WO2006115281A1 - Wire for cardiac pacemakers - Google Patents

Wire for cardiac pacemakers Download PDF

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Publication number
WO2006115281A1
WO2006115281A1 PCT/JP2006/308793 JP2006308793W WO2006115281A1 WO 2006115281 A1 WO2006115281 A1 WO 2006115281A1 JP 2006308793 W JP2006308793 W JP 2006308793W WO 2006115281 A1 WO2006115281 A1 WO 2006115281A1
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WO
WIPO (PCT)
Prior art keywords
adhesive layer
wire
patch
electrode
heart
Prior art date
Application number
PCT/JP2006/308793
Other languages
French (fr)
Japanese (ja)
Inventor
Yukako Fukuhira
Eiichi Kitazono
Hiroaki Kaneko
Yoshihiko Sumi
Yuji Narita
Hideaki Kagami
Yuichi Ueda
Minoru Ueda
Original Assignee
Teijin Limited
National University Corporation Nagoya University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Teijin Limited, National University Corporation Nagoya University filed Critical Teijin Limited
Priority to JP2007514788A priority Critical patent/JP4889043B2/en
Publication of WO2006115281A1 publication Critical patent/WO2006115281A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0587—Epicardial electrode systems; Endocardial electrodes piercing the pericardium

Definitions

  • the present invention relates to a temporary cardiac pacemaker wire. More specifically, the present invention relates to a heart pacemaker wire that can fix an electrode to heart tissue without sewing the electrode to heart tissue.
  • Implanting temporary pacemaker myocardial electrodes and leads after cardiac surgery is routinely performed as an effective means of diagnosing and treating arrhythmia during and after surgery, and to cope with unforeseen circumstances. ing.
  • the electrode is fixed by applying a sewing thread directly to the myocardium with a needle.
  • This temporary pacemaker myocardial electrode needs to be pulled out of the body after surgery after the patient's condition has stabilized.
  • the electrode is sewn to the myocardium with a coiled wire, it is rare, but when it is removed, the heart and blood vessels are damaged by the coil and the myocardium is cleaved by the suture thread. May cause fatal complications.
  • An object of the present invention is to provide a “wire for cardiac pacemaker” (hereinafter sometimes abbreviated as “wire”) capable of fixing an electrode to the surface of the heart without being sewn to the myocardium. It is an object of the present invention to provide a wire having good adhesion to the surface of the heart without adversely affecting the living body, and the present invention can be extracted without causing damage to the heart, blood vessels, etc. In addition, an object of the present invention is to provide a patch and a film used for the wire, and to provide a wire for a cardiac pacemaker. Another object of the present invention is to provide a heart basing method using a cardiac pacemaker wire.
  • the inventors found that a film mainly composed of a biodegradable polymer and having an uneven portion on one surface has good adhesion to the heart surface due to the action of the uneven portion, and completed the present invention. It was found that the biodegradable polymer was decomposed after a predetermined period of time after adhering to the heart surface, and the present invention was completed by finding that the electrode could be easily removed from the heart surface without damaging the tissue.
  • the present invention is a cardiac pacemaker wire comprising a patch having an adhesive layer and a lead having an electrode at its end,
  • the adhesive layer is a film mainly composed of a biodegradable polymer.
  • One surface is the adhesive surface (eight surfaces), and the A surface is concave and convex at a rate of 1 to 100% of the total surface area.
  • the electrode is a wire exposed on the A side of the adhesive layer.
  • the present invention is a patch for adhering an electrode to the surface of a heart, and has an adhesive layer, and the adhesive layer is a film mainly composed of a biodegradable polymer, and one surface has an adhesive surface (eight surfaces). And the A surface is a patch having uneven portions at a ratio of 1 to 100% of the total surface area.
  • the present invention is a film mainly composed of a biodegradable polymer, wherein at least one surface has an uneven structure in which pores having a pore diameter of 0.1 to 20 are arranged in a honeycomb shape for fixing an electrode to a heart surface It is a film.
  • the patch is applied to the heart surface with the side A of the adhesive layer facing the heart. And a method of installing the wire for the heart base maker.
  • the present invention also includes a method for pacing the heart using the above-mentioned cardiac pacemaker wire.
  • FIG. 1 is a schematic external view of an example of the wire of the present invention.
  • FIG. 2 is a schematic cross-sectional view of an example of the wire of the present invention.
  • FIG. 3 is a schematic cross-sectional view of an example of a wire according to the present invention.
  • FIG. 4 is a schematic cross-sectional view of an example of the wire of the present invention.
  • FIG. 5 is a schematic cross-sectional view of an example of a wire according to the present invention.
  • FIG. 6 is a schematic cross-sectional view of an example of the wire of the present invention.
  • FIG. 7 is a photomicrograph of the concavo-convex portion of the adhesive layer produced in Example 1.
  • FIG. 8 is a micrograph of the uneven portion of the adhesive layer produced in Example 3.
  • Fig. 9 is a schematic diagram showing an 82-cam configuration.
  • FIG. 10 is a schematic diagram showing an 82-cam configuration.
  • FIG. 11 is a photomicrograph of the uneven part of the adhesive layer produced in Example 4.
  • FIG. 12 is a photomicrograph of the concavo-convex portion of the adhesive layer produced in Example 5.
  • the patch of the present invention is a patch for adhering an electrode to the heart surface, and has an adhesive layer, and the adhesive layer is a film mainly composed of a biodegradable polymer. Eight sides)
  • the A side is a patch having irregularities at a ratio of 1 to 100% of the total surface area.
  • Preferred embodiments of the patch include an embodiment having only an adhesive layer, an embodiment having an adhesive layer and a cover layer, and an embodiment having an adhesive layer, a holding layer and a cover layer.
  • the average total thickness of the patch is preferably 10 to 300 m, more preferably 10 to 200 m.
  • the adhesive layer is a film mainly composed of a biodegradable polymer.
  • the film preferably contains 80 to 100% by weight, more preferably 90 to 100% by weight of biodegradable polymer as a polymer component.
  • biodegradable polymers include aliphatic polyesters and aliphatic polycarbonates.
  • the aliphatic polyester include polylactic acid, lactic acid-glycolic acid copolymer, polyhydroxybutyric acid, poly strength prolactone, lactic acid-force prolactone copolymer, polyethylene adipate, and polybutylene adipate.
  • the aliphatic polycarbonate include polybutylene carbonate, polyethylene carbonate and the like. Moreover, these copolymers and a mixture may be sufficient. Of these, polylactic acid, lactic acid-glycolic acid copolymer, polystrength prolactone, and lactic acid-strength prolactone copolymer are preferable.
  • the copolymerization molar ratio (lactic acid glycolic acid) is preferably 1Z99 to 99Z1, more preferably 10Z90 to 90/10, and even more preferably 25 75 to 7525.
  • the copolymerization molar ratio (lactic acid Z force prolactone) is preferably 1Z99 to 99/1, more preferably 5/95 to 95Z5, and even more preferably 10 Z90 to 90 10 is there.
  • the film may contain a polymer other than the biodegradable polymer as a polymer component.
  • Other polymers include, for example, polystyrene, polyvinyl alcohol, poly (ethylene-covinyl acetate), poly (hydroxyethyl methacrylate). Rate), vinyl-based polymers and copolymers thereof, poly (carbonates), poly (urethanes), condensation polymers such as nylon, and biocompatible polymers such as these copolymers.
  • the film is preferably composed of 0 to 20% by weight, more preferably 0 to 10% by weight of biocompatible polymer.
  • the film may contain a phospholipid.
  • phospholipids those extracted from animal tissues or artificially synthesized can be used without regard to their origin.
  • the phospholipid is preferably at least one selected from the group consisting of phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylglycerol and derivatives thereof. More preferred are phosphatidylethanolamines, and more preferred is L- ⁇ -phosphatidylethanolamine monooleoyl.
  • the adhesive layer is preferably 0.1 to 100 parts by weight, more preferably 0.2 to 10 parts by weight, and still more preferably 0.5 to 2 parts by weight with respect to 100 parts by weight of the biodegradable polymer. It is preferred to contain an amount of phospholipid. Further, the film may contain other components such as a softening agent, an adhesion improver, and a drug as long as the object of the present invention is not impaired.
  • the adhesive layer has one surface as the adhesive surface (eight surfaces) and the other surface as the B surface.
  • the A surface has irregularities at a ratio of 1 to 100% with respect to the total surface area.
  • the proportion of the concavo-convex portion is preferably 10 to 100%, more preferably 20 to 100% with respect to the total surface area of the A surface. It is preferable that the peripheral part of A surface has an uneven part.
  • the concavo-convex portion preferably has pores having a pore diameter of 0.1 to 20 m, more preferably 0.5 to 18 m, and still more preferably 1 to 15. The pores are preferably arranged uniformly.
  • a pore diameter means the diameter of the pore in the uneven
  • the pores are preferably arranged in a honeycomb shape.
  • the double cam-like arrangement means a structure in which regular hexagons are arranged adjacent to each other as shown in FIG. Therefore, the positional relationship between the pores of the concavo-convex portion corresponds to the positional relationship between regular hexagons shown in FIG. Therefore, six pores are arranged around one pore.
  • FIG. 10 shows a state in which circular pores are arranged in a honeycomb shape.
  • the pores are substantial Are preferably the same shape. Therefore, it is preferable that the plurality of pores have substantially the same shape, and six pores are arranged around one pore.
  • the shape of the pores is not limited but is preferably circular. If the radius of the pore is r and the distance between the centers of adjacent pores is a, then r and a are preferably expressed as 1 ⁇ a Z 2 r ⁇ 2.
  • the depth of the pores is preferably 0.1 to 20 m, more preferably 0.5 to 18 m, and still more preferably 1 to 15 m.
  • the concavo-convex portion may be formed of a projection such as a cilia shape, a columnar shape, a prismatic shape, or a flat plate shape.
  • the ratio (HZD) of the height (H) of the protrusion to the minimum thickness or the minimum diameter (D) of the protrusion is preferably larger than 1.
  • the minimum thickness or the minimum diameter is preferably 10 nm to 50 ⁇ m.
  • the height of the convex portion is preferably 10 nm to 100 m.
  • the thickness of the adhesive layer is preferably 10 to 300 / xm, and more preferably 10 to 200 / m.
  • the shape of the adhesive layer is preferably a circle, an ellipse, or a polygon.
  • the size is about 2-5 cm in diameter or major axis, and about 2-5 cm in diagonal length.
  • the film having an uneven portion constituting the adhesive layer of the present invention can be preferably produced by the following method. That is, the film
  • organic solvents such as chloroform and methylene chloride, aromatic hydrocarbons such as benzene, toluene and xylene, esters such as ethyl acetate and butyl acetate, and water-insoluble ketones such as methyl isobutyl ketone , Carbon dioxide, etc. these These organic solvents may be used alone or as a mixture of these solvents.
  • the solute concentration of one polymer component and phospholipid in the polymer solution is preferably
  • solute concentration 0.01 to 10% by weight, more preferably 0.05 to 5% by weight. If the solute concentration is lower than 0.01% by weight, the resulting film has insufficient mechanical strength, which is not desirable. On the other hand, if it exceeds 10% by weight, the solute concentration becomes too high, and a sufficient uneven structure may not be obtained.
  • the weight ratio of the polymer component to the phospholipid in the polymer solution is preferably 1: 1 to 1,000: 1.
  • the film preferably contains a phospholipid.
  • grooved part includes a casting process and an evaporation process.
  • the casting process is a process in which a polymer solution is cast on a substrate to obtain a liquid film. Such a process can be performed by pouring the polymer solution onto the substrate.
  • inorganic materials include glass, metal, and silicon wafers.
  • polymer include polypropylene, polyethylene, and polyether ketone.
  • liquid include water, liquid paraffin, and liquid polyether.
  • the evaporation process is a process in which water vapor with a relative humidity of 30 to 100% is sprayed on the liquid film to evaporate the organic solvent.
  • the relative humidity is preferably 50 to 95%, more preferably 50 to 90%.
  • a relative humidity of less than 30% is not preferable because condensation on the liquid film is insufficient.
  • the ambient temperature may be a temperature at which the organic solvent gradually evaporates, and is preferably 10 to 30 ° C., more preferably room temperature.
  • the organic solvent evaporates and water vapor condenses on the liquid film surface, forming water droplets. This takes away latent heat when the organic solvent evaporates, and the temperature of the liquid film surface This is because water vapor in the atmosphere is condensed on the liquid film surface.
  • the surface tension between the condensed water vapor and the organic solvent is reduced by the action of the hydrophilic group in the polymer, and the condensed water vapor aggregates into minute water droplets.
  • microscopic water droplets packed in a hexagonal arrangement are arranged on the liquid film surface.
  • the water droplets sink into the liquid film, and the surface of the liquid film has a structure in which the water droplets surrounded by the polymer are regularly arranged.
  • the organic solvent in the liquid film completely evaporates, Form a film.
  • the water droplets generated by condensation are evaporated.
  • the water droplets evaporate, leaving pores that are uniformly arranged on the polymer surface.
  • pores having a pore diameter of 0.1 to 20 m are regularly formed in a honeycomb shape.
  • the pore diameter is preferably 0.5 to 18 / m, more preferably :! ⁇ 1 5 ⁇ .
  • the back surface that was in contact with the substrate is a flat surface with no pores.
  • the depth of the pores is preferably 0.1 to 20; iim, and more preferably 0.5 to 18 / zm.
  • the film thickness is thinner than the size of the water droplet, a film having fine pores is obtained.
  • Particularly suitable for fixing electrodes on the heart surface is a film mainly composed of the aforementioned biodegradable polymer, and at least one surface has pores having a pore diameter of 0.1 to 20 m in a honeycomb shape. It is a film which has the uneven structure arrange
  • the film having the concavo-convex portion constituting the adhesive layer can be produced by extrusion using a mold having concavo-convex, lithography, nanoimprinting after film formation, laser processing, or the like.
  • the adhesive layer preferably has an electrode window penetrating from the A surface to the B surface. An electrode is placed in the electrode window, and the electrode is brought into contact with the heart surface. Further, when the adhesive layer is manufactured, the adhesive layer and the conductor may be integrally formed so that the conductor is present in the liquid film and the electrode is exposed on the A surface side of the adhesive layer. When the electrodes are bipolar, the two electrodes may be exposed from the electrode window as long as both electrodes cannot be contacted, or an electrode window may be provided for each electrode. (Cover layer)
  • the patch of the present invention preferably has a cover layer on the B surface of the adhesive layer in order to prevent the electrode from being exposed to the outer surface of the patch.
  • the cover layer is preferably a film mainly composed of the aforementioned biodegradable polymer.
  • the cover layer and the adhesive layer may be the same polymer or different polymers.
  • the biodegradable polymer that forms the cover layer is preferably one that is more easily decomposed than the biodegradable polymer that forms the adhesive layer.
  • the cover layer is preferably formed of a lactic acid monodaricholic acid copolymer.
  • the cover layer may have uneven portions such as an adhesive layer, but may be a smooth film.
  • the conducting wire can be fixed by crimping the conducting wire between the cover layer and the adhesive layer.
  • the thickness of the cover layer is preferably 10 to 300 w m, and more preferably 20 to 200 / m.
  • the cover layer preferably has the same shape as the adhesive layer except that there is no electrode window.
  • the cover layer may be a single layer or a laminated layer.
  • a polymer solution containing a polymer component and an organic solvent is cast on a substrate and the solvent is removed, or an extrusion method such as an inflation extrusion method or a T-die extrusion method, a force render method, etc. Can be manufactured.
  • the polymer component and the organic solvent can be the same as those used for the production of the adhesive layer.
  • the solute concentration of the polymer solution is preferably 1 to 40% by weight, more preferably 5 to 30% by weight.
  • the holding layer is preferably a film mainly composed of the aforementioned biodegradable polymer.
  • the holding layer and the adhesive layer may be the same type of polymer or different types of polymers.
  • the holding layer may have uneven portions such as an adhesive layer, but may be a smooth film.
  • the lead wire can be fixed by pressing the lead wire between the holding layer and the adhesive layer.
  • the thickness of the holding layer is preferably 10 to 100 xm, more preferably 20 to 80. It is.
  • the holding layer preferably has the same shape as the adhesive layer.
  • the holding layer may be a single layer or a stacked layer.
  • the holding layer is a casting method in which a polymer solution containing a polymer component and an organic solvent is cast on a substrate and the solvent is removed, or an extrusion method such as an inflation extrusion method or a T-die extrusion method, a calendar method, etc. Can be manufactured.
  • the solute concentration of the polymer solution is preferably 1 to 40% by weight, more preferably 5 to 30% by weight.
  • the wire of this invention is comprised from the above-mentioned patch and conducting wire.
  • the lead has an electrode at a position far from the heart pacemaker main body side, and a connector on the heart pacemaker main body side.
  • the electrode is exposed on the A side of the adhesive layer.
  • the electrode contacts the heart surface and transmits the electrical signal from the heart base manufacturer to the heart muscle.
  • the electrode is made of a conductive metal material.
  • the electrode is preferably about the same diameter as the conductor and about 1 to 2 mm in length. This is because it is necessary to pull out the implanted cardiac wire outside the body without damaging human tissue after a predetermined period after cardiac surgery.
  • the electrode may be monopolar or more than bipolar. In the case of bipolar or more, it can have two or more electrodes, a proximal electrode on the side closer to the heart pacemaker body and a distal electrode on the far side.
  • the connector is for connection to the heart pacemaker body. Since the wire of the present invention punctures the chest wall after cardiac surgery and connects it to the cardiac pacemaker body outside the body, it is preferable to provide a chest wall puncture needle at the end of the connector pin.
  • the diameter of the conducting wire is preferably less than 1 mm, more preferably 0.2 to 0.8 mm, and the outer surface is covered with an insulator.
  • the length is about 400 to 700 mm.
  • the wire 1 of the present invention will be described with reference to FIGS. 1 to 6 are schematic diagrams for explaining the appearance and cross-sectional structure of the wire of the present invention, and the scales of the conductors, electrodes, and layers are not unified.
  • FIG. 1 is an example of the appearance of the wire (monopolar) of the present invention.
  • One electrode (4) is installed in an electrode window provided in the center of the patch, and a connector pin and a chest wall puncture needle (8) are installed at the other end.
  • the patch is formed by an adhesive layer (1) and a cover layer (7).
  • FIG. 2 is a schematic illustration of an example of a cross section of a wire patch of the present invention.
  • the electrode (4) is crimped to the cover layer (7) and is opened on the electrode window (5) opened in the adhesive layer (1).
  • the conducting wire (3) is fixed by being pressed between the adhesive layer (1) and the cover layer (7).
  • the cover layer or the holding layer may be a single layer or a laminate as described above.
  • FIG. 3 is an embodiment in which the holding layer (6) is laminated between the B surface of the adhesive layer (1) and the cover layer (7) in the embodiment of FIG.
  • the conducting wire (3) is fixed by being pressed between the adhesive layer (1) and the holding layer (6).
  • the cover layer or the holding layer may be a single layer or a laminate as described above.
  • FIG. 4 shows an embodiment in which the holding layer (6) is laminated on the B surface of the adhesive layer (1), and a cover layer (7) is laminated on the holding layer (6).
  • the electrode (4) is crimped to the cover layer (7).
  • the conducting wire (3) is pressed and fixed between the holding layer (6) and the cover layer (7).
  • the cover layer or the holding layer may be a single layer or a laminate as described above.
  • FIG. 5 shows a state in which the conductor (3) is present when the adhesive layer (1) is manufactured, and the conductor is disposed in the adhesive layer (1).
  • FIG. 6 is an embodiment in which the cover layer (7) is laminated in the embodiment of FIG.
  • the cover layer may be a single layer or a laminate as described above.
  • the wire of the present invention performs a median sternotomy, and after reaching the heart, incises the pericardium and reaches the pericardium, and then attaches it to the surface of the left ventricle, left atrium, right ventricle, or right atrium. Can be used.
  • the present invention includes a method of installing a wire for a cardiac pacemaker, comprising attaching the patch to the heart surface with the side A of the adhesive layer facing the heart. It is preferable to apply the patch to the heart surface after the patch has been warmed to near the heart temperature. Warm The temperature is preferably from room temperature to the heart temperature. The patch can be heated in warm water or a thermostatic bath. By warming the patch to near the heart temperature, the adhesion of the patch to the heart surface is improved.
  • it is also preferable to apply a patch to the surface of the heart by applying an agent that enhances the adhesion to the heart surface to the side A of the adhesive layer.
  • a cardiac surgery method including the step of installing the cardiac pacemaker wire of the present invention.
  • the wire patch is applied to the heart surface with the side A of the adhesive layer facing the heart.
  • the wire for a cardiac pacemaker of the present invention can be used in a method for temporarily basing the heart during and after cardiac surgery. Therefore, according to the present invention, there is provided a heart basing method using the wire for a cardiac pacemaker of the present invention.
  • the operation can be performed, for example, by the following method.
  • median sternotomy and pericardium are opened to reach the pericardium, and extracorporeal circulation is established (extracorporeal circulation is not performed for heartbeat surgery).
  • extracorporeal circulation is not performed for heartbeat surgery.
  • the patch electrode of the present invention is applied to the heart surface.
  • This patch can be made more adhesive by warming it to near body temperature before use.
  • the patch electrode is preferably placed along the pericardium toward the left ventricle or on the diaphragm surface so as to be covered with the pericardium.
  • the patch electrode can be moved to another location if the base threshold is not good.
  • the end of the side connecting the pacemaker body with the other chest wall puncture needle penetrates the rectus abdominis muscle from the diaphragm surface and, after exiting the skin, cuts off the chest wall puncture sputum and connects it to the pacemaker body.
  • the implanted cardiac wire should be removed within 2 weeks after the surgery.
  • the oil was mixed with PLCA at a ratio of 1 to 200 (by weight) to prepare a polymer solution.
  • the polymer solution was cast on a glass substrate to obtain a liquid film.
  • water vapor was sprayed on the liquid film at room temperature and humidity of 70% to gradually evaporate the solvent and to condense the water vapor on the surface of the liquid film to form water droplets, and then evaporate the water droplets to prepare a film.
  • the obtained film was a non-penetrating film having a concavo-convex portion in which pores having a pore diameter of about 5 // m were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and the thickness was 10 / m. .
  • Fig. 7 shows a photomicrograph of the uneven part of the film. This film was heat-treated at 60 ° C. for 10 minutes, cut into a circle with a diameter of 4 cm, and the center with 6 mm biopsy.
  • a smooth film having a diameter of 4 cm was prepared in the same manner as the cover layer.
  • the film thickness was 52 ⁇ m.
  • the center was cut out with a 6 mm diameter biopsy to produce a window for the electrode.
  • the conductor was placed so that the electrode was in the center of the cover layer, and the conductor was pressed onto the cover layer with a cotton swab soaked in salted himethylene.
  • the holding layer was overlaid on the electrode side of the cover layer and again heat treated at 60 ° C for 10 minutes. Furthermore, an adhesive layer is placed on the upper surface of the holding layer so that the concavo-convex part becomes the outermost layer, heat-treated at 60 ° C. for 10 minutes, and shown in FIG. A wire having a cross-sectional structure was produced.
  • a film having a film thickness of 57 m was obtained using P L G A in the same manner as in Example 1. This film was cut into a circle with a diameter of 4 cm, stacked in two, and heat treated at 60 for 10 minutes to form a cover layer.
  • the adhesive layer produced in Example 1 was used.
  • a film having a thickness of 48 m was produced using PLCCA in the same manner as in Example 1, and the center portion was cut out with a biopsy having a diameter of 6 mm to form an electrode window.
  • Example 2 The same operation as in Example 1 was performed to manufacture a wire having the cross-sectional structure shown in FIG. 4 (the cover layer is a laminate).
  • Example 1 The same operation as in Example 1 was performed except that a dog (age 2 years 4 months, female, beagle) was used as the test animal.
  • the results are shown in Table 1. Slightly above the basing threshold Although there was a rise, it was confirmed that it was possible to drive without problems for 14 days. On the 14th day after the operation, the wire was pulled out and it was confirmed that it was pulled out without resistance. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the wire, no intracardiac hemorrhage was observed by cardiac ultrasonography, and no signs of cardiac tambonase, pericardial thickening or myocardial dilatation were observed.
  • a film having a thickness of 46 m was obtained using PLGA in the same manner as in Example 1. This film was cut into a circle with a diameter of 4 cm, stacked in two, and heat treated at 60 ° C for 10 minutes to form a cover layer.
  • the obtained film had uneven portions in which pores having a pore diameter of about 4/2 m were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and a non-penetrating film having a thickness of 8 / m. It was.
  • Fig. 8 shows a photomicrograph of the film irregularities. This film was heat-treated at 60 ° C for 10 minutes, cut into a 4 cm diameter circle, and the center was cut out with 6 mm biopsy.
  • PLCA lactic acid monostrength prolactone copolymer
  • Example 1 The same operation as in Example 1 was performed to produce a wire having the cross-sectional structure shown in FIG. 4 (the cover layer is a laminate).
  • (Operation check) The same operation as in Example 1 was performed except that a dog (age 2 years 6 months, female, beagle) was used as a test animal. The results are shown in Table 1. A slight increase in the basing threshold was observed, but it was confirmed that the system could operate without any problems for 14 days. On the 14th day after the operation, the wire was pulled out and it was confirmed that it was pulled out without resistance. The results are shown in Table 1. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the wire, no echocardiogram was observed on echocardiography, and no signs of cardiac tambonase, pericardial thickening or myocardial dilatation were observed.
  • a polymer solution was prepared by mixing at a ratio (weight) of 1 200 to PLCA. The polymer solution was cast on a glass substrate to obtain a liquid film.
  • the obtained film was a non-penetrating film having a concavo-convex portion in which pores having a pore diameter of about 9 were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and the thickness was 15 m.
  • a photomicrograph of the film irregularities is shown in Fig. 11. This film was heat-treated at 60 ° C. for 10 minutes, cut into a circular shape with a diameter of .3 cm, and the center was cut with a 6 mm biopsy. (Holding layer)
  • a smooth film with a diameter of 3 cm was prepared using P L C A in the same manner as the cover layer.
  • the film thickness was 5 7 m.
  • the center was cut out with a 6 mm diameter biopsy to produce a window for the electrode.
  • the conductor was placed so that the electrode was at the center of the cover layer, and the conductor was pressed onto the cover layer with a cotton swab soaked in methylene chloride.
  • the holding layer was superimposed on the electrode side of the cover layer, and heat treatment was performed again at 60 for 10 minutes.
  • an adhesive layer is placed on the upper surface of the holding layer so that the uneven portion becomes the outermost layer, and heat treatment is performed at 60 ° C. for 10 minutes, and the adhesive layer, the holding layer, the cover layer, and the conductive wire are formed.
  • the dog '(age 10 months, male, beagle) was given general anesthesia, and then reached the chest cavity with the 4th intercostal thoracotomy in the lower left supine position.
  • the pericardium was incised to reach the pericardium, and the wire created above was applied to the left ventricle.
  • the chest wall was punctured, the connector pin was taken out of the body, the pericardium was sutured closed, the chest wall was closed, and the operation was completed. Wire one
  • the basing threshold was measured over time on the day of surgery, on the 1st, 3rd, 5th, 7th, and 14th days after surgery. The results are shown in Table 1. Although a slight increase in the pacing threshold was observed, it was confirmed that it could operate without any problems for 14 days. On the 4th day after surgery, the wire was pulled out and it was confirmed that it was pulled out without resistance. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the ear, no cardiac pericardial hemorrhage was observed by cardiac B ultrasound, and no signs of cardiac tambonase, pericardial thickening, or myocardial dilatation were observed.
  • PLCA lactic acid-strength prolactone copolymer
  • the obtained film had a concavo-convex portion in which pores having a pore diameter of about 4.5 were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and a non-penetrating film having a thickness of 10 im.
  • Fig. 12 shows a photomicrograph of the uneven part of the film. This film was heat-treated at 60 at 10 minutes, cut into a 3 cm diameter circle, and the center was cut out with a 6 mm biopsy.
  • a smooth film having a diameter of 3 cm was produced in the same manner as the cover layer.
  • the film thickness was 42 im.
  • the center was cut out with a biopsy with a diameter of 6 mm to produce a window for the electrode.
  • the conductor was placed so that the electrode was at the center of the cover layer, and the conductor was pressed onto the cover layer with a cotton swab soaked in methylene chloride.
  • the holding layer was overlaid on the electrode side of the cover layer and again heat treated at 60 ° C for 10 minutes. Furthermore, an adhesive layer is placed on the upper surface of the holding layer so that the concavo-convex part becomes the outermost layer, and heat-treated at 60 ° C. for 10 minutes, and shown in FIG. A wire having a cross-sectional structure was produced.
  • Example 1 The same operation check operation as in Example 1 was performed except that Heart Wire (Model 6 4 92: Medtronic) was used as a test substance. Table 1 shows the results (average soil standard deviation for each measurement day for a total of 7 measurements). table 1
  • the wire patch of the present invention is a film mainly composed of a biodegradable polymer.
  • the electrode can be easily removed from the surface of the heart after a certain period of time has passed since it has broken down in the body. Therefore, according to the wire of the present invention, the incidence of complications can be reduced, and the patient's QOL (Quality of life) can be improved.
  • the wire of the present invention does not need to be sewn to the myocardium, it is extremely easy to install. Therefore, the stress of the surgeon during the operation can be reduced, and the operation time can be shortened.
  • the wire of the present invention has an advantage that it can be used without considering the influence of the adhesive on the human body because the electrode can be fixed to the heart without using an adhesive or the like. Industrial applicability
  • the wire 1 of the present invention can fix the electrode to the heart tissue without sewing the electrode to the heart tissue, it is easy to change the fixing portion, and when the wire is removed, damage to the heart and blood vessels caused by the coil There is no myocardial dehiscence by sewing thread, and it is useful as a wire for cardiac pacemakers.

Abstract

It is intended to provide a wire for cardiac pacemakers whereby electrodes can be fixed to the cardiac surface without stitching on the cardiac muscle. A wire for cardiac pacemakers which comprises a patch having an adhesive layer and a conductor wire having an electrode at the front end thereof, wherein a) the adhesive layer is a film which is mainly made of a biodegradable polymer and has, on one surface (face A) serving as the adhesive face, peaks and valleys at a ratio of from 1 to 100% of the total surface area of the face A, and b) the distal electrode is exposed in the adhesive layer in the face A side, and a patch and a film to be used in the wire.

Description

明 細 書 心臓ペースメーカ一用ワイヤー  Memo book Heart pacemaker wire
技術分野 Technical field
本発明は、 一時的心臓ペースメーカー用ワイヤ一に関する。 さらに詳しくは、 心臓組織に電極を縫着することなく、 心臓組織に電極を固定することができる心 臓ペースメーカー用ワイヤーに関する。 背景技術  The present invention relates to a temporary cardiac pacemaker wire. More specifically, the present invention relates to a heart pacemaker wire that can fix an electrode to heart tissue without sewing the electrode to heart tissue. Background art
心臓外科手術後に、 一時的ペースメーカー用の心筋電極および導線を留置する ことは、 術中 ·術後の不整脈の診断および治療、 さらには不測の事態に対処でき る有効な手段として、 定常的に行われている。 この場合、 電極は心筋に直接針で 縫着糸をかけ縫着して固定している。 この一時的ペースメーカーの心筋電極は、 手術後、 患者の容態が安定した後、 体外に引き抜く必要がある。  Implanting temporary pacemaker myocardial electrodes and leads after cardiac surgery is routinely performed as an effective means of diagnosing and treating arrhythmia during and after surgery, and to cope with unforeseen circumstances. ing. In this case, the electrode is fixed by applying a sewing thread directly to the myocardium with a needle. This temporary pacemaker myocardial electrode needs to be pulled out of the body after surgery after the patient's condition has stabilized.
しかし、 電極はコイル状のワイヤ一で心筋に縫着されているので、 まれではあ るが抜去時にコイルによる心臓、 血管の損傷や縫着糸による心筋の裂開により大 量出血、 心タンボナーゼなど、 致命的な合併症を引き起こすことがある。  However, since the electrode is sewn to the myocardium with a coiled wire, it is rare, but when it is removed, the heart and blood vessels are damaged by the coil and the myocardium is cleaved by the suture thread. May cause fatal complications.
また、 固定後に閾値などのデ一夕不良あるいはベーシング不良が起こった場合、 固定箇所を変更する必要がある。 しかし、 固定箇所を変更するには心筋に固着し た縫合糸を切ることが必要であり容易ではない。  In addition, if there is a failure in the threshold or other basing failure after fixing, it is necessary to change the fixing location. However, changing the fixation site requires cutting the suture that is attached to the myocardium, which is not easy.
そのため、 接着剤層で被覆されたパッチを用いて心臓表面に電極を固定するこ とが提案されている （特許文献 1参照)。 しかし、 かかる提案は、 パッチと接着 剤層との接着性および接着剤層と心臓表面との接着性のバランスを充分検討しな ければ、 実用上支障が生じる場合がある。 また接着剤の生体へ与える影響も無視 できない。  For this reason, it has been proposed to fix an electrode on the heart surface using a patch coated with an adhesive layer (see Patent Document 1). However, such a proposal may cause practical problems if the balance between the adhesiveness between the patch and the adhesive layer and the adhesiveness between the adhesive layer and the heart surface is not fully studied. Also, the effect of adhesives on the living body cannot be ignored.
(特許文献 1 ) 特開 2 0 0 2— 4 5 3 4 5号公報 発明の開示 本発明は、 心筋に縫着することなく、 心臓表面に電極を固定することが可能な 心臓ペースメーカ "用ワイヤー （以下、 ワイヤーと略することがある） を提供す ることを目的とする。 また、 本発明は、 生体へ悪影響を与えることがなく、 心臓 表面への接着性が良好なワイヤ一を提供することを目的とする。 さらに、 本発明 は、 心臓、 血管など損傷を引き起こすことなく抜去することができるワイヤーを 提供することを目的とする。 加えて、 本発明は、 該ワイヤーに用いるパッチおよ びフィルムを提供することを目的とする。 また本発明は、 心臓ペースメーカー用 ワイヤーの設置方法を提供することを目的とする。 また本発明は心臓ペースメ一 カー用ワイヤーを用いた心臓のベーシング方法を提供することを目的とする。 本発明者は、 生分解性ポリマーから主としてなり、 一方の表面に凹凸部を有す るフィルムが、 その凹凸部の作用により心臓表面への接着性が良好であることを 見出し本発明を完成した。 また生分解性ポリマーは、 心臓表面に接着した後、 所 定の期間が経過すると分解が進み、 電極を心臓表面から組織を損傷することなく 容易に取り外すことができることを見出し本発明を完成した。 (Patent Document 1) Japanese Patent Laid-Open No. 2000-45 3 4 5 Disclosure of Invention An object of the present invention is to provide a “wire for cardiac pacemaker” (hereinafter sometimes abbreviated as “wire”) capable of fixing an electrode to the surface of the heart without being sewn to the myocardium. It is an object of the present invention to provide a wire having good adhesion to the surface of the heart without adversely affecting the living body, and the present invention can be extracted without causing damage to the heart, blood vessels, etc. In addition, an object of the present invention is to provide a patch and a film used for the wire, and to provide a wire for a cardiac pacemaker. Another object of the present invention is to provide a heart basing method using a cardiac pacemaker wire. The inventors found that a film mainly composed of a biodegradable polymer and having an uneven portion on one surface has good adhesion to the heart surface due to the action of the uneven portion, and completed the present invention. It was found that the biodegradable polymer was decomposed after a predetermined period of time after adhering to the heart surface, and the present invention was completed by finding that the electrode could be easily removed from the heart surface without damaging the tissue.
即ち本発明は、 接着層を有するパッチ、 並びに末端に電極を有する導線からな る心臓ペースメーカー用ワイヤーであって、  That is, the present invention is a cardiac pacemaker wire comprising a patch having an adhesive layer and a lead having an electrode at its end,
a ) 接着層は、 生分解性ポリマーから主としてなるフィルムであり、 一方の表面 を接着面 （八面） とし、 A面にはその全表面積に対して 1〜1 0 0 %の割合で凹 凸部を有し、 a) The adhesive layer is a film mainly composed of a biodegradable polymer. One surface is the adhesive surface (eight surfaces), and the A surface is concave and convex at a rate of 1 to 100% of the total surface area. Part
b ) 電極は、 接着層の A面側に露出しているワイヤーである。 b) The electrode is a wire exposed on the A side of the adhesive layer.
本発明は、 心臓表面に電極を接着させるためのパッチであって、 接着層を有し、 該接着層は、 生分解性ポリマーから主としてなるフィルムであり、 一方の表面を 接着面 （八面） とし、 A面にはその全表面積に対して 1〜1 0 0 %の割合で凹凸 部を有するパッチである。  The present invention is a patch for adhering an electrode to the surface of a heart, and has an adhesive layer, and the adhesive layer is a film mainly composed of a biodegradable polymer, and one surface has an adhesive surface (eight surfaces). And the A surface is a patch having uneven portions at a ratio of 1 to 100% of the total surface area.
本発明は、 生分解性ポリマーから主としてなるフィルムであって、 少なくとも 一方の表面は、 孔径 0 . 1〜2 0 の細孔がハニカム状に配置された凹凸構造 を有する心臓表面への電極固定用のフィルムである。  The present invention is a film mainly composed of a biodegradable polymer, wherein at least one surface has an uneven structure in which pores having a pore diameter of 0.1 to 20 are arranged in a honeycomb shape for fixing an electrode to a heart surface It is a film.
また本発明は、 接着層の A面を心臓側にして、 パッチを心臓表面に貼付するこ とからなる上記心臓べ一スメーカー用ワイヤーの設置方法を包含する。 また本発 明は、 上記心臓ペースメーカー用ワイヤーを用いた心臓のぺ一シング方法を包含 する。 図面の簡単な説明 In the present invention, the patch is applied to the heart surface with the side A of the adhesive layer facing the heart. And a method of installing the wire for the heart base maker. The present invention also includes a method for pacing the heart using the above-mentioned cardiac pacemaker wire. Brief Description of Drawings
図 1 本発明のワイヤーの一例の外観略図である。  FIG. 1 is a schematic external view of an example of the wire of the present invention.
図 2 本発明のワイヤーの一例の断面略図である。  FIG. 2 is a schematic cross-sectional view of an example of the wire of the present invention.
図 3 本発明のワイヤ一の一例の断面略図である。  FIG. 3 is a schematic cross-sectional view of an example of a wire according to the present invention.
図 4 本発明のワイヤーの一例の断面略図である。  FIG. 4 is a schematic cross-sectional view of an example of the wire of the present invention.
図 5 本発明のワイヤ一の一例の断面略図である。  FIG. 5 is a schematic cross-sectional view of an example of a wire according to the present invention.
図 6 本発明のワイヤーの一例の断面略図である。  FIG. 6 is a schematic cross-sectional view of an example of the wire of the present invention.
図 7 実施例 1で製造した接着層の凹凸部の顕微鏡写真である。  7 is a photomicrograph of the concavo-convex portion of the adhesive layer produced in Example 1. FIG.
図 8 実施例 3で製造した接着層の凹凸部の顕微鏡写真である。  FIG. 8 is a micrograph of the uneven portion of the adhesive layer produced in Example 3.
図 9 八二カム状の配置を示す略図である。  Fig. 9 is a schematic diagram showing an 82-cam configuration.
図 1 0 八二カム状の配置を示す略図である。  FIG. 10 is a schematic diagram showing an 82-cam configuration.
図 1 1 実施例 4で製造した接着層の凹凸部の顕微鏡写真である。  FIG. 11 is a photomicrograph of the uneven part of the adhesive layer produced in Example 4.
図 1 2 実施例 5で製造した接着層の凹凸部の顕微鏡写真である。  FIG. 12 is a photomicrograph of the concavo-convex portion of the adhesive layer produced in Example 5.
符号の説明 Explanation of symbols
1 髓 ϋ  1 髓 ϋ
2 凹凸部  2 Concavity and convexity
3 導線  3 conductor
4 電極  4 electrodes
5 電極用窓  5 Electrode window
6 保持層  6 Retaining layer
7 カバー層  7 Cover layer
8 胸壁穿刺用針 発明を実施するための最良の形態 本発明のパッチは、 心臓表面に電極を接着させるためのパッチであって、 接着 層を有し、 該接着層は、 生分解性ポリマーから主としてなるフィルムであり、 一 方の表面を接着面 （八面） とし、 A面にはその全表面積に対して 1〜100%の 割合で凹凸部を有するパッチである。 パッチの好ましい態様として、 接着層のみ の態様、 接着層およびカバー層を有する態様、 並びに接着層、 保持層およびカバ —層を有する態様が挙げられる。 いずれの態様においてもパッチの平均総厚さは 好ましくは 10〜300 m、 さらに好ましくは 10〜200 mである。 8 Chest wall puncture needle BEST MODE FOR CARRYING OUT THE INVENTION The patch of the present invention is a patch for adhering an electrode to the heart surface, and has an adhesive layer, and the adhesive layer is a film mainly composed of a biodegradable polymer. Eight sides) The A side is a patch having irregularities at a ratio of 1 to 100% of the total surface area. Preferred embodiments of the patch include an embodiment having only an adhesive layer, an embodiment having an adhesive layer and a cover layer, and an embodiment having an adhesive layer, a holding layer and a cover layer. In any embodiment, the average total thickness of the patch is preferably 10 to 300 m, more preferably 10 to 200 m.
(接着層）  (Adhesive layer)
接着層は、 生分解性ポリマーから主としてなるフィルムである。 フィルムは、 ポリマー成分として、 好ましくは 80〜100重量％、 より好ましくは 90〜1 00重量％の生分解性ポリマーを含有する。  The adhesive layer is a film mainly composed of a biodegradable polymer. The film preferably contains 80 to 100% by weight, more preferably 90 to 100% by weight of biodegradable polymer as a polymer component.
生分解性ポリマーとしては、 脂肪族ポリエステル、 脂肪族ポリカーボネートが 挙げられる。 脂肪族ポリエステルとして、 ポリ乳酸、 乳酸ーグリコール酸共重合 体、 ポリヒドロキシ酪酸、 ポリ力プロラクトン、 乳酸—力プロラクトン共重合体、 ポリエチレンアジペート、 ポリブチレンアジペートなどが挙げられる。 脂肪族ポ リカーポネートとして、 ポリブチレンカーボネー卜、 ポリエチレンカーボネー卜 等が挙げられる。 また、 これらの共重合体、 混合物でもよい。 中でも、 ポリ乳酸、 乳酸ーグリコール酸共重合体、 ポリ力プロラクトン、 乳酸一力プロラクトン共重 合体が好ましい。 乳酸ーグリコール酸共重合体の場合、 共重合モル比 （乳酸ノグ リコール酸） は、 好ましくは 1Z99〜99Z1、 より好ましくは 10Z90〜 90/10, さらに好ましくは 25 75〜75 25である。 乳酸一力プロラ クトン共重合体の場合、 共重合モル比 （乳酸 Z力プロラクトン） は、 好ましくは 1Z99〜99/1、 より好ましくは 5/95〜95Z5、 さらに好ましくは 1 0Z90〜90 10である。  Examples of biodegradable polymers include aliphatic polyesters and aliphatic polycarbonates. Examples of the aliphatic polyester include polylactic acid, lactic acid-glycolic acid copolymer, polyhydroxybutyric acid, poly strength prolactone, lactic acid-force prolactone copolymer, polyethylene adipate, and polybutylene adipate. Examples of the aliphatic polycarbonate include polybutylene carbonate, polyethylene carbonate and the like. Moreover, these copolymers and a mixture may be sufficient. Of these, polylactic acid, lactic acid-glycolic acid copolymer, polystrength prolactone, and lactic acid-strength prolactone copolymer are preferable. In the case of a lactic acid-glycolic acid copolymer, the copolymerization molar ratio (lactic acid glycolic acid) is preferably 1Z99 to 99Z1, more preferably 10Z90 to 90/10, and even more preferably 25 75 to 7525. In the case of a lactic acid monostrength prolacton copolymer, the copolymerization molar ratio (lactic acid Z force prolactone) is preferably 1Z99 to 99/1, more preferably 5/95 to 95Z5, and even more preferably 10 Z90 to 90 10 is there.
フィルムは、 ポリマー成分として生分解性ポリマー以外の他のポリマーを含有 していてもよい。 他のポリマーとして、 例えばポリスチレン、 ポリビニルアルコ ール、 ポリ（エチレンーコービニルアセテート)、 ポリ（ヒドロキシェチルメ夕クリ レート)、 などのビニル系ポリマーやこれらのコポリマー、 ポリ（カーボネート)、 ポリ（ウレタン)、 ナイロンなどの縮合系ポリマーやこれらのコポリマーなどの生 体適合性ポリマーが挙げられる。 フィルムは、 好ましくは 0〜2 0重量％、 より 好ましくは 0〜 1 0重量％の生体適合性ポリマーで構成される。 The film may contain a polymer other than the biodegradable polymer as a polymer component. Other polymers include, for example, polystyrene, polyvinyl alcohol, poly (ethylene-covinyl acetate), poly (hydroxyethyl methacrylate). Rate), vinyl-based polymers and copolymers thereof, poly (carbonates), poly (urethanes), condensation polymers such as nylon, and biocompatible polymers such as these copolymers. The film is preferably composed of 0 to 20% by weight, more preferably 0 to 10% by weight of biocompatible polymer.
フィルム中にはリン脂質を含有していてもよい。 リン脂質としては、 動物組織 から抽出したものでも、 また人工的に合成して製造したものでもその起源を問う ことなく使用できる。 リン脂質としてはホスファチジルエタノールァミン、 ホス ファチジルコリン、 ホスファチジルセリン、 ホスファチジルグリセロールおよび それらの誘導体からなる群から選択されてなる少なくとも一種であることが好ま しい。 より好ましくはホスファチジルエタノールアミン類であり、 さらに好まし くは L—α—ホスファチジルエタノールァミン一ジォレオイルである。  The film may contain a phospholipid. As phospholipids, those extracted from animal tissues or artificially synthesized can be used without regard to their origin. The phospholipid is preferably at least one selected from the group consisting of phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, phosphatidylglycerol and derivatives thereof. More preferred are phosphatidylethanolamines, and more preferred is L-α-phosphatidylethanolamine monooleoyl.
接着層は、 1 0 0重量部の生分解性ポリマーに対し、 好ましくは 0 . 1〜1 0 0重量部、 より好ましくは 0 . 2〜1 0重量部、 さらに好ましくは 0 . 5〜2重 量部のリン脂質を含有することが好ましい。 またフィルムには本発明の目的を損 なわない範囲で、 例えば柔軟剤、 接着性向上剤や薬剤などの他の成分を含んでい ても良い。  The adhesive layer is preferably 0.1 to 100 parts by weight, more preferably 0.2 to 10 parts by weight, and still more preferably 0.5 to 2 parts by weight with respect to 100 parts by weight of the biodegradable polymer. It is preferred to contain an amount of phospholipid. Further, the film may contain other components such as a softening agent, an adhesion improver, and a drug as long as the object of the present invention is not impaired.
接着層は、 一方の表面を接着面 （八面） とし、 他方の表面を B面とする。 A面 にはその全表面積に対して 1〜 1 0 0 %の割合で凹凸部を有する。 凹凸部の割合 は、 A面にはその全表面積に対して、 好ましくは 1 0〜1 0 0 %、 より好ましく は 2 0〜 1 0 0 %である。 A面の周辺部には凹凸部を有していることが好ましい。 凹凸部は、 好ましくは孔径 0 . 1〜2 0 m、 より好ましくは 0 . 5〜1 8 m、 さらに好ましくは 1〜1 5 の細孔を有する。 細孔は均一に配置されてい ることが好ましい。 孔径は凹凸部表面における細孔の直径のことを言う。  The adhesive layer has one surface as the adhesive surface (eight surfaces) and the other surface as the B surface. The A surface has irregularities at a ratio of 1 to 100% with respect to the total surface area. The proportion of the concavo-convex portion is preferably 10 to 100%, more preferably 20 to 100% with respect to the total surface area of the A surface. It is preferable that the peripheral part of A surface has an uneven part. The concavo-convex portion preferably has pores having a pore diameter of 0.1 to 20 m, more preferably 0.5 to 18 m, and still more preferably 1 to 15. The pores are preferably arranged uniformly. A pore diameter means the diameter of the pore in the uneven | corrugated | grooved part surface.
また細孔は、 ハニカム状に配置されていることが好ましい。 本発明においてハ 二カム状の配置とは、 図 9に示すように正六角形が隣接されて配置された構造の ことを言う。 従って、 凹凸部の細孔同士の位置関係は、 図 9に示す正六角形同士 の位置関係と対応する。 従って、 一つ細孔の周辺には 6個の細孔が配置されてい る。 図 1 0に円形の細孔がハニカム状に配置された状態を示す。 細孔は、 実質的 に同一形状であることが好ましい。 従って、 複数の細孔は実質的に同一形状であ り、 一つ細孔の周辺には 6個の細孔が配置されていることが好ましい。 細孔の形 は問わないが円形であることが好ましい。 細孔の半径を rとし、 隣接する細孔の 中心間の距離を aとすると、 rと aとは、 1 < a Z 2 r < 2で表されることが好 ましい。 The pores are preferably arranged in a honeycomb shape. In the present invention, the double cam-like arrangement means a structure in which regular hexagons are arranged adjacent to each other as shown in FIG. Therefore, the positional relationship between the pores of the concavo-convex portion corresponds to the positional relationship between regular hexagons shown in FIG. Therefore, six pores are arranged around one pore. FIG. 10 shows a state in which circular pores are arranged in a honeycomb shape. The pores are substantial Are preferably the same shape. Therefore, it is preferable that the plurality of pores have substantially the same shape, and six pores are arranged around one pore. The shape of the pores is not limited but is preferably circular. If the radius of the pore is r and the distance between the centers of adjacent pores is a, then r and a are preferably expressed as 1 <a Z 2 r <2.
細孔の深さは、 好ましくは 0 . 1〜2 0 、 より好ましくは 0 . 5〜1 8 m、 さらに好ましくは 1〜1 5 mである。 また凹凸部は、 繊毛状、 円柱状、 角 柱状、 平板状などの突起で形成されていてもよい。 突起の高さ （H) と凸部の最 小厚みあるいは最小直径 （D) の比 （HZD) は 1より大きいことが好ましい。 凸部の大きさは、 最小厚みあるいは最小直径が 1 0 nmから 5 0 ^ mであること が好ましい。 凸部の高さは、 1 0 nmから 1 0 0 mであることが好ましい。 接着層の厚さは、 好ましくは 1 0〜3 0 0 /x m、 さらに好ましくは 1 0〜2 0 0 / mである。 接着層の形状は、 円形、 楕円形、 多角形であることが好ましい。 大きさは、 直径若しくは長径で 2〜5 c m、 対角線の長さで 2〜 5 c m程度であ る。  The depth of the pores is preferably 0.1 to 20 m, more preferably 0.5 to 18 m, and still more preferably 1 to 15 m. Further, the concavo-convex portion may be formed of a projection such as a cilia shape, a columnar shape, a prismatic shape, or a flat plate shape. The ratio (HZD) of the height (H) of the protrusion to the minimum thickness or the minimum diameter (D) of the protrusion is preferably larger than 1. As for the size of the convex portion, the minimum thickness or the minimum diameter is preferably 10 nm to 50 ^ m. The height of the convex portion is preferably 10 nm to 100 m. The thickness of the adhesive layer is preferably 10 to 300 / xm, and more preferably 10 to 200 / m. The shape of the adhesive layer is preferably a circle, an ellipse, or a polygon. The size is about 2-5 cm in diameter or major axis, and about 2-5 cm in diagonal length.
本発明の接着層を構成する凹凸部を有するフィルムは好ましくは、 以下の方法 で製造することができる。 即ち、 該フィルムは、  The film having an uneven portion constituting the adhesive layer of the present invention can be preferably produced by the following method. That is, the film
( 1 ) ポリマー成分、 リン脂質および有機溶媒を含有するポリマー溶液を基板上 にキャストし、 液状膜を形成する工程、  (1) A step of casting a polymer solution containing a polymer component, a phospholipid and an organic solvent on a substrate to form a liquid film,
( 2 ) 液状膜に相対湿度 3 0〜1 0 0 %の水蒸気を吹き付け、 有機溶媒を蒸発さ せると共に、 水蒸気を液状膜表面に結露させ水滴を形成させ、 ついで、 水滴を蒸 発させる工程、  (2) A process of spraying water vapor with a relative humidity of 30 to 100% on the liquid film to evaporate the organic solvent, condensing the water vapor on the surface of the liquid film to form water droplets, and then evaporating the water droplets.
により製造することができる。 Can be manufactured.
上記の方法においては液状膜上に微小な水滴粒子を形成させることが必須であ り、 使用する有機溶媒は非水溶性である必要がある。 よって有機溶媒として、 ク ロロホルム、 塩化メチレン等のハロゲン系有機溶剤、 ベンゼン、 トルエン、 キシ レン等の芳香族炭化水素、 酢酸ェチル、 酢酸ブチル等のエステル類、 メチルイソ プチルケトン、 などの非水溶性ケトン類、 二硫ィ匕炭素などが挙げられる。 これら の有機溶媒は単独またはこれらの溶媒を混合して使用してもよい。 In the above method, it is essential to form fine water droplet particles on the liquid film, and the organic solvent to be used must be water-insoluble. Therefore, as organic solvents, halogen-based organic solvents such as chloroform and methylene chloride, aromatic hydrocarbons such as benzene, toluene and xylene, esters such as ethyl acetate and butyl acetate, and water-insoluble ketones such as methyl isobutyl ketone , Carbon dioxide, etc. these These organic solvents may be used alone or as a mixture of these solvents.
ポリマー溶液中の、 ポリマ一成分とリン脂質とを併せた溶質濃度は好ましくは The solute concentration of one polymer component and phospholipid in the polymer solution is preferably
0. 0 1〜1 0重量％、 より好ましくは 0. 0 5〜5重量％でぁる。 溶質濃度が 0 . 0 1重量％より低いと得られるフィルムの力学強度が不足し望ましくない。 また 1 0重量％を超えると溶質液濃度が高くなりすぎ、 十分な凹凸構造が得られ ないことがある。 0.01 to 10% by weight, more preferably 0.05 to 5% by weight. If the solute concentration is lower than 0.01% by weight, the resulting film has insufficient mechanical strength, which is not desirable. On the other hand, if it exceeds 10% by weight, the solute concentration becomes too high, and a sufficient uneven structure may not be obtained.
ポリマ一溶液中のポリマー成分とリン脂質との重量比は 1 ： 1から 1， 0 0 0 ： 1であることが好ましい。 接着層表面に凹凸を形成させるため、 フィルム中 にはリン脂質を含有させることが好ましい。 特にハニカム状の細孔を形成させる ために、 リン脂質を含有させることが好ましい。 より好ましくは 1 0 ： 1〜5 0 0 ： 1であり、 さらに好ましくは 5 0 ： ：!〜 2 0 0 ： 1である。 リン脂質がポリ マー成分に対して 1 , 0 0 0分の 1未満では均一なハニカム構造が得られないこ とがある。 また、 該重量比が 1 ： 1を超えるとフィルムとしての自己支持性を有 さないことがあり、 コストも高く、 経済性に乏しいため好ましくない。  The weight ratio of the polymer component to the phospholipid in the polymer solution is preferably 1: 1 to 1,000: 1. In order to form irregularities on the surface of the adhesive layer, the film preferably contains a phospholipid. In particular, it is preferable to contain a phospholipid in order to form honeycomb-shaped pores. More preferably, it is 10: 1 to 5500: 1, and more preferably 500 ::! To 2200: 1. If the phospholipid is less than 1 / 100th of the polymer component, a uniform honeycomb structure may not be obtained. On the other hand, if the weight ratio exceeds 1: 1, the film may not have a self-supporting property, and the cost is high, and the economical efficiency is poor.
凹凸部を有する接着層の製造法はキャス卜工程と蒸発工程を含む。  The manufacturing method of the contact bonding layer which has an uneven | corrugated | grooved part includes a casting process and an evaporation process.
キャスト工程は、 ポリマー溶液を基板上にキャストし、 液状膜を得る工程であ る。 かかる工程はポリマー溶液を基板上に流し込むことで行なうことができる。 基板としては、 無機材料、 ポリマーまたは液体を使用することができる。 無機 材料として、 ガラス、 金属、 シリコンウェハ一等が挙げられる。 ポリマーとして、 ポリプロピレン、 ポリエチレン、 ポリエーテルケトン等が挙げられる。 液体とし て、 水、 流動パラフィン、 液状ポリエーテル等が挙げられる。  The casting process is a process in which a polymer solution is cast on a substrate to obtain a liquid film. Such a process can be performed by pouring the polymer solution onto the substrate. As the substrate, inorganic materials, polymers, or liquids can be used. Examples of inorganic materials include glass, metal, and silicon wafers. Examples of the polymer include polypropylene, polyethylene, and polyether ketone. Examples of the liquid include water, liquid paraffin, and liquid polyether.
蒸発工程は、 液状膜に相対湿度 3 0〜1 0 0 %の水蒸気を吹き付け、 有機溶媒 を蒸発させる工程である。 相対湿度は好ましくは 5 0〜 9 5 %、 より好ましくは 5 0〜 9 0 %である。 相対湿度が 3 0 %未満では液状膜上への結露が不十分にな り好ましくない。 雰囲気温度は、 有機溶媒が徐々に蒸発する温度であればよく、 好ましくは 1 0〜3 0 °C、 より好ましくは室温である。  The evaporation process is a process in which water vapor with a relative humidity of 30 to 100% is sprayed on the liquid film to evaporate the organic solvent. The relative humidity is preferably 50 to 95%, more preferably 50 to 90%. A relative humidity of less than 30% is not preferable because condensation on the liquid film is insufficient. The ambient temperature may be a temperature at which the organic solvent gradually evaporates, and is preferably 10 to 30 ° C., more preferably room temperature.
この工程では、 有機溶媒が蒸発すると共に、 水蒸気が液状膜表面に結露し.水滴 が形成される。 これは有機溶媒が蒸発するとき潜熱を奪い、 液状膜表面の温度が 下がり、 雰囲気中の水蒸気が液状膜表面に結露するからである。 ポリマー中の親 水基の働きによって結露した水蒸気と有機溶媒との間の表面張力が減少し、 結露 した水蒸気は凝集し微小な水滴となる。 有機溶媒が蒸発するに伴い、 液状膜表面 にへキサゴナル配置で最密充填された微小な水滴が並ぶ。 有機溶媒の蒸発が進む に伴い、 液状膜中に水滴は沈下し、 液状膜の表面は、 ポリマーに囲まれた水滴が 規則正しく配置された構造となり、 液状膜中の有機溶媒が完全に蒸発し、 フィル ムを形成する。 ついで、 結露により生じた水滴を蒸発させる。 水滴が蒸発するこ とにより、 ポリマー表面に均一に配置された細孔が残る。 In this process, the organic solvent evaporates and water vapor condenses on the liquid film surface, forming water droplets. This takes away latent heat when the organic solvent evaporates, and the temperature of the liquid film surface This is because water vapor in the atmosphere is condensed on the liquid film surface. The surface tension between the condensed water vapor and the organic solvent is reduced by the action of the hydrophilic group in the polymer, and the condensed water vapor aggregates into minute water droplets. As the organic solvent evaporates, microscopic water droplets packed in a hexagonal arrangement are arranged on the liquid film surface. As the evaporation of the organic solvent progresses, the water droplets sink into the liquid film, and the surface of the liquid film has a structure in which the water droplets surrounded by the polymer are regularly arranged. The organic solvent in the liquid film completely evaporates, Form a film. Next, the water droplets generated by condensation are evaporated. The water droplets evaporate, leaving pores that are uniformly arranged on the polymer surface.
得られるフィルムの表面には、 孔径 0 . 1〜2 0 mの細孔が規則正しくハニ カム状に形成される。 細孔の孔径は、 好ましくは 0 . 5〜1 8 / mであり、 より 好ましくは：！〜 1 5 μπιである。  On the surface of the obtained film, pores having a pore diameter of 0.1 to 20 m are regularly formed in a honeycomb shape. The pore diameter is preferably 0.5 to 18 / m, more preferably :! ~ 1 5 μπι.
フィルムの厚さが充分厚い場合は、 基板に接していた裏面は細孔が貫通してい ない平らな面となる。 この場合、 細孔の深さは、 好ましくは 0 . l〜2 0 ;ii mで あり、 より好ましくは 0 . 5〜1 8 /z mである。 また、 膜厚が水滴の大きさより も薄い場合は、 細孔が貫通したフィルムが得られる。  When the film is sufficiently thick, the back surface that was in contact with the substrate is a flat surface with no pores. In this case, the depth of the pores is preferably 0.1 to 20; iim, and more preferably 0.5 to 18 / zm. In addition, when the film thickness is thinner than the size of the water droplet, a film having fine pores is obtained.
心臓表面に電極を固定するのに特に適しているのは、 前述の生分解性ポリマー から主としてなるフィルムであって、 少なくとも一方の表面は、 孔径 0 . 1〜2 0 mの細孔がハニカム状に配置された凹凸構造を有するフィルムである。  Particularly suitable for fixing electrodes on the heart surface is a film mainly composed of the aforementioned biodegradable polymer, and at least one surface has pores having a pore diameter of 0.1 to 20 m in a honeycomb shape. It is a film which has the uneven structure arrange | positioned in.
接着層を構成する凹凸部を有するフィルムは、 上記方法の他、 凹凸を有した铸 型を用いた押出成形、 リソグラフィー、 フィルム形成後ナノインプリンティング、 またレーザー加工などにより製造することができる。  In addition to the method described above, the film having the concavo-convex portion constituting the adhesive layer can be produced by extrusion using a mold having concavo-convex, lithography, nanoimprinting after film formation, laser processing, or the like.
(電極用窓）  (Electrode window)
接着層は、 A面から B面へ貫通する電極用窓を有することが好ましい。 この電 極用窓中に電極を配置し、 心臓表面に電極を接触させる。 また接着層を製造する 際に、 導線を液状膜中に存在させ、 電極を接着層の A面側に露出するように、 接 着層と導線を一体に成形してもよい。 電極が双極の場合は両電極が接触可能とな らない限り、 電極用窓から二つの電極が露出するようにしても良いし、 各電極ご とに電極用窓を設けても良い。 (カバー層） The adhesive layer preferably has an electrode window penetrating from the A surface to the B surface. An electrode is placed in the electrode window, and the electrode is brought into contact with the heart surface. Further, when the adhesive layer is manufactured, the adhesive layer and the conductor may be integrally formed so that the conductor is present in the liquid film and the electrode is exposed on the A surface side of the adhesive layer. When the electrodes are bipolar, the two electrodes may be exposed from the electrode window as long as both electrodes cannot be contacted, or an electrode window may be provided for each electrode. (Cover layer)
本発明のパッチは、 電極がパッチの外表面に露出することを防止するため接着 層の B面上に、 カバー層を有することが好ましい。 カバー層は前述の生分解性ポ リマーから主としてなるフィルムであることが好ましい。 カバー層と接着層とは 同種のポリマーでも異種のポリマーでもよい。 カバー層を形成する生分解性ポリ マーは、 接着層を形成する生分解性ポリマーよりも分解され易いものが好ましい。 具体的には、 接着層が乳酸一力プロラクトン共重合体で形成されるとき、 カバー 層は乳酸一ダリコール酸共重合体で形成されることが好ましい。  The patch of the present invention preferably has a cover layer on the B surface of the adhesive layer in order to prevent the electrode from being exposed to the outer surface of the patch. The cover layer is preferably a film mainly composed of the aforementioned biodegradable polymer. The cover layer and the adhesive layer may be the same polymer or different polymers. The biodegradable polymer that forms the cover layer is preferably one that is more easily decomposed than the biodegradable polymer that forms the adhesive layer. Specifically, when the adhesive layer is formed of a lactic acid monostrength prolactone copolymer, the cover layer is preferably formed of a lactic acid monodaricholic acid copolymer.
カバ一層は、 接着層のような凹凸部を有していてもよいが、 平滑なフィルムで あってもよい。 カバー層と接着層との間に導線を圧着することにより導線を固定 することができる。  The cover layer may have uneven portions such as an adhesive layer, but may be a smooth film. The conducting wire can be fixed by crimping the conducting wire between the cover layer and the adhesive layer.
カバー層の厚さは、 好ましくは 1 0〜3 0 0 w m、 さらに好ましくは 2 0〜2 0 0 / mである。 カバー層は電極用窓がない以外は接着層と同じ形状であること が好ましい。 カバー層は、 単層でもよく、 積層であってもよい。  The thickness of the cover layer is preferably 10 to 300 w m, and more preferably 20 to 200 / m. The cover layer preferably has the same shape as the adhesive layer except that there is no electrode window. The cover layer may be a single layer or a laminated layer.
カバー層は、 ポリマー成分および有機溶媒を含有するポリマー溶液を基板上に キャストし、 溶媒を除去するキャスト方法、 またはインフレーション押出成形法、 Tダイ押出成形法などの押出成形法、 力レンダ一法などにより製造することがで きる。 ポリマー成分および有機溶媒は、 接着層の製造に使用するものと同じもの を使用することができる。 ポリマー溶液の溶質濃度は、 好ましくは 1〜4 0重 量％、 より好ましくは 5〜3 0重量％である。  For the cover layer, a polymer solution containing a polymer component and an organic solvent is cast on a substrate and the solvent is removed, or an extrusion method such as an inflation extrusion method or a T-die extrusion method, a force render method, etc. Can be manufactured. The polymer component and the organic solvent can be the same as those used for the production of the adhesive layer. The solute concentration of the polymer solution is preferably 1 to 40% by weight, more preferably 5 to 30% by weight.
(保持層）  (Holding layer)
接着層を補強するために、 接着層の B面とカバー層との間に保持層を有するこ とが好ましい。 保持層は前述の生分解性ポリマーから主としてなるフィルムであ ることが好ましい。 保持層と接着層とは同種のポリマ一でも異種のポリマ一でも よい。 保持層は、 接着層のような凹凸部を有していても良いが、 平滑なフィルム であってもよい。 保持層と接着層との間に導線を圧着することにより導線を固定 することができる。  In order to reinforce the adhesive layer, it is preferable to have a holding layer between the B surface of the adhesive layer and the cover layer. The holding layer is preferably a film mainly composed of the aforementioned biodegradable polymer. The holding layer and the adhesive layer may be the same type of polymer or different types of polymers. The holding layer may have uneven portions such as an adhesive layer, but may be a smooth film. The lead wire can be fixed by pressing the lead wire between the holding layer and the adhesive layer.
保持層の厚さは、 好ましくは 1 0〜1 0 0 x m、 さらに好ましくは 2 0〜8 0 である。 保持層は接着層と同じ形状であることが好ましい。 保持層は、 単層 でもよく、 積層であってもよい。 The thickness of the holding layer is preferably 10 to 100 xm, more preferably 20 to 80. It is. The holding layer preferably has the same shape as the adhesive layer. The holding layer may be a single layer or a stacked layer.
保持層は、 ポリマー成分および有機溶媒を含有するポリマー溶液を基板上にキ ャストし、 溶媒を除去するキャスト方法、 またはインフレーション押出成形法、 Tダイ押出成形法などの押出成形法、 カレンダ一法などにより製造することがで きる。 ポリマー溶液の溶質濃度は、 好ましくは 1〜4 0重量％、 より好ましくは 5〜3 0重量％である。  The holding layer is a casting method in which a polymer solution containing a polymer component and an organic solvent is cast on a substrate and the solvent is removed, or an extrusion method such as an inflation extrusion method or a T-die extrusion method, a calendar method, etc. Can be manufactured. The solute concentration of the polymer solution is preferably 1 to 40% by weight, more preferably 5 to 30% by weight.
<ワイヤー > <Wire>
本発明のワイヤーは、 前述のパッチおよび導線から構成される。 導線は、 心臓 ペースメーカ一本体側から見て遠い位置に電極を有し、 心臓ペースメーカー本体 側にコネクタ一を有する。  The wire of this invention is comprised from the above-mentioned patch and conducting wire. The lead has an electrode at a position far from the heart pacemaker main body side, and a connector on the heart pacemaker main body side.
電極は接着層の A面側に露出している。 電極は心臓表面に接触して、 心臓べ一 スメーカ一からの電気信号を心筋に伝える。 電極は導電性の金属材料で形成され る。 電極は、 直径が導線と同程度で、 長さは l〜2 mm程度が好ましい。 これは、 心臓外科手術後の所定の期間が経過した後に、 心臓埋込ワイヤーを人体の組織を 損傷することなく体外に引き抜く必要があるためである。 電極は単極でも双極以 上でもよい。 双極以上の場合、 心臓ペースメーカ一本体に近い側の近位電極と、 遠い側の遠位電極の 2つ以上の電極を有することができる。  The electrode is exposed on the A side of the adhesive layer. The electrode contacts the heart surface and transmits the electrical signal from the heart base manufacturer to the heart muscle. The electrode is made of a conductive metal material. The electrode is preferably about the same diameter as the conductor and about 1 to 2 mm in length. This is because it is necessary to pull out the implanted cardiac wire outside the body without damaging human tissue after a predetermined period after cardiac surgery. The electrode may be monopolar or more than bipolar. In the case of bipolar or more, it can have two or more electrodes, a proximal electrode on the side closer to the heart pacemaker body and a distal electrode on the far side.
コネクタ一は、 心臓ペースメーカー本体へ接続するためのものである。 本発明 のワイヤーは、 心臓外科手術後、 胸壁を穿刺して体外の心臓ペースメーカー本体 と接続するため、 コネクターピンの末端には胸壁穿刺用針を設けることが好まし い。  The connector is for connection to the heart pacemaker body. Since the wire of the present invention punctures the chest wall after cardiac surgery and connects it to the cardiac pacemaker body outside the body, it is preferable to provide a chest wall puncture needle at the end of the connector pin.
導線の直径は好ましくは l mm未満、 さらに好ましくは 0 . 2〜0 . 8 mmで あり、 外表面は絶縁体で被覆されている。 長さは 4 0 0〜7 0 0 mm程度である。 本発明のワイヤ一を図 1〜6に基づき説明する。 図 1〜6は、 本発明のワイヤ 一の外観および断面構造を説明するための略図であり、 導線、 電極、 各層の大き さの縮尺は統一されていない。  The diameter of the conducting wire is preferably less than 1 mm, more preferably 0.2 to 0.8 mm, and the outer surface is covered with an insulator. The length is about 400 to 700 mm. The wire 1 of the present invention will be described with reference to FIGS. 1 to 6 are schematic diagrams for explaining the appearance and cross-sectional structure of the wire of the present invention, and the scales of the conductors, electrodes, and layers are not unified.
図 1は、 本発明のワイヤー （単極） の外観の一例である。 導線 （3 ) の末端に ある電極 （4) はパッチ中央に設けられた電極用窓に設置され、 もう一方の末端 には、 コネクターピンおよび胸壁穿刺用針 （8) がー体となり設置されている。 パッチは、 接着層 （1) およびカバー層 （7) により形成されている。 FIG. 1 is an example of the appearance of the wire (monopolar) of the present invention. At the end of the conductor (3) One electrode (4) is installed in an electrode window provided in the center of the patch, and a connector pin and a chest wall puncture needle (8) are installed at the other end. The patch is formed by an adhesive layer (1) and a cover layer (7).
図 2は、 本発明のワイヤーのパッチの断面の一例の略図である。 接着層 （1) の A面には凹凸部 （2) があり、 電極 （4) は、 カバー層 （7) に圧着され、 接 着層 （1) に開けられた電極用窓 （5) に配置され A面側で露出している。 導線 (3) は、 接着層 （1) とカバー層 （7) の間に圧着され固定されている。 ここ でカバー層または保持層は、 前述のとおり単層でも積層でも良い。  FIG. 2 is a schematic illustration of an example of a cross section of a wire patch of the present invention. There is an uneven part (2) on the A side of the adhesive layer (1), and the electrode (4) is crimped to the cover layer (7) and is opened on the electrode window (5) opened in the adhesive layer (1). Arranged and exposed on side A. The conducting wire (3) is fixed by being pressed between the adhesive layer (1) and the cover layer (7). Here, the cover layer or the holding layer may be a single layer or a laminate as described above.
図 3は、 図 2の態様において、 保持層 （6) が、 接着層 （1) の B面とカバー 層 （7) の間に積層された態様である。 導線 （3) は、 接着層 （1) と保持層 (6) との間に圧着され固定されている。 ここでカバー層または保持層は、 前述 のとおり単層でも積層でも良い。  FIG. 3 is an embodiment in which the holding layer (6) is laminated between the B surface of the adhesive layer (1) and the cover layer (7) in the embodiment of FIG. The conducting wire (3) is fixed by being pressed between the adhesive layer (1) and the holding layer (6). Here, the cover layer or the holding layer may be a single layer or a laminate as described above.
図 4は、 接着層 （1) の B面上に保持層 （6) が積層され、 保持層 （6) 上に カバ一層 （7) 力積層された態様である。 電極 （4) は、 カバ一層 （7) に圧着 されている。 導線 （3) は、 保持層 （6) とカバ一層 （7) との間に圧着され固 定されている。 ここでカバ一層または保持層は、 前述のとおり単層でも積層でも 良い。  FIG. 4 shows an embodiment in which the holding layer (6) is laminated on the B surface of the adhesive layer (1), and a cover layer (7) is laminated on the holding layer (6). The electrode (4) is crimped to the cover layer (7). The conducting wire (3) is pressed and fixed between the holding layer (6) and the cover layer (7). Here, the cover layer or the holding layer may be a single layer or a laminate as described above.
図 5は、 接着層 （1) を製造する際に、 導線 （3) を存在させ、 接着層 （1) 中に導線を配置した態様である。  FIG. 5 shows a state in which the conductor (3) is present when the adhesive layer (1) is manufactured, and the conductor is disposed in the adhesive layer (1).
図 6は、 図 5の態様において、 カバー層 （7) を積層した態様である。 ここで カバー層は、 前述のとおり単層でも積層でも良い。  FIG. 6 is an embodiment in which the cover layer (7) is laminated in the embodiment of FIG. Here, the cover layer may be a single layer or a laminate as described above.
(ワイヤ一の設置）  (Installing one wire)
本発明のワイヤーは、 胸骨正中切開を行い、 心臓に到達後、 心膜を切開し心嚢 内に達した後、 左心室、 左心房、 右心室または右心房のいずれかの表面に貼り付 け使用することができる。  The wire of the present invention performs a median sternotomy, and after reaching the heart, incises the pericardium and reaches the pericardium, and then attaches it to the surface of the left ventricle, left atrium, right ventricle, or right atrium. Can be used.
従って本発明は、 接着層の A面を心臓側にして、 パッチを心臓表面に貼付する ことからなる心臓ペースメーカー用ワイヤ一の設置方法を包含する。 パッチを心 臓の温度付近まで温めた後、 パッチを心臓表面に貼付することが好ましい。 温め る温度は室温以上心臓の温度以下が好ましい。 パッチは、 温水や恒温槽などで温 めることができる。 パッチを心臓の温度付近まで温めることにより、 パッチの心 臓表面への接着性が向上する。 ここで接着層の A面に心臓表面への接着性を高め る剤を塗布してパッチを心臓表面に貼付することも好ましい。 Therefore, the present invention includes a method of installing a wire for a cardiac pacemaker, comprising attaching the patch to the heart surface with the side A of the adhesive layer facing the heart. It is preferable to apply the patch to the heart surface after the patch has been warmed to near the heart temperature. Warm The temperature is preferably from room temperature to the heart temperature. The patch can be heated in warm water or a thermostatic bath. By warming the patch to near the heart temperature, the adhesion of the patch to the heart surface is improved. Here, it is also preferable to apply a patch to the surface of the heart by applying an agent that enhances the adhesion to the heart surface to the side A of the adhesive layer.
本発明によれば、 本発明の心臓ペースメーカー用ワイヤーを設置する工程を含 む心臓の手術方法が提供される。 ワイヤーのパッチは、 その接着層の A面を心臓 側にして心臓表面に貼付する。 本発明の心臓ペースメーカ一用ワイヤーは、 心臓 手術中および術後における心臓の一時的べ一シング方法に用いることができる。 よって本発明によれば、 本発明の心臓ペースメーカ一用ワイヤーを用いた心臓の ベーシング方法が提供される。  According to the present invention, there is provided a cardiac surgery method including the step of installing the cardiac pacemaker wire of the present invention. The wire patch is applied to the heart surface with the side A of the adhesive layer facing the heart. The wire for a cardiac pacemaker of the present invention can be used in a method for temporarily basing the heart during and after cardiac surgery. Therefore, according to the present invention, there is provided a heart basing method using the wire for a cardiac pacemaker of the present invention.
手術は例えば以下の方法で行なうことができる。 即ち、 胸骨正中切開および心 膜を切開して心嚢内に到達し、 体外循環を確立後 （心拍動下手術の場合は体外循 環は行わない） 修復手術を施行する。 手術手技が終了し体外循環から離脱後、 あ るいは心拍動が再開した後、 本発明のパッチ電極を心臓表面に貼付する。 本パッ チは使用前に、 体温付近温度に温めることで、 より接着性を高めることも可能で ある。 パッチ電極は心膜で覆われるように、 心膜に沿って左心室側へ、 あるいは 横隔膜面に留置することが好ましい。 本パッチ電極はべ一シング閾値が良好でな い場合は別の場所へ移動することが可能である。 もう一方の胸壁穿刺用針の付い たペースメーカー本体を接続する側の末端は横隔膜面より腹直筋を貫通し、 皮膚 に出した後、 胸壁穿刺用釙を切り離し、 ペースメーカー本体に接続する。 手術終 了後、 2週間以内に心臓埋込ワイヤーは抜去する。 実施例  The operation can be performed, for example, by the following method. In other words, median sternotomy and pericardium are opened to reach the pericardium, and extracorporeal circulation is established (extracorporeal circulation is not performed for heartbeat surgery). After the surgical procedure is completed and the patient leaves the extracorporeal circulation, or after the heartbeat is resumed, the patch electrode of the present invention is applied to the heart surface. This patch can be made more adhesive by warming it to near body temperature before use. The patch electrode is preferably placed along the pericardium toward the left ventricle or on the diaphragm surface so as to be covered with the pericardium. The patch electrode can be moved to another location if the base threshold is not good. The end of the side connecting the pacemaker body with the other chest wall puncture needle penetrates the rectus abdominis muscle from the diaphragm surface and, after exiting the skin, cuts off the chest wall puncture sputum and connects it to the pacemaker body. The implanted cardiac wire should be removed within 2 weeks after the surgery. Example
実施例 1 Example 1
(カバー層）  (Cover layer)
1 5重量％に調製した、 乳酸ーグリコール酸共重合体 （P L GA、 分子量 9 0， 0 0 0、 共重合モル比 =乳酸 Zグリコール酸 = 7 5 2 5 ) ノクロロホルム溶液 をガラス基板上にキャストした後、 クロ口ホルムを室温で蒸発させフィルムを作 製し、 60°Cにて 10分間熱処理を行った。 膜厚は 48wmであった。 このフィ ルムを直径 4 cmの円形に切り出し、 カバー層を製造した。 1 Lactic acid-glycolic acid copolymer (PL GA, molecular weight 90, 0 00, copolymerization molar ratio = lactic acid Z glycolic acid = 7 5 2 5) prepared in 5% by weight was cast on a glass substrate After that, the black mouth form is evaporated at room temperature to make a film. And heat-treated at 60 ° C for 10 minutes. The film thickness was 48 wm. The film was cut into a 4 cm diameter circle to produce a cover layer.
(接着層）  (Adhesive layer)
乳酸—力プロラクトン共重合体 （PLCA、 分子量 163， 000、 共重合モ ル比 =乳酸ノ力プロラクトン =88Z12) のクロ口ホルム溶液 （5 g/L) に、 ホスファチジルエタノールアミンージォレオイルを PLCAに対し 1ノ 200の 割合 （重量） で混合し、 ポリマ一溶液を調製した。 ポリマー溶液をガラス基板上 にキャストし、 液状膜を得た。  Lactic acid-force prolactone copolymer (PLCA, molecular weight 163,000, copolymer mole ratio = lactate no-force prolactone = 88Z12) was added to a phosphatidylethanolamine-diolate in a clot mouth form solution (5 g / L). The oil was mixed with PLCA at a ratio of 1 to 200 (by weight) to prepare a polymer solution. The polymer solution was cast on a glass substrate to obtain a liquid film.
次に、 液状膜を室温、 湿度 70%の水蒸気を吹き付け、 溶媒を徐々に蒸発させ ると共に水蒸気を液状膜表面に結露させ水滴を形成させ、 ついで水滴を蒸発させ フィルムを調製した。  Next, water vapor was sprayed on the liquid film at room temperature and humidity of 70% to gradually evaporate the solvent and to condense the water vapor on the surface of the liquid film to form water droplets, and then evaporate the water droplets to prepare a film.
得られたフィルムは、 全表面に孔径約 5 //mの細孔が均一にハニカム状に配置 された凹凸部を有し、 裏面は平滑で、 厚さ 10 / mの非貫通フィルムであった。 フィルムの凹凸部の顕微鏡写真を図 7に示す。 このフ'イルムを 60°Cにて 10分 間熱処理を行い、 直径 4 cmの円形に切り出し、 中心部を 6 mmのバイオプシで 切り抜いた。  The obtained film was a non-penetrating film having a concavo-convex portion in which pores having a pore diameter of about 5 // m were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and the thickness was 10 / m. . Fig. 7 shows a photomicrograph of the uneven part of the film. This film was heat-treated at 60 ° C. for 10 minutes, cut into a circle with a diameter of 4 cm, and the center with 6 mm biopsy.
(保持層）  (Holding layer)
PLCAを用いて、 カバー層と同様に直径 4 cmの平滑フィルムを作製した。 膜厚は 52 ^mだった。 中心部を直径 6 mmのバイオプシで切り抜き、 電極用の 窓を製造した。  Using PLCA, a smooth film having a diameter of 4 cm was prepared in the same manner as the cover layer. The film thickness was 52 ^ m. The center was cut out with a 6 mm diameter biopsy to produce a window for the electrode.
(ワイヤーの組み立て）  (Assembling the wire)
電極がカバー層の中心にくるように導線を配置し、 塩ィヒメチレンを含ませた綿 棒で導線を押さえカバー層の上に固定した。 保持層をカバー層の電極側に重ね合 わせ、 再度 60°Cにて 10分間熱処理を行った。 さらに、 保持層の上面に接着層 を、 凹凸部が最外層となるように重ね合わせ、 60°Cにて 10分間熱処理を行い、 接着層、 保持層、 カバー層および導線からなる図 4に示す断面構造を有するワイ ヤーを製造した。 平均膜厚は 11 l /mであった （n = 5の平均値を測定)。. (動作確認） 犬 （年齢 2歳 7ヶ月、 雄、 ビーグル） に全身麻酔を施した後、 左下側臥位にて、 右第 4肋間開胸で胸腔内に到達した。 心膜を切開し心嚢内に達し、 上記で作成し たワイヤ一を左心室側に貼付した。 胸壁を穿刺し、 コネクターピンを体外に取り 出した後、 心膜を縫合閉鎖後、 胸壁を閉胸し、 手術を終えた。 ワイヤ一は Medtroni c Analyser2290 を用いて、 ぺーシング閾値を術当日、 術後 1日目、 3 日目、 5日目、 7日目、 1 4日目と経時的に測定した。 その結果を表 1に示す。 ぺ一シング閾値のわずかな上昇が見られたが 1 4日間にわたり問題なく運転でき ることを確認した。 術後 1 4日目にワイヤーを引き抜き、 抵抗なく、 引き抜ける ことを確認した。 ワイヤー抜去時に不整脈を発生することはなかった。 さらにヮ ィヤー抜去後、 心臓超音波検査で心嚢内出血は認めず、 心タンボナ一ゼの兆候も 認められなかった。 The conductor was placed so that the electrode was in the center of the cover layer, and the conductor was pressed onto the cover layer with a cotton swab soaked in salted himethylene. The holding layer was overlaid on the electrode side of the cover layer and again heat treated at 60 ° C for 10 minutes. Furthermore, an adhesive layer is placed on the upper surface of the holding layer so that the concavo-convex part becomes the outermost layer, heat-treated at 60 ° C. for 10 minutes, and shown in FIG. A wire having a cross-sectional structure was produced. The average film thickness was 11 l / m (measured average value of n = 5). (Operation check) The dog (age 2 years 7 months, male, beagle) was given general anesthesia, and then reached the chest cavity with the right intercostal thoracotomy in the lower left supine position. The pericardium was incised to reach the pericardium, and the wire 1 created above was attached to the left ventricle side. The chest wall was punctured, the connector pin was taken out of the body, the pericardium was sutured closed, the chest wall was closed, and the operation was completed. Wire 1 was measured using a Medtronic Analyzer 2290, and the pacing threshold was measured over time on the day of surgery, on the 1st, 3rd, 5th, 7th, and 14th days after surgery. The results are shown in Table 1. Although a slight increase in the pacing threshold was observed, it was confirmed that it could operate without any problems for 14 days. On the 4th day after surgery, the wire was pulled out and it was confirmed that it was pulled out without resistance. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the ear, cardiac ultrasonography showed no intrapericardial hemorrhage and no signs of cardiac tambonase.
実施例 2 Example 2
(カバー層）  (Cover layer)
実施例 1と同様に P L G Aを用いて膜厚 5 7 mのフィルムを得た。 このフィ ルムを直径 4 c mの円形に切り出し、 2枚重ねにし、 6 0でにて 1 0分間熱処理 を行いカバ一層とした。  A film having a film thickness of 57 m was obtained using P L G A in the same manner as in Example 1. This film was cut into a circle with a diameter of 4 cm, stacked in two, and heat treated at 60 for 10 minutes to form a cover layer.
(接着層）  (Adhesive layer)
実施例 1で製造した接着層を用いた。  The adhesive layer produced in Example 1 was used.
(保持層）  (Holding layer)
実施例 1と同様に P L C Aを用いて膜厚 4 8 mのフィルムを製造し、 中心部 を直径 6 mmのバイォプシで切り抜き、 電極用の窓とした。  A film having a thickness of 48 m was produced using PLCCA in the same manner as in Example 1, and the center portion was cut out with a biopsy having a diameter of 6 mm to form an electrode window.
(ワイヤーの組み立て）  (Assembling the wire)
実施例 1と同様の操作を行い図 4に示す断面構造 （カバー層は積層である） を 有するワイヤーを製造した。 パッチの平均膜厚は 1 7 0 であった （n = 5の 平均値を測定)。  The same operation as in Example 1 was performed to manufacture a wire having the cross-sectional structure shown in FIG. 4 (the cover layer is a laminate). The average film thickness of the patch was 1700 (measured average value of n = 5).
(動作確認）  (Operation check)
被験動物として犬 （年齢 2歳 4ヶ月、 雌、 ビーグル） を用いる以外は、 実施例 1と同じ操作を行なった。 その結果を表 1に示す。 ベーシング閾値のわずかな上 昇が見られたが 14日間にわたり問題なく運転できることを確認した。 術後 14 日目にワイヤ一を引き抜き、 抵抗なく、 引き抜けることを確認した。 ワイヤ一抜 去時に不整脈を発生することはなかった。 さらにワイヤ一抜去後、 心臓超音波検 査で心嚢内出血は認められず、 心タンボナーゼの兆候、 心膜の肥厚や心筋の拡張 障害も認められなかった。 The same operation as in Example 1 was performed except that a dog (age 2 years 4 months, female, beagle) was used as the test animal. The results are shown in Table 1. Slightly above the basing threshold Although there was a rise, it was confirmed that it was possible to drive without problems for 14 days. On the 14th day after the operation, the wire was pulled out and it was confirmed that it was pulled out without resistance. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the wire, no intracardiac hemorrhage was observed by cardiac ultrasonography, and no signs of cardiac tambonase, pericardial thickening or myocardial dilatation were observed.
実施例 3 Example 3
(カバー層）  (Cover layer)
実施例 1と同様に PL G Aを用いて膜厚 46 mのフィルムを得た。 このフィ ルムを直径 4 cmの円形に切り出し、 2枚重ねにし、 60°Cにて 10分間熱処理 を行いカバー層とした。  A film having a thickness of 46 m was obtained using PLGA in the same manner as in Example 1. This film was cut into a circle with a diameter of 4 cm, stacked in two, and heat treated at 60 ° C for 10 minutes to form a cover layer.
(接着層）  (Adhesive layer)
乳酸—力プロラクトン共重合体 （PLCA、 分子量 163, 000、 共重合モ ル比 乳酸 カプロラクトン =76Z24) を使用した以外は実施例 1と同様の 操作を行い接着層を得た。 得られたフィルムは、 全表面に孔径約 4/2 mの細孔が 均一にハニカム状に配置された凹凸部を有し、 裏面は平滑で、 厚さ 8 / mの非貫 通フィルムであった。 フィルムの凹凸部の顕微鏡写真を図 8に示す。 このフィル ムを 60°Cにて 10分間熱処理を行い、 直径 4 cmの円形に切り出し、 中心部を 6 mmのバイォプシで切り抜いた。  An adhesive layer was obtained in the same manner as in Example 1, except that a lactic acid-force prolactone copolymer (PLCA, molecular weight 163,000, copolymer mole ratio lactic acid caprolactone = 76Z24) was used. The obtained film had uneven portions in which pores having a pore diameter of about 4/2 m were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and a non-penetrating film having a thickness of 8 / m. It was. Fig. 8 shows a photomicrograph of the film irregularities. This film was heat-treated at 60 ° C for 10 minutes, cut into a 4 cm diameter circle, and the center was cut out with 6 mm biopsy.
(保持層の製造）  (Manufacture of retaining layer)
乳酸一力プロラクトン共重合体 （PLCA、 分子量 163， 000、 共重合モ ル比 乳酸/力プロラクトン =76Z 24) を使用した以外は実施例 1と同様に PLC Aを用いて膜厚 51 mフィルムを製造し、 中心部を直径 6 mmのバイオ プシで切り抜き、 電極用の窓とした。  51 m film thickness using PLC A in the same manner as in Example 1 except that lactic acid monostrength prolactone copolymer (PLCA, molecular weight 163,000, copolymer mole ratio lactic acid / force prolactone = 76Z 24) was used. A film was manufactured, and the center was cut out with a 6 mm diameter biopsy to form a window for the electrode.
(ワイヤーの組み立て）  (Assembling the wire)
実施例 1と同様の操作を行い図 4に示す断面構造 （カバー層は積層である） を 有するワイヤ一を製造した。 平均膜厚は 149 mであった （n = 5の平均値を 測定)。 . (動作確認） 被験動物として犬 （年齢 2歳 6ヶ月、 雌、 ビーグル） を用いる以外は、 実施例 1と同じ操作を行なった。 その結果を表 1に示す。 ベーシング閾値のわずかな上 昇が見られたが 14日間にわたり問題なく運転できることを確認した。 術後 14 日目にワイヤーを引き抜き、 抵抗なく、 引き抜けることを確認した。 その結果を 表 1に示す。 ワイヤー抜去時に不整脈を発生することはなかった。 さらにワイヤ 一抜去後、 心臓超音波検査で心嚢内出血は認められず、 心タンボナーゼの兆候、 心膜の肥厚や心筋の拡張障害も認められなかつた。 The same operation as in Example 1 was performed to produce a wire having the cross-sectional structure shown in FIG. 4 (the cover layer is a laminate). The average film thickness was 149 m (measured average value of n = 5). (Operation check) The same operation as in Example 1 was performed except that a dog (age 2 years 6 months, female, beagle) was used as a test animal. The results are shown in Table 1. A slight increase in the basing threshold was observed, but it was confirmed that the system could operate without any problems for 14 days. On the 14th day after the operation, the wire was pulled out and it was confirmed that it was pulled out without resistance. The results are shown in Table 1. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the wire, no echocardiogram was observed on echocardiography, and no signs of cardiac tambonase, pericardial thickening or myocardial dilatation were observed.
実施例 4 Example 4
(カバー層）  (Cover layer)
15重量％に調製した、 乳酸—グリコール酸共重合体 （PLGA、 分子量 90, 000、 共重合モル比 ==乳酸 グリコ一ル酸 = 75 Z25) Zクロ口ホルム溶液 をガラス基板上にキャストした後、 クロ口ホルムを室温で蒸発させフィルムを作 製し、 60°Cにて 10分間熱処理を行った。 得られたフィルムの厚みは 75 であった。 このフィルムを直径 3 cmの円形に切り出し、 カバ一層を製造した。 (接着層）  Lactic acid-glycolic acid copolymer (PLGA, molecular weight 90, 000, copolymerization molar ratio == lactic acid glycolic acid = 75 Z25) after casting the Z-Clo-form solution on a glass substrate The film was evaporated by evaporating the black mouth form at room temperature and heat-treated at 60 ° C for 10 minutes. The thickness of the obtained film was 75. This film was cut into a circle with a diameter of 3 cm, and a cover layer was produced. (Adhesive layer)
乳酸一力プロラクトン共重合体 （PLCA、 分子量 163, 000、 共重合モ ル比 =乳酸 Z力プロラクトン =88/12) のクロ口ホルム溶液 （5 gZL) に、 ホスファチジルエタノールァミン一ジォレオイルを PLCAに対し 1 200の 割合 （重量） で混合し、 ポリマー溶液を調製した。 ポリマー溶液をガラス基板上 にキャストし、 液状膜を得た。  A phosphatidylethanolamine monodiol oil is added to a black mouth form solution (5 gZL) of lactic acid monostrength prolactone copolymer (PLCA, molecular weight 163,000, copolymer mole ratio = lactic acid Z force prolactone = 88/12). A polymer solution was prepared by mixing at a ratio (weight) of 1 200 to PLCA. The polymer solution was cast on a glass substrate to obtain a liquid film.
次に、 液状膜に、 室温、 湿度 70%の水蒸気を吹き付け、 溶媒を徐々に蒸発さ せると共に水蒸気を液状膜表面に結露させ水滴を形成させ、 ついで水滴を蒸発さ せフィルムを調製した。  Next, water vapor at room temperature and humidity of 70% was sprayed on the liquid film to gradually evaporate the solvent and to condense the water vapor on the liquid film surface to form water droplets, and then the water droplets were evaporated to prepare a film.
得られたフィルムは、 全表面に孔径約 9 の細孔が均一にハニカム状に配置 された凹凸部を有し、 裏面は平滑で、 厚さ 15 mの非貫通フィルムであった。 フィルムの凹凸部の顕微鏡写真を図 1 1に示す。 このフィルムを 60°Cにて 10 分間熱処理を行い、 直径.3 cmの円形に切り出し、 中心部を 6 mmのバイオプシ で切り抜いた。 (保持層） The obtained film was a non-penetrating film having a concavo-convex portion in which pores having a pore diameter of about 9 were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and the thickness was 15 m. A photomicrograph of the film irregularities is shown in Fig. 11. This film was heat-treated at 60 ° C. for 10 minutes, cut into a circular shape with a diameter of .3 cm, and the center was cut with a 6 mm biopsy. (Holding layer)
P L C Aを用いて、 カバ一層と同様に直径 3 c mの平滑フィルムを作製した。 膜厚は 5 7 mだった。 中心部を直径 6 mmのバイオプシで切り抜き、 電極用の 窓を製造した。  A smooth film with a diameter of 3 cm was prepared using P L C A in the same manner as the cover layer. The film thickness was 5 7 m. The center was cut out with a 6 mm diameter biopsy to produce a window for the electrode.
(ワイヤーの組み立て）  (Assembling the wire)
電極がカバー層の中心にくるように導線を配置し、 塩化メチレンを含ませた綿 棒で導線を押さえカバー層の上に固定した。 保持層をカバ一層の電極側に重ね合 わせ、 再度 6 0でにて 1 0分間熱処理を行った。 さらに、 保持層の上面に接着層 を、 凹凸部が最外層となるように重ね合わせ、 6 0 °Cにて 1 0分間熱処理を行い、 接着層、 保持層、 カバ一層および導線からなる図 4に示す断面構造を有するワイ ヤーを製造した。 平均膜厚は 1 4 5 であった （n = 5の平均値を測定)。  The conductor was placed so that the electrode was at the center of the cover layer, and the conductor was pressed onto the cover layer with a cotton swab soaked in methylene chloride. The holding layer was superimposed on the electrode side of the cover layer, and heat treatment was performed again at 60 for 10 minutes. Furthermore, an adhesive layer is placed on the upper surface of the holding layer so that the uneven portion becomes the outermost layer, and heat treatment is performed at 60 ° C. for 10 minutes, and the adhesive layer, the holding layer, the cover layer, and the conductive wire are formed. A wire having the cross-sectional structure shown in FIG. The average film thickness was 1 45 (measured average value of n = 5).
(動作確認）  (Operation check)
犬'（年齢 1 0ヶ月、 雄、 ビーグル） に全身麻酔を施した後、 左下側臥位にて、 右第 4肋間開胸で胸腔内に到達した。 心膜を切開し心嚢内に達し、 上記で作成し たワイヤーを左心室側に貼付した。 胸壁を穿刺し、 コネクターピンを体外に取り 出した後、 心膜を縫合閉鎖後、 胸壁を閉胸し、 手術を終えた。 ワイヤ一は The dog '(age 10 months, male, beagle) was given general anesthesia, and then reached the chest cavity with the 4th intercostal thoracotomy in the lower left supine position. The pericardium was incised to reach the pericardium, and the wire created above was applied to the left ventricle. The chest wall was punctured, the connector pin was taken out of the body, the pericardium was sutured closed, the chest wall was closed, and the operation was completed. Wire one
Medtronic Analyser2290 を用いて、 ベーシング閾値を術当日、 術後 1日目、 3 日目、 5日目、 7日目、 1 4日目と経時的に測定した。 その結果を表 1に示す。 ぺ一シング閾値のわずかな上昇が見られたが 1 4日間にわたり問題なく運転でき ることを確認した。 術後 1 4日目にワイヤーを引き抜き、 抵抗なく、 引き抜ける ことを確認した。 ワイヤー抜去時に不整脈を発生することはなかった。 さらにヮ ィヤー抜去後、 心 B蔵超音波検査で心嚢内出血は認められず、 心タンボナーゼの兆 候、 心膜の肥厚や心筋の拡張障害も認められなかった。 Using a Medtronic Analyzer 2290, the basing threshold was measured over time on the day of surgery, on the 1st, 3rd, 5th, 7th, and 14th days after surgery. The results are shown in Table 1. Although a slight increase in the pacing threshold was observed, it was confirmed that it could operate without any problems for 14 days. On the 4th day after surgery, the wire was pulled out and it was confirmed that it was pulled out without resistance. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the ear, no cardiac pericardial hemorrhage was observed by cardiac B ultrasound, and no signs of cardiac tambonase, pericardial thickening, or myocardial dilatation were observed.
実施例 5 Example 5
(カバー層）  (Cover layer)
1 5重量％に調製した、 乳酸—グリコール酸共重合体 （P L GA、 分子量 9 0 , 0 0 0、 共重合モル比 ^乳酸 グリコール酸 = 7 5 / 2 5 ) クロ口ホルム溶液 をガラス基板上にキャストした後、 クロ口ホルムを室温で蒸発させフィルムを作 製し、 60でにて 10分間熱処理を行った。 得られたフィルムの厚みは 98 m であった。 このフィルムを直径 3 cmの円形に切り出し、 カバー層を製造した。 (接着層） 15 Lactic acid-glycolic acid copolymer (PL GA, molecular weight 90, 0 00, copolymerization molar ratio ^ lactic acid glycolic acid = 75/25) prepared to 5% by weight on a glass substrate After casting, the black mouth form is evaporated at room temperature to make a film. And heat-treated at 60 for 10 minutes. The thickness of the obtained film was 98 m. This film was cut into a circle having a diameter of 3 cm to produce a cover layer. (Adhesive layer)
乳酸一力プロラクトン共重合体 （PLCA、 分子量 163, 000、 共重合モ ル比 =乳酸/力プロラクトン =88Z12) のクロ口ホルム溶液 （5 g/L) に、 ホスファチジルエタノールアミンージォレオイルを PL CAに対し 1ノ 200の 割合 （重量） で混合し、 ポリマー溶液を調製した。 ポリマー溶液をガラス基板上 にキャストし、 液状膜を得た。  A phosphatidylethanolamine-diolate was added to a black mouth form solution (5 g / L) of lactic acid-strength prolactone copolymer (PLCA, molecular weight 163,000, copolymer mole ratio = lactic acid / force prolactone = 88Z12). Oil was mixed with PL CA at a ratio of 1 to 200 (weight) to prepare a polymer solution. The polymer solution was cast on a glass substrate to obtain a liquid film.
次に、 液状膜に、 室温、 湿度 70%の水蒸気を吹き付け、 溶媒を徐々に蒸発さ させると共に水蒸気を液状膜表面に結露させ水滴を形成させ、 ついで水滴を蒸発 させフィルムを調製した。  Next, water vapor at room temperature and humidity of 70% was sprayed on the liquid film to gradually evaporate the solvent and to condense the water vapor on the liquid film surface to form water droplets, and then evaporate the water droplets to prepare a film.
得られたフィルムは、 全表面に孔径約 4. 5 の細孔が均一にハニカム状に 配置された凹凸部を有し、 裏面は平滑で、 厚さ 10 imの非貫通フィルムであつ た。 フィルムの凹凸部の顕微鏡写真を図 12に示す。 このフィルムを 60でにて 10分間熱処理を行い、 直径 3 cmの円形に切り出し、 中心部を 6mmのバイオ プシで切り抜いた。  The obtained film had a concavo-convex portion in which pores having a pore diameter of about 4.5 were uniformly arranged in a honeycomb shape on the entire surface, the back surface was smooth, and a non-penetrating film having a thickness of 10 im. Fig. 12 shows a photomicrograph of the uneven part of the film. This film was heat-treated at 60 at 10 minutes, cut into a 3 cm diameter circle, and the center was cut out with a 6 mm biopsy.
(保持層）  (Holding layer)
PLC Aを用いて、 カバー層と同様に直径 3 cmの平滑フィルムを作製した。 膜厚は 42 imだった。 中心部を直径 6mmのバイオプシで切り抜き、 電極用の 窓を製造した。  Using PLC A, a smooth film having a diameter of 3 cm was produced in the same manner as the cover layer. The film thickness was 42 im. The center was cut out with a biopsy with a diameter of 6 mm to produce a window for the electrode.
(ワイヤーの組み立て）  (Assembling the wire)
電極がカバー層の中心にくるように導線を配置し、 塩化メチレンを含ませた綿 棒で導線を押さえカバー層の上に固定した。 保持層をカバー層の電極側に重ね合 わせ、 再度 60°Cにて 10分間熱処理を行った。 さらに、 保持層の上面に接着層 を、 凹凸部が最外層となるように重ね合わせ、 60°Cにて 10分間熱処理を行い、 接着層、 保持層、 カバー層および導線からなる図 4に示す断面構造を有するワイ ヤーを製造した。 平均膜厚は 147 mであった （n= 5の平均値を測定)。  The conductor was placed so that the electrode was at the center of the cover layer, and the conductor was pressed onto the cover layer with a cotton swab soaked in methylene chloride. The holding layer was overlaid on the electrode side of the cover layer and again heat treated at 60 ° C for 10 minutes. Furthermore, an adhesive layer is placed on the upper surface of the holding layer so that the concavo-convex part becomes the outermost layer, and heat-treated at 60 ° C. for 10 minutes, and shown in FIG. A wire having a cross-sectional structure was produced. The average film thickness was 147 m (measured average value of n = 5).
(動作確認） 犬 （年齢 2歳 8ヶ月、 雌、 ビーグル） に全身麻酔を施した後、 左下側臥位にて、 右第 4肋間開胸で胸腔内に到達した。 心膜を切開し心嚢内に達し、 上記で作成し たワイヤーを左心室側に貼付した。 胸壁を穿刺し、 コネクターピンを体外に取り 出した後、 心膜を縫合閉鎖後、 胸壁を閉胸し、 手術を終えた。 ワイヤーは Medtronic Analyser2290 を用いて、 ぺ一シング閾値を術当日、 術後 1日目、 3 日目、 5日目、 7日目、 1 4日目と経時的に測定した。 その結果を表 1に示す。 ベーシング閾値のわずかな上昇が見られたが 1 4日間にわたり問題なく運転でき ることを確認した。 術後 1 4日目にワイヤーを引き抜き、 抵抗なく、 引き抜ける ことを確認した。 ワイヤー抜去時に不整脈を発生することはなかった。 さらにヮ ィヤー抜去後、 心臓超音波検査で心嚢内出血は認められず、 心タンボナ一ゼの兆 候、 心膜の肥厚や心筋の拡張障害も認められなかった。 (Operation check) The dog (age 2 years 8 months, female, beagle) was given general anesthesia, and then reached the chest cavity with the right intercostal thoracotomy in the lower left supine position. The pericardium was incised to reach the pericardium, and the wire created above was applied to the left ventricle. The chest wall was punctured, the connector pin was taken out of the body, the pericardium was sutured closed, the chest wall was closed, and the operation was completed. For the wire, the pacing threshold was measured over time on the day of surgery, the first day, the third day, the fifth day, the seventh day, and the 14th day after surgery using Medtronic Analyzer 2290. The results are shown in Table 1. Although there was a slight increase in the basing threshold, it was confirmed that the system could operate without any problems for 14 days. On the 4th day after surgery, the wire was pulled out and it was confirmed that it was pulled out without resistance. Arrhythmia did not occur when the wire was removed. Furthermore, after removal of the neck, echocardiography showed no intrapericardial hemorrhage, no signs of cardiac tambonase, no pericardial thickening, and no myocardial dilatation.
参考例 1 Reference example 1
被験物質としてハートワイヤ （Model 6 4 9 2 ： Medtronic) を用いる以外は、 実施例 1と同じ動作確認操作を行った。 その結果 （計 7回の各計測日の平均値 土標準偏差） を表 1に示す。 表 1  The same operation check operation as in Example 1 was performed except that Heart Wire (Model 6 4 92: Medtronic) was used as a test substance. Table 1 shows the results (average soil standard deviation for each measurement day for a total of 7 measurements). table 1
Figure imgf000021_0001
発明の効果
Figure imgf000021_0001
The invention's effect
本発明のワイヤーは、 電極を心筋に縫着することなく固定できるので、 該ワイ ヤーを体外へ引き抜く際に、 心臓組織などを損傷する恐れが少ない。 また本発明 のワイヤーのパッチは、 '生分解性ポリマーから主としてなるフィルムであり、 生 体内で分解し所定の期間が経過した後、 心臓表面から電極を容易に取り外すこと ができる。 よって、 本発明のワイヤーによれば、 合併症の発症率を低下させるこ とができ、 患者の Q〇L (Qu a l i t y o f l i f e) を向上させること ができる。 Since the wire of the present invention can be fixed without sewing the electrode to the myocardium, there is little risk of damaging heart tissue or the like when the wire is pulled out of the body. The wire patch of the present invention is a film mainly composed of a biodegradable polymer. The electrode can be easily removed from the surface of the heart after a certain period of time has passed since it has broken down in the body. Therefore, according to the wire of the present invention, the incidence of complications can be reduced, and the patient's QOL (Quality of life) can be improved.
さらに、 本発明のワイヤーは、 電極を心筋に縫着する必要が無いため装着が極 めて簡便である。 よって、 手術時の外科医のストレスを軽減でき、 手術時間を短 縮することができる。  Furthermore, since the wire of the present invention does not need to be sewn to the myocardium, it is extremely easy to install. Therefore, the stress of the surgeon during the operation can be reduced, and the operation time can be shortened.
加えて、 本発明のワイヤーは、 接着剤などを用いることなく、 電極を心臓に固 定できるので、 接着剤の人体へ与える影響を考慮することなく使用することがで きるという利点も有する。 産業上の利用可能性  In addition, the wire of the present invention has an advantage that it can be used without considering the influence of the adhesive on the human body because the electrode can be fixed to the heart without using an adhesive or the like. Industrial applicability
本発明のワイヤ一は、 心臓組織に電極を縫着することなく、 心臓組織に電極を 固定することができるので、 固定箇所の変更が容易であり、 また抜去時にコイル による心臓、 血管の損傷や縫着糸による心筋の裂開がなく、 心臓ペースメーカ一 用ワイヤーとして有用である。  Since the wire 1 of the present invention can fix the electrode to the heart tissue without sewing the electrode to the heart tissue, it is easy to change the fixing portion, and when the wire is removed, damage to the heart and blood vessels caused by the coil There is no myocardial dehiscence by sewing thread, and it is useful as a wire for cardiac pacemakers.

Claims

請 求 の 範 囲 The scope of the claims
1. 接着層を有するパッチ、 並びに末端に電極を有する導線からなる心臓べ一 スメーカー用ワイヤーであって、 1. a wire for a cardiac base manufacturer comprising a patch having an adhesive layer and a lead having an electrode at its end,
a) 接着層は、 生分解性ポリマーから主としてなるフィルムであり、 一方の表面 を接着面 （八面） とし、 A面にはその全表面積に対して 1〜100%の割合で凹 凸部を有し、 a) The adhesive layer is a film mainly composed of a biodegradable polymer. One surface is the adhesive surface (eight surfaces), and the A surface has concave and convex portions at a ratio of 1 to 100% of the total surface area. Have
b) 電極は、 接着層の A面側に露出しているワイヤ一。 b) The electrode is the same wire exposed on the A side of the adhesive layer.
2. 接着層の他方の表面 （B面） 上に、 カバー層が積層されている請求項 1記 載のワイヤー。 2. The wire according to claim 1, wherein a cover layer is laminated on the other surface (B surface) of the adhesive layer.
3. 接着層の B面とカバー層との間に保持層が積層されてレ ^る請求項 2記載の ワイヤー。 3. The wire according to claim 2, wherein a holding layer is laminated between the B surface of the adhesive layer and the cover layer.
4. 凹凸部には、 孔径 0. 1〜20 mの細孔が均一に配置されている請求項 1記載のワイヤー。 4. The wire according to claim 1, wherein pores having a pore diameter of 0.1 to 20 m are uniformly arranged in the concavo-convex portion.
5. 凹凸部には、 孔径 0. 1〜20 xmの細孔がハニカム状に配置されている 請求項 1記載のワイヤ一。 5. The wire according to claim 1, wherein pores having a pore diameter of 0.1 to 20 xm are arranged in a honeycomb shape in the concavo-convex portion.
6. 生分解性ポリマーが、 ポリ乳酸、 乳酸ーグリコール酸共重合体、 ポリヒド ロキシ酪酸、 ポリ力プロラクトン、 乳酸一力プロラクトン共重合体、 ポリエチレ ンアジべ一ト、 ポリブチレンアジべ一卜からなる群から選ばれる少なくとも一種 である請求項 1記載のワイヤー。 6. The biodegradable polymer is composed of polylactic acid, lactic acid-glycolic acid copolymer, polyhydroxybutyric acid, polystrength prolactone, lactic acid monostrength prolactone copolymer, polyethylene adiene, polybutylene adiene The wire according to claim 1, wherein the wire is at least one selected from the group.
7. 接着層は、 100重量部の生分解性ポリマーおよび 0. 1〜100重量部 のリン脂質からなる請求項 1記載のワイヤー。 7. The wire according to claim 1, wherein the adhesive layer comprises 100 parts by weight of a biodegradable polymer and 0.1 to 100 parts by weight of phospholipid.
8. 接着層は、 A面から B面へ貫通する電極用窓を有し、 電極は電極用窓に配 置されている請求項 1記載のワイヤー。 8. The wire according to claim 1, wherein the adhesive layer has an electrode window penetrating from the A surface to the B surface, and the electrode is disposed in the electrode window.
9. 導線の心臓ペースメーカー側末端に、 胸壁穿刺用針を有する請求項 1に記 載のワイヤー。 9. The wire according to claim 1, further comprising a chest wall puncture needle at a cardiac pacemaker side end of the lead.
10. パッチの厚さが 10〜300 imである請求項 1に記載のワイヤー。 10. The wire of claim 1, wherein the patch has a thickness of 10 to 300 im.
11. 心臓表面に電極を接着させるためのパッチであって、 接着層を有し、 該 接着層は、 生分解性ポリマーから主としてなるフィルムであり、 一方の表面を接 着面 （八面） とし、 A面にはその全表面積に対して 1〜100%の割合で凹凸部 を有する、 パッチ。 11. A patch for adhering an electrode to the surface of a heart, having an adhesive layer, the adhesive layer being a film mainly composed of a biodegradable polymer, with one surface as an adhesive surface (eight surfaces) A patch having irregularities on the A surface at a ratio of 1 to 100% of its total surface area.
12. 接着層の他方の表面 （B面） 上に、 カバー層が積層されている請求項 1 1記載のパッチ。 12. The patch according to claim 11, wherein a cover layer is laminated on the other surface (side B) of the adhesive layer.
13. 接着層の B面とカバー層との間に保持層が積層されている請求項 11記 載のパッチ。 13. The patch according to claim 11, wherein a holding layer is laminated between the B surface of the adhesive layer and the cover layer.
14. 厚さが 10〜300 imである請求項 11に記載のパッチ。 14. The patch according to claim 11, wherein the thickness is 10 to 300 im.
15. 生分解性ポリマーから主としてなるフィルムであって、 少なくとも一方 の表面は、 ？ L径 0. 1〜20 の細孔がハニカム状に配置された凹凸構造を有 する心臓表面への電極固定用のフィルム。 15. A film mainly composed of biodegradable polymer, at least one surface of which is? A film for fixing an electrode to the heart surface having an uneven structure in which pores having an L diameter of 0.1 to 20 are arranged in a honeycomb shape.
16. 接着層の A面を心臓側にして、 パッチを心臓表面に貼付することからな る請求項 1記載の心臓ペースメーカー用ワイヤーの設置方法。 16. The method for installing a cardiac pacemaker wire according to claim 1, wherein the patch is attached to the heart surface with the side A of the adhesive layer facing the heart.
17. パツチを心臓の温度付近まで温めた後、 パツチを心臓表面に貼付するこ とからなる請求項 16記載の設置方法。 17. The installation method according to claim 16, wherein the patch is attached to the heart surface after the patch is warmed to near the heart temperature.
18. 請求項 1記載の心臓ペースメーカー用ワイヤーを用いた心臓のぺ一シン グ方法。 18. A method for pacing the heart using the cardiac pacemaker wire according to claim 1.
PCT/JP2006/308793 2005-04-22 2006-04-20 Wire for cardiac pacemakers WO2006115281A1 (en)

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WO2015170344A1 (en) 2014-05-09 2015-11-12 Council Of Scientific & Industrial Research An improved next generation off-laboratory polymer chip electrode
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