Case #: JP S57-110236A
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`(19) Japan Patent
`Office (JP)
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`(12) JAPANESE UNEXAMINED PATENT
`APPLICATION PUBLICATION (A)
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`(11) Patent Application
`Publication No.
`S57-110236
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`(51)Int. Cl.3 Ident. Code Int. Ref. No. (43) Publication Date July 9, 1982 (Showa 57)
` A 61 B 10/00 104
`7437-4C
` 5/00
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`6530-4C
` G 01 N 27/30
`7363-2G
` 27/46
`7363-2G
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`(54) POLAROGRAPHY SENSOR
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`(21) Application No. JPA S55-187377
`(22) Date of Filing December 26, 1980
` (Showa 55)
`(72) Inventor Bunji HAGIWARA
` 2-8-17 Fujishirodai,
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`SPECIFICATION
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`Suita-shi
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`(71) Applicant Bunji HAGIWARA
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`2-8-17 Fujishirodai,
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`Suita-shi
`(74) Agent
`Ryuji TOSHIMA, Attorney
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`1. Title of the Invention
` POLAROGRAPHY SENSOR
`2. Scope of Claims
`What is claimed is:
`1.
`A polarography sensor comprising:
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`a metal wire having at least an electrode reaction surface made of a precious metal;
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`an insulating layer covering a surface of the metal wire surface that excludes a surface of the
`metal wire that is the electrode reaction surface and a surface of the metal wire that is a connecting
`terminal to an external electronic circuit; and
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`a blood coagulation inhibiting coating made of a plastic permeable to homogenously
`dispersed heparin provided so as to cover the insulating layer outer surface and the electrode reaction
`surface.
`2.
`The polarography sensor according to claim 1, further comprising:
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`a semipermeable and hydrophilic contamination inhibiting coating between the electrode
`reaction surface and an insulating layer in the vicinity thereof, and the blood coagulation inhibiting
`coating.
`3.
`A polarography sensor comprising:
`a metal wire having at least an electrode reaction surface made of a precious metal;
`
`No. of Inventions: 4
`Examination Request Status: Requested
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` (11 pages total)
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`Dexcom Exhibit 1005
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`a hard first insulating layer covering a predetermined portion of a surface of the metal wire
`surface including an area surrounding the electrode reaction surface but excluding a surface of the
`metal wire that is the electrode reaction surface and a surface of the metal wire that is a connecting
`terminal to an external electronic circuit;
`a soft second insulating layer covering a surface that connects to the surface covered by the
`first insulating layer of the surface of the precious metal wire surface that excludes the surface of the
`metal wire that is the electrode reaction surface and the surface of the metal wire that is the connecting
`terminal to the external electronic circuit; and
`a blood coagulation inhibiting coating, made of a plastic permeable to homogenously
`dispersed heparin provided so as to cover; a flexible plastic tube covering the electrode reaction
`surface and the area surrounding said surface except the first insulating layer outer surface and the
`second layer outer surface; and at least the electrode reaction surface and the first insulating layer
`outer surface.
`4.
`The polarography sensor according to claim 3, further comprising:
`a semipermeable and hydrophilic contamination inhibiting coating between the electrode
`reaction
`surface and an insulating layer in the vicinity thereof, and the blood coagulation inhibiting coating.
`5.
`A polarography sensor comprising:
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`a metal wire having at least an electrode reaction surface made of a precious metal;
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`an insulating layer covering a surface of the metal wire surface that excludes a surface of the
`metal wire that is the electrode reaction surface and a surface of the metal wire that is a connecting
`terminal to an external electronic circuit; and
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`a blood coagulation inhibiting coating made of a plastic permeable to homogenously
`dispersed heparin provided so as to cover; a standard reference electrode provided on the insulating
`layer outer surface; and at least the insulating layer outer surface including the electrode reaction
`surface, and a target electrode outer surface.
`6.
`The polarography sensor according to claim 5, further comprising:
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`a semipermeable and hydrophilic contamination inhibiting coating between the electrode
`reaction
`surface and an insulating layer in the vicinity thereof, and the blood coagulation inhibiting coating.
`7.
`A polarography sensor comprising:
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`a metal wire having at least an electrode reaction surface made of a precious metal;
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`an insulating layer covering a surface of the metal wire surface that excludes a surface of the
`metal wire that is the electrode reaction surface and a surface of the metal wire that is a connecting
`terminal to an external electronic circuit;
`a plastic layer fixed by evenly dispersing an enzyme used in a substance to be measured
`provided so as to cover the electrode reaction surface and the insulating layer outer surface in the
`vicinity thereof; and
`a blood coagulation inhibiting coating made of a plastic permeable to homogenously
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`dispersed heparin provided so as to cover at least the outer layer of the plastic layer.
`8.
`The polarography sensor according to claim 7, further comprising:
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`a semipermeable and hydrophilic contamination inhibiting coating between the electrode
`reaction surface and an insulating layer in the vicinity thereof, and the plastic layer fixed by the
`enzyme.
`3. Detailed Description of the Invention
`
`The present invention relates to a polarography sensor used by being inserted into a blood
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`vessel, and, in particular, to a technique for inhibiting a blood coagulation reaction from occurring
`when the sensor is inserted into a blood vessel.
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`In general, the concentration of an oxidizing substance or a reducing substance contained in
`an aqueous solution can be measured through polarography using a measuring electrode (working
`electrode) made of a precious metal such as platinum, gold, and the like. In a case where O2, which is
`an oxidizing (reducing) molecule, is measured; low voltage of 0.5 to 0.7 V is applied to a measuring
`electrode (cathode) made of Pt, Au, Ag, and the like, and to an Ag/AgCl standard reference electrode
`(anode). A reduction reaction expressed by;
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`occurs in the measuring electrode, and an oxidation reaction expressed by;
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`occurs in the standard reference electrode, and thus electric current flows between the two electrodes.
`Furthermore, in a case where H2, which is a reducing substance, is measured; high voltage (0.1 to 0.4
`V) is applied to a measuring electrode (anode) made of Pt, Au, and the like, to which Pt or Pt-black
`has adhered, and to an Ag/AgCl standard reference electrode (cathode). An oxidation reaction
`expressed by;
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`occurs in the measuring electrode, and a reducing reaction expressed by;
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`occurs in the standard reference electrode, and thus electric current flows between the two electrodes.
`Because the electric currents are proportional to the concentrations (partial pressures) of the O2 or the
`H2 under appropriate conditions, the concentrations of the O2 or the H2 can be measured based on the
`electric current values. This type of measuring method can also be applied to oxidizing substances
`and reducing substances other than O2 and H2. However, the voltage value applied between the
`electrodes and the materials of the electrodes must be suitably selected with respect to the type of
`substance to be measured. In many cases, the concentrations of substances targeted for measurement
`can be measured, even in substances that are difficult to measure directly using polarography, by
`fixing enzymes, which act in the substances targeted for measurement, on reaction surfaces of
`measuring electrodes and in the vicinities thereof, and then measuring reactants or generated
`substances by means of polarography. In an example where glucose is measured, glucose oxidase is
`fixed on a measuring electrode surface made of a precious metal, and in the vicinity thereof, as an
`enzyme, a reaction represented by;
`glucose + O2+H2O  gluconic acid + H2O2
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`is produced in the measuring electrode, and then, the glucose concentration can be measured either by
`measuring the O2 concentration using the aforementioned cathodic reduction method, or by
`measuring H2O2 using an anodic oxidation method like that represented by the formula shown below.
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`Substances other than the glucose described above can also be measured with much higher selectivity
`(specificity) than with direct polarography that uses a method like that described above, which
`method measures O2 or H2O2 by producing reactions like the reactions shown in the following
`chemical formulas by causing ascorbic acid, uric acid, noradrenaline, and the like, present in blood to
`fix enzymes such as ascorbate oxidase, uricase, monoamine oxidase, and the like, to a measuring
`electrode.
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`L-ascobyl acid + 1/2O2  L- dehydroascorbic acid + H2O
`Uric acid + 2H2O + O2  allantoin + CO2 + H2O2
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`Noradrenaline + H2O + O2  dihydroxy mandelic acid + NH3 + H2O2
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`Dexcom Exhibit 1005
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`While a very large variety of substances can be measured through direct polarography using
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`precious metal electrodes or through indirect polarography using electrodes with fixed enzymes, as
`described above, if these electrodes are given long and slender forms and used as intravenous
`polarography sensors to be inserted into blood vessels, this would enable extremely important
`observations for clinical and research purposes because doing so would allow continuous
`measurement and recording of the concentrations of all types of intravascular components. However,
`measurement using such intravenous polarography sensors has conventionally had the following two
`difficult problems. Those problems being;
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`(1) Substances with medium to high molecular weights such as proteins, peptides, lipids,
`nucleotides, and the like, adhere to electrode reaction surfaces, and thus electrode activity diminishes
`over time because the electrode surfaces become contaminated.
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`(2) Most of the substances that form electrodes possess qualities that cause blood coagulation,
`and thus electrode surfaces cause blood to coagulate, which not only poses risks to animals and
`humans but reduces the reactivity of the electrodes. By the way, the problem described in item (1)
`can be solved relatively easily by covering electrode reaction surfaces with semipermeable
`membranes. However, it is extremely difficult to solve the problem described in item (2).
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`The present invention relates to techniques for solving the problem described in item (2), and
`thus an object thereof is to prevent danger to animals and humans and to improve measurement
`accuracy in cases where direct or enzymatic (indirect) polarography is applied to animals or humans
`and the concentrations of important blood components such as O2, N2O, H2, ascorbic acid, glucose,
`uric acid, adrenaline based hormones, and the like, are continuously measured. Means like the
`following are conceivable as means for inhibiting blood coagulation with respect to instruments that
`make contact with blood.
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`(a) Cover tools and materials in substances that are highly resistant to coagulation such as
`Teflon and silicon.
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`(b) Chemically bond heparin, which is a natural anticoagulant, to the surfaces of tools and
`materials.
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`(c) Apply substances containing heparin to the surfaces of tools and materials so that the
`heparin dissolves gradually into the blood.
`In the case of the means described in item (a), because anticoagulant plastics such as Teflon and
`silicon, and the like, are, without exception, hydrophobic and thus do not transmit water or
`electrolytes, such plastics cannot be used in polarography electrodes other than relatively large
`electrolytic non-transmission type composite electrodes, making it impossible to apply them to very
`fine transmission type intravenous polarography sensors. Furthermore, in the case of the means
`described in item (b), while methods for chemically bonding heparin to tool and material surfaces are
`technically relatively simple, said methods generally cannot achieve sufficient blood coagulation
`inhibiting effects. This is thought to be caused by the fact that heparin molecules are substances that
`express blood coagulation inhibiting effects when in a dissolved state. Therefore, the inventors
`studied the means described in item (c) to develop a polarography sensor with electrodes covered in a
`coating created by homogeneously dispersing heparin as fine particulates in a hydrophilic plastic to
`be described later, and were thus able to achieve a significant blood coagulation inhibiting effect. The
`present invention is described in detail below with reference to the figures.
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`FIG. 1 (A) through FIG. 1 (D) are all cross sectional views of polarography sensors
`illustrating embodiments of the present invention. Note that the diameters of the four types of
`polarography sensors illustrated in FIG. 1 (A) through FIG. 1 (D) are all 0.3 to 2.0 mm, the sensors
`illustrated in FIG. 1 (A), FIG. 1 (C), and FIG. 1 (D) are all 100 to 200 mm long, and the sensor
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`illustrated in FIG. 1 (B) is about 150 to 1200 mm long.
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`The sensor illustrated in FIG. 1 (A) is a polarography sensor the forms a needle like
`separation type measuring electrode. An outer surface of a precious metal wire 1, except an electrode
`reaction surface 2 and a surface in the vicinity of the back end forming a connecting terminal 3 to an
`external electronic circuit, is covered with an insulating layer 4 made of glass, enamel, or the like.
`The electrode reaction surface 2 and the outer surface of the insulating layer 4, which is not in the
`vicinity of the electrode reaction surface, are covered by a metal tube 7 made of a stainless steel tube,
`and the like, for a needle upon which an adhesive such as an epoxy resin, and the like, has been
`applied. A portion of the front end of the insulating layer protrudes several millimeters past the metal
`tube 7, and the portion of the side surface of the precious metal wire 1 that is exposed from the
`insulating layer 4 in this protruding portion is the electrode reaction surface 2. The outermost surface
`of this polarography sensor is a plastic coating 6 permeable to homogenously dispersed heparin so as
`to inhibit blood coagulation. That is, a portion of the insulating layer 4 outer surface, including the
`electrode reaction surface 2, not covered by the metal tube 7, and the outer surface of the metal tube 7
`are covered by the plastic coating 6. Furthermore, in the present embodiment, a contamination
`inhibiting coating 5 is provided between the electrode reaction surface 2 and the insulating layer 4 in
`the vicinity thereof, and the plastic coating 6 in order to prevent the electrode reaction surface 2 from
`becoming inactive due to contamination from proteins, and the like, in blood. The contamination
`inhibiting coating 5 is made of semipermeable (a property whereby relatively large molecules are
`blocked and relatively small molecules are transmitted) and hydrophilic plastics such as acyl
`celluloses, cellulose ethers, collodion, cellophane, vinyl acetate, hydron, and the like. The plastic
`coating 6, in which heparin is homogenously dispersed, will be described in detail below. That is,
`while this plastic is not generally classified as a water absorbent plastic like plastics that are water
`permeable and highly hydrophilic such as hydron, collagen, various types of cellulose esters (acetyl
`cellulose, butyryl cellulose, nitrocellulose, and the like), various types of cellulose ethers (methyl
`cellulose, carboxy methyl cellulose, ethyl cellulose, propyl cellulose, and the like), vinyl acetate, and
`the like, and like certain types of polyamides, polyesters, phenolic resins, vinyl chloride resins, and
`the like, any type of plastic having some degree of hydrophilicity and water permeability and enough
`ion permeability for an electrode reaction can be used. In order to form the plastic coating 6 in which
`heparin has been dispersed in this way on the outermost surface of a polarography sensor, any plastic
`that is hydrophilic or slightly hydrophilic, like those described above, is first dissolved in a suitable
`solvent to produce an approximately 0.5 to 5.0% aqueous solution, and then a heparin aqueous
`solution is dispersed in this plastic aqueous solution by dripping a small amount (1/100 to 1/10 of the
`contents) of a 1,000 to 10,000 (unit/ml) heparin aqueous solution into this plastic solution while this
`solution is being stirred vigorously, which results in the heparin being finely precipitated therein to
`thus exhibit a homogeneously dispersed state. Normally, this dispersion solution is processed using
`ultrasonic waves to enhance the degree of dispersion thereof. Next, this polarography sensor with the
`contamination inhibiting coating 5 formed in the vicinity of the front end thereof is immersed in the
`plastic solution in which heparin has been dispersed homogeneously, removed, and then held in
`mid-air to thus evaporate the plastic solvent and form a thin coating. This type of immersion and
`drying operation is normally repeated two to three times, however, because this method must be
`suitably performed based on the type and concentration of the plastic such that there will be a blood
`coagulation inhibiting effect even if the plastic coating is only formed in the vicinity of the front end
`of a sensor, it is preferable that the coating be formed on nearly the entire outermost surface of the
`sensor as on the sensor in the present embodiment. Note that while the electrode reaction surface 2
`was provided on a side surface in the vicinity of the front end of the precious metal wire 1, the front
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`end surface of the precious metal wire 1 may be an electrode reaction surface like that illustrated in
`FIG. 1 (B) through FIG. 1 (D).
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`Note that while the blood coagulation inhibiting coating 6 was adhered to the outer surface of
`the contamination inhibiting coating 5 in the present embodiment, because the blood coagulation
`inhibiting coating typically has a contamination inhibiting effect, it may be adhered directly to a
`insulating layer 4 having no contamination inhibiting coating. This is also true for FIG. 1 (B), (C),
`and (D) described below.
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`Note further that while the electrode protecting metal tube 7 is used in the present
`embodiment, a tube of something other than metal may also also be used, furthermore, if a tough
`material is selected for the insulating layer 4, the tube can be omitted. This also applies to FIG. (C)
`and (D) described below.
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`Next, the sensor illustrated in FIG. 1 (B) is a polarography sensor that forms a flexible
`separation type measuring electrode. The same reference symbols have been used in FIG. 1 (B) for
`parts that correspond to those in FIG. 1 (A), and detailed descriptions thereof are omitted. In FIG. 1
`(B), a flexible tube 8 made of Teflon, silicon, or the like, is used in place of the metal tube 7 in FIG. 1
`(A), the front end of the precious metal wire 1 surface is covered with the hard insulating coating 4
`made of glass or enamel, and a portion of the wire connected to the portion thereof covered by the
`hardened insulating coating 4 is covered by an insulating coating 9 made of a flexible resin.
`Therefore, most of this polarography sensor is flexible and can thus be inserted deep (for example to
`the heart) along the inside of a vein. While the electrode reaction surface 2 is provided on the front
`end surface of the precious metal wire 1 in FIG. 1 (B), said surface may be formed on a side surface of
`the precious metal wire 1, as illustrated in FIG. 1 (A). An adequate blood coagulation inhibiting
`effect can be achieved as long as only an electrode vicinity on the front end of the sensor is covered by
`a plastic coating in which heparin has been homogeneously dispersed when a flexible anticoagulant
`material such as Teflon silicon is used as the flexible plastic tube 8 in a polarography sensor like that
`in the present embodiment.
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`The polarography sensor illustrated in FIG. 1 (C) forms a needle like composite electrode,
`having a measuring electrode 1 and a standard reference electrode 10, inside an integrated sensor.
`The measuring electrode is the same precious metal wire 1 as in the polarography sensors in FIG. 1
`(A) and FIG. 1 (B), and the standard reference electrode 10 is made of Ag/AgCl. The standard
`reference electrode 10 is formed by shaving thin a portion of the metal tube 7 made of stainless steel
`near the electrode front end thereof, depositing silver and performing silver plating thereon, and then
`performing chloride argentation using hydrochloric acid or potassium chloride on a portion thereof
`through an electrolytic method. Because the metal tube 7 performs the role of this Ag/AgCl standard
`reference electrode, a terminal 11 to an external electronic circuit is attached to the back end of this
`metal tube 7 using a special solder.
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`Note that the metal tube 7 can be omitted as described above, however, in this case, a silver
`tube or a chloride argentated silver wire is used as the standard reference electrode, and a thin coated
`wire is used in place of the metal tube 7. Furthermore, the methods for forming the semipermeable
`contamination inhibiting coating 5 and blood coagulation inhibiting coating 6 are the same as the
`method described for FIG. 1 (A) above, even in the case of the composite electrode in FIG. 1 (C).
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`FIG. 1 (D) is a polarography sensor that forms an electrode for indirect polarography for
`applying an enzymatic reaction where a porous plastic layer 12 is formed that homogeneously
`disperses and fixes an enzyme on the contamination inhibiting coating 5 of the electrode reaction
`surface 2 of the measuring electrode classified in the embodiment described in FIG. 1 (A), which
`plastic layer is, in turn, covered by the blood coagulation inhibiting coating 6. In this case, a variety
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`of enzymes like glucose oxidase for measuring glucose, uricase for measuring uric acid, and
`ascorbate oxidase for measuring ascorbic acid can be used as the enzyme, and the fact that the
`concentration of the active substances in the enzyme is selectively measured by the electrode
`detecting and measuring reaction substances (mainly H2O2 or O2) caused by these enzymes using a
`polarographic method is as was described above.
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`FIG. 2 is a drawing illustrating a method for applying the various intravenous polarography
`sensors illustrated in FIG. 1 (A) through (D) inside veins. FIG. 2 illustrates a case where a separated
`measuring electrode sensor (FIG. 1 (A), (B), and (D)) is used, and where this measuring electrode 21
`is inserted in a vein 27 using an insertion catheter (branula needle) 25, having a ring 26 attached to
`one end for stopping the flow of liquids, and thus projected into blood 28 from the end of the catheter
`having an electrode reaction surface. A standard reference electrode container 24 housing a standard
`reference electrode 22 and an electrolytic solution 23 is linked to a side surface of the insertion
`catheter 25, and the standard reference electrode 22 is thus electrically linked to the front end reaction
`surface of the measuring electrode through the electrolytic solution. A normal Ag/AgCl standard
`reference electrode is used as the standard reference electrode 22 and physiological saline is used as
`the electrolytic solution 23, which gradually flows into the blood using a normal drip method. A
`prescribed load voltage is applied between the measuring electrode and the standard reference
`electrode of an electrode system configured in this way by using a power circuit 31 based on a
`measuring substance, and thus the intravasular concentrations of target substances can be
`continuously known by using a current width increaser 32 to increase the width of the current flowing
`between the electrodes, and recording the width using a recorder 33.
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`Note that because the measuring electrode and the standard reference electrode form a
`composite and thus both make contact with blood in the case of a composite electrode like that in
`FIG. 1 (C), the standard reference electrode 22, the electrolytic solution 23, and the standard reference
`electrode container 24 in FIG. 2 are not necessary.
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`While cases were described that use precious metal wires as measuring electrode configuring
`bodies in the descriptions of polarography sensor structures in FIG. 1 (A) through (D) above, because
`only the electrode reaction surface requires noble metal properties, that is, non-variability, base metal
`wires with precious metal wires connected only to the front ends thereof may be used, furthermore,
`base metal wires, with precious metals vapor deposited or plated on the front ends thereof, may also
`be used.
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`FIG. 3 is an example of results from a test comparing the stability and responsiveness of the
`sensor according to the present invention, with a blood coagulation inhibiting coating (6 in FIG. 1
`(B)) applied to the end thereof, to the stability and responsiveness of a conventional sensor to which
`the coating has not been applied in a case where the intravenous polarography sensor according to the
`present invention is used in the state described based on FIG. 1 (B) to measure oxygen in blood. In
`this example, the two sensors described above were placed, one in the left and one in the right femoral
`arteries of a dog anesthetized with Nembutal using the catheter 25 and the method illustrated in FIG.
`2, and then voltage of – 0.6 V was applied to the standard reference electrodes 22 in the measuring
`electrodes 21 of these sensors. The dog was allowed to breathe air with the incorporation of
`occasional 10 second or five minute pulses of 50% oxygen breathing while the electrolytic current
`value of the sensor was recorded by two PENRUDAs. The vertical axis in the figure illustrates the
`current value in terms of partial oxygen pressure (oxygen concentration) based on a test value using
`millimeters of mercury pressure in accordance with common practice. Note that because this test is
`performed at 38°C, an O2 partial pressure of 100 mmHg can be converted into an O2 concentration of
`0.137 μmoles/l. The horizontal axis illustrates time in minute units, however, 300 minutes (five
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`hours) during the test are omitted. Recorded value A in FIG. 3 is the recorded value of the sensor
`according to the present invention treated with a blood coagulation inhibiting coating, B is the
`recorded value of a conventional sensor not treated with such a coating, these values were recorded
`simultaneously using two PENRUDAs, and the time of B is shifted a distance equivalent to five
`minutes to the right of A in order to show pen intersections as well as possible. Note that both A and
`B were given five coats of 7.5% cellulose acetate as contamination inhibiting coatings while A was
`also given two additional coats of 5% cellulose triacetate in which 200 unit/ml of heparin has been
`dispersed. Two measuring electrodes were initially placed so that the front ends thereof extended part
`way into the catheter 25 in FIG. 2, test physiological saline (variously having PO2 values of 0 mmHg
`and 150 mmHg in a liquid allowed to reach equilibrium with nitrogen or air at 38°C) was gradually
`passed therethrough, and then recording was started after sensitivity was allowed to standardize. The
`recorded value from a to b in FIG. 3 illustrates the PO2 values of both sensors while in contact with
`this air equilibrium solution. After the test described above was finished, the sensors were pushed at
`point b so their ends protruded from the catheters 25 and thus made contact with blood, the recorded
`values showed arterial blood values like those indicated by curves A and B. Next, the dog was
`switched from breathing air to breathing 50% oxygen for exactly 10 seconds at point c, where the
`recorded values of both A and B exhibit sharp peaks. Next, 50% oxygen breathing was performed for
`five minutes at point d, where curve A achieved a PO2 value of about 295 mmHg while B achieved
`only about 285 mmHg. Furthermore, a difference between the air breathing values of A and B
`gradually became obvious such that by the 50 minute mark the PO2 values were 100 mmHg and 96
`mmHg, respectively. This indicates that with B electrode sensitivity began to drop off as blood
`coagulation began to adhere to the electrode. Measurement continued for five hours, and while the
`sensitivity of B dropped off dramatically to thus indicate a value about ½ of that of the initial value for
`the first time, A maintained sensitivity close to the initial sensitivity. Note that it can be seen from
`observing the impact of the 50% O2 breathing performed for 10 seconds and five minutes at points f
`and g that A has changed little from the initial period while the shape of B has collapsed significantly
`and electrode responsiveness has deteriorated. The ends of the electrodes were once again pulled
`back into the catheters 25 at point h and thus brought back into contact with the test solution (PO2 150
`mmHg), and, when electrode sensitivities were compared at the end of the test, it was found that
`sensitivity had dropped by about 4% in A, and by about 50% in B. Note that visual observation at the
`end of the test revealed that the entire end surface of sensor B, which was not treated with a blood
`coagulation inhibiting coating, was covered with a red blood clot (sticky blood coagulation) while no
`such clot was observed on sensor A, which was treated with a blood coagulation inhibiting coating.
`
`It is clear from the test results described above that the blood coagulation inhibiting coating
`according to the present invention exhibits remarkable sensitivity and responsiveness for intravenous
`polarography sensors, furthermore, it is presumed that the coating is also effective in preventing the
`risk of blood coagulation.
`4. Brief Description of the Drawings
`
`FIG. 1 (A) through (D) are cross sectional views that each illustrate a polarography sensor
`according to the present invention, FIG. 2 is a drawing illustrating a method that applies a
`polarography sensor according to the present invention to measure an intravascular substance, FIG. 3
`is a chart illustrating the recording of changes over time in a polarography sensor according to the
`present invention and a conventional polarography sensor when the two sensors were each applied to
`a vein of a dog as an oxygen measuring electrode.
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`1…precious metal wire, 2…electrode reaction surface, 4…insulating layer,
`5…contamination inhibiting coating, 6…blood coagulation inhibiting coating, 10…standard
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`reference electrode, 12…plastic layer
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`FIG. 2
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`FIG. 1 (A)
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`FIG. 1 (B)
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`FIG. 1 (C)
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`FIG. 1 (D)
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`FIG. 3
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`O2 partial pressure (mmHg)
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`Amendments (Voluntary)
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`March 4
`February 20, 1981
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`Director General of Patent Office, Dear Sirs
`1. Indication of Incident
`1980, JPA No. 187377
`2. Title of Invention
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`POLAROGRAPHY SENSOR
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`3. Amending Party
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`Relation to the Incident:
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`Address:
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`Name:
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`4. Agent
` 2-8-10
`110-1 Shibata-machi, Kita-ku, Osaka ₸530
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`Address:
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`Name:
`(6292) Ryuji TOSHIMA, attorney
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`Patent Applicant
`2-8-17 Fujishirodai, Suita-shi, Osaka
`Bunji HAGIWARA
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`5. Subject of Amendment
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` Stamp [Patent Office,
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`March 6, 1981, 2nd Application Section,
`ll
`bl
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