310.
  • Cylindrical electrode 30.! which is this embodiment forms the anode, is typically made from commercially pure titanium coated with a ruthenium oxide and iridium oxide- based electrocatalytic (active) coating suitable for the evolution of chlorine from a chloride solution.
  • Rod electrode 304 which in this embodiment forms the cathode, is typically made from titanium and can be machined from an 8mm stock bar to a uniform cross-section over its effective length, which is typically about 210mm ⁇ 0.5mm.
  • a coating such as ruthenium oxide and iridium oxide based electrocatalytic (active) coating, for example, suitable for the evolution of chlorine from a chloride solution.
  • Semi-permeable ceramic membrane 306 forming a separator and creating the anode and cathode chambers 308 and 310 can be composed of aluminium oxide (80%), zirconium oxide (18.5%) and yttrium oxide (1.5%), and preferably has a porosity of about 50- 70%, a pore size of 0.3 to 0.5 microns and a wall thickness of 0.5mm +0.3mm/-0.1mm.
  • the ceramic of certain embodiments of membrane 306 is described in the specification of patent application GB 2354478 (Sterilox Medical (Europe) Limited), the subject matter of which is incorporated herein by reference.
  • Ceramic membrane 306 can be made of any other suitable semi-permeable or ion-selective material of ceramics other than the aluminium oxide, zirconium oxide and yttrium oxide ceramic described above.
  • the surface area of the anode can be largely defined by the quantities of output solution desired to be produced and available free chlorine content desired in that solution.
  • an anode surface area of 0.065 to 0.095 m 2 can be utilized.
  • Such a surface area can be made up by a number of electrolytic cells working in parallel.
  • An anode area of 0.070 to 0.090 m2 is more preferable, and an anode surface area of 0.075 to 0.085 m 2 is even more preferable.
  • each anode is within the range 1.5 to 2.5 kAm '2 , more preferably 1.7 to 2.2 kAm “2 , and still more preferably 1.85 to 1.95 kAm "2 .
  • cell 300 is provided with entry passages 312 and 314 to permit the saline solution to enter cell 300 and flow upwards through the anode and cathode chambers 308 and 310 to be discharged as anolyte and catholyte through exit passages 316 and 318 respectively.
  • the anolyte containing available free chlorine constitutes the output solution.
  • a group of cells can be connected together to form a cell pack 63.
  • a cell pack comprising eight cells connected together in parallel hydraulically and in series electrically may generate about 200 litres/hour of output solution.
  • the flow rate through the anode chamber may vary between 100 to 220 1/h.
  • a flow rate of 150 to 210 1/h is more preferred and a flow rate of 185 to 205 1/h is even more preferred.
  • the flow rate can also be any value within the expressed ranges.
  • the person skilled in the art will appreciate that the flow rate can be altered beyond such a range but still produce the solution of the invention by varying the number of cells/surface area of anode.
  • the flow rate per anode surface area of 1.25 x 103 to 2.75 x 103 lh "! m "2 can be used produce an embodiment of an electrolyzed saline solution of the invention.
  • the flow rate can also take any value with the aforementioned range.
  • the flow rate is 1.87 x 103 to 2.63 x 103 Ih -1 In '2 and more preferably the flow rate is 2.31 x 103 to 2.56 x 103 Ih "1 m '2 .
  • the skilled person can obtain the required current to produce a suitable solution by setting the flow rate to that just described and varying the current until the solution produced has the suitable specifications.
  • the current range is 15 to 25 A, inclusive of all intermediate values. In certain embodiments, a current range of 17 to 22 A is used and in certain embodiments a current range of 18.5 to 19.5 A is used.
  • the residual salt concentration of an embodiment of an electrolyzed saline solution can be from 2.0 g/1 to 90 g/1. In certain embodiments, the residual salt concentration is greater than 9 g/1 and in certain embodiments, the residual salt concentration is 70-90 g/1. This residual salt concentration can result from the entire desired amount of salt being added during the input and pre-processing stage or less than the entire desired amount of salt being added during the input and pre-processing stages and the remainder of the desired amount of salt being added after the production stage.
  • Fibroblasts are flattened, irregular-shaped, connective tissue cells which are ubiquitous in fibrous connective tissue. They secrete components of the extracellular matrix, including collagen, and play an important role in tissue regeneration.
  • the cells are incubated under sterile conditions in an electrolyzed saline solution containing primarily hypochlorous acid and including sodium hypochlorite and other oxidized chlorine species, having a pH range from 4 to 7 and a redox potential of around 1000 mV.
  • an electrolyzed saline solution containing primarily hypochlorous acid and including sodium hypochlorite and other oxidized chlorine species, having a pH range from 4 to 7 and a redox potential of around 1000 mV.
  • a range of dilutions of electrolyzed saline solution at different pH levels is investigated.
  • the electrolyzed saline solution used in the trials is the product of the electrolysis of an aqueous saline solution passed over a mixture of catalysts on titanium electrodes to give a mixture of oxidizing species, particularly hypochlorous acid (HOCl) at a concentration of about 144 mg/1 to 400 mg/1 available free chlorine (Cl).
  • HOCl hypochlorous acid
  • the electrolyzed saline solution is produced as required for each test; the apparatus (supplied by Sterilox Medical Limited, Abingdon, UK) is operated to give a final solution redox potential of >950 mV. Appropriate dilutions of the electrolyzed saline solution are made, and the pH of the final solution is adjusted using a phosphate buffer.
  • HDF cells are seeded in normal (10%) fetal calf serum (FCS) and Dulbecco's Modified Eagle Medium (DMEM) at 1.5 x 10 3 cells/well. After 24 hours, the medium is changed to low (0.4%) FCS/DMEM. After a further 48 hours incubation, electrolyzed saline solution at varying concentrations is added to the cells. The viability of the cells is observed, using a standard absorption assay, 3 and 6 days after the application of electrolyzed saline solution.
  • Trial 1 HDF cells are incubated with electrolyzed saline solution in a range of dilutions at a pH of 4.3. The dilutions used are: 1, 1/3, 1/7, 1/14, 1/28, 1/56, 1/112, 1/224, 1/448 1/896, 1/1792 and 0.
  • HDF cells incubated with electrolyzed saline solution at pH 5.4 show no inhibition of cell growth, even in the presence of a 1/7 dilution of electrolyzed saline solution.
  • the electrolyzed saline solution based on hypochlorous acid is identical to that described in Example 1.
  • HDF cells are seeded in 10% FCS/DMEM at 5.times.lO.sup.3 cells/well. After incubation at 31° C for 72 hours, ' dilutions of electrolyzed saline solution are prepared in HBSS and added to the cells. The viability of the cells is ascertained by a standard absorption assay at time intervals of 15 minutes up to one hour from the addition of the electrolyzed saline solution.
  • Trial 1 HDF cells are incubated with electrolyzed saline solution in a range of dilutions at a pH of 4.3. The dilutions used are: 1, 1/3, 1/7, 1/14, 1/2, 1//56, 1/112, 1/224, 1/448, 1/896, 1/1792 and 0.
  • Dilutions of electrolyzed saline solution at 1/24 and 1/20 induces slight damage to the cells while dilution of 1/16or less induces cell death.
  • Example 1 The results of these trials support the results shown in Example 1 in that, while electrolyzed saline solution at pH 4.0 to 4.3 and pH 6.2 induce damage to cultured HDF cells, greater cytotoxic effects; are seen at the lower pH.
  • HK cells (subcultured, P2, FS, 7 years) are seeded at 8 x 10 3 cells/well and incubated at 31 0 C in CLONETICS® (Biowhittaker, US) serum-free medium with complete supplements, hereinafter referred to as; keratinocyte growth medium (KGM), in four 24-well plates. After 24 hours incubation the medium in plates 1 and 2 was changed to CLONETICS® (Biowhittaker, US) serum-free medium, without complete supplements, hereinafter referred to as keratinocyte basal medium (KBM).
  • CLONETICS® Biowhittaker, US serum-free medium with complete supplements
  • electrolyzed saline solution diluted in KBM at pH 5.4 is added to plates 1 and 2
  • electrolyzed saline solution diluted in KGM is added to plates 3 and 4.
  • the dilutions of electrolyzed saline solution are: 1/10, 1/20, 1/50, 1/100, 1/150, and 0.
  • the pH of the final electrolyzed saline solution solution is adjusted using a phosphate buffer.
  • the absorption assay shows that, on both day 3 and day 5, cell proliferation has occurred in the presence of all dilutions of electrolyzed saline solution. At day 5, the level of cell proliferation has reached a significant level compared to cell growth in the absence of electrolyzed saline solution.
  • KBM with lower concentrations of supplements is used as a holding medium, with or without electrolyzed saline solution.
  • HK cells (thawed, P2, FS, 7 years) are seeded to six 96-weil plates at 3.times.lO.sup.3 cells/well in KGM. After incubation for 24 hours, the medium in plates 1 and 2 is changed to KBM with 20% supplements, and the medium in plates 3 and 4 is changed to KBM with 50% supplements.
  • electrolyzed saline solution diluted in KBM with 20% supplements is added to plates 1 and 2
  • electrolyzed saline solution diluted in KBM with 50% supplements is added to plates 3 and 4
  • plates 5 and 6 received electrolyzed saline solution diluted in complete KGM.
  • the dilutions of electrolyzed saline solution are: 1/7, 1/10, 1/15, 1/20, 1/40, 1/60, 1/100, 1/500, 1/1000, 1/2000, 1/4000 and 0.
  • the cells are incubated for a further 3 days in the presence of electrolyzed saline solution, after which time, a standard absorption assay is carried out on plates I 3 3 and 5 to ascertain the viability of the cells, and the medium in plates 2, 4 and 6 is changed to KGM. Plates 2, 4 and 6 are assayed after a further 1 48 hours of incubation.
  • Dermal keratinocytes cultured in the presence of KGM and electrolyzed saline solution show enhanced cell proliferation, and no cytotoxicity is seen in the presence of electrolyzed saline solution.
  • a preliminary clinical evaluation of electrolyzed saline solution based on hypochlorous acid is carried out on one patient with chronic venous ulcers on both left and right legs.
  • the aim of the trial is to determine whether the bacterial status of the ulcers is altered and the bed of the ulcer improved by treatment with electrolyzed saline solution.
  • the patient's legs is immersed in 40 liters of electrolyzed saline solution in a hydrobath for fifteen minutes before being allowed to dry. An intermediate assessment without treatment is carried out after one week.
  • a second treatment with electrolyzed saline solution is repeated after two weeks in which the patient is subjected to three fifteen-minute washes at approximately three-hour intervals.
  • Post-treatment clinical evaluation is carried out one and several days after the second treatment.
  • the patient reports that the treatment is comfortable and free from pain.
  • the appearances of the ulcers on both legs are markedly improved when assessed five hours after treatment.
  • the patient is seen one week after the first treatment and is treated with conventional therapy, including potassium permanganate.
  • conventional therapy including potassium permanganate.
  • the effect of these on the appearance of the leg ulcers following treatment does not appear to be as striking as that seen with electrolyzed saline solution.
  • a second treatment with electrolyzed saline solution is repeated a further week later, and similar beneficial results are obtained.
  • the ulcers In between the treatment periods the ulcers have become sloughy on both legs.
  • the ulcer bed is whitish due to effervescence.
  • a cleansing effect is seen after the later two washes, and a marked improvement is seen with the state of the ulcer 18 hours after the first wash.
  • Proteus ssp pre-treatment 2 3.O x IO 3 Coliforms 1.5 x lO 4 coliforms
  • the HOCl solution used was generated by electrolyzing a concentrated solution of salt to a solution consisting of over 97% HOCl at pH 5.4-5.8, with a >950mV redox potential.
  • the concentration of HOCl used was 150- 180 parts per million chlorine radicals.
  • the HOCl wash was administered twice a week for three weeks and then once a week for nine weeks. During the nine week period, patients continued to have routine dressing changes and reapplication of the compression bandage at home once a week.
  • topical antibacterial agents wexe applied during both phases of the trial when necessary. These were restricted to metronidazole, silver sulphadiazine, cadexomer iodine and Aquacel Ag (ConvaTec). The antibiotics were used sparingly, and when the data were analyzed appeared not to have had a major therapeutic effect on their own.
  • the benefits of HOCl treatment are shown in Table 4 and 5.
  • the invention has applicability to burns, to organ transplants in relation to which current practice is to disinfect organs with antibiotics for two weeks before they are used in a patient, to disinfection of valve-replacements, and to surface wounds, open wounds and plural cavity infections which are exhibiting drug-resistance.

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Abstract

La présente invention concerne des procédés de traitement des blessures ouvertes, telles qu'une blessure ouverte chronique réfractaire, par l'administration d'une solution salée électrolysée comprenant de l'acide hypochloreux. L'invention concerne également un procédé permettant de soulager la douleur associée aux blessures ouvertes par l'administration d'une solution salée électrolysée. L'invention concerne en outre des procédés de traitement combiné dans lesquels une solution salée électrolysée est administrée après ou en même temps que la pose d'un pansement compressif ordinaire.
EP06845416A 2005-12-13 2006-12-13 Procede de traitement des blessures ouvertes par l'acide hypochloreux Withdrawn EP1959972A4 (fr)

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US11452778B2 (en) 2011-03-18 2022-09-27 Urgo Us, Inc. Stabilized hypohalous acid solutions
ES2741480T3 (es) * 2011-03-18 2020-02-11 Urgo Us Inc Soluciones estabilizadas de ácido hipohaloso
EP2543359A1 (fr) * 2011-07-08 2013-01-09 Caliopa AG Gel pour la traitement des plaies
DE102011055182A1 (de) * 2011-11-09 2013-05-16 Monopharm Beratungs- Und Handelsgesellschaft Mbh Anolyt, Verfahren zu dessen Herstellung und dessen Verwendung
US20140328945A1 (en) * 2013-05-03 2014-11-06 Aquaxo, Inc. METHOD FOR STABILIZING AN ELECTROCHEMICALLY GENERATED SANITIZING SOLUTION HAVING A PREDETERMINED LEVEL OF FREE AVAILABLE CHLORINE AND pH
EP4000685A1 (fr) * 2013-11-14 2022-05-25 RM2 Technology LLC Systèmes et appareils d'ablation de tissus à l'aide de l'électrolyse et de la perméabilisation
CN112998846A (zh) 2015-05-01 2021-06-22 因特科学股份有限公司 用于使用脉冲形状设计的组织消融的方法、系统及设备
CN108849971A (zh) * 2018-07-15 2018-11-23 西安青叶生物科技有限公司 一种利用弱酸性次氯酸水型消毒液的配制及其使用方法
GB2599795A (en) * 2020-09-15 2022-04-13 Facerestoration Ltd Lavage techniques and virucidal compositions comprising hypochlorous solutions
CN113244264A (zh) * 2021-06-07 2021-08-13 青岛威巴克生物技术有限公司 一种促溃疡面愈合的新型保护剂

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