WO2010090098A1 - Method for producing antimicrobial medical instrument, and antimicrobial medical instrument - Google Patents

Method for producing antimicrobial medical instrument, and antimicrobial medical instrument Download PDF

Info

Publication number
WO2010090098A1
WO2010090098A1 PCT/JP2010/050958 JP2010050958W WO2010090098A1 WO 2010090098 A1 WO2010090098 A1 WO 2010090098A1 JP 2010050958 W JP2010050958 W JP 2010050958W WO 2010090098 A1 WO2010090098 A1 WO 2010090098A1
Authority
WO
WIPO (PCT)
Prior art keywords
silver
medical device
antibacterial
based particles
particles
Prior art date
Application number
PCT/JP2010/050958
Other languages
French (fr)
Japanese (ja)
Inventor
直人 竹村
Original Assignee
テルモ株式会社
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 テルモ株式会社 filed Critical テルモ株式会社
Priority to JP2010549438A priority Critical patent/JP5639481B2/en
Publication of WO2010090098A1 publication Critical patent/WO2010090098A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/005—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters containing a biologically active substance, e.g. a medicament or a biocide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0009—Making of catheters or other medical or surgical tubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0043—Catheters; Hollow probes characterised by structural features
    • A61M25/0045—Catheters; Hollow probes characterised by structural features multi-layered, e.g. coated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
    • A61L2300/104—Silver, e.g. silver sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0043—Catheters; Hollow probes characterised by structural features
    • A61M2025/0056—Catheters; Hollow probes characterised by structural features provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir

Definitions

  • the present invention relates to a method for producing an antibacterial medical device and an antibacterial medical device produced thereby.
  • the present invention relates to a central venous catheter that is placed in a blood vessel when performing central venous nutrition.
  • a central venous catheter which is one of medical devices
  • bacteria may enter the body through the skin puncture site or lumen of the catheter and cause bacterial infection. Severe infection can result in sepsis.
  • catheter-related bacteremia CR-BSI
  • the patient may die due to CR-BSI.
  • Patent Document 1 discloses an in-vivo insertion tube (catheter) having antibacterial properties by mixing a predetermined amount of an antibacterial agent such as a silver-substituted inorganic ion exchanger with a base material. ) Is described. Also in Patent Document 2, a silver compound is introduced (coating) on the surface of a base material, specifically, an amino acid derivative, an anionic surfactant, a compound having a carboxyl group or a sulfone group on the base material, etc. It is described that a urinary catheter having antibacterial properties is produced by absorbing a compound capable of binding to silver ions and then immersing it in an aqueous silver compound solution such as silver acetate.
  • an antibacterial agent such as a silver-substituted inorganic ion exchanger
  • JP-A-5-220216 (Claims 1 to 4)
  • JP-A-11-290449 (Claims 1 to 5)
  • the present invention was created to solve such problems, and its purpose is to provide a method for manufacturing an antibacterial medical device that can maintain antibacterial properties at a high level over a long period of time, and an antibacterial medical device manufactured thereby. Is to provide.
  • a method for manufacturing an antibacterial medical device includes a first step of manufacturing a medical device with a material containing an element capable of forming a complex with silver, A second step of introducing silver-based particles on the surface; and a third step of fixing the silver-based particles on the surface of the medical device by heat-treating the medical device into which the silver-based particles have been introduced. To do.
  • a medical device having an element capable of forming a complex with silver is produced.
  • the silver-based particles introduced into the surface of the medical device in the second step can form a complex with the element on the surface of the medical device or can form a complex with silver by the heat treatment in the third step. Due to the reducing action, pure silver particles are obtained, and the silver-based particles are firmly fixed to the surface of the medical device. As a result, the elution amount of silver-based particles eluted from the surface of the medical device during use, particularly the elution amount in the initial stage, can be reduced, so that the elution amount is maintained at a high level over a long period of time.
  • the method for manufacturing an antibacterial medical device produces a medical device using a material that does not contain an element capable of forming a complex with silver, and then introduces the element onto the surface of the medical device.
  • a first step a second step of introducing silver-based particles on the surface of the medical device into which the element has been introduced, and a heat treatment of the medical device into which the silver-based particles have been introduced to form a silver-based material on the surface of the medical device
  • a third step of fixing the particles is a third step of fixing the particles.
  • a medical device having an element capable of forming a complex with silver is produced.
  • the silver-based particles introduced into the surface of the medical device in the second step can form a complex with the element on the surface of the medical device or can form a complex with silver by the heat treatment in the third step. Due to the reducing action, pure silver particles are obtained, and the silver-based particles are firmly fixed to the surface of the medical device. As a result, the elution amount of silver-based particles eluted from the surface of the medical device during use, particularly the elution amount in the initial stage, can be reduced, so that the elution amount is maintained at a high level over a long period of time.
  • the method for manufacturing an antibacterial medical device according to the present invention further includes a fourth step of coating the surface of the medical device with an antithrombotic material after the third step.
  • antithrombogenicity is provided to the surface of a medical device by performing the 4th step which coat
  • the method for manufacturing an antibacterial medical device according to the present invention is characterized in that the element is one or more elements selected from S, N, O and P.
  • the silver introduced into the surface of the medical device in the heat treatment of the third step by producing a medical device having one or more elements selected from S, N, O and P in the first step.
  • the system particles easily form a complex, and the silver particles are more firmly fixed on the surface of the medical device.
  • the amount of silver-based particles eluted from the surface of the medical device during use is maintained at a higher level over a long period of time.
  • the method for manufacturing an antibacterial medical device according to the present invention is characterized in that, in the third step, the medical device into which the silver-based particles are introduced is heat-treated at 80 to 300 ° C.
  • the silver-based particles introduced to the surface of the medical device can easily form a complex, and the silver-based particles are more firmly fixed to the surface of the medical device.
  • the amount of silver-based particles eluted from the surface of the medical device during use is maintained at a higher level over a long period of time.
  • the amount of elution in the initial stage can be reduced, the amount of elution is maintained at a higher level over a long period of time.
  • the silver-based particles are pure silver particles or silver salt particles of any one or more of silver nitrate, silver acetate, silver azide and silver perchlorate. It is characterized by being.
  • the silver-based particles are pure silver particles, a complex containing pure silver particles is formed on the surface of the medical device, and the silver-based particles are firmly fixed on the surface of the medical device.
  • the silver-based particles are silver salt particles, the silver salt particles become pure silver particles due to the reducing action of elements capable of forming a complex with silver, and some of them form a complex containing pure silver particles.
  • the silver particles are firmly fixed on the surface of the medical device.
  • the amount of silver-based particles eluted from the surface of the medical device during use is maintained at a higher level over a long period of time.
  • the amount of elution in the initial stage can be reduced, the amount of elution is maintained at a higher level over a long period of time.
  • the antibacterial medical device according to the present invention is manufactured by the above manufacturing method.
  • grains (nanosilver particle) are firmly fixed to the surface of a medical device by manufacturing with the said manufacturing method.
  • the amount of silver-based particles (nanosilver particles) eluted from the surface of the medical device during use is maintained at a high level over a long period of time.
  • antithrombogenicity is imparted.
  • an antibacterial medical device in which the growth or infection of attached bacteria is suppressed for a long time and the antibacterial property can be maintained at a high level for a long time is produced.
  • an antibacterial medical device with antithrombogenic properties is produced.
  • the growth or infection of attached bacteria can be suppressed over a long period of time, and the antibacterial property can be maintained at a high level over a long period of time.
  • antithrombogenicity is imparted to the antibacterial medical device.
  • the antibacterial medical device is a medical device imparted with antibacterial properties, such as a central venous catheter, a Foley catheter, a gastric tube catheter, an infusion tube, a ventilator, a dressing material, a feeding tube, Sutures and the like.
  • the parts constituting the antibacterial medical instrument for example, the main body part 2, the tip part 3, the hub 4, the connecting tube 5 and the connector 6 constituting the central venous catheter 1 shown in FIG. Shall be included.
  • FIG. 1 is an external view showing the configuration of the central venous catheter.
  • the first method of the present invention includes a first step of producing a medical device with a material containing an element capable of forming a complex with silver, and a second step of introducing silver-based particles on the surface of the medical device. And a third step of fixing the silver-based particles on the surface of the medical device by heat-treating the medical device into which the silver-based particles have been introduced.
  • the contrast agent inorganic compounds such as barium sulfate, barium carbonate, bismuth oxide, bismuth subcarbonate and tungsten are used.
  • each step will be described.
  • the element capable of forming a complex with silver is an element having a lone electron pair, and preferably one or more elements selected from S, N, O and P.
  • a material containing these elements specifically, a material having a functional group containing an element (for example, thiol group, amino group, carboxyl group, phosphino group, etc.) is preferably a polymer material, such as polyurethane, Nylon, polycarbonate, polyester, silicone resin, or a resin composition obtained by combining two or more of these resins can be used.
  • a method for producing a medical device a conventional method for producing a medical device can be used, for example, extrusion molding, injection molding, or the like.
  • silver-based particles are introduced on the surface of the medical device.
  • the silver-based particles are preferably pure silver particles or silver salt particles, and more preferably nano silver particles or silver salt nanoparticles.
  • the nano silver particles or silver salt nanoparticles are silver particles having a particle size of 10 ⁇ 9 m to 10 ⁇ 8 m.
  • the silver-based particles only need to change into pure silver particles by heat treatment after the introduction, for example, not only pure silver particles but also silver nitrate other than pure silver, silver acetate, silver azide, excess Even silver salt particles of silver chlorate or a mixture thereof may be used as long as they can be converted into pure silver particles by heat treatment after introduction.
  • the solvent is preferably an organic solvent or a mixed solvent of water and an organic solvent.
  • the organic solvent tetrahydrofuran, dimethylformamide, dimethylacetamide, cyclohexanone, methyl ethyl ketone, dimethyl sulfoxide, acetone, methanol, ethanol, isopropanol, diethyl ether, hexane and the like can be used.
  • the organic solvent is preferably a hydrophobic organic solvent (for example, cyclohexanone, methyl ethyl ketone).
  • the concentration of the silver-based particle solution is preferably 10 to 10,000 ppm when the silver-based particles are nano silver particles.
  • the medical device into which the silver-based particles are introduced is heat-treated to fix the silver-based particles on the surface of the medical device. That is, a complex is formed by the element (for example, S, N, O, P) present on the surface of the medical device and silver-based particles. Thereby, silver-type particle
  • the silver-based particles are pure silver particles
  • the pure silver particles introduced onto the surface of the medical device by heat treatment or the like and an element capable of forming a complex with silver form a complex
  • the silver-based particles are medical. It is firmly fixed to the surface of the instrument.
  • the silver-based particles are silver salt particles
  • the silver salt particles introduced to the surface of the medical device by heat treatment or the like become pure silver particles due to the reducing action of an element capable of forming a complex with silver. .
  • a part of the pure silver particles and the element form a complex, and the silver-based particles are firmly fixed to the surface of the medical device.
  • the heat treatment temperature is preferably 80 to 300 ° C, more preferably 100 to 200 ° C.
  • the heat treatment temperature is less than 80 ° C.
  • silver-based particles are likely to be insufficiently fixed, and the amount of silver-based particles eluted at the initial stage is likely to increase when a medical instrument is used.
  • the elution amount of silver-based particles eluted from the medical device cannot be maintained at a high level over a long period of time, and it becomes difficult to maintain the antibacterial properties of the medical device over a long period of time.
  • the heat treatment temperature exceeds 300 ° C., changes in physical properties of the polymer material constituting the medical device and deterioration of the silver-based particles are likely to occur.
  • the heat treatment time is preferably 1 to 72 hours at 80 ° C. and 10 seconds to 1 hour at 300 ° C. If the heat treatment time is short, the fixation of the silver particles tends to be insufficient, and if the heat treatment time is long, the physical properties of the polymer material change and the silver particles are likely to deteriorate.
  • the second method of the present invention includes a first step of producing a medical device with a material that does not contain an element capable of forming a complex with silver, and then introducing the element onto the surface of the medical device; A second step of introducing silver-based particles onto the surface of the medical device into which the element has been introduced; and a third step of heat-treating the medical device into which the silver-based particles have been introduced to fix the silver-based particles on the surface of the medical device. And a step.
  • each step will be described.
  • the element capable of forming a complex with silver is an element having a lone pair of electrons, as in the first method, and is selected from S, N, O and P More than element is preferable.
  • a polymeric material or a metal material is preferable.
  • the polymer material polyethylene, polypropylene, polyvinyl chloride, or a resin composition obtained by combining two or more of these resins can be used.
  • the method for producing a medical device a conventional method for producing a medical device can be used as in the first method, and extrusion molding, injection molding, or the like can be used.
  • the first step as a method for introducing the element into the surface of the medical device, plasma treatment using a compound containing the element (for example, N 2 O gas) as a target, functional group containing the element (for example, (Graft polymerization of thiol group, amino group, carboxyl group) or coating of a compound containing the element can be used.
  • a compound containing the element for example, N 2 O gas
  • functional group containing the element for example, (Graft polymerization of thiol group, amino group, carboxyl group) or coating of a compound containing the element
  • the second step and the third step are the same as the first method described above, description thereof is omitted.
  • the second method for the purpose of ensuring the contrast of the medical device, multilayer forming of the contrast agent and uniform dispersion of the contrast agent material may be performed.
  • the method for manufacturing an antibacterial medical device according to the present invention includes the fourth step of coating the surface of the medical device with an antithrombogenic material after the third step in the first method or the second manufacturing method. Further, it may be included.
  • a method of coating a solution in which the antithrombotic material is dissolved by a dipping method, a spray method, or the like is used.
  • the solvent that dissolves the antithrombotic material include organic solvents such as acetone, methanol, ethanol, isopropanol, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, and cyclohexanone.
  • the antithrombotic material is made of a biological material such as a mucopolysaccharide such as heparin or a protein such as urokinase, or a non-biological material such as a water-insoluble nonionic polymer.
  • the water-insoluble nonionic polymer is preferably at least one selected from the group consisting of polyalkoxyalkyl (meth) acrylates, polyalkylene glycols, insolubilized polyalkyl (meth) acrylamides and polyvinylpyrrolidone.
  • the antibacterial medical device is manufactured by the first or second method. And an antibacterial medical device is manufactured by the said 1st or 2nd method, A silver particle is firmly fixed to the surface of a medical device, and antibacterial property is maintained at a high level over a long period of time.
  • the antibacterial medical device to be manufactured is a central venous catheter, a Foley catheter, a gastric tube catheter, an infusion tube, a ventilator, a dressing material, a feeding tube, a suture, and the like. .
  • the central venous catheter 1 placed in the blood vessel shown in FIG. 1 is preferable.
  • the central venous catheter 1 includes a tube-shaped main body 2 having a lumen (not shown) through which a drug solution or the like flows.
  • the central venous catheter 1 includes a tube-shaped distal end portion 3 joined to the distal end side of the main body portion 2, a hub 4 joined to the proximal end side of the main body portion 2, and a drug solution joined to the hub 4.
  • a connection tube 5 for injection and a connector 6 joined to the proximal end side of the connection tube 5 may be provided.
  • the distal side refers to the side inserted into the body
  • the proximal side refers to the side operated by the operator.
  • the antibacterial medical device is provided as an antibacterial medical device by imparting antibacterial properties to each of a plurality of components constituting the antibacterial medical device by the first or second method, and then joining the components. Also good.
  • antibacterial properties are imparted by manufacturing the main body 2, the tip 3, the hub 4, the connection tube 5 and the connector 6 by the first or second method.
  • a joining method a joining method such as adhesion using an adhesive, fusion by heat or ultrasonic waves, fitting by thermal contraction, or the like is used.
  • Each component is made of the same or different material among the materials described above.
  • the heat treatment (third step) in the first or second method may be performed after joining the components.
  • an antithrombotic material may be coated (fourth step).
  • a method for using the antibacterial medical device according to the present invention will be described using a central venous catheter used for central venous nutrition as an example.
  • a central venous catheter used for central venous nutrition
  • the first method is to introduce a central venous catheter into the blood vessel through the outer lumen while the outer needle is removed after introducing a puncture needle having a separable outer tube into the blood vessel and leaving the outer mantle. Through the cannula method).
  • the inner needle is removed, the guide wire is introduced into the blood vessel with the mantle remaining, and the guide wire is removed after the mantle is removed.
  • a central venous catheter is inserted and the guide wire is removed (Seldinger method).
  • any method can be preferably used.
  • Example 1 Comparative Example 1
  • a polyurethane tube having an outer diameter of 2.5 mm and an inner diameter of 1.75 mm was prepared using polyurethane (manufactured by Nippon Milactone Co., Ltd., trade name: E990), and a nano silver colloid solution (nanopoly) was formed on the surface of the polyurethane tube.
  • an antibacterial tube was produced by heat treatment at 150 ° C. for 30 minutes.
  • the comparative example 1 produced the antibacterial tube like Example 1 except not giving the heat processing for 150 degreeC x 30 minutes.
  • Example 1 Samples having a total surface area of 32 ⁇ 5 cm 2 were cut from the antibacterial tubes of Example 1 and Comparative Example 1. Next, this sample was immersed in a suspension of Staphylococcus aureus (10 mL), and after immersion for a predetermined period, using this bacterial suspension and the sample, the silver elution amount (ppm / day) and the antibacterial activity, respectively. The change in value over time was measured. The silver elution amount was measured using an ICP emission analyzer (Seiko Instruments), and the antibacterial activity value was measured using the shake method defined in the Antibacterial Test Technology Council Standard. The results are shown in FIG. 2 and FIG. FIG. 2 is a graph showing the change over time in the silver elution amount, and FIG. 3 is a graph showing the change over time in the antibacterial activity value.
  • Example 1 compared with Comparative Example 1, the amount of elution of silver is at a high level even after an immersion time of 10 days. It was confirmed that the sex was maintained.
  • Example 2 comparative example 2
  • a polypropylene sheet having a thickness of 0.4 mm was produced using polypropylene, and this polypropylene sheet was subjected to plasma treatment in an atmosphere of N 2 O gas.
  • a nanosilver colloidal solution (trade name Nanomix, manufactured by Nanopoly Co., Ltd., 3000 ppm ethanol solution) was applied and dried on the surface of the plasma-treated sheet, and then heat-treated at 150 ° C. for 30 minutes to prepare an antibacterial sheet.
  • an antibacterial sheet was produced in the same manner as in Example 2 except that the plasma treatment was not performed on the polypropylene sheet.
  • FIG. 4 is a graph showing changes in the elution amount of silver.
  • Example 2 the amount of silver elution was lower than that in Comparative Example 2. Therefore, it was confirmed that by performing the plasma treatment, the silver elution amount in the initial stage of use can be lowered, so that the silver elution amount can be maintained at a high level for a long period of time and antibacterial properties can be maintained for a long period of time.
  • Example 3 to 6, Comparative Example 3 a polyurethane tube having an outer diameter of 2.5 mm and an inner diameter of 1.75 mm was prepared using polyurethane (manufactured by Nippon Milactone Co., Ltd., trade name: E990), and a nano silver colloid solution was formed on the surface of the polyurethane tube. (Nanopoly Co., Ltd., trade name Nanomix, 3000 ppm ethanol solution) is applied and dried, and then subjected to heat treatment under predetermined conditions (heat treatment temperature: 80, 100, 150, 190 ° C., heat treatment time: 0 to 25 hours) to be antibacterial A tube was prepared.
  • predetermined conditions heat treatment temperature: 80, 100, 150, 190 ° C., heat treatment time: 0 to 25 hours
  • the comparative example 3 produced the antibacterial tube like Example 3 except not heat-processing (room temperature: untreated). Then, samples were cut out from the antibacterial tubes of Examples 3 to 6 and Comparative Example 3 in the same manner as in Example 2, and the silver elution amount was measured. The measurement result of the silver elution amount is as shown in FIG. FIG. 5 is a graph showing changes in the elution amount of silver.
  • the amount of silver elution was lower than that in Comparative Example 3. Therefore, by performing heat treatment, it was confirmed that the silver elution amount in the initial stage of use can be lowered, so that the silver elution amount can be maintained at a high level over a long period of time and the antibacterial property can be maintained over a long period of time. Further, when the heat treatment temperature was 100 ° C. or higher, it was confirmed that the amount of elution of silver can be lowered by a short heat treatment, and thus the economy is excellent.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pulmonology (AREA)
  • Anesthesiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Materials Engineering (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Disclosed is a method for producing an antimicrobial medical instrument, which is characterized by comprising a first step wherein a medical instrument is formed from a material which contains an element capable of forming a complex with silver, a second step wherein silver-based particles are introduced to the surface of the medical instrument, and a third step wherein the silver-based particles are immobilized on the surface of the medical instrument by subjecting the medical instrument, to which the silver-based particles have been introduced, to a heat treatment.  Also disclosed is an antimicrobial medical instrument which is characterized by being produced by the above-specified production method.

Description

抗菌性医療器具の製造方法および抗菌性医療器具Antibacterial medical device manufacturing method and antibacterial medical device
　本発明は、抗菌性医療器具の製造方法およびそれによって製造される抗菌性医療器具に関するものである。特に、中心静脈栄養術を施行する際に血管内に留置する中心静脈カテーテルに関するものである。 The present invention relates to a method for producing an antibacterial medical device and an antibacterial medical device produced thereby. In particular, the present invention relates to a central venous catheter that is placed in a blood vessel when performing central venous nutrition.
　従来、医療器具の1つである中心静脈カテーテルにおいては、カテーテルの皮膚刺入部あるいは内腔を介して細菌が体内に進入し、細菌感染を起こすことがある。感染が重篤であると敗血症になる可能性もある。カテーテル先端付着菌と敗血症の原因菌が一致する場合を特にカテーテル関連菌血症（ＣＲ－ＢＳＩ：ｃａｔｈｅｔｅｒ　ｒｅｌａｔｅｄ－ｂｌｏｏｄｓｔｒｅａｍ　ｉｎｆｅｃｔｉｏｎ）といい、ＣＲ－ＢＳＩによって患者が死亡することもある。 Conventionally, in a central venous catheter, which is one of medical devices, bacteria may enter the body through the skin puncture site or lumen of the catheter and cause bacterial infection. Severe infection can result in sepsis. The case where the catheter tip adherent bacteria and the causative bacteria of the sepsis coincide is particularly referred to as catheter-related bacteremia (CR-BSI), and the patient may die due to CR-BSI.
　このような問題を回避するにあたり、ＣＲ－ＢＳＩが疑われたり、ＣＲ－ＢＳＩと診断されたりした場合には、抗生物質の投与や新しいカテーテルへの交換などが行なわれることが一般的である。しかしながら、ＣＲ－ＢＳＩは留置時の合併症であるが、上記処置は本来の治療内容から逸脱するため、医療機関にとっては医療コストを増大させる要因となる。そこで、抗菌性が高いカテーテルの開発が要望されている。 In order to avoid such problems, when CR-BSI is suspected or diagnosed with CR-BSI, antibiotics are generally administered or a new catheter is exchanged. However, although CR-BSI is a complication at the time of indwelling, the above-mentioned treatment deviates from the original treatment content, which causes a medical cost increase for medical institutions. Therefore, development of a catheter with high antibacterial properties is desired.
　このような抗菌性カテーテルの製造方法として、特許文献１には、基材に対して所定量の銀置換無機イオン交換体等の抗菌剤を混合することによって抗菌性を有する体内挿入用チューブ（カテーテル）を製造することが記載されている。また、特許文献２にも、基材の表面に銀化合物を導入（コーティング）、具体的には、基材に対してアミノ酸誘導体、陰イオン界面活性剤、カルボキシル基またはスルホン基を有する化合物等の銀イオンと結合可能な化合物を吸収せしめた後、酢酸銀等の銀化合物水溶液に浸漬することによって抗菌性を有する導尿カテーテルを製造することが記載されている。 As a method for producing such an antibacterial catheter, Patent Document 1 discloses an in-vivo insertion tube (catheter) having antibacterial properties by mixing a predetermined amount of an antibacterial agent such as a silver-substituted inorganic ion exchanger with a base material. ) Is described. Also in Patent Document 2, a silver compound is introduced (coating) on the surface of a base material, specifically, an amino acid derivative, an anionic surfactant, a compound having a carboxyl group or a sulfone group on the base material, etc. It is described that a urinary catheter having antibacterial properties is produced by absorbing a compound capable of binding to silver ions and then immersing it in an aqueous silver compound solution such as silver acetate.
特開平５－２２０２１６号公報（請求項１～請求項４）JP-A-5-220216 (Claims 1 to 4) 特開平１１－２９０４４９号公報（請求項１～請求項５）JP-A-11-290449 (Claims 1 to 5)
　しかしながら、特許文献１および特許文献２に記載されたカテーテルの製造方法においては、銀化合物（抗菌剤）の基材に対する結合力が弱く、銀化合物（抗菌剤）の粒径も大きいため、カテーテル使用の際にカテーテル内腔を流れる薬液、体液等によって、銀化合物（抗菌剤）が短期に溶出する。そのため、製造されたカテーテルの抗菌性を長期にわたって高いレベルに維持できないという問題がある。また、カテーテル以外の医療器具の製造においても、抗菌性については同様な問題がある。 However, in the catheter manufacturing methods described in Patent Document 1 and Patent Document 2, since the binding force of the silver compound (antibacterial agent) to the base material is weak and the particle size of the silver compound (antibacterial agent) is large, the catheter is used. At this time, the silver compound (antibacterial agent) elutes in a short period of time by chemicals, body fluids, and the like flowing through the catheter lumen. Therefore, there is a problem that the antibacterial property of the manufactured catheter cannot be maintained at a high level over a long period of time. Further, in the manufacture of medical devices other than catheters, there are similar problems regarding antibacterial properties.
　そこで、本発明は、このような問題を解決すべく創案されたもので、その目的は抗菌性を長期にわたって高いレベルに維持できる抗菌性医療器具の製造方法およびそれによって製造される抗菌性医療器具を提供することにある。 Therefore, the present invention was created to solve such problems, and its purpose is to provide a method for manufacturing an antibacterial medical device that can maintain antibacterial properties at a high level over a long period of time, and an antibacterial medical device manufactured thereby. Is to provide.
　前記課題を解決するために、本発明に係る抗菌性医療器具の製造方法は、銀と錯体を形成することが可能な元素を含む材料で医療器具を作製する第１ステップと、前記医療器具の表面に銀系粒子を導入する第２ステップと、前記銀系粒子が導入された医療器具を熱処理して、前記医療器具の表面に銀系粒子を固定する第３ステップとを含むことを特徴とする。 In order to solve the above problems, a method for manufacturing an antibacterial medical device according to the present invention includes a first step of manufacturing a medical device with a material containing an element capable of forming a complex with silver, A second step of introducing silver-based particles on the surface; and a third step of fixing the silver-based particles on the surface of the medical device by heat-treating the medical device into which the silver-based particles have been introduced. To do.
　前記手順によれば、第1ステップにおいて、銀と錯体を形成することが可能な元素を有する医療器具が作製される。また、第２ステップで医療器具の表面に導入された銀系粒子が、第３ステップの熱処理によって、医療器具の表面の元素と錯体を形成するか、銀と錯体を形成することが可能な元素の還元作用により純銀粒子になり、銀系粒子が医療器具の表面に強固に固定される。その結果、使用の際に医療器具の表面から溶出する銀系粒子の溶出量、特に、初期段階の溶出量を少なくできるため、溶出量が長期にわたって高いレベルに維持される。 According to the above procedure, in the first step, a medical device having an element capable of forming a complex with silver is produced. In addition, the silver-based particles introduced into the surface of the medical device in the second step can form a complex with the element on the surface of the medical device or can form a complex with silver by the heat treatment in the third step. Due to the reducing action, pure silver particles are obtained, and the silver-based particles are firmly fixed to the surface of the medical device. As a result, the elution amount of silver-based particles eluted from the surface of the medical device during use, particularly the elution amount in the initial stage, can be reduced, so that the elution amount is maintained at a high level over a long period of time.
　また、本発明に係る抗菌性医療器具の製造方法は、銀と錯体を形成することが可能な元素を含まない材料で医療器具を作製し、その後、前記医療器具の表面に前記元素を導入する第１ステップと、前記元素が導入された医療器具の表面に銀系粒子を導入する第２ステップと、前記銀系粒子が導入された医療器具を熱処理して、前記医療器具の表面に銀系粒子を固定する第３ステップとを含むことを特徴とする。 In addition, the method for manufacturing an antibacterial medical device according to the present invention produces a medical device using a material that does not contain an element capable of forming a complex with silver, and then introduces the element onto the surface of the medical device. A first step, a second step of introducing silver-based particles on the surface of the medical device into which the element has been introduced, and a heat treatment of the medical device into which the silver-based particles have been introduced to form a silver-based material on the surface of the medical device And a third step of fixing the particles.
　前記手順によれば、第1ステップにおいて、銀と錯体を形成することが可能な元素を有する医療器具が作製される。また、第２ステップで医療器具の表面に導入された銀系粒子が、第３ステップの熱処理によって、医療器具の表面の元素と錯体を形成するか、銀と錯体を形成することが可能な元素の還元作用により純銀粒子になり、銀系粒子が医療器具の表面に強固に固定される。その結果、使用の際に医療器具の表面から溶出する銀系粒子の溶出量、特に、初期段階の溶出量を少なくできるため、溶出量が長期にわたって高いレベルに維持される。 According to the above procedure, in the first step, a medical device having an element capable of forming a complex with silver is produced. In addition, the silver-based particles introduced into the surface of the medical device in the second step can form a complex with the element on the surface of the medical device or can form a complex with silver by the heat treatment in the third step. Due to the reducing action, pure silver particles are obtained, and the silver-based particles are firmly fixed to the surface of the medical device. As a result, the elution amount of silver-based particles eluted from the surface of the medical device during use, particularly the elution amount in the initial stage, can be reduced, so that the elution amount is maintained at a high level over a long period of time.
　また、本発明に係る抗菌性医療器具の製造方法は、前記第３ステップの後に、前記医療器具の表面に抗血栓性材料を被覆する第４ステップをさらに含むことを特徴とする。
　前記手順によれば、抗血栓性材料を被覆する第４ステップを行うことによって、医療器具の表面に抗血栓性が付与される。 In addition, the method for manufacturing an antibacterial medical device according to the present invention further includes a fourth step of coating the surface of the medical device with an antithrombotic material after the third step.
According to the said procedure, antithrombogenicity is provided to the surface of a medical device by performing the 4th step which coat | covers antithrombogenic material.
　また、本発明に係る抗菌性医療器具の製造方法は、前記元素が、Ｓ、Ｎ、ＯおよびＰから選ばれる１元素以上であることを特徴とする。 The method for manufacturing an antibacterial medical device according to the present invention is characterized in that the element is one or more elements selected from S, N, O and P.
　前記手順によれば、第1ステップにおいてＳ、Ｎ、ＯおよびＰから選ばれる１元素以上を有する医療器具が作製されることによって、第３ステップの熱処理において、医療器具の表面に導入された銀系粒子が錯体を形成しやすくなり、医療器具の表面に銀系粒子がさらに強固に固定される。その結果、使用の際に医療器具の表面から溶出する銀系粒子の溶出量が長期にわたってさらに高いレベルに維持される。 According to the above procedure, the silver introduced into the surface of the medical device in the heat treatment of the third step by producing a medical device having one or more elements selected from S, N, O and P in the first step. The system particles easily form a complex, and the silver particles are more firmly fixed on the surface of the medical device. As a result, the amount of silver-based particles eluted from the surface of the medical device during use is maintained at a higher level over a long period of time.
　また、本発明に係る抗菌性医療器具の製造方法は、前記第３ステップにおいて、前記銀系粒子が導入された医療器具を８０～３００℃で熱処理することを特徴とする。 The method for manufacturing an antibacterial medical device according to the present invention is characterized in that, in the third step, the medical device into which the silver-based particles are introduced is heat-treated at 80 to 300 ° C.
　前記手順によれば、熱処理を所定温度で行うことによって、医療器具の表面に導入された銀系粒子が錯体を形成しやすくなり、医療器具の表面に銀系粒子がさらに強固に固定される。その結果、使用の際に医療器具の表面から溶出する銀系粒子の溶出量が長期にわたってさらに高いレベルに維持される。特に、初期段階の溶出量を少なくできるため、溶出量が長期にわたってさらに高いレベルに維持される。 According to the above procedure, by performing the heat treatment at a predetermined temperature, the silver-based particles introduced to the surface of the medical device can easily form a complex, and the silver-based particles are more firmly fixed to the surface of the medical device. As a result, the amount of silver-based particles eluted from the surface of the medical device during use is maintained at a higher level over a long period of time. In particular, since the amount of elution in the initial stage can be reduced, the amount of elution is maintained at a higher level over a long period of time.
　また、本発明に係る抗菌性医療器具の製造方法は、前記銀系粒子が、純銀粒子、または、硝酸銀、酢酸銀、アジ化銀および過塩素酸銀のいずれか１つ以上の銀塩粒子であることを特徴とする。 Further, in the method for producing an antibacterial medical device according to the present invention, the silver-based particles are pure silver particles or silver salt particles of any one or more of silver nitrate, silver acetate, silver azide and silver perchlorate. It is characterized by being.
　前記手順によれば、銀系粒子が純銀粒子であることによって、医療器具の表面に純銀粒子を含む錯体を形成し、医療器具の表面に銀系粒子が強固に固定される。また、銀系粒子が銀塩粒子であることによって、銀塩粒子が、銀と錯体を形成することが可能な元素の還元作用により純銀粒子になり、その一部が純銀粒子を含む錯体を形成し、医療器具の表面に銀系粒子が強固に固定される。その結果、使用の際に医療器具の表面から溶出する銀系粒子の溶出量が長期にわたってさらに高いレベルに維持される。特に、初期段階の溶出量を少なくできるため、溶出量が長期にわたってさらに高いレベルに維持される。 According to the above procedure, since the silver-based particles are pure silver particles, a complex containing pure silver particles is formed on the surface of the medical device, and the silver-based particles are firmly fixed on the surface of the medical device. In addition, since the silver-based particles are silver salt particles, the silver salt particles become pure silver particles due to the reducing action of elements capable of forming a complex with silver, and some of them form a complex containing pure silver particles. In addition, the silver particles are firmly fixed on the surface of the medical device. As a result, the amount of silver-based particles eluted from the surface of the medical device during use is maintained at a higher level over a long period of time. In particular, since the amount of elution in the initial stage can be reduced, the amount of elution is maintained at a higher level over a long period of time.
　本発明に係る抗菌性医療器具は、前記の製造方法によって製造されることを特徴とする。
　前記構成によれば、前記製造方法によって製造されることによって、医療器具の表面に銀系粒子（ナノ銀粒子）が強固に固定される。その結果、使用の際に医療器具の表面から溶出する銀系粒子（ナノ銀粒子）の溶出量が長期にわたって高いレベルに維持される。また、抗血栓性が付与される。 The antibacterial medical device according to the present invention is manufactured by the above manufacturing method.
According to the said structure, silver type particle | grains (nanosilver particle) are firmly fixed to the surface of a medical device by manufacturing with the said manufacturing method. As a result, the amount of silver-based particles (nanosilver particles) eluted from the surface of the medical device during use is maintained at a high level over a long period of time. In addition, antithrombogenicity is imparted.
　本発明に係る抗菌性医療器具の製造方法によれば、付着した細菌の増殖または感染が長期にわたって抑制され、抗菌性が長期にわたって高いレベルに維持できる抗菌性医療器具が製造される。また、抗血栓性が付与された抗菌性医療器具が製造される。
　本発明に係る抗菌性医療器具によれば、付着した細菌の増殖または感染が長期にわたって抑制され、抗菌性が長期にわたって高いレベルに維持できる。また、抗菌性医療器具に抗血栓性が付与される。 According to the method for producing an antibacterial medical device according to the present invention, an antibacterial medical device in which the growth or infection of attached bacteria is suppressed for a long time and the antibacterial property can be maintained at a high level for a long time is produced. In addition, an antibacterial medical device with antithrombogenic properties is produced.
According to the antibacterial medical device of the present invention, the growth or infection of attached bacteria can be suppressed over a long period of time, and the antibacterial property can be maintained at a high level over a long period of time. Moreover, antithrombogenicity is imparted to the antibacterial medical device.
中心静脈カテーテルの構成を示す外観図である。It is an external view which shows the structure of a central venous catheter. 銀溶出量の経時変化を示すグラフである。It is a graph which shows a time-dependent change of silver elution amount. 抗菌活性値の経時変化を示すグラフである。It is a graph which shows a time-dependent change of an antibacterial activity value. 銀溶出量の変化量を示すグラフである。It is a graph which shows the variation | change_quantity of silver elution amount. 銀溶出量の変化量を示すグラフである。It is a graph which shows the variation | change_quantity of silver elution amount.
　本発明に係る抗菌性医療器具の製造方法について説明する。
　本発明において、抗菌性医療器具とは、抗菌性が付与された医療器具であって、例えば、中心静脈カテーテル、フォーリーカテーテル、胃管カテーテル、輸液チューブ、人工呼吸器、ドレッシング材、フィーディングチューブ、縫合糸等である。また、抗菌性医療器具を構成する部品、例えば、図１に示す中心静脈カテーテル１を構成する本体部２、先端部３、ハブ４、接続チューブ５およびコネクター６も、本発明の抗菌性医療器具に含まれるものとする。なお、図１は、中心静脈カテーテルの構成を示す外観図である。 A method for producing an antibacterial medical device according to the present invention will be described.
In the present invention, the antibacterial medical device is a medical device imparted with antibacterial properties, such as a central venous catheter, a Foley catheter, a gastric tube catheter, an infusion tube, a ventilator, a dressing material, a feeding tube, Sutures and the like. Further, the parts constituting the antibacterial medical instrument, for example, the main body part 2, the tip part 3, the hub 4, the connecting tube 5 and the connector 6 constituting the central venous catheter 1 shown in FIG. Shall be included. FIG. 1 is an external view showing the configuration of the central venous catheter.
　本発明の第１の方法は、銀と錯体を形成することが可能な元素を含む材料で医療器具を作製する第１ステップと、前記医療器具の表面に銀系粒子を導入する第２ステップと、前記銀系粒子が導入された医療器具を熱処理して、前記医療器具の表面に銀系粒子を固定する第３ステップとを含むことを特徴とする。 The first method of the present invention includes a first step of producing a medical device with a material containing an element capable of forming a complex with silver, and a second step of introducing silver-based particles on the surface of the medical device. And a third step of fixing the silver-based particles on the surface of the medical device by heat-treating the medical device into which the silver-based particles have been introduced.
　また、第１の方法では、医療器具の造影性を確保する目的で、造影剤の多層成形、造影剤の材料への均一分散を行ってもよい。造影剤としては、硫酸バリウム、炭酸バリウム、酸化ビスマス、次炭酸ビスマス、タングステン等の無機化合物が用いられる。
　以下、各ステップについて説明する。 In the first method, for the purpose of ensuring the contrast of the medical device, multilayer formation of the contrast agent and uniform dispersion of the contrast agent in the material may be performed. As the contrast agent, inorganic compounds such as barium sulfate, barium carbonate, bismuth oxide, bismuth subcarbonate and tungsten are used.
Hereinafter, each step will be described.
　第1ステップにおいて、銀と錯体を形成することが可能な元素とは、孤立電子対を有する元素であって、Ｓ、Ｎ、ＯおよびＰから選ばれる１元素以上が好ましい。そして、これらの元素を含む材料、具体的には元素を含む官能基（例えば、チオール基、アミノ基、カルボキシル基、フォスフィノ基等）を有する材料としては、高分子材料が好ましく、例えば、ポリウレタン、ナイロン、ポリカーボネイト、ポリエステル、シリコーン樹脂または、これらの樹脂のうちの２種以上を組み合わせて得た樹脂組成物等が使用できる。さらに、医療器具の作製方法については、従来の医療器具の作製方法が使用でき、例えば、押出成形、射出成形等が使用できる。 In the first step, the element capable of forming a complex with silver is an element having a lone electron pair, and preferably one or more elements selected from S, N, O and P. A material containing these elements, specifically, a material having a functional group containing an element (for example, thiol group, amino group, carboxyl group, phosphino group, etc.) is preferably a polymer material, such as polyurethane, Nylon, polycarbonate, polyester, silicone resin, or a resin composition obtained by combining two or more of these resins can be used. Furthermore, as a method for producing a medical device, a conventional method for producing a medical device can be used, for example, extrusion molding, injection molding, or the like.
　第２ステップでは、医療器具の表面に銀系粒子を導入する。銀系粒子は、純銀粒子または銀塩粒子であることが好ましく、ナノ銀粒子または銀塩ナノ粒子であることがさらに好ましい。ここで、ナノ銀粒子または銀塩ナノ粒子とは、粒径１０－９ｍ～１０－８ｍの銀粒子である。また、銀系粒子は、導入後の熱処理等により、純銀粒子に変化するものであればよく、例えば、純銀粒子のみならず、溶液中において、純銀以外の硝酸銀、酢酸銀、アジ化銀、過塩素酸銀またはその混合物の銀塩粒子であっても、導入後の熱処理等により、純銀粒子に変化するものであればよい。 In the second step, silver-based particles are introduced on the surface of the medical device. The silver-based particles are preferably pure silver particles or silver salt particles, and more preferably nano silver particles or silver salt nanoparticles. Here, the nano silver particles or silver salt nanoparticles are silver particles having a particle size of 10 −9 m to 10 −8 m. Further, the silver-based particles only need to change into pure silver particles by heat treatment after the introduction, for example, not only pure silver particles but also silver nitrate other than pure silver, silver acetate, silver azide, excess Even silver salt particles of silver chlorate or a mixture thereof may be used as long as they can be converted into pure silver particles by heat treatment after introduction.
　銀系粒子の導入方法については、コーティング、スパッタリング、化学メッキ等が使用できる。コーティングには、銀系粒子溶液が使用され、溶媒としては有機溶媒または水と有機溶媒の混合溶媒が好ましい。有機溶媒としては、テトラハイドロフラン、ジメチルホルムアミド、ジメチルアセトアミド、シクロヘキサノン、メチルエチルケトン、ジメチルスルホキシド、アセトン、メタノール、エタノール、イソプロパノール、ジエチルエーテル、ヘキサン等が使用できる。さらに、有機溶媒としては疎水性有機溶媒（例えば、シクロヘキサノン、メチルエチルケトン）が好ましい。疎水性有機溶媒を使用することによって、医療器具の表面への銀系粒子の固定が溶媒乾燥時の吸着水分によって妨げられることがないため、医療器具の表面に十分な量の銀系粒子が固定される。なお、銀系粒子溶液の濃度は、銀系粒子がナノ銀粒子の場合には１０～１００００ｐｐｍが好ましい。 For the method of introducing silver-based particles, coating, sputtering, chemical plating, or the like can be used. For coating, a silver particle solution is used, and the solvent is preferably an organic solvent or a mixed solvent of water and an organic solvent. As the organic solvent, tetrahydrofuran, dimethylformamide, dimethylacetamide, cyclohexanone, methyl ethyl ketone, dimethyl sulfoxide, acetone, methanol, ethanol, isopropanol, diethyl ether, hexane and the like can be used. Furthermore, the organic solvent is preferably a hydrophobic organic solvent (for example, cyclohexanone, methyl ethyl ketone). By using a hydrophobic organic solvent, fixation of silver particles on the surface of the medical device is not hindered by moisture adsorbed during solvent drying, so a sufficient amount of silver particles are fixed on the surface of the medical device. Is done. The concentration of the silver-based particle solution is preferably 10 to 10,000 ppm when the silver-based particles are nano silver particles.
　第３ステップでは、銀系粒子が導入された医療器具を熱処理して、医療器具の表面に銀系粒子を固定させる。すなわち、医療器具の表面に存在する前記元素（例えば、Ｓ，Ｎ，Ｏ、Ｐ）と銀系粒子とで錯体を形成させる。これにより、医療器具の表面に銀系粒子が固定される。その結果、医療器具に抗菌性が付与される。 In the third step, the medical device into which the silver-based particles are introduced is heat-treated to fix the silver-based particles on the surface of the medical device. That is, a complex is formed by the element (for example, S, N, O, P) present on the surface of the medical device and silver-based particles. Thereby, silver-type particle | grains are fixed to the surface of a medical device. As a result, antibacterial properties are imparted to the medical device.
　銀系粒子が純銀粒子の場合には、熱処理等によって、医療器具の表面に導入された純銀粒子と、銀と錯体を形成することが可能な元素とが錯体を形成し、銀系粒子が医療器具の表面に強固に固定される。また、銀系粒子が銀塩粒子の場合には、熱処理等によって、医療器具の表面に導入された銀塩粒子が、銀と錯体を形成することが可能な元素の還元作用により純銀粒子になる。そして、純銀粒子の一部と前記元素とが錯体を形成し、銀系粒子が医療器具の表面に強固に固定される。 When the silver-based particles are pure silver particles, the pure silver particles introduced onto the surface of the medical device by heat treatment or the like and an element capable of forming a complex with silver form a complex, and the silver-based particles are medical. It is firmly fixed to the surface of the instrument. When the silver-based particles are silver salt particles, the silver salt particles introduced to the surface of the medical device by heat treatment or the like become pure silver particles due to the reducing action of an element capable of forming a complex with silver. . A part of the pure silver particles and the element form a complex, and the silver-based particles are firmly fixed to the surface of the medical device.
また、熱処理温度としては、８０～３００℃が好ましく、１００～２００℃がさらに好ましい。熱処理温度が８０℃未満であると、銀系粒子の固定が不十分になりやすく、医療器具を使用した際、初期段階での銀系粒子の溶出量が増加しやすい。その結果、医療器具から溶出する銀系粒子の溶出量が長期にわたって高いレベルに維持できず、医療器具の抗菌性を長期にわたって維持しにくくなる。熱処理温度が３００℃を超えると、医療器具を構成する高分子材料の物性変化、および、銀系粒子の劣化が生じやくなる。さらに、熱処理時間は、８０℃では１～７２時間、３００℃では１０秒～１時間が好ましい。熱処理時間が短いと銀系粒子の固定が不十分になりやすく、熱処理時間が長いと高分子材料の物性変化、および、銀系粒子の劣化が生じやすくなる。 The heat treatment temperature is preferably 80 to 300 ° C, more preferably 100 to 200 ° C. When the heat treatment temperature is less than 80 ° C., silver-based particles are likely to be insufficiently fixed, and the amount of silver-based particles eluted at the initial stage is likely to increase when a medical instrument is used. As a result, the elution amount of silver-based particles eluted from the medical device cannot be maintained at a high level over a long period of time, and it becomes difficult to maintain the antibacterial properties of the medical device over a long period of time. When the heat treatment temperature exceeds 300 ° C., changes in physical properties of the polymer material constituting the medical device and deterioration of the silver-based particles are likely to occur. Further, the heat treatment time is preferably 1 to 72 hours at 80 ° C. and 10 seconds to 1 hour at 300 ° C. If the heat treatment time is short, the fixation of the silver particles tends to be insufficient, and if the heat treatment time is long, the physical properties of the polymer material change and the silver particles are likely to deteriorate.
　本発明の第２の方法は、銀と錯体を形成することが可能な元素を含まない材料で医療器具を作製し、その後、前記医療器具の表面に前記元素を導入する第１ステップと、前記元素が導入された医療器具の表面に銀系粒子を導入する第２ステップと、前記銀系粒子が導入された医療器具を熱処理して、前記医療器具の表面に銀系粒子を固定する第３ステップとを含むことを特徴とする。以下、各ステップについて説明する。 The second method of the present invention includes a first step of producing a medical device with a material that does not contain an element capable of forming a complex with silver, and then introducing the element onto the surface of the medical device; A second step of introducing silver-based particles onto the surface of the medical device into which the element has been introduced; and a third step of heat-treating the medical device into which the silver-based particles have been introduced to fix the silver-based particles on the surface of the medical device. And a step. Hereinafter, each step will be described.
　第１ステップにおいて、銀と錯体を形成することが可能な元素とは、前記した第１の方法と同様に、孤立電子対を有する元素であって、Ｓ、Ｎ、ＯおよびＰから選ばれる１元素以上が好ましい。そして、これらの元素を含まない材料としては、高分子材料または金属材料が好ましい。高分子材料としては、ポリエチレン、ポリプロピレン、ポリ塩化ビニル、または、これらの樹脂のうちの２種以上を組み合わせて得た樹脂組成物等が使用できる。また、医療器具の作製方法については、前記した第１の方法と同様に、従来の医療器具の作製方法が使用でき、押出成形、射出成形等が使用できる。 In the first step, the element capable of forming a complex with silver is an element having a lone pair of electrons, as in the first method, and is selected from S, N, O and P More than element is preferable. And as a material which does not contain these elements, a polymeric material or a metal material is preferable. As the polymer material, polyethylene, polypropylene, polyvinyl chloride, or a resin composition obtained by combining two or more of these resins can be used. As for the method for producing a medical device, a conventional method for producing a medical device can be used as in the first method, and extrusion molding, injection molding, or the like can be used.
　また、第１ステップにおいて、医療器具の表面に前記元素を導入する方法としては、前記元素を含む化合物（例えば、Ｎ２Ｏガス）をターゲットとして用いるプラズマ処理、前記元素を含む官能基（例えば、チオール基、アミノ基、カルボキシル基）のグラフト重合、または、前記元素を含む化合物のコーティング等が使用できる。 In the first step, as a method for introducing the element into the surface of the medical device, plasma treatment using a compound containing the element (for example, N 2 O gas) as a target, functional group containing the element (for example, (Graft polymerization of thiol group, amino group, carboxyl group) or coating of a compound containing the element can be used.
　第２ステップおよび第３ステップは、前記した第１の方法と同様であるので、説明を省略する。また、第２の方法では、前記した第１の方法と同様に、医療器具の造影性を確保する目的で、造影剤の多層成形、造影剤の材料への均一分散を行ってもよい。 Since the second step and the third step are the same as the first method described above, description thereof is omitted. In the second method, as in the first method described above, for the purpose of ensuring the contrast of the medical device, multilayer forming of the contrast agent and uniform dispersion of the contrast agent material may be performed.
　本発明に係る抗菌性医療器具の製造方法は、前記した第１の方法または第２の製造方法において、第３ステップの後に、前記医療器具の表面に抗血栓性材料を被覆する第４ステップをさらに含んでもよい。 The method for manufacturing an antibacterial medical device according to the present invention includes the fourth step of coating the surface of the medical device with an antithrombogenic material after the third step in the first method or the second manufacturing method. Further, it may be included.
　第４ステップにおいて、医療器具の表面に抗血栓性材料を被覆する方法としては、抗血栓性材料が溶解した溶液を、デッピング法やスプレー法等によってコーティングする方法等を用いる。そして、抗血栓性材料を溶解する溶媒としては、アセトン、メタノール、エタノール、イソプロパノール、テトラヒドロフラン、Ｎ，Ｎ－ジメチルホルムアミド、Ｎ，Ｎ－ジメチルアセトアミド、シクロヘキサノン等の有機溶媒がある。 In the fourth step, as a method of coating the surface of the medical device with the antithrombotic material, a method of coating a solution in which the antithrombotic material is dissolved by a dipping method, a spray method, or the like is used. Examples of the solvent that dissolves the antithrombotic material include organic solvents such as acetone, methanol, ethanol, isopropanol, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide, and cyclohexanone.
　そして、抗血栓性材料としては、ヘパリン等のムコ多糖類やウロキナーゼ等のタンパク質等の生体由来材料、または、非水溶性ノニオン系高分子等の非生体由来材料からなるものである。そして、非水溶性ノニオン系高分子としては、ポリアルコキシアルキル（メタ）アクリレート、ポリアルキレングリコール、不溶化処理されたポリアルキル（メタ）アクリルアミドおよびポリビニルピロリドンからなる群から選択される少なくとも１つが好ましい。 The antithrombotic material is made of a biological material such as a mucopolysaccharide such as heparin or a protein such as urokinase, or a non-biological material such as a water-insoluble nonionic polymer. The water-insoluble nonionic polymer is preferably at least one selected from the group consisting of polyalkoxyalkyl (meth) acrylates, polyalkylene glycols, insolubilized polyalkyl (meth) acrylamides and polyvinylpyrrolidone.
　次に、本発明に係る抗菌性医療器具について説明する。
　抗菌性医療器具は、前記第１または第２の方法で製造されることを特徴とする。そして、抗菌性医療器具は、前記第１または第２の方法で製造されることによって、銀系粒子が医療器具の表面に強固に固定され、抗菌性が長期にわたって高いレベルに維持される。また、本発明において、製造される抗菌性医療器具は、前記したように、中心静脈カテーテル、フォーリーカテーテル、胃管カテーテル、輸液チューブ、人工呼吸器、ドレッシング材、フィーディングチューブ、縫合糸等である。好ましくは、図１に示す血管内に留置される中心静脈カテーテル１である。 Next, the antibacterial medical device according to the present invention will be described.
The antibacterial medical device is manufactured by the first or second method. And an antibacterial medical device is manufactured by the said 1st or 2nd method, A silver particle is firmly fixed to the surface of a medical device, and antibacterial property is maintained at a high level over a long period of time. In the present invention, as described above, the antibacterial medical device to be manufactured is a central venous catheter, a Foley catheter, a gastric tube catheter, an infusion tube, a ventilator, a dressing material, a feeding tube, a suture, and the like. . The central venous catheter 1 placed in the blood vessel shown in FIG. 1 is preferable.
　図１に示すように、中心静脈カテーテル１は、薬液等が流れる内腔（図示せず）を有するチューブ状の本体部２を備えるものである。また、中心静脈カテーテル１は、本体部２の先端側に接合されたチューブ状の先端部３を備えると共に、本体部２の基端側に接合されたハブ４と、ハブ４に接合された薬液注入のための接続チューブ５と、接続チューブ５の基端側に接合されたコネクター６を備えてもよい。なお、本発明において、先端側とは体内に挿入する側、基端側とは術者によって操作する側をいう。 As shown in FIG. 1, the central venous catheter 1 includes a tube-shaped main body 2 having a lumen (not shown) through which a drug solution or the like flows. The central venous catheter 1 includes a tube-shaped distal end portion 3 joined to the distal end side of the main body portion 2, a hub 4 joined to the proximal end side of the main body portion 2, and a drug solution joined to the hub 4. A connection tube 5 for injection and a connector 6 joined to the proximal end side of the connection tube 5 may be provided. In the present invention, the distal side refers to the side inserted into the body, and the proximal side refers to the side operated by the operator.
　また、抗菌性医療器具は、抗菌性医療器具を構成する複数の部品毎に前記第１、または第２の方法で抗菌性を付与し、その後、各部品を接合することによって抗菌性医療器具としてもよい。例えば、図１に示すように、本体部２、先端部３、ハブ４、接続チューブ５およびコネクター６を前記第１または第２の方法で製造することによって抗菌性を付与し、その後、各部品を接合することによって、中心静脈カテーテル１とする。ここで、接合方法としては、接着剤を使用した接着、熱または超音波による融着、熱収縮による嵌合等の接合方法を用いる。なお、各部品は、前記した材料のうちの同種または異種の材料からなる。また、第１または第２の方法における熱処理（第３ステップ）は、各部品の接合後に行ってもよい。さらに、抗血栓性材料の被覆（第４ステップ）を行ってもよい。 In addition, the antibacterial medical device is provided as an antibacterial medical device by imparting antibacterial properties to each of a plurality of components constituting the antibacterial medical device by the first or second method, and then joining the components. Also good. For example, as shown in FIG. 1, antibacterial properties are imparted by manufacturing the main body 2, the tip 3, the hub 4, the connection tube 5 and the connector 6 by the first or second method. To obtain a central venous catheter 1. Here, as a joining method, a joining method such as adhesion using an adhesive, fusion by heat or ultrasonic waves, fitting by thermal contraction, or the like is used. Each component is made of the same or different material among the materials described above. Further, the heat treatment (third step) in the first or second method may be performed after joining the components. Furthermore, an antithrombotic material may be coated (fourth step).
　次に、本発明に係る抗菌性医療器具の使用方法について、中心静脈栄養法に使用される中心静脈カテーテルを例にとって説明する。一般的に、中心静脈栄養法に使用される中心静脈カテーテルの使用方法（血管内への挿入方法）については、図示しないが、大きく２通りの方法がある。１つ目は、分割可能な外套管を有する穿刺針を血管内に導入後、内針を抜去し、外套を残した状態で外套内腔を介して血管内に中心静脈カテーテルを挿入する方法（スルーザカニューラ法）である。また、２つ目は、外套管を有する留置針を血管内に導入後、内針を抜去し、外套を残した状態で、ガイドワイヤーを血管内に導入し、外套を抜去後そのガイドワイヤーを介して中心静脈カテーテルを挿入し、ガイドワイヤーを抜去する方法（セルジンガー法）である。本発明の中心静脈カテーテルでは、いずれの方法でも好ましく使用することができる。 Next, a method for using the antibacterial medical device according to the present invention will be described using a central venous catheter used for central venous nutrition as an example. In general, there are two methods of using a central venous catheter (insertion method into a blood vessel) used for central venous nutrition, although not shown. The first method is to introduce a central venous catheter into the blood vessel through the outer lumen while the outer needle is removed after introducing a puncture needle having a separable outer tube into the blood vessel and leaving the outer mantle. Through the cannula method). Secondly, after the indwelling needle having a mantle tube is introduced into the blood vessel, the inner needle is removed, the guide wire is introduced into the blood vessel with the mantle remaining, and the guide wire is removed after the mantle is removed. In this method, a central venous catheter is inserted and the guide wire is removed (Seldinger method). In the central venous catheter of the present invention, any method can be preferably used.
　次に、本発明の実施例および比較例について、チュ－ブを例にとって説明する。
（実施例１、比較例１）
　実施例１は、ポリウレタン（日本ミラクトン株式会社製、商品名：Ｅ９９０）を用いて外径２．５ｍｍ、内径１．７５ｍｍのポリウレタンチューブを作製し、このポリウレタンチューブの表面にナノ銀コロイド溶液（ナノポリ株式会社製、商品名ナノミックス、１０００ｐｐｍエタノール溶液）を塗布乾燥後、１５０℃×３０分の熱処理を施して抗菌性チューブを作製した。また、比較例１は、１５０℃×３０分の熱処理を施さないこと以外は、実施例１と同様にして抗菌性チューブを作製した。 Next, examples and comparative examples of the present invention will be described by taking a tube as an example.
(Example 1, Comparative Example 1)
In Example 1, a polyurethane tube having an outer diameter of 2.5 mm and an inner diameter of 1.75 mm was prepared using polyurethane (manufactured by Nippon Milactone Co., Ltd., trade name: E990), and a nano silver colloid solution (nanopoly) was formed on the surface of the polyurethane tube. After coating and drying (trade name Nanomix, 1000 ppm ethanol solution), an antibacterial tube was produced by heat treatment at 150 ° C. for 30 minutes. Moreover, the comparative example 1 produced the antibacterial tube like Example 1 except not giving the heat processing for 150 degreeC x 30 minutes.
　実施例１および比較例１の抗菌性チューブから、全表面積が３２±５ｃｍ２のサンプルを切り出した。次に、このサンプルを黄色ブドウ球菌懸濁液（１０ｍＬ）中で振とう浸漬させ、所定期間浸漬後、この菌懸濁液およびサンプルを用いて、それぞれ銀溶出量（ｐｐｍ／日）および抗菌活性値の経時変化を測定した。なお、銀溶出量についてはＩＣＰ発光分析装置（セイコーインスツルメンツ）を用いて測定し、抗菌活性値については抗菌試験技術協議会規格に定められたシェーク法を用いて測定した。その結果を図２および図３に示す。図２は銀溶出量の経時変化を示すグラフ、図３は抗菌活性値の経時変化を示すグラフである。 Samples having a total surface area of 32 ± 5 cm 2 were cut from the antibacterial tubes of Example 1 and Comparative Example 1. Next, this sample was immersed in a suspension of Staphylococcus aureus (10 mL), and after immersion for a predetermined period, using this bacterial suspension and the sample, the silver elution amount (ppm / day) and the antibacterial activity, respectively. The change in value over time was measured. The silver elution amount was measured using an ICP emission analyzer (Seiko Instruments), and the antibacterial activity value was measured using the shake method defined in the Antibacterial Test Technology Council Standard. The results are shown in FIG. 2 and FIG. FIG. 2 is a graph showing the change over time in the silver elution amount, and FIG. 3 is a graph showing the change over time in the antibacterial activity value.
　図２および図３に示すように、実施例１では、比較例１と比べて、浸漬時間１０日を過ぎても、銀溶出量が高いレベルにあるため、抗菌活性値が高く、長期にわたって抗菌性が維持されていることが確認された。 As shown in FIG. 2 and FIG. 3, in Example 1, compared with Comparative Example 1, the amount of elution of silver is at a high level even after an immersion time of 10 days. It was confirmed that the sex was maintained.
（実施例２、比較例２）
　実施例２は、ポリプロピレンを用いて厚さ０．４ｍｍのポリプロピレンシートを作製し、このポリプロピレンシートにＮ２Ｏガスの雰囲気でプラズマ処理を施した。このプラズマ処理シートの表面にナノ銀コロイド溶液（ナノポリ株式会社製、商品名ナノミックス、３０００ｐｐｍエタノール溶液）を塗布乾燥後、１５０℃×３０分の熱処理を施して抗菌性シートを作製した。また、比較例２は、ポリプロピレンシートへのプラズマ処理を施さないこと以外は、実施例２と同様にして抗菌性シートを作製した。 (Example 2, comparative example 2)
In Example 2, a polypropylene sheet having a thickness of 0.4 mm was produced using polypropylene, and this polypropylene sheet was subjected to plasma treatment in an atmosphere of N 2 O gas. A nanosilver colloidal solution (trade name Nanomix, manufactured by Nanopoly Co., Ltd., 3000 ppm ethanol solution) was applied and dried on the surface of the plasma-treated sheet, and then heat-treated at 150 ° C. for 30 minutes to prepare an antibacterial sheet. In Comparative Example 2, an antibacterial sheet was produced in the same manner as in Example 2 except that the plasma treatment was not performed on the polypropylene sheet.
　実施例２および比較例２の抗菌性シートから、全表面積が３２±５ｃｍ２のサンプルを切り出した。次に、このサンプルを水（１０ｍＬ）中に浸漬（２４時間）させ、浸漬後の水溶液を用いて、ＩＣＰ発光分析装置を用いて銀溶出量（ｐｐｍ）を測定した。なお、銀溶出量の変化を確認するため、熱処理前（未処理）のシートについても同様に銀溶出量（ｐｐｍ）を測定した。その結果を図４に示す。図４は銀溶出量の変化を示すグラフである。 Samples having a total surface area of 32 ± 5 cm 2 were cut out from the antibacterial sheets of Example 2 and Comparative Example 2. Next, this sample was immersed in water (10 mL) (24 hours), and the silver elution amount (ppm) was measured using an ICP emission analyzer using the aqueous solution after immersion. In addition, in order to confirm the change of the silver elution amount, the silver elution amount (ppm) was similarly measured for the sheet before heat treatment (untreated). The result is shown in FIG. FIG. 4 is a graph showing changes in the elution amount of silver.
　図４に示すように、実施例２では、比較例２と比べて、銀溶出量が低いレベルであった。したがって、プラズマ処理を行うことによって、使用の際の初期段階における銀溶出量を低くできるため、銀溶出量を長期にわたって高いレベルに維持でき、長期にわたって抗菌性を維持できることが確認された。 As shown in FIG. 4, in Example 2, the amount of silver elution was lower than that in Comparative Example 2. Therefore, it was confirmed that by performing the plasma treatment, the silver elution amount in the initial stage of use can be lowered, so that the silver elution amount can be maintained at a high level for a long period of time and antibacterial properties can be maintained for a long period of time.
（実施例３～６、比較例３）
　実施例３～６は、ポリウレタン（日本ミラクトン株式会社製、商品名：Ｅ９９０）を用いて外径２．５ｍｍ、内径１．７５ｍｍのポリウレタンチューブを作製し、このポリウレタンチューブの表面にナノ銀コロイド溶液（ナノポリ株式会社製、商品名ナノミックス、３０００ｐｐｍエタノール溶液）を塗布乾燥後、所定条件（熱処理温度：８０、１００、１５０、１９０℃、熱処理時間：０～２５時間）で熱処理を施して抗菌性チューブを作製した。また、比較例３は、熱処理を施さないこと（室温：未処理）以外は実施例３と同様にして抗菌性チューブを作製した。そして、実施例３～６、比較例３の抗菌性チューブから、実施例２と同様にして、サンプルを切り出し、銀溶出量を測定した。銀溶出量の測定結果は図５に示すとおりである。図５は銀溶出量の変化を示すグラフである。 (Examples 3 to 6, Comparative Example 3)
In Examples 3 to 6, a polyurethane tube having an outer diameter of 2.5 mm and an inner diameter of 1.75 mm was prepared using polyurethane (manufactured by Nippon Milactone Co., Ltd., trade name: E990), and a nano silver colloid solution was formed on the surface of the polyurethane tube. (Nanopoly Co., Ltd., trade name Nanomix, 3000 ppm ethanol solution) is applied and dried, and then subjected to heat treatment under predetermined conditions (heat treatment temperature: 80, 100, 150, 190 ° C., heat treatment time: 0 to 25 hours) to be antibacterial A tube was prepared. Moreover, the comparative example 3 produced the antibacterial tube like Example 3 except not heat-processing (room temperature: untreated). Then, samples were cut out from the antibacterial tubes of Examples 3 to 6 and Comparative Example 3 in the same manner as in Example 2, and the silver elution amount was measured. The measurement result of the silver elution amount is as shown in FIG. FIG. 5 is a graph showing changes in the elution amount of silver.
　図５に示すように、実施例３～６では、比較例３と比べて、銀溶出量が低いレベルであった。したがって、熱処理を行うことによって、使用の際の初期段階における銀溶出量を低くできるため、銀溶出量を長期にわたって高いレベルに維持でき、長期にわたって抗菌性を維持できることが確認された。また、熱処理温度が１００℃以上であると、短時間の熱処理で銀溶出量を低くできるため、経済性に優れることが確認された。 As shown in FIG. 5, in Examples 3 to 6, the amount of silver elution was lower than that in Comparative Example 3. Therefore, by performing heat treatment, it was confirmed that the silver elution amount in the initial stage of use can be lowered, so that the silver elution amount can be maintained at a high level over a long period of time and the antibacterial property can be maintained over a long period of time. Further, when the heat treatment temperature was 100 ° C. or higher, it was confirmed that the amount of elution of silver can be lowered by a short heat treatment, and thus the economy is excellent.
　１　　　中心静脈カテーテル
　２　　　本体部
　３　　　先端部
　４　　　ハブ
　５　　　接続チューブ
　６　　　コネクター DESCRIPTION OF SYMBOLS 1 Central venous catheter 2 Body part 3 Tip part 4 Hub 5 Connection tube 6 Connector

Claims (7)

  1. 　銀と錯体を形成することが可能な元素を含む材料で医療器具を作製する第１ステップと、
    　前記医療器具の表面に銀系粒子を導入する第２ステップと、
    　前記銀系粒子が導入された医療器具を熱処理して、前記医療器具の表面に銀系粒子を固定する第３ステップとを含むことを特徴とする抗菌性医療器具の製造方法。     A first step of making a medical device with a material comprising an element capable of forming a complex with silver;
    A second step of introducing silver-based particles to the surface of the medical device;
    And a third step of fixing the silver-based particles on the surface of the medical device by heat-treating the medical device into which the silver-based particles have been introduced.
  2. 　銀と錯体を形成することが可能な元素を含まない材料で医療器具を作製し、その後、前記医療器具の表面に前記元素を導入する第１ステップと、
    　前記元素が導入された医療器具の表面に銀系粒子を導入する第２ステップと、
    　前記銀系粒子が導入された医療器具を熱処理して、前記医療器具の表面に銀系粒子を固定する第３ステップとを含むことを特徴とする抗菌性医療器具の製造方法。     Making a medical device with an element-free material capable of forming a complex with silver, and then introducing the element to the surface of the medical device;
    A second step of introducing silver-based particles onto the surface of the medical device into which the element has been introduced;
    And a third step of fixing the silver-based particles on the surface of the medical device by heat-treating the medical device into which the silver-based particles have been introduced.
  3. 　前記第３ステップの後に、前記医療器具の表面に抗血栓性材料を被覆する第４ステップをさらに含むことを特徴とする請求の範囲第１項または第２項に記載の抗菌性医療器具の製造方法。 The antibacterial medical device according to claim 1 or 2, further comprising a fourth step of coating the surface of the medical device with an antithrombotic material after the third step. Method.
  4. 　前記元素は、Ｓ、Ｎ、ＯおよびＰから選ばれる１元素以上であることを特徴とする請求の範囲第１項または第２項に記載の抗菌性医療器具の製造方法。 3. The method for producing an antibacterial medical device according to claim 1 or 2, wherein the element is one or more elements selected from S, N, O, and P.
  5. 　前記第３ステップにおいて、前記銀系粒子が導入された医療器具を８０～３００℃で熱処理することを特徴とする請求の範囲第１項または第２項に記載の抗菌性医療器具の製造方法。 The method for producing an antibacterial medical device according to claim 1 or 2, wherein, in the third step, the medical device into which the silver-based particles are introduced is heat-treated at 80 to 300 ° C.
  6. 　前記銀系粒子は、純銀粒子、または、硝酸銀、酢酸銀、アジ化銀および過塩素酸銀のいずれか１つ以上の銀塩粒子であることを特徴とする請求の範囲第１項または第２項に記載の抗菌性医療器具の製造方法。 The first or second claim, wherein the silver-based particles are pure silver particles or one or more silver salt particles of silver nitrate, silver acetate, silver azide and silver perchlorate. The manufacturing method of the antibacterial medical device of description.
  7. 　請求の範囲第１項または第２項に記載の製造方法によって製造されることを特徴とする抗菌性医療器具。 An antibacterial medical device manufactured by the manufacturing method according to claim 1 or 2.
PCT/JP2010/050958 2009-02-09 2010-01-26 Method for producing antimicrobial medical instrument, and antimicrobial medical instrument WO2010090098A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2010549438A JP5639481B2 (en) 2009-02-09 2010-01-26 Antibacterial medical device manufacturing method and antibacterial medical device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2009-027151 2009-02-09
JP2009027151 2009-02-09

Publications (1)

Publication Number Publication Date
WO2010090098A1 true WO2010090098A1 (en) 2010-08-12

Family

ID=42542001

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2010/050958 WO2010090098A1 (en) 2009-02-09 2010-01-26 Method for producing antimicrobial medical instrument, and antimicrobial medical instrument

Country Status (2)

Country Link
JP (1) JP5639481B2 (en)
WO (1) WO2010090098A1 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0428375A (en) * 1990-05-24 1992-01-30 Nippon Zeon Co Ltd Medical tube
JPH04197363A (en) * 1990-11-29 1992-07-16 Furukawa Electric Co Ltd:The Manufacture of catheter
JP2005511144A (en) * 2001-12-03 2005-04-28 シー・アール・バード・インク Microbial-resistant medical device, microbial-resistant polymer coating and production method thereof
JP2007029736A (en) * 2005-07-27 2007-02-08 Cordis Corp Catheter shaft tube and its manufacture method

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0428375A (en) * 1990-05-24 1992-01-30 Nippon Zeon Co Ltd Medical tube
JPH04197363A (en) * 1990-11-29 1992-07-16 Furukawa Electric Co Ltd:The Manufacture of catheter
JP2005511144A (en) * 2001-12-03 2005-04-28 シー・アール・バード・インク Microbial-resistant medical device, microbial-resistant polymer coating and production method thereof
JP2007029736A (en) * 2005-07-27 2007-02-08 Cordis Corp Catheter shaft tube and its manufacture method

Also Published As

Publication number Publication date
JPWO2010090098A1 (en) 2012-08-09
JP5639481B2 (en) 2014-12-10

Similar Documents

Publication Publication Date Title
AU2009305471B2 (en) Medical device with controllably releasable antibacterial agent
JP7009574B2 (en) Application of antibacterial agent to medical equipment
DE69831939T2 (en) COMPOUND LAYERS FOR SURFACE COATINGS MEDICAL ARTICLES
EP2968677B1 (en) Devices with anti-thrombogenic and anti-microbial treatment
US7820284B2 (en) Microbe-resistant medical device, microbe-resistant polymeric coating and methods for producing same
JP5799023B2 (en) Medical device for short-term use with a rapidly releasable antimicrobial agent
JP5820804B2 (en) Method for producing antibacterial medical device
JPH0757236B2 (en) Method for making substrate surface anti-agglomerate and / or anti-infective
JPH02234767A (en) Anti-infecting and anti-thrombus forming medical appliance and making thereof
US20040106912A1 (en) Method and composition for producing catheters with antibacterial property
JP2012520126A (en) Medical devices containing nitroprusside and antibacterial agents
US20140356901A1 (en) Method and Device for Detecting Device Colonization
JP5639481B2 (en) Antibacterial medical device manufacturing method and antibacterial medical device
JP2010179031A (en) Method of manufacturing antibacterial medical instrument and antibacterial medical instrument
CN109758620B (en) Long-acting antibacterial degradable ureteral stent and preparation method thereof
WO2010090097A1 (en) Antibacterial catheter, and method for manufacturing same
CN108815583B (en) Super-hydrophilic antibacterial ureter based on amino nano-silver molecular brush and preparation method thereof
JPH10248918A (en) Medical device and its production
CN110141782A (en) Graphene oxide artificial cochlea electrode and preparation method thereof
JP2005334216A (en) Antibacterial catheter
CN108837185B (en) Super-hydrophilic antibacterial ureter and preparation method thereof
EP4061436B1 (en) Nitric oxide and chlorhexidine releasing catheter for anti-platelet and antimicrobial dual functionality
JPH09276392A (en) Medical guide wire and its manufacturing process
CN116212123A (en) Preparation method and application of antibacterial hydrogel

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 10738436

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2010549438

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 10738436

Country of ref document: EP

Kind code of ref document: A1