EP1007149A1 - Antibakterielle medizinische vorrichtungen - Google Patents
Antibakterielle medizinische vorrichtungenInfo
- Publication number
- EP1007149A1 EP1007149A1 EP98900581A EP98900581A EP1007149A1 EP 1007149 A1 EP1007149 A1 EP 1007149A1 EP 98900581 A EP98900581 A EP 98900581A EP 98900581 A EP98900581 A EP 98900581A EP 1007149 A1 EP1007149 A1 EP 1007149A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- electrodes
- dressing
- electrode
- hydrogen peroxide
- field
- 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- Withdrawn
Links
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 12
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 52
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000001301 oxygen Substances 0.000 claims abstract description 19
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000000541 pulsatile effect Effects 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 22
- 241000894006 Bacteria Species 0.000 claims description 13
- 239000004020 conductor Substances 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 230000001580 bacterial effect Effects 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 239000002250 absorbent Substances 0.000 claims description 3
- 230000002745 absorbent Effects 0.000 claims description 3
- 229920001940 conductive polymer Polymers 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 230000005684 electric field Effects 0.000 abstract description 5
- 230000007774 longterm Effects 0.000 abstract description 2
- 239000007943 implant Substances 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 description 28
- 229920001817 Agar Polymers 0.000 description 24
- 239000008272 agar Substances 0.000 description 24
- 102000016938 Catalase Human genes 0.000 description 15
- 108010053835 Catalase Proteins 0.000 description 15
- 239000006916 nutrient agar Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 241000191963 Staphylococcus epidermidis Species 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 239000000499 gel Substances 0.000 description 7
- 206010052428 Wound Diseases 0.000 description 6
- 239000004744 fabric Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 3
- 238000005868 electrolysis reaction Methods 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000005611 electricity Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 208000034309 Bacterial disease carrier Diseases 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 208000032840 Catheter-Related Infections Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000006161 blood agar Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 239000007382 columbia agar Substances 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-M hydroperoxide group Chemical group [O-]O MHAJPDPJQMAIIY-UHFFFAOYSA-M 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002824 redox indicator Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- QGVNJRROSLYGKF-UHFFFAOYSA-N thiobarbital Chemical compound CCC1(CC)C(=O)NC(=S)NC1=O QGVNJRROSLYGKF-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 description 1
- -1 water Chemical compound 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/326—Applying electric currents by contact electrodes alternating or intermittent currents for promoting growth of cells, e.g. bone cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/205—Applying electric currents by contact electrodes continuous direct currents for promoting a biological process
Definitions
- This invention concerns a method of using medical devices intended for relatively long term use, of the order of a day or more, in a location extending on or at least partially within a patient's body, or in contact with an open wound, and extends to surgical dressings.
- Such devices include a variety of kinds, such as catheters, cannulae, shunts, specialised or surgical dressings and orthopaedic deployment in a temporary or permanent role. It is estimated that two-thirds of all patients admitted to hospital have such a device inserted or applied during their stay.
- An object of the present invention is to reduce this infection problem by way of a measure involving, in general terms, provision of the device with means to generate an electric field over its interface surface, which field acts to inhibit bacterial attachment and colonisation on and adjacent that surface.
- US Patent 5154165 is relevant, and the entire file is incorporated herein by reference.
- a method of generating hydrogen peroxide at a device applied to a body in the presence of water comprises the steps of: providing a field-generating means comprising two electrodes and a separate power source producing a defined, or determinable.
- the concentration of dissolved oxygen in plasma, at 0.14 mmol/1, is amply aerobic.
- the generating means comprises a conductor for or in connection with an electrical circuit, the conductor being supported by the device and the circuit being operable to generate the appropriate field by way of the conductor.
- the conductor can be supported as a coating over the device and so itself define the interface surface, or it can be embedded as a wire or other configuration within the device suitably, in this event, to follow the outer surface shape of the device.
- the current is preferably within the range 1-100 ⁇ A, and for many sites in the body is preferably 1-20 ⁇ A, such as 1-10 ⁇ A.
- the electric field is preferably unidirectionally negative and is preferably continuously maintained in a substantially constant manner, but there is no reason to suppose that a pulsatile or otherwise varying negative field cannot be used to effect the desired action.
- the field should necessarily be unidirectionally negative.
- a field of alternating polarity can interfere with the ionic exchange process between the bacterial cell wall and surrounding medium and so act to inhibit colonisation between bursts of hydrogen peroxide generation.
- an alternating field for this purpose need not necessarily be symmetrically cyclic, but can be asymmetrical.
- the field of the invention can act against infection in other ways than bactericidal hydrogen peroxide production.
- electroporation can be caused in cells subject to the field and this could facilitate the action of drugs and/or natural immune response mechanisms on bacteria in the vicinity of the device.
- drugs such as antibiotics, often exhibit a positive surface charge they can be beneficially attracted to and retained in the same vicinity.
- the electrode especially the negative electrode, and any conductive surface associated therewith that is intended for contact with or insertion into the body, may advantageously be non-metallic, e.g. of carbon or conductive polymer or may contain an organic matrix to facilitate production of H 2 O 2 , or chlorine or both, such as a conductive gel, possibly using additives or materials reducing the work function of the surface to facilitate said production and reduce overall energy consumption.
- the invention also provides a surgical dressing for use as described above, and a surgical dressing comprising a flexible non-conducting material having a plurality of electrically separated non-metallic electrodes applied thereon.
- FIGS. 1 -3 diagrammatically illustrate respectively different experiments conducted during development of the invention
- FIGS 4 and 5 similarly illustrate, by way of example, respectively different forms of device according to the invention.
- FIG. 6 illustrates a surgical dressing according to the invention, with a central negative electrode.
- a stainless steel wire 10 was located along a plastics cannula 11 with a free end portion of the wire being wound around the tip portion of the cannula to form an electrode 12.
- the other end of the wire 10 was connected to the negative terminal of a constant current generator 13, a further stainless steel wire 14 being connected to the positive terminal of the generator and extending to an "indifferent" electrode 15 at its free end.
- the cannula tip plus its electrode 12 was placed, with the indifferent electrode 15, in mutually spaced manner in a turbid aqueous broth 16 of
- Staphylococcus epidermidis at about 10 7 cfu ml "1 , the broth being retained in aerobic conditions within the confines of an O-ring 17 mounted on a glass slide 18.
- the generator 13 was then operated to pass a small current of 1-10 or 1-100 ⁇ A between the electrodes for a period of 1 -1.5 hours. After such operation clear areas appeared around the cannula and its electrode, that is to say there were insufficient bacteria in this area to make it turbid, and there were no bacteria visible on the cannula surface. At the same time the broth closely around the indifferent electrode appeared more turbid than that further spaced. The clear areas coincided with where H 2 O 2 was present having been electrochemically generated on the electrode 12 from available oxygen and water. For comparative purposes the same arrangement was set up and left for 1.5 hours without generator operation and, in the result, the broth remained evenly turbid.
- a petri dish 30 holding agar 31 was flooded with a broth of Staphylococcus epidermidis and allowed to dry such that about 10 6 cfu bacteria were deposited, this being insufficient to give visible turbidity.
- two pairs of hypodermic needles 32 were inserted in the agar in like mutually spaced manner to serve as electrodes.
- One such pair of electrodes was connected by wires 33 to respective terminals of a constant current source 34, while the other pair were left unconnected as control electrodes, and the dish incubated overnight at 37 °C with the source operating at about 10 ⁇ A.
- the bacteria grew to form a confluent turbid lawn over the agar surface except for a clear zone 35 of about 3 mm diameter around the electrode connected to the source negative terminal, in which zone there was no bacterial growth.
- the device of Figure 4 is a catheter 40 comprising an elongate tubular body 41 of plastics material.
- the distal end portion or tip has a rounded closed end 42, while the proximal end portion terminates in a socket 43 of Luer or other form.
- the catheter is of double lumen form, having a larger lumen 44 communicating the socket 43 with apertures 45 in the wall of the tip for fluid transmission through the catheter, and a smaller lumen 46 closed at its ends.
- a wire 47 extends through the smaller lumen 46 and at its ends penetrates the catheter wall in sealed manner.
- the distal end portion for entry into a patient has an external electrode coating 48 of metal, carbon or other conductive material connected with the adjacent end of wire 47 and at the proximal end portion the end of the wire is connected with an electrical terminal 49.
- the catheter will be connected by way of terminal 49 with the negative terminal of a constant current generator 50, suitably powered by a 1.5 V battery to generate an output of 1-10 ⁇ A, the generator having its positive terminal connected to a skin electrode 51 of conventional form, such as used in ECG monitoring and the like, for application to the patient.
- the device of Figure 5 is similar to that of Figure 4 except that in this case the distal electrode, denoted at 54, is embedded within the material of the catheter body to follow the outer surface shape of the body. This electrode is subjected to a potential of about 100 V by a battery-powered dc-to-dc converter having a current output limitation facility set no higher than 1 ⁇ A for patient safety in the event of breakdown of the catheter material insulation around the electrode during use.
- intravascular catheters made of 15% carbon-impregnated polyurethane, with an external diameter of 2.3 mm, and which conducted electricity, were steam-sterilised at 100°C for 30 minutes, which did not disrupt the plastic polymers.
- the catheters were connected to a 9 V alkaline battery in series with a variable high stability carbon film resistor to generate a constant direct current of between 10 to 100 ⁇ A.
- flow of electric current was confirmed by placing an ammeter in series in the circuit.
- Nutrient agar was prepared by adding agar of final concentration 1.5% w/v, to nutrient broth.
- Blood agar was prepared by supplementing Columbia agar with 7% defibrinated horse blood.
- a continuous culture broth for biofilm was used, consisting of glycerol, lO mM; (NH 4 ) 2 SO 4 6 mM; MgS0 4 , 0.5 mM; KC1, 13.5 mM; KH 2 PO 4 , 28 mM; Na 2 HPO 4 , 72 mM; thiamine, 1 mg/1: biotin, 1.5 mg/l; peptone, 3 mg/1.
- the medium was buffered to pH 7.4. All media were sterilised by autoclaving at 121 °C for 15 minutes.
- the agar plate was then incubated at 37 °C, in air for 16 hours.
- the second agar plate was flooded with 0.5 ml of a freshly prepared catalase solution which had 1500 units of activity (one unit decomposes 1.0 ⁇ mole of H 2 0 2 per minute at pH 7.0 at 25 °C at 10.3 mM H 2 0 2 ).
- This agar plate was then left at room temperature for up to 5 minutes to allow the catalase to be absorbed by the agar.
- Two catheters were then placed perpendicularly in the agar, and electric current of 10 ⁇ A was applied as described above. This plate was then incubated at 37 °C, in air, for 16 hours.
- the final agar plate of the set was placed in an anaerobic cabinet with an atmosphere of 10% CO 2 , 10% H 2 and 80% N 2 at 37 °C. After 10 minutes, two catheters were placed in the nutrient agar plate and connected to one electrical device as described above. The plate was then incubated under these conditions for 16 hours.
- a reus NCIMB 6571 and S. epidermidis NCIMB 12721 were tested six times at each concentration of catalase.
- Four ⁇ l of staphylococcal suspension were spread onto each of five nutrient agar plates.
- Two catheters were then placed in each nutrient agar plate as described above.
- An electrical device which generated 10 ⁇ A was connected to the catheters of one of the five plates and was then incubated in air, at 37 °C.
- Another plate with the two catheters connected to an electrical device which generated 10 ⁇ A was placed in an anaerobic container.
- Campylobacter System (Oxiod BR 60) which was prepared according to the manufacturer ' s instructions were immediately placed in the container which was then sealed and incubated at 37 °C. Microaerophilic condition (approximately 5% oxygen) was achieved within 30 minutes. The remaining three nutrient agar plates with the catheters were placed in an anaerobic cabinet. An electrical device which generated either 10, 75 or 100 ⁇ A DC was then connected to the catheters of each plate via external leads. All 5 nutrient agar plates were incubated for 16 hours and then the diameter of the inhibition zone measured as described above. S. aureus NCIMB 6571 and S. epidermidis NCIMB 12721 were each tested six times.
- an indicator strip to detect H 2 0 2 was placed on the nutrient agar within the inhibition zone.
- the strip contained a peroxide which transfers oxygen from a peroxide or a hydroperoxide group to an organic redox indicator.
- the indicator is then converted to a blue-coloured oxidation product which can be visually detected.
- the strip measures between 0.5 to 25.0 mg/1 hydrogen peroxide semi-quantitatively. The presence of hydrogen peroxide less than 0.5 mg/1 was indicated by the presence of blue colour on the reaction area.
- the diameter of the inhibition zone around the cathode was reduced as oxygen concentration decreased as under micro conditions (Table II).
- Table II The diameter of the inhibition zone around the cathode was reduced as oxygen concentration decreased as under micro conditions.
- Hydrogen peroxide was detected in the agar within the inhibition zone around the cathode only. It is supposed that the overall reaction O 2 + 2e + 2H 2 0 ⁇ H 2 0 2 + 20H " , more correctly rendered as O 2 + 2e + 2H + ⁇ H 2 0 2 , occurs at the cathode. The need for oxygen, and the need for a source of hydrogen ion such as water, can be seen. The concentration of H 2 O 2 was up to 20 mg/1 (0.59 mmol/1) at the catheter-agar interface and gradually diminished over a 2-3 mm distance from the catheter surface. Within the zone of inhibition in the agar with added catalase, hydrogen peroxide was not detected.
- this invention is the first to exploit an electric current as low as 10 ⁇ A, when applied to a multi-ion solution, to electrolyse ions in the solution such as to produce the antibacterial substance hydrogen peroxide at the cathode.
- an electric current as low as 10 ⁇ A
- generation of hydrogen peroxide (+0.68 V) at the cathode and production of chlorine (+1.4 V) at the anode take place concurrently.
- other bactericidal substances such as H0 2 , ozone, OC1 are also produced. These reaction products can be controlled by the current.
- Other studies have previously used metallic electrodes to demonstrate the inhibitory effects of electric current on micro-organisms (Blenkinsopp et al., 1992.
- Table 1 Zones of inhibition produced around the cathode under aerobic and anaerobic conditions with or without catalase.
- the catalase (1500 units in total) was spread over the nutrient agar plate.
- Zone diam. 1 (mm): mean ⁇ S.D.,n 6
- the zone of inhibition was measured from edge to edge across the centre of the catheter and the external diameter of the catheter was 2.3 mm
- the zone of inhibition was measured from edge to edge through the centre of the catheter and the external diameter of the catheter was 2.3 mm
- a surgical dressing is " shown according to the invention.
- a substrate 2 of flexible non-conducting material is provided as a backing for the dressing.
- the material may for example be of a woven fabric or a thin plastics film.
- an electrode 1 is fabricated of conducting gel (as for example used in heart monitors) coated by conventional techniques onto the substrate 2.
- a dressing fabric 4 Overlying the electrode 1 is a dressing fabric 4 which may itself be arranged for contacting a patient's body or may have a supplementary layer suitable for such contacting.
- the dressing fabric 4 carries a coating of (normally the same) conducting gel forming a second electrode 1.
- the gel or the fabric 4 may be hygroscopic so as to absorb neighbouring liquid to provide liquid (normally aqueous) communication between the electrodes 1, providing conductivity and a source of H 2 O 2 .
- the gel may have a supplementary absorbent dressing placed on it as necessary in use.
- the gel preferably incorporates substances which lower the work function of the dressing (so as to encourage H 2 O 2 formation).
- the electrodes 1 are connected via respective connecting leads 3 to an external electric power source, and the geometrical form of the final assembly is such as to optimise and direct the electric field produced by passage of controlled current.
- Figure 6 shows a simple two-electrode arrangement, but other more complex electrode configurations for specific uses may be desirable, for example multiple electrode dressings may be required.
- the central electrode 1 i.e. that on "top " of the drawing, and closer to the patient's skin
- the central electrode 1 would essentially be made negative with respect to the outer electrode 1 and because the central electrode could be in contact with a wound it may be covered with a water absorbing surgical coating or fabric.
- chlorine may be produced by electrolysis through the electrodes, and may be beneficial to wound protection.
- metallised electrodes e.g. of aluminium
- the electrodes may be of the same or different substances.
- the substrate 2 and the fabric 4 as shown in Figure 6 are one and the same, with the outer electrode 1 being exactly as drawn, i.e. a ring around the inner electrode with an insulated lead 3, rather than being a continuous layer behind (and shielded by an intervening layer from) the inner electrode.
- the electrodes may be on the face of the dressing opposite to that which is to be applied to the body, or on that face of the dressing which is to be applied facing the body, or one or some on each face.
- a supplementary dressing may be provided in the latter two cases, between the electrode and the patient's body, and may be porous or absorbent to allow the generated hydrogen peroxide to be effective.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cell Biology (AREA)
- Molecular Biology (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Electrotherapy Devices (AREA)
- Materials For Medical Uses (AREA)
- Water Treatment By Electricity Or Magnetism (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9700875.9A GB9700875D0 (en) | 1997-01-16 | 1997-01-16 | Medical devices |
GB9700875 | 1997-01-16 | ||
PCT/GB1998/000087 WO1998031420A1 (en) | 1997-01-16 | 1998-01-12 | Antibacterial medical devices |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1007149A1 true EP1007149A1 (de) | 2000-06-14 |
Family
ID=10806102
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98900581A Withdrawn EP1007149A1 (de) | 1997-01-16 | 1998-01-12 | Antibakterielle medizinische vorrichtungen |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1007149A1 (de) |
JP (1) | JP2001508684A (de) |
GB (1) | GB9700875D0 (de) |
WO (1) | WO1998031420A1 (de) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1395241B9 (de) | 2001-05-25 | 2005-06-15 | Medtronic, Inc. | Implantierbare medizinische vorrichtung mit kontrollierter freigabe von gasförmigen mitteln |
US9028858B2 (en) * | 2003-02-26 | 2015-05-12 | Coloplast A/S | Assembly for the preparation of a medical device having a coating comprising hydrogen peroxide |
US8708978B2 (en) | 2005-03-17 | 2014-04-29 | Impactcare Aps | Article to be inserted in a body cavity having biologically inhibiting surfaces and use and preparation of the article |
WO2012177803A1 (en) | 2011-06-20 | 2012-12-27 | Sri International | Self - sterilizing catheter with titanium dioxide photocatalyst thin film upon uv radiation |
WO2012177807A1 (en) * | 2011-06-20 | 2012-12-27 | Sri International | Electrochemical disinfection of implanted catheters |
EP3322451B1 (de) * | 2015-07-14 | 2021-03-24 | Washington State University | Elektrochemische reduktion oder vorbeugung von infektionen |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4411648A (en) * | 1981-06-11 | 1983-10-25 | Board Of Regents, The University Of Texas System | Iontophoretic catheter device |
US4569673A (en) * | 1984-01-12 | 1986-02-11 | Battelle Development Corporation | Bacterial barrier for indwelling catheters and other medical devices |
GB8813395D0 (en) * | 1988-06-07 | 1988-07-13 | Elliott T S J | Medical devices |
GB9109166D0 (en) * | 1991-04-27 | 1991-06-12 | Byrne Phillip O | Method of concentrating bacteria and devices employing that method |
EP0739209A4 (de) * | 1993-12-17 | 2000-04-12 | Albert M Kligman | Verfahren zur behandlung von papulo-pusteln und komedonen der haut |
-
1997
- 1997-01-16 GB GBGB9700875.9A patent/GB9700875D0/en active Pending
-
1998
- 1998-01-12 JP JP53392298A patent/JP2001508684A/ja active Pending
- 1998-01-12 EP EP98900581A patent/EP1007149A1/de not_active Withdrawn
- 1998-01-12 WO PCT/GB1998/000087 patent/WO1998031420A1/en not_active Application Discontinuation
Non-Patent Citations (1)
Title |
---|
See references of WO9831420A1 * |
Also Published As
Publication number | Publication date |
---|---|
GB9700875D0 (en) | 1997-03-05 |
WO1998031420A1 (en) | 1998-07-23 |
JP2001508684A (ja) | 2001-07-03 |
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