EP0511331A4 - Electrically conductive methods and systems for treatment of blood and other body fluids and/or synthetic fluids with electric forces - Google Patents
Electrically conductive methods and systems for treatment of blood and other body fluids and/or synthetic fluids with electric forcesInfo
- Publication number
- EP0511331A4 EP0511331A4 EP19910917874 EP91917874A EP0511331A4 EP 0511331 A4 EP0511331 A4 EP 0511331A4 EP 19910917874 EP19910917874 EP 19910917874 EP 91917874 A EP91917874 A EP 91917874A EP 0511331 A4 EP0511331 A4 EP 0511331A4
- Authority
- EP
- European Patent Office
- Prior art keywords
- blood
- electrically conductive
- tubing
- vessel
- electrically
- 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- Withdrawn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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
-
- 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
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
- A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
-
- 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
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3601—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit
- A61M1/3603—Extra-corporeal circuits in which the blood fluid passes more than once through the treatment unit in the same direction
Definitions
- TITLE Electrically Conductive Methods and Systems For Treatment of Blood and Other Body Fluids and/or Synthetic Fluids With Electric Forces
- the present invention has been devised to attenuate any bacteria, virus, parasites and/or fungus contained, in blood contributed by a donor to the point that any such contaminant is rendered ineffective for infecting a normally healthy human cell, but does not make the blood biologically unfit for use in humans. Similar problems exist with respect to the
- STITUTE SHEET treatment of other body fluids such as amniotic fluids.
- the treatment method and system is also applicable to mammals other than humans.
- the present invention provides new electrically conductive methods and systems for transferring blood or other body fluids, such as amniotic fluids, and/or synthetic fluids such as tissue culture medium from a donor to a transfusion recipient or to a storage receptacle, or for recirculating a single donor's blood or other body fluids through components of a treatment system external of the body or by implant devices for purging contaminants using a novel electrically conductive vessel for direct electric treatment of blood or other body fluids, such as amniotic fluids, with electric field forces of appropriate electric field strength to attenuate such contaminants to the extent that bacteria, virus, or fungus, or parasites contained in the blood or other body fluids are rendered ineffective to infect or affect normally healthy human cells.
- the treatment does not render the blood or other body fluids biologically unfit for use in humans or other mammals after the treatment.
- the new methods and systems according to the invention achieve these ends without requiring time consuming
- the invention achieves the electric field force treatment during the normally occurring transfer processing from a donor to a recipient or to a collection receptacle, or recirculation of a single donor's blood or other body fluids, such as amniotic fluids.
- Figure 1 is a diagrammatic, fragmentary, elevational view of a new blood transfer system using a novel electrically conductive treatment vessel in the form of conductive tubing to directly treat blood being transferred to a storage receptacle with electric field forces according to the invention;
- Figure 2 is an enlarged, horizontal cross sectional view of the novel electrically conductive tubing treatment vessel taken across lines 2-2 of Figure 1;
- Figure 3 is a longitudinal, vertical sectional view of the novel electrically conductive tubing treatment vessel taken along the staggered section lines 3-3 of Figure 2;
- Figure 4 is a view similar to Figure 2 showing a different construction of the novel electrically conductive tubing treatment vessel
- Figure 5 is a view similar to Figure 3, taken along the staggered section lines 5-5 of
- Figure 6 is a diagrammatic, fragmentaryr elevational view showing a different modification of a novel blood transfer system using the novel electrically conductive tubing treatment vessel, and which employs a blood pump and a blood flow regulator;
- Figure 7 is an enlarged cross sectional view, similar to Figure 2"that shows an electrically conductive tubing treatment vessel fabricated from longitudinally extending, integrally molded strips of alternate polarity, conductive polymer interconnected by integrally molded, insulating, longitudinally extending strips made of polymer or other insulating material;
- Figure 8 is a diagrammatic, fragmentary elevational view showing a different form of a blood transfer system according to the invention wherein a small electrically conductive vessel in the form of a short piece of tubing and a miniaturized battery power source are implanted in the arm of a human being to provide a novel electrically conductive blood and other body fluid treatment system which operates in a closed loop, recirculating manner;
- Figure 9 is a partial/ diagrammatic sectional view of the upper arm portion of a human being and shows in greater detail the construction of a specially designed miniaturized, electrically conductive treatment vessel with associated miniaturized battery electric power source for use in the implant treatment system shown in Figure 8;
- Figure 10 illustrates the details of construction of a somewhat different form of miniaturized electrified treatment tubing for use in an implanted treatment system of the type shown
- Figures 11 and 11 ⁇ illustrate still a different construction for the electrified treatment tubing for use in practicing the invention wherein the tubing has a square or rectangular cross section with upper and lower conductive sides and intervening right and left sides separating the two conductive sides made from plastic or other suitable electrical insulating material;
- Figure 12 is a perspective top and side view of a novel electrified, closed, octagonally- s aped, flat, box-like treatment vessel having an enlarged cross sectional area relative to the cross sectional diameter of the inlet and outlet tubes supplying the interior of the treatment vessel;
- Figure 12 ⁇ is a partial, cross sectional view of the enlarged treatment vessel shown in Figure 12;
- Figure 13 is a perspective view of a second form of enlarged cross sectional area treatment vessel having an exterior shape similar to that of Figure 12, but wherein the electrically conductive electrodes of the treatment vessel comprise interleaved conductive plates with one set of alternate ones of the plates being electrically insulated from the remaining set, and wherein different polarity electric potentials are applied to the respective sets.
- the electrode plates may be formed from an electrically conductive porous material;
- Figure 13 ⁇ is a partial, cross sectional view taken through the electrically conductive treatment vessel shown in Figure 13;
- Figure 14 is a longitudinal sectional view of still a different form of enlarged diameter electrified treatment vessel wherein the vessel is in the form of an elongated cylinder, and the sets of conductive electrodes mounted therein are concentrically arrayed within the interior of the treatment vessel and maintained at different electric potentials;
- Figure 14A is a cross sectional view of Figure 14 taken through plane A- ⁇ ;
- Figure 15 is an enlarged longitudinal sectional view of still another form of an enlarged cross sectional area treatment vessel according to the invention wherein.the electrically conductive electrodes of the treatment vessel are comprised by longitudinally extending needle-like electrodes with alternate ones of the needle-like electrodes being provided with opposite polarity electric potentials;
- Figure 15A is a cross sectional view of the treatment vessel shown in Figure 15 taken through plane ⁇ -A of Figure 15;
- FIG 16 is a perspective view of still another form of enlarged cross sectional area treatment vessel according to the invention wherein the treatment vessel comprises a relatively large block of insulating material having parallel, longitudinally extending, open ended tubes formed through its length.
- the tubes are provided with electrically separated, opposed, parallel extending conductive plate electrodes which have opposite polarity electric potentials applied thereto.
- the ends of the tubes open into and are supplied from, or supply, respective reservoirs formed on the respective ends of the central block of insulating material containing the tubes, with inlet and outlet conduits for body fluids to be treated connected to the free ends of the respective
- Figure 17 is a perspective view of an enlarged cross sectional area treatment vessel similar to Figure 16 wherein the body of the treatment vessel is cylindrical in nature;
- Figure 18 is a diagrammatic, fragmentary elevational view of a human blood or other body fluid treatment system according to the invention employing one of the larger cross sectional dimension fluid treatment vessels shown in any one of Figures 12-16 of the drawings, and which is suitable for use in a .continuous flow through recirculating body- fluid treatment system;
- Figure 19 is a diagrammatic, fragmentary elevational view of still another human blood or other body fluid, closed loop, recirculating treatment system according to the invention designed for use with the enlarged diameter fluid treatment vessels illustrated in Figures 12-16, and which employs both inlet and outlet fluid pumps on each side of the treatment vessel.
- the system can be operated in an intermittent manner to allow batch treatment of the body fluids to fully take place before passage of the body fluids being treated back to the patient;
- Figure 20 is a partially disassembled, perspective view of a non-flow through, single batch, body fluid treatment vessel according to the invention which is open to atmosphere on the upper side thereof to allow a clear view of the body fluids being treated during operation of the process; and
- Figure 20 ⁇ is a diagrammatic, fragmentary side view of an assembled, open sided, treatment vessel of the type shown in Figure 20 connected to a source of electric power.
- Figure 1 is a schematic illustration of one form of novel blood transfer system according to the invention.
- Figure 1 shows an electrically conductive blood treatment vessel constructed according to the invention which is in the form of intravenous-type tubing 11 interconnected between a hypodermic needle 12 and a blood storage receptacle 14.
- the needle 12 is inserted in an artery or vein of the arm 13 of a blood donor and the tubing 11 leads from the arm 13 to the receptacle 14.
- the system could be set up to transfer blood from the storage receptacle 14 to the arm of a recipient or could be designed to recirculate the blood through electrified tubing 11 back to the donor.
- the electrically conductive tubing 11 may be of any desired length as indicated by the break at 15 so that it can be appropriately set up to lead from a comfortable position for the donor fro whose arm 13 the blood is being taken to a proper storage location for the receptacle 14.
- Figure 2 is a cross sectional view of the electrically conductive tubing 11 taken through plane 2-2 of Figure 1.
- the tubing 11 may be from 1 to about 20 millimeters in inside diameter, although it may be larger or smaller in diameter depending upon the intended application.
- the tubing may have a cross sectional dimension of about 5 millimeters.
- the tubing diameter must be designed to result in a flow-through rate corresponding to the natural circulatory blood flow rate of the patient in which the system is implanted, and must be long enough to assure effective electrification treatment at the flow rate selected.
- the tubing 11 is formed from plastic, rubber, medical grade polymer, or other suitable material which is compatible with human fluids and/or tissue.
- a plurality of physically separated, electrically conductive surface segments form opposed, parallel electrodes shown at 16 and 16A on the inside of tubing 11 from electrically conductive materials such as platinum, platinum alloys, silver, silver or platinum covered alloys, or other similar conductive materials such as conductive polymers, or silver or platinum covered polymers which are compatible with human fluids and tissue.
- electrically conductive materials such as platinum, platinum alloys, silver, silver or platinum covered alloys, or other similar conductive materials such as conductive polymers, or silver or platinum covered polymers which are compatible with human fluids and tissue.
- the spacing between opposed electrodes 16 and 16A is of the order of 1 to 19 millimeters and perhaps may be more or less dependent upon the application and the conductivity of the body fluids being treated.
- Figure 3 is a longitudinally extending sectional view along the axis of tubing 11 taken through staggered section lines 3-3 of Figure 2.
- the electrically conductive surface segments 16 and 16A all comprise longitudinally extending, zebra ⁇ like stripe or strip electrodes which extend longitudinally in parallel with the longitudinal axis of the tubing 11. In between each
- SUBSTITUTE SHEET longitudinally extending conductive stripe electrode 16 or 16 ⁇ is a longitudinally extending electric insulating area 17 which electrically isolates the alternate electrically conductive, zebra-like stripe electrodes 16 and 16 ⁇ one from the other.
- a first set of alternate electrically conductive surface stripes 16 are electrically connected in common to a first annular terminal buss 18 which circumferentially surrounds the tubing 11 and is embedded within the sidewalls of the tubing.11 at a suitable point along its length.
- the design is such that the first annular terminal buss 18 is electrically isolated from the remaining second set of alternate, electrically conductive surface stripe electrodes 16 ⁇ and is electrically connected through a conductor terminal 19 to a first polarity (positive) source of electric excitation potential shown in Figure 1 as a battery 20.
- all of the first set of positive electrically conductive stripes 16 are physically and electrically connected in common to the first annular terminal buss 18 so that all of the conductive stripes 16 are maintained at a constant, positive polarity electric excitation potential.
- a second annular terminal buss 21, which circumferentially surrounds the tubing 11, is embedded within the tubing 11 at a point along its length displaced from the position of the first annular terminal buss 18 and is spaced inwardly towards the inside diameter of the tubing relative to the first annular buss 18.
- the second annular terminal buss 21 is provided with an outside terminal conductor connection 22 for connecting the annular buss 21 to a negative polarity source of electric potential on the battery 20 as shown in the system drawing of Figure 1.
- the second set of alternate electrically conductive surface stripes 16 ⁇ are all provided with internal connector studs which physically and electrically connect all of the 16 ⁇ stripes in common to the second annular terminal buss 21 so that all of these conductive stripes will be maintained at a negative polarity potential opposite to that from the positive polarity potential applied to the first set of electrically conductive stripes 16 by annular buss 18.
- the source of electric potential may constitute a direct current voltage battery 20 connected to the conductor terminals 19 and 22 through electric supply conductors 23 and 24 preferably by a double pole, double throw, on-off control switch 25.
- voltage controlling variable resistors 26 and 27 also are included in the electric supply conductors 23 and 24 in order to control the value of the excitation voltage developed between the alternate sets of conductive surface stripes 16, 16 ⁇ . While a battery has been illustrated as a source of direct current excitation potential in the system of
- SUBSTITUTE SHEET Figure 1 it is believed obvious to those skilled in the art that any known direct current source of excitation potential could be used in place of the battery 20.
- the donor whose blood is to be taken, or the recipient who is to be given blood, or is to have his or her blood recycled is placed on a cot with his or her arm 13 extended and the interconnecting electrically conductive tubing 11 having the hypodermic needle 12 for withdrawal, or supplying, or recycling of blood set up as shown in Figure 1.
- the control switch 25 is closed so that an electric field is built up across the oppositely disposed electrically conductive zebra-like stripes 16, 16 ⁇ , etc.
- the hypodermic needle should be electrically isolated via conventional electrically insulating IV tubing from any of the zebra stripe electrodes 16, 16 ⁇ so that the donor/recipient does not receive a shock. By this precaution, he or she will not even be aware of the existence of the electric field within the electrically conductive tubing 11. With the transfer system thus conditioned, the hypodermic needle is inserted into a vein in the donor's/recipient's arm and blood is withdrawn, given, or recycled through tubing 11.
- Recent experiments have proven that exposure to electric fields induced by-supply voltages of 2-4 volts produces electric current flow through blood of the order of 1 to 100 microamperes. Effectiveness is dependent primarily upon length of time of treatment (which may range from about one to twelve minutes) and the magnitude of the biologically compatible current flow at current densities within the range noted above.
- treatment of AIDS virus in media at 100 microamperes for 3 minutes has been observed to substantially attenuate (render ineffective) the AIDS virus.
- Treatment at other current densities and lengths of time will have a similar attenuating effect.
- undesirable contaminants such as virus, bacteria, fungus and/or parasites will be adequately attenuated.
- the contaminants are rendered ineffective by the sustained action of the electric current as the blood travels from the needle 12 to the storage bag 14, or vice versa, or in a recycling mode.
- the length of travel of the blood through the sustained electric field induced current flow also can be adjusted so that the blood is subjected to the electric field force for time periods of the order of from about 1 to 12 minutes at least. At the current noted above this is
- S E SHEET believed adequate to attenuate (render ineffective) bacteria, virus (including the AIDS virus) , parasites and/or fungus entrained in blood or other body fluids, but does not render the fluids unfit for human use or impair their biological usefulness.
- the species of the invention shown in Figures 2 and 3 is advantageous since it is possible to fabricate the treatment tubing by pre- forming the conductive segments 16 and 16 ⁇ on the tubing walls while it is in a flat planar condition, and then rolling the walls into tubular form using a suitable mandrel.
- the adjoining longitudinal edges of the planar member after rolling are thereafter heat sealed along a longitudinally extending seam located within one of the electrically insulating sections 17.
- Particular attention must be paid to the juncture of the ends of the annular terminal busses 18 and 21 during the rolling and heat sealing steps to assure that good electrical interconnection and continuity at these junctures of the annular terminal busses is provided in the completed treatment tubing.
- the conductive electrode segments 16, 16 ⁇ may be electro-deposited, chemically formed, separately formed conductive polymer surfaces, or conductive foil or wires adhesively secured to the side walls of the tubing 11 in advance of the rolling and sealing using techniques well known in the printed circuit and integrated circuit manufacturing technologies.
- Figure 6 is a diagrammatic, f agmentary, elevational view of a modified blood transfer system using the novel electrically conductive treatment tubing in accordance with the invention.
- a modified blood transfer system using the novel electrically conductive treatment tubing in accordance with the invention.
- a modified blood transfer system using the novel electrically conductive treatment tubing in accordance with the invention.
- SUBSTITUTE SHEET blood pump 28 of conventional, commercially available construction is inserted in the tubing 11 at some point along its length.
- the blood pump 28 is electrically isolated from the zebra striped conductive surfaces 16, 16 ⁇ by suitable insulators 29 formed on the blood input-output connections of pump 28. Provision for electrically bypassing the blood pump 28 (if need be) is made through the shunt conductors 30, 30A which maintain electrical continuity of the direct current excitation potential applied to the conductive stripes 16, 16 ⁇ on each side of pu p 281
- the direct current excitation source 20 and its connection to the electrically conductive tubing 11 has not been shown in Figure 6 but would have to be provided.
- a separate source of excitation current for running the blood pump 28 is provided from a conventional 110 volt alternating current source through the input terminals 31, 31 ⁇ .
- a blood flow regulating valve 37 inserted in the system at the output of blood pump 28 and within the by-pass loop 30, 30 ⁇ for the conductive stripes 16, 16 ⁇ .
- the electrified transfer system safely can be employed in a closed loop recycling system for withdrawing blood from a patient, electrically treating the blood as described above and then returning the electrically treated blood to the patient. This procedure is referred to herein as recycling.
- the system of Figure 6 also can be used in those situations where the blood flow of a donor's blood is not sufficient to assure supply of an adequate amount of blood to or from the collection receptacle 14 or other recipient. It may also be
- SUBSTITUTE SHEET desirable to have a blood flow regulating valve such as 37 in non-pump systems.
- Figures 4 and 5 of the drawings show another embodiment of the invention wherein the electrically conductive treatment tubing 11 includes electrically conductive electrode segments 32 and 32 ⁇ which are in the form of zebra stripes that extend radially around the inside diameter of tubing 11 in spaced-apart,*-alternating polarity, conductive annular bands 32 and 32A separated by insulating surface bands 111 which serve to electrically isolate the respective first set of conductive zebra stripes 32 from the second set of conductive zebra stripes 32A.
- the first set of alternate ones of the electrically conductive annular stripes 32 are electrically connected in common to a first longitudinally extending terminal buss bar 33 that is embedded within tubing 11 in parallel witli the longitudinal axis of the tubing and electrically isolated from the remaining second set of alternate electrically conductive annular stripes 32 ⁇ .
- the first longitudinally extending terminal buss bar 33 is designed for connection to a first polarity (positive) source of electric excitation potential through a supply conductor connection 35 on the exterior surface of the tubing 11.
- a second longitudinally extending terminal buss bar 34 is. embedded within the body of tubing 11 and is electrically connected to the remaining second set of alternate electrically conductive annular stripes 32 ⁇ .
- the second longitudinally extending terminal buss bar 34 is electrically isolated from the first longitudinally extending terminal buss 33 and the first set of alternate electrically annular stripes 32.
- SUBSTITUTE SHEET 33 is designed for connection to a second polarity (negative) source of electric excitation potential of opposite polarity from that of the first polarity source of excitation potential.
- an input supply conductor connection 36 is directly connected through the exterior surface of tubing 11 and to the second longitudinally treatment extending terminal buss bar 34.
- the "embodiment of the invention shown in Figures 4 and 5 is physically arranged in a blood transfer system in the manner illustrated in Figure .1 of the drawings with the positive polarity and negative polarity zebra annular stripes being connected to the respective positive polarity and negative polarity terminals of an excitation battery 20 via control switch 25.
- a blood pump such as 28 and blood flow regulating valve 37 shown in Figure 6 can be included in the blood transfer system employing electrified tubing shown in Figures 4 and 5.
- a blood transfer system employing the embodiment of the invention shown in Figures 4 and 5 would be electrically excited in advance of injection of the hypodermic needle 12 into the arm of a blood donor so that all blood passing through the tubing 11 will be subjected to electric forces produced between the alternate polarity annularly formed conductive bands 32 and 32A.
- the length of the electrified field as related to the flow of blood through electrified tubing 11 should correspond to at least the 1-6 minute treatment time mentioned earlier.
- the electric field force intensity applied to the blood by means of the electrified tubing is anticipated to be of the order of 2 to 4 volts similar to the embodiment of the invention shown in Figures 1-3.
- Figure 7 of the drawings is a cross sectional view of another embodiment of the invention which is substantially different from those previously described.
- the material used for fabrication of the tubing 11 is one of the new space-age polymer materials which can be either highly electrically conductive, insulating, or semiconducting and may have values of conductivity ranging from essentially fully conductive to insulating.
- the conductive surface areas on the inside diameter of the tubing 11 are actually formed into segments, such as 11C, of the
- the intervening segments of the tubing HI which separate the conductive segments IIC are integrally formed from the highly insulating polymer material.
- Suitable positive polarity and negative polarity potentials are applied to the exterior surface areas of alternate ones of the sets of conductive polymer segments IIC from-a source of electric potential via the conductors 23 and 24 as illustrated schematically in Figure 7.
- the embodiment of the invention shown in Figure 7 is much simpler and hence less expensive to make in that it requires fewer processing steps than the embodiments of the invention shown in Figures 1-6.
- the embodiment of the invention shown in Figure 7 would be used in a blood transfer system similar to that shown in Figure 1 or 6 with or without a blood pump 28 and blood flow regulating valve 37 to effect transfer of blood from a donor to a receptacle or recipient in the event of a transfusion or recycling.
- a blood transfer system similar to that shown in Figure 1 or 6 with or without a blood pump 28 and blood flow regulating valve 37 to effect transfer of blood from a donor to a receptacle or recipient in the event of a transfusion or recycling.
- During the blood transfer process again it would be necessary to provide alternate polarity, DC electric excitation potentials to the spaced-apart, alternate sets of positive polarity and negative electrically conductive polymer segments IIC prior to passing blood through the tubing 11.
- FIG 8 is a fragmentary, diagrammatic, elevational view showing a-form of blood treatment system according to the invention wherein a small electrically conductive vessel 41 in the form of a short piece of electrified tubing and a miniaturized battery power source 42 are implanted in the arm of a human being.
- the electrified tubing 41 may be in the form of any of the prior disclosed electrified tubing structures described with relation to Figures 1-7, but which are fabricated in miniaturized form so that the tubing 41 can be inserted in a section of or surrounding a vein 44 of the arm 13 of a patient whose blood is being treated.
- the implantation is such that the blood of the patient 44 naturally is pumped through the short piece of electrified tubing 41 while circulating blood to the hand of the patient and thereby form a closed loop, recirculating, implanted treatment system that comprises an integral part of the circulatory system of the patient being treated. Because the parameters of such an implanted system are necessarily small, a single passage through the implanted electrified tube 14 may accomplish a relatively small attenuation of contaminants in the blood. Therefore, it is the repeated passage of small portions of the patient's blood continuously twenty-four hours a day and for as many days as are needed which will gradually attenuate the
- Figure 9 is a partial, fragmentary, sectional view of the upper arm portion 13 of a vein or artery of a patient in which a treatment system according to the invention has been implanted, and shows in greater detail the construction of a specialized, miniaturized, electrically conductive treatment vessel with associated miniaturized battery electric power source for use in an implanted treatment system as shown in Figure 8.
- the electrified vessel 41 is in the form of an outer housing 45 that is in the shape of a football which is implanted within the interior walls 44 of an artery or a vein 44.
- the outer housing 45 is comprised by a central, cylindrically-shaped portion 45M of solid conductor such as platinum which is biocompatible with human blood and tissue and has integrally formed, conically-shaped porous ends 45C which are attached to and form an electrically conductive screen grid (at the same potential) as the mid portion 45M.
- the conical end portions 45C both are perforated and may be in the nature of a screen or mesh wire and of the same material composition as the mid portion 45M.
- Disposed within the outer housing 45 is a inner housing 46 which is tear-drop shaped and secured within the central portion 45M of the outer housing by suitable insulating support spider legs 47.
- the inner housing 46 likewise is formed from platinum or otlier suitable biocompatible conductive material and has supported within its interior a miniaturized battery 42 secured to the conductive walls of inner housing 46 by conductive support legs 48.
- the support legs 48 serve as terminal
- SUBSTITUTE SHEET connectors from one terminal of battery 42 to the inner housing 46 so that it is maintained at one polarity excitation potential.
- the remaining opposite polarity terminal of miniaturized battery 42 is connected through an insulated conductor 49 to the central portion 45M of outer housing 45 whereby the entire outer housing including the meshed conical end portions 45C are maintained at the opposite polarity potential.
- the electrified vessel shown in Figure 9 is activated by connection to batter.y 42 so that a difference of potential exists between the inner and outer housings 45 and 46.
- FIG 10 is a fragmentary, diagrammatic view of a partial vein or artery 44 showing in greater detail the cylindrical or tubular electrified treatment vessel 41 originally described with relation to Figure 8.
- This implant treatment vessel 41 is miniaturized so that it is in effect an open-ended cylinder in shape and has a diameter comparable to that of a large vein or artery and so that it can be grafted or implanted into the vein or artery as illustrated in Figure 10.
- the tubular treatment vessel 41 may be designed pursuant to Figures 2 and 3 of the drawings, for example.
- the battery source of power 42 is annular in shape and is slipped over the tubular treatment vessel 41 in the manner shown.
- Figure 10 only a cross sectional view of the annular collar-shaped battery 42 is illustrated. At the point where the battery 42 fits over the tubular treatment vessel 41, the respective positive and negative terminals of the battery are exposed to engage the corresponding positive and negative supply terminals 19 and 22 of the tube 41 so that the resulting battery powered
- SUBSTITUTE SHEET structure has a minimum exterior profile to facilitate implantation. From a comparison of Figure 10 to Figure 9 of the drawings, it will be appreciated that the Figure 10 treatment vessel introduces some flow restriction in the vein or artery in which it is implanted and for this reason the construction shown in Figure 10 is preferred.
- FIGS 11 and 11 ⁇ of the drawings illustrate a construction .for the electrified treatment vessel 51 wherein the treatment vessel is in the form of square or rectangular cross ⁇ ectionally-shaped open*-ended tubing.
- the treatment tubing 51 provided with a square or rectangular shape so that provision of opposed, parallel conductive electrode surfaces 51U and 51L is greatly simplified as best seen in-Figure HA of the drawings which is a cross sectional view taken through plane HA-HA of Figure 11.
- Figure 12 is a perspective view of a novel, electrified, closed, octagonally-shaped, flat, box- like treatment vessel 60 according to the invention which provides an enlarged cross-sectional area relative to the cross .sectional diameter of the inlet and outlet tubing supplying the interior of the treatment vessel whereby increased through-put of a fluid being treated can be achieved in a given time period.
- the treatment vessel 60 shown in Figure 12 is comprised essentially of upper and lower, octagonally-shaped, flat insulating plates 61 and 62, respectively, of an insulating material which is compatible with human blood and/or other body fluids.
- octagonally-shaped, conductive electrode members 63 and 64 Disposed immediately below and above the upper and lower plates 61 and 62 are octagonally-shaped, conductive electrode members 63 and 64, respectively, which are separated and electrically isolated one from the other by a surrounding electric insulating gasket member 65.
- the entire structure is sandwiched together and held in assembled relation by threaded thru-pins 66 as best seen in Figure 12 ⁇ of the drawings.
- the insulating gasket 65 which may be of teflon defines an open space 67 between the two conductive electrode members 63 and 64 into which the blood or other body fluid to be treated is introduced via inlet and outlet conduits 68 and 69.
- Opposite polarity electric potentials are applied to respective conductive plates 63 and 64 to produce an electric field force across the intermediate space 67 through which the fluids being treated flow between electrode plates 63 and 64.
- FIG 13 is a perspective view of another form of enlarged cross sectional area treatment vessel 70 having an exterior shape similar to that of the treatment vessel shown in Figure 12.
- the electrified treatment vessel shown in Figure 13 differs from that in Figure 12, however, in the construction of its electrically conductive electrodes which comprise a plurality of interleaved, conductive, flat, electrode plates 71 and 71 ⁇ .
- the electrode plates 71 are secured in and project inwardly from a right hand (RH) conductive end plate 72R as shown in Figure 13 ⁇ .
- RV right hand
- the alternate set of flat electrode plates 71A are secured to and project inwardly from a corresponding conductive end plate 72L on the left hand end of the treatment vessel 70.
- the conductive end plates 72R and 72L and c ⁇ acting insulating side plates 73 which insulate the conducting end plates from one another, form an octagonally-shaped box frame which is closed by upper and lower insulating top and bottom insulating plates 74 and 75.
- the conductive end plates 72R and 72L have a central opening formed therein into which inlet and outlet tubes 76 and 77 are secured as best seen in Figure 13 for providing inlet and outlet flow through connection to the treatment vessel 70.
- SUBSTITUTE SHEET 71 and 71 ⁇ extend parallel to one another and are provided with different polarity electric potentials supplied to the respective sets of interleaved electrode plates via the respective conductive end members 72R and 72L.
- the respective flat conductive electrode plates 71 and 71 ⁇ may be fabricated from a perforated material as shown in Figure 13B of the drawings. Also, it may be desirable .that some form of thermal insulation, or a thermally controlled chamber be provided around the exterior of the treatment vessel 70 as indicated ' by the thermal insulation 78 shown in Figure 13 ⁇ .
- electrified treatment vessel 70 shown in Figures 13, 13 ⁇ and 13B functions in essentially the same manner as was described earlier with respect to Figures 1-7 to effect attenuation of contaminants such as bacteria, virus and fungus contained in blood and/or other body fluids being treated in the flow through treatment vessel of Figure 13.
- Figure 14 is a longitudinal sectional view of still another form of enlarged cross sectional area, electrified treatment vessel 80.
- the treatment vessel 80 shown in Figure 14 is in the form of an open-ended, elongated cylinder 81 whose cylindrical walls are fabricated from an insulating material which is biocompatible with human blood and/or other body fluids and whose open ends are closed by circular-shaped conductive end pieces 82 and 83.
- Inlet and outlet tubular openings 84 and 85 are provided to the interior of cylindrical housing 81 through centrally formed apertures in the circular end plates 82 and 83.
- Within the interior of the cylindrical, insulating housing 81 at least two, separate, concentric, perforated.
- SUBSTITUTE SHEET cylindrically-shaped electrode members 86 and 87 are provided which extend longitudinally through the interior of the outer cylindrical housing 81.
- the first set of concentric, perforated, electrically conductive electrodes 86 is embedded in and supported by the conductive end plate 82 which serves as an electrical terminal for applying electric potentials to all of the concentric electrode member 86-
- the concentric, perforated, conductive electrode member 87 is physically supported by and electrically connected to the conductive end plate 83 for the supply of an opposite polarity potential thereto.
- one or more additional perforated concentric electrode members similar to 86 may be spaced apart from the inner concentric electrode member 86 outwardly along the diameter of the circular end member 82 with additional perforated concentric electrode members 87 being sandwiched between the two electrode members 86 and spaced apart therefrom so as to provide an electric field force between all the spaced apart, separated electrically conductive electrode members 86 and 87.
- a conductive surface 89 may be formed around the interior walls of the outer, insulating cylindrical housing member 81 and electrically connected to the conductive end plate 82 or 83 which is opposite in polarity to the outermost concentric electrode members 86 or 87. This will assure that the entire interior of the treatment 80 vessel cross sectional area is crossed by the electric field force and all blood or other body fluid passing the cylindrical housing member 81 is subjected to biologically compatible low electric current flow as a consequence of the electric fields produced between the different
- S UBSTITUTE SHEET concentric electrode members including the coated surface 89 within the interior insulating housing member 81.
- the embodiment of the invention shown in Figure 14 and 14A operates in substantially the same manner as described with relation to earlier embodiments of the invention to assure production of biologically compatible electric current flow through the blood or other body fluid being treated in the treatment vessel 80.
- FIG. 15 is a'.longitudinal sectional view of still another embodiment of an enlarged cross- sectional area treatment vessel 90.
- the treatment vessel 90 again comprises an outer, hollow, open- ended cylindrically-shaped, insulating body member 91 whose open ends are closed by electrically conductive, circular end plates 92 and 93, respectively.
- Inlet and outlet tubular openings 94 and 95 are provided through the central axial opening in the conductive end plates 92 and 93 for passage of blood and/or other body fluids being treated into the interior of the treatment vessel 90.
- the conductive end plates 92 and 93 have respective sets of opposite polarity potential needle-like electrodes 96 and 97, respectively, projecting therefrom inwardly into the interior of the treatment vessel 90.
- Figure 15 ⁇ is a cross sectional view taken through plane A- ⁇ of Figure 15 and shows how the array of needle-like electrodes appear within the interior of the treatment vessel 90.
- the treatment vessel 90 will function in substantially the same manner as has been described previously with relation to" earlier described embodiments of the invention.
- FIG 16 is a perspective view of still another form of enlarged cross sectional area treatment vessel 100 according to the invention and Figure 16 ⁇ is a partial cross sectional view taken through plane 16 ⁇ -16 ⁇ of Figure 16.
- the treatment vessel 100 comprises a relatively large rectangular-shaped block 101 of electrical insulating material which is biocompatible with blood and/or other human body fluids.
- the insulating block 101 has a plurality of parallel, longitudinally extending, open-ended, tubular- shaped openings 102 formed therein through the entire length of the block.
- the tubes 102 are provided with electrically isolated, opposed, parallel extending conductive plate electrodes, best seen in Figure 16A, which have opposite polarity electric potentials applied thereto.
- One set of these electrodes formed for example by the lower electrode 109 in each tube, extend out to and engage a conductive surface coating formed on one end of the insulating block, for example 101R, and the remaining upper electrodes 109 form a second set which extend out of the left hand end of the tubes and contact a conductive coating formed on the remaining end 101L of block 101.
- Respective, opposite polarity electric potentials are supplied
- SUBSTITUTE SHEET to the respective conductive surfaces 101R and 101L so that a potential difference exists between the sets of positive and negative polarity electrodes within each longitudinally extending tube in block 101.
- the ends of the tubes 102 open into and are supplied from, or supply, respective header reservoirs 103 and 104 formed on the respective opposite ends of the block of insulating material 101.
- Each of the reservoirs 103 and 104 has a centrally formed opening for receiving either an inlet tube 105 applied to header 103 or an outlet tube 106 secured to header 104 for supply of blood or other body fluids to be treated to and from the treatment vessel 100.
- a blood pump or other fluid pump can be inserted between the supply tube 105 and header 103, or between outlet tube 106 and the or outlet from the header reservoir 104, or both.
- both inlet and outlet pumps can be used.
- the electrified treatment vessel 100 shown in Figure 16 functions in the same manner as those species of treatment vessels described previously.
- vents such as shown at 107 and 108 in Figure 16 to the inlet reservoir 103 and/or the outlet reservoir 104 with the vents that can be selectively operated by valves that can be automatically or manually controlled for venting off gases that might be trapped in the tops of reservoirs and which otherwise might interfere with the proper operation of the electrified treatment vessel.
- suitable venting apparatus may be provided to other of the large cross sectional area electrified treatment vessels described previously.
- Figure 17 is a perspective view of still
- SUBSTITUTE SHEET another enlarged cross-sectional area treatment vessel 110 which is similar in all respects to the treatment vessel shown in Figure 16 with the exception that the body or block of insulating material 101 through which the elongate tubular openings are made, is cylindrically shaped as illustrated in Figure 17.
- the embodiment of the invention shown in Figure 17 would be identical to Figure 16 in the fabrication and operation of its component parts including the reservoir headers 103 and 104 and would operate in a similar manner. '
- Figure 18 is a diagrammatic, sketch of a human blood or other body fluid treatment system employing one of the larger cross-sectional dimension fluid treatment vessels 60, such as any one of those shown in Figures 12-17 of the drawings.
- the particular fluid treatment system shown in Figure 18 is for a continuous flow-through recirculating body fluid treatment wherein blood is withdrawn from the arm 13 of a patient and supplied through IV tubing 111 to a commercially available blood pump 28 and thence to an electrified treatment vessel 60.
- the treatment vessel 60 may be like any of the treatment vessels described with relation to Figures 12-17 of the drawings wherein the blood or other body fluid being treated is exposed to a low voltage, low current electric current flow for attenuating to the point of rendering them ineffective, any contaminants entrained in the blood, such as bacteria, virus and fungus.
- the treated blood appearing at the output of the treatment vessel 60 then is recirculated back through IV tubing 112 to the arm 13 of the patient whose blood or other body fluid is being treated. If desired, IV tubing 111 and 112 could be used.
- SUBSTITUTE SHEET also be treatment tubing such as described in Figures 1-7 and 11. This could provide double treatment for the fluid if that were desirable. In the event that the entire treatment does not take place in an air conditioned, temperature controlled room, then it may be desirable to provide a temperature controlled enclosure indicated by dotted lines 113 around at least the pump 28, electrified treatment vessel 60 and the interconnecting IV tubing sections 111 and 112 in order to assure maintaining a substantially constant viscosity of the blood or body fluid being treated.
- the system of Figure 18 would be used in a continuous flow-through recirculating treatment system wherein blood from the patient's arm 13 is supplied through pump 28 to the treatment vessel 60 where it is treated and then discharged back through tubing section 112 to the arm of the patient.
- the flow rate of the blood thus processed would be adjusted to correspond substantially to the natural flow rate of blood circulated through the patient's body to the extent possible.
- Figure 19 is a diagrammatic sketch of a form of closed loop, flow-through recirculating
- FIG. 19 differs from Figure 18 in that an inlet pump 28 and an outlet pump 28' are connected to, respectively, the intake to and outlet from the electrified treatment vessel 60.
- an inlet control valve 113 and an outlet control valve 114 also can be interconnected between the inlet pump 28 and the intake to -the treatment vessel 60 and between the output from the treatment vessel 60 and the intake to the outlet blood pump 28'.
- These inlet and outlet control valves indicated at 113 and 114 preferably, are automatically operated in a time sequence which allows the system of Figure 19 to be operated as a two pump, start-stop flow through system.
- the first pump 28 When operated in this manner, the first pump 28 is allowed to operate and discharge blood from the arm 13 of the patient to be pumped into the treatment vessel 60 and thereafter is closed off with both the inlet and outlet valves 113 and 114 in their closed condition. At this point electrification treatment of the blood or other body fluid takes place for a predetermined, scheduled time period to assure adequate attenuation to the point of rendering ineffective the contaminant bacteria, virus or fungus. Upon completion of the pre-scheduled treatment period, the outlet valve 114 is opened and outlet pump 28 » actuated to return the treated blood to the arm of the patient 13. Operation in the semi-continuous, start-stop, batch fashion will assure that adequate electrified treatment of the blood has been accomplished while achieving this end in a somewhat continuous manner suitable for use in a closed loop, recycling blood treatment process.
- Figure 20 is a partially disassembled.
- FIG. 20 ⁇ is a diagrammatic sketch of the assembled treatment vessel 120 shown in Figure 20 connected to a source of direct current electric power 128.
- Power source 128 was capable of providing substantially constant voltage across the conductive electrodes of the treatment vessel 120 at a given voltage setting, ranging between 0.2 volts and 12 volts DC, and for a given electrical resistivity of a sample being treated, and provided essentially constant current through the batch sample in the treatment vessel.
- a set of spaced-apart, parallel electrodes 125 and 126 are supported in suitably formed channels in the respective end partitions 121 and 122 by threaded studs (not shown) securing the electrodes 125 and 126 in opposed parallel relationship by means of bolts (not shown) threaded into threaded openings 127 in the tops of the end partitions 121 and 122.
- the electrodes 125 and 126 were connected to the negative and positive terminals, respectively, of the battery source of direct current electric power shown at 128 in Figure 20 ⁇ .
- the resulting structure results in a non-flow treatment vessel or cell defined by the vertically extending slot formed in a 1 millimeter wide central portion of the central segment 123 of the vessel.
- SUBSTITUTE SHEET vertically extending slot defines an open-sided treatment well 129 which is 1 millimeter across between electrodes 125 and 126, 1.56 millimeters in length and 8.32 millimeters in depth.
- a non-flow vessel or cell included a pair of platinum electrodes 1 mm apart inserted into a well 1.56 mm in length and 8.32 mm in depth.
- the non-flow vessel was connected to a direct current source capable of creating an electric field at a constant voltage and constant amperage.
- a suspension of the human immunodeficiency virus type 1 (HIV-1) was placed into this well.
- HAV-1 human immunodeficiency virus type 1
- An aliquot of approximately 10 al of the virus suspension was placed into the well. Thereafter, the viral suspension was exposed to direct currents ranging from 0 icroamps for up to 12 minutes to 100 microamp for up to 6 minutes. Intermediate currents of 25, 50 and 75 microamps were used to expose similar viral aliquots.
- a matrix of current and time was employed as shown in Table 1. After the exposure of the viral suspension to electric currents, the contents of the non-flow vessel where removed and placed into sterile microtubes. Five ⁇ ul of each sample were removed and diluted with 95 ul tissue culture medium supplemented with 10% fetal calf serum (FCS) .
- FCS fetal calf serum
- CEM-SS human T lymphoblastoid cell line
- SUBSTITUTE SHEET is well documented that the viral titer used is directly correlated with the number of syncytia formed. Therefore, evaluation of infectivity of HIV-I can be used with this assay.
- Experiment No. 2 used a different human T lymphoblastoid cell line named H9. This cell line, in contrast to CEM-SS cells, produces, upon exposure to HIV-i, many viral particles. The amount of virus produced is proportional to the amount of virus to which the cells are exposed.
- control viral aliquot for up to 4 days.
- the cells were placed into microtiter plate wells and monitored for formation of syncytia every 24 hours by microscopic observation.
- syncytia every 24 hours by microscopic observation.
- Experiment #2 A separate and independent assay to determine the ability of electric current to alter HIV-1 infectivity using H9 cells was employed.
- the basic strategy was similar to that used for the CEM cells with the exception that the initial suspension of treated and controlled viral stock was incubated with 10 5 H9 cells for 2 hours at 37°C. Thereafter, the cell virus suspensions were further diluted to 5 ml in standard tissue culture medium. The cell-viral suspensions were then incubated for up to 14 days at 37°C 5% CO j . At 3 day intervals (beginning at day 2) , aliquots of cell suspension were removed from each sample. The aliquots were centrifuged at 1,000 rpm for 5 minutes in order to pellet the cells.
- SUBSTITUTE SHEET semi-qualitatively viral infection by HIV-I.
- the supernatant samples from each of the tests and time points were examined using standard reverse transcriptase assay.
- the results of a representative experiment are shown in Table 3.
- the results of this experiment indicate that the ability of HIV-1 to infect H9 cells is attenuated by the magnitude of the electrical currents to which the virus is exposed. Additionally, at lower current magnitude, but with prolonged exposure time, attenuation of viral infectivity is achieved. That is, analogous to the results observed using syncytium formation and the CEM-SS cell line, either increased current or increased duration of exposure time was inversely proportional to the amount of reverse transcriptase produced by the cell line.
- the excitation voltage supplied to the conductive tubing may in fact exceed the 0.2 to 12 volt range indicated for most treatments.
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US07/615,800 US5139684A (en) | 1990-08-06 | 1990-11-16 | Electrically conductive methods and systems for treatment of blood and other body fluids and/or synthetic fluids with electric forces |
US615800 | 1990-11-16 |
Publications (2)
Publication Number | Publication Date |
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EP0511331A1 EP0511331A1 (en) | 1992-11-04 |
EP0511331A4 true EP0511331A4 (en) | 1993-07-28 |
Family
ID=24466854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP19910917874 Withdrawn EP0511331A4 (en) | 1990-11-16 | 1991-07-12 | Electrically conductive methods and systems for treatment of blood and other body fluids and/or synthetic fluids with electric forces |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0511331A4 (en) |
JP (1) | JPH05504503A (en) |
AU (1) | AU8725491A (en) |
CA (1) | CA2072888A1 (en) |
GB (1) | GB2256439A (en) |
WO (1) | WO1992008536A1 (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2783427A1 (en) * | 1998-09-04 | 2000-03-24 | Eric Ponce | DEVICE AND METHOD FOR DESTROYING MICROORGANISMS, ESPECIALLY BY EXTRA-BODY ROUTE |
US7052480B2 (en) * | 2002-04-10 | 2006-05-30 | Baxter International Inc. | Access disconnection systems and methods |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US592735A (en) * | 1897-10-26 | X j john t | ||
US672231A (en) * | 1900-12-07 | 1901-04-16 | Walter Lauder | Device for the purification of water. |
US2490730A (en) * | 1946-02-12 | 1949-12-06 | Dubilier William | Device for electrically treating liquids |
US3753886A (en) * | 1971-02-11 | 1973-08-21 | R Myers | Selective destruction of bacteria |
US3878564A (en) * | 1972-04-14 | 1975-04-22 | Shang J Yao | Blood and tissue detoxification method |
US3994799A (en) * | 1973-04-17 | 1976-11-30 | Yao Shang J | Blood and tissue detoxification apparatus |
US3965008A (en) * | 1974-03-15 | 1976-06-22 | Dawson Gerald C | Portable water sterilization device |
-
1991
- 1991-07-12 WO PCT/US1991/004938 patent/WO1992008536A1/en not_active Application Discontinuation
- 1991-07-12 AU AU87254/91A patent/AU8725491A/en not_active Abandoned
- 1991-07-12 CA CA002072888A patent/CA2072888A1/en not_active Abandoned
- 1991-07-12 JP JP3516594A patent/JPH05504503A/en active Pending
- 1991-07-12 EP EP19910917874 patent/EP0511331A4/en not_active Withdrawn
-
1992
- 1992-07-15 GB GB9215050A patent/GB2256439A/en not_active Withdrawn
Non-Patent Citations (1)
Title |
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See references of WO9208536A1 * |
Also Published As
Publication number | Publication date |
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GB2256439A (en) | 1992-12-09 |
WO1992008536A1 (en) | 1992-05-29 |
GB9215050D0 (en) | 1992-09-16 |
EP0511331A1 (en) | 1992-11-04 |
JPH05504503A (en) | 1993-07-15 |
CA2072888A1 (en) | 1992-05-17 |
AU8725491A (en) | 1992-06-11 |
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