WO2021059780A1 - 医療器具および医療器具の製造方法 - Google Patents

医療器具および医療器具の製造方法 Download PDF

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Publication number
WO2021059780A1
WO2021059780A1 PCT/JP2020/030405 JP2020030405W WO2021059780A1 WO 2021059780 A1 WO2021059780 A1 WO 2021059780A1 JP 2020030405 W JP2020030405 W JP 2020030405W WO 2021059780 A1 WO2021059780 A1 WO 2021059780A1
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Prior art keywords
medical device
silicone
antibacterial agent
catheter
base material
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English (en)
French (fr)
Japanese (ja)
Inventor
直人 竹村
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Terumo Corp
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Terumo Corp
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Priority to JP2021548418A priority Critical patent/JP7561746B2/ja
Publication of WO2021059780A1 publication Critical patent/WO2021059780A1/ja
Priority to US17/701,619 priority patent/US12458733B2/en
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    • 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
    • A61L29/08—Materials for coatings
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/727—Heparin; Heparan
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • 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
    • A61L29/08—Materials for coatings
    • A61L29/085—Macromolecular materials
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • A61M25/09—Guide wires
    • 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
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A61L2300/206—Biguanides, e.g. chlorohexidine
    • 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
    • A61L2300/40—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
    • A61L2300/406—Antibiotics
    • 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
    • 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
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • A61M25/09—Guide wires
    • A61M2025/09133—Guide wires having specific material compositions or coatings; Materials with specific mechanical behaviours, e.g. stiffness, strength to transmit torque
    • 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
    • A61M2207/00—Methods of manufacture, assembly or production
    • A61M2207/10—Device therefor
    • 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
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles

Definitions

  • the present invention relates to a medical device and a method for manufacturing the medical device.
  • Medical devices such as catheters and indwelling needles that are inserted into the body are used for the purpose of infusion and blood transfusion.
  • a medical device one in which the surface is treated with silicone in order to impart lubricity and reduce friction at the time of puncture is known.
  • Japanese Patent Application Laid-Open No. 61-355870 states that a surface treatment is performed with a composition containing a reaction product of an amino group-containing silane and an epoxy group-containing silane and a reaction product of a silanol group-containing polydiorganosiloxane as a main component.
  • Epoxy needles have been disclosed.
  • the injection needle described in Japanese Patent Publication No. 61-355870 certainly has excellent piercing characteristics by coating the surface with silicone.
  • an object of the present invention is to provide a medical device having excellent slipperiness (particularly, piercing characteristics) and exhibiting excellent antibacterial properties. ..
  • the present inventor conducted diligent research in order to solve the above problems. As a result, it has been found that the above-mentioned problem can be solved by a medical device having a mottled structure containing silicone and an antibacterial agent on the surface.
  • FIG. 1 is a laser micrograph showing the surface structure of the catheter of the example.
  • XY indicating a range means "X or more and Y or less”.
  • operations and physical properties are measured under the conditions of room temperature (25 ⁇ 1 ° C.) / relative humidity of 40 to 50% RH.
  • One form of the present invention is a medical device having a patchy structure containing silicone and an antibacterial agent on the surface. Since the medical device has a patchy structure containing silicone and an antibacterial agent on its surface, it has excellent slipperiness (particularly, piercing property) and can exhibit excellent antibacterial property.
  • the "surface" of a medical device means the surface of a material constituting the medical device with which blood or the like comes into contact when the medical device is used, and the surface portion of a hole in the material.
  • the surface means the outer surface and / or the inner surface.
  • the silicone according to this embodiment is not particularly limited, and biocompatible silicone can be appropriately used.
  • As the silicone crosslinked silicone is preferably used from the viewpoint of morphological stability.
  • Crosslinked silicones are silicones that contain three-dimensional bonds.
  • Specific examples of the crosslinked silicone include a reaction product of an amino group-containing silane and an epoxy group-containing silane described in Japanese Patent Publication No. 61-355870 or Japanese Patent Publication No. 62-52796, and a silanol group-containing polydiorgano. Examples thereof include reaction products with siloxane, and copolymers of aminoalkylsiloxane and dimethylsiloxane described in Japanese Patent Publication No. 46-3627.
  • amino group-containing silanes examples include ⁇ -aminopropyltriethoxysilane, ⁇ -aminopropylmethyldiethoxysilane, N- ( ⁇ -aminoethyl) aminomethyltrimethoxysilane, and ⁇ - ( ⁇ -aminoethyl) aminopropyltrimethoxy.
  • Silane, ⁇ - (N- ( ⁇ -aminoethyl) amino) propylmethyldimethoxysilane, N- ( ⁇ -aminoethyl) aminomethyltributoxysilane, ⁇ - (N- ( ⁇ - (N- ( ⁇ -aminoethyl)) ) Amino) Ethyl) Amino) Propyltrimethoxysilane and the like are exemplified.
  • Examples of the epoxy group-containing silane include ⁇ -glycidoxypropyltrimethoxysilane, ⁇ -glycidoxypropylmethyldimethoxysilane, ⁇ - (3,4-epoxycyclohexyl) ethyltrimethoxysilane, and ⁇ - (3,4-epoxy). Examples thereof include cyclohexyl) ethylmethyldimethoxysilane, ⁇ - (3,4-epoxycyclohexyl) ethyltriethoxysilane, and ⁇ - (3,4-epoxycyclohexyl) ethylmethyldiethoxysilane.
  • a polydiorganosiloxane containing a silanol group has at least one silanol group in one molecule.
  • the viscosity of the polydiorganosiloxane containing a silanol group is 0.00002 to 1 m 2 / s, preferably 0.0001 to 0.1 m 2 / s at 25 ° C. When the viscosity is 0.00002 m 2 / s or more, sufficient piercing property can be obtained. When the viscosity is 1 m 2 / s or less, handling before curing becomes easy.
  • Examples of the organic group bonded to the silicon atom of the silanol group include an alkyl group such as a methyl group, a phenyl group and a vinyl group.
  • the organic group is preferably a methyl group or a phenyl group, and more preferably a methyl group, from the viewpoint of easiness of synthesizing the polydiorganosiloxane.
  • Specific examples of polydiorganosiloxane containing a silanol group include polydimethylsiloxane having one end clogged with a silanol group and the other end clogged with a trimethylsilyl group, and polydimethylsiloxane having both ends clogged with a silanol group. , Polymethylphenylsiloxane with both ends clogged with silanol groups and the like.
  • the reaction product of the amino group-containing silane and the epoxy group-containing silane can be obtained by heating the amino group-containing silane and the epoxy group-containing silane while stirring.
  • the reaction ratio of the amino group-containing silane to the epoxy group-containing silane is 0.5 to 3.0 mol, preferably 0.75 to 1.5 mol, of the epoxy group-containing silane with respect to 1 mol of the amino group-containing silane.
  • the reaction product of the reaction product of the amino group-containing silane and the epoxy group-containing silane (component A) and the polydiorganosiloxane containing the silanol group (component B) contains the component A and the component B, if necessary. It can be obtained by reacting with heating using a solvent.
  • the blending ratio of the A component and the B component is 0.1 to 10% by mass for the A component and 90 to 99.9% by mass for the B component with respect to the total of the A component and the B component.
  • the compounding ratio is preferably 1 to 5% by mass for the A component and 95 to 99% by mass for the B component.
  • a commercially available product can be used as the crosslinked silicone.
  • examples of commercially available products that can be used include MDX4-4159 (manufactured by Dow Chemical Co., Ltd.).
  • Silicone can be used alone or in combination of two or more.
  • the antibacterial agent according to this embodiment is not particularly limited as long as it is a fat-soluble or water-soluble antibacterial agent used in the field of medical devices, and examples thereof include organic antibacterial agents and natural antibacterial agents. Therefore, an organic antibacterial agent is preferable.
  • organic antibacterial agents examples include chlorhexidine acetate, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diphosfanylate, alexidine, polyaminopropylbiguanide, polyhexanide, rifampine, minocycline hydrochloride, benzalkonium, benzalkonium.
  • natural antibacterial agents include protamine, ⁇ -polylysine, lysozyme, spice extract, tree extract and the like.
  • the antibacterial agent is selected from chlorhexidine acetate, rifampin, benzalkonium heparin and minocycline hydrochloride from the viewpoint of exerting the effects of the present invention more.
  • the antibacterial agent can be used alone or in combination of two or more.
  • the mass ratio (silicone: antibacterial agent) of the silicone (total amount when two or more types are used) and the antibacterial agent (total amount when two or more types are used) contained in the patchy structure according to this embodiment is From the viewpoint of more exerting the effect of the present invention, it is preferably 1: 0.01 to 1, and more preferably 1: 0.05 to 0.2.
  • the surface of the medical device is composed of a patchy structure.
  • the surface of the medical device is formed in an uneven shape. That is, in one embodiment, the mottled structure includes a convex portion formed on the surface and a concave portion formed on the surface.
  • the protrusions formed on the surface contain silicones and antibacterial agents.
  • the recesses formed on the surface are substantially uncovered and the surface of the substrate is exposed.
  • the convex portion has a portion in which a plurality of granular objects are randomly connected to form a winding linear body in a plan view.
  • the concave portion surrounds the convex portion in a plan view so that the linear body of the convex portion is relatively dispersed.
  • a mottled shape Such a state in which convex portions and concave portions are mixed is called a mottled shape.
  • the mottled structure can be confirmed by observing with a laser microscope (objective lens 150 times).
  • FIG. 1 is an image showing an example of the patchy structure of this embodiment, and is a laser micrograph of the catheter surface of Examples 1 to 4 described later.
  • the dark part corresponds to the convex part
  • the light part corresponds to the concave part.
  • the dark part corresponding to the convex part extends in a random direction and is connected to other parts, and is connected at a plurality of places.
  • the light-colored recesses surround the protrusions and are connected to other recesses.
  • the surface of the medical device is in a state in which convex portions and concave portions are mixed in this way.
  • a structure in which a dark-colored part is connected to another part at multiple points can also be expressed as a mesh structure.
  • the dark-colored portion corresponding to the convex portion extends linearly, but there are also portions that are dispersed independently.
  • the light-colored recesses surround the protrusions and are connected to other recesses.
  • the convex portion contains silicone and an antibacterial agent.
  • the medical device of this embodiment has an excellent slipperiness (particularly, piercing property) and exhibits excellent antibacterial property because the surface of the base material has a mottled structure containing silicone and an antibacterial agent. Can be done.
  • the silicone and the antibacterial agent form a mottled shape on the surface of the base material with an appropriate size and distribution to exhibit slipperiness and antibacterial properties.
  • the mechanism by which the silicone and the antibacterial agent become mottled is considered to be related to the interaction between the base material, the silicone and the antibacterial agent.
  • the average convex width of the patchy structure is preferably 0.1 to 10 ⁇ m, more preferably 0.5 to 5 ⁇ m, from the viewpoint that the effects of the present invention can be more exhibited.
  • the average recess width of the mottled structure is preferably 0.1 to 10 ⁇ m, more preferably 0.5 to 5 ⁇ m.
  • the ratio of the average convex portion width to the average concave portion width (average convex portion width / average concave portion width) of the mottled structure is preferably 0.1 to 0 from the viewpoint that the effect of the present invention can be more exhibited. It is 5, more preferably 0.3 to 3, and even more preferably 0.4 to 2.
  • the average convex width and the average concave width of the mottled structure can be measured by the following methods.
  • the surface of a medical device having a patchy structure is observed with a laser microscope (VKX-100, manufactured by KEYENCE, objective lens 150 times, monitor magnification 3000 times), and an image is taken. Analyze the captured image with image analysis software. Specifically, an arbitrary straight line (first straight line) is drawn on the image, and a second straight line orthogonal to the first straight line is drawn. The convex portion that intersects each straight line is defined as the convex width, and the concave portion is defined as the concave width.
  • the average convex width is obtained by arithmetically averaging the convex widths obtained from at least 9 points.
  • the average concave width is obtained by making the concave width obtained from at least 9 points and arithmetically averaging the obtained concave widths.
  • the convex width a and the concave width b are compared to the convex width a and the concave width b measured in the X direction and the convex width a'and the concave width b'measured in the Y direction.
  • the mottled structure according to this embodiment may further contain components other than silicone and antibacterial agents.
  • components other than silicone and antibacterial agents include hydrophilic polymers such as polymethoxyethyl acrylate (PMEA) that is soluble in polyethylene glycol, silicone, and a solvent common to antibacterial agents, and organic compounds having a pharmacological action.
  • PMEA polymethoxyethyl acrylate
  • the weight average molecular weight of polyethylene glycol is, for example, 100 to 10,000,000, preferably 200 to 4000000, and more preferably 400 to 500,000.
  • a value measured by gel permeation chromatography (GPC) using polystyrene as a standard substance and tetrahydrofuran (THF) as a mobile phase is adopted.
  • Examples of the medical device of this embodiment include devices used in contact with body fluids and blood. As described above, since the surface of the medical device has a mottled structure containing silicone and an antibacterial agent, it has excellent slipperiness (particularly, piercing characteristics) and can exhibit excellent antibacterial properties. Therefore, the medical device of this embodiment may be used for any purpose as long as it requires piercing properties and / or antibacterial properties. For example, catheters, sheaths, cannulas, needles, three-way stopcocks, guide wires and the like can be mentioned. Other examples include blood circuits, dialysis machines, artificial (auxiliary) hearts, artificial lungs, indwelling needles, artificial kidneys, stents, and the like.
  • the above structure can be provided on the outer surface of at least a part of the device in order to improve slipperiness when it comes into contact with the body cavity.
  • the above structure is provided on the surface of at least a part of the internal space in order to improve the slipperiness when inserting the other device. be able to.
  • the medical device of this embodiment is suitably used as an indwelling catheter because it can achieve both slipperiness, particularly piercing property and antibacterial property.
  • the medical device of the invention according to the above embodiment has a patchy structure containing silicone and an antibacterial agent on its surface.
  • the method for manufacturing the medical device is not particularly limited, but the base material is coated with a mixed solution containing silicone and an antibacterial agent to form a mottled structure containing silicone and an antibacterial agent on the surface of the base material. Is preferable.
  • another embodiment of the present invention comprises coating a substrate with a mixed solution containing a silicone and an antibacterial agent to form a mottled structure containing the silicone and the antibacterial agent on the surface of the substrate. It is a manufacturing method.
  • the method for preparing the mixed solution is not particularly limited, and for example, it can be prepared by dissolving silicone and an antibacterial agent in a solvent.
  • the solvent is not particularly limited as long as it can dissolve silicone, an antibacterial agent and, if necessary, other components.
  • a solvent for the above-mentioned crosslinked silicone and antibacterial agents such as chlorhexidine acetate, riffampin, benzalkonium heparin, and minocycline hydrochloride, dichloropentafluoropropane, methylene chloride, hydrochlorofluoroolefin, trans-1, 2-Dichloroethylene, chloroform, etc. can be used.
  • Alcohols such as methanol, ethanol, and isopropyl alcohol or other substances may be added to these solvents in order to increase the solubility in antibacterial agents.
  • the concentration of silicone in the mixed solution is not particularly limited as long as it can form a mottled structure on the surface of the base material, but is, for example, 0.1 to 20 w / v%, preferably 1 to 10 w / v%. ..
  • the concentration of the antibacterial agent in the mixed solution is not particularly limited as long as it can form a patchy structure on the surface of the base material, but is, for example, 0.1 w / v% or more and less than 2.0 w / v%, preferably 0. .1 to 1.0 w / v%.
  • the mixed solution according to the production method of this embodiment contains 1 to 10 w / v% silicone and 0.1 to 1.0 w / v% antibacterial agent.
  • the material of the base material of the medical device is not particularly limited, and for example, polyolefins such as polyethylene, polypropylene, and ethylene- ⁇ -olefin copolymers and modified polyolefins; polyamides; polyimides; polyurethanes; polyethylene terephthalate (PET) and polybutylene.
  • polyolefins such as polyethylene, polypropylene, and ethylene- ⁇ -olefin copolymers and modified polyolefins
  • polyamides such as polyethylene, polypropylene, and ethylene- ⁇ -olefin copolymers and modified polyolefins
  • polyamides such as polyamide, polyimides; polyurethanes; polyethylene terephthalate (PET) and polybutylene.
  • PET polyethylene terephthalate
  • Polyesters such as terephthalate (PBT), polycyclohexane terephthalate, polyethylene-2,6-naphthalate; polyvinyl chloride; polyvinylidene chloride (PVDC); polytetrafluoroethylene (PTFE), ethylene-tetrafluoroethylene copolymer (ETFE) Examples thereof include various polymer materials such as fluororesin such as, metal, ceramic, carbon, and composite materials thereof.
  • the above polymer material may be a stretched material (for example, ePTFE).
  • the shape of the base material is appropriately selected according to the use of the medical device and the like, and can take a shape such as a tube shape, a sheet shape, or a rod shape.
  • the form of the base material is not limited to the molded product using the above-mentioned materials alone, and can also be used in a blend molded product, an alloyed molded product, a multi-layer molded product, and the like.
  • the base material may be a single layer or may be laminated. At this time, when the base materials are laminated, the base materials of each layer may be the same or different.
  • the method of coating the mixed solution on the substrate is not particularly limited, and the coating / printing method, the dipping method (dip method, dip coating method), the spray method (spray method), the spin coating method, the mixed solution impregnated sponge coating method, etc. , Conventionally known methods can be used.
  • the method of coating the mixed solution on the substrate is a dipping method.
  • the immersion temperature is not particularly limited, and is, for example, 10 to 50 ° C, preferably 15 to 40 ° C.
  • the immersion time is not particularly limited, and is, for example, 10 seconds to 30 minutes.
  • the base material When forming a mottled structure on a narrow and narrow inner surface such as a catheter, a guide wire, or an injection needle, the base material may be immersed in a mixed solution to reduce the pressure inside the system to defoam. By defoaming under reduced pressure, the solution can be quickly permeated into the narrow and narrow inner surface, and the formation of mottled structures can be promoted.
  • the base material After immersing the base material in the mixed solution, the base material is taken out and dried.
  • the speed at which the base material is pulled up is not particularly limited, and is, for example, 5 to 50 mm / sec.
  • the drying conditions (temperature, time, etc.) are not particularly limited as long as they can form a mottled structure on the surface of the base material.
  • the drying temperature is preferably 20 to 150 ° C.
  • the drying time is preferably 20 minutes to 2 hours, more preferably 30 minutes to 1 hour.
  • the pressure condition at the time of drying is not limited at all, and it can be performed under normal pressure (atmospheric pressure), or it may be performed under pressurization or depressurization.
  • drying means for example, an oven, a vacuum dryer, etc. can be used, but in the case of natural drying, a drying means (device) is not particularly required.
  • the base material having a mottled structure containing silicone and an antibacterial agent on the surface by the above method can be used as it is as a medical device, but the base material having a mottled structure may be washed if necessary.
  • the cleaning method is not particularly limited, and examples thereof include a method of immersing a base material having a mottled structure in a cleaning solvent, and a method of showering a base material having a mottled structure with a cleaning solvent.
  • the cleaning solvent is not particularly limited as long as it does not dissolve the patchy structure, but water is preferable.
  • the water is preferably RO water, pure water, ion-exchanged water or distilled water, and more preferably RO water.
  • the drying method after washing is not particularly limited, and a conventionally known method can be used.
  • a medical device having a patchy structure containing silicone and an antibacterial agent on the surface can be manufactured.
  • Example 1 Chlorhexidine acetate (manufactured by Tokyo Kasei Co., Ltd.) and crosslinked silicone prepared based on Coating Agent Preparation Example 1 described in Japanese Patent Publication No. 61-355870 have concentrations of 0.5 w / v% and 3 w / v, respectively.
  • a mixed solution was prepared by dissolving in Asahiclean AK225 (dichloropentafluoropropane; manufactured by Asahi Glass Co., Ltd.) so as to be%.
  • Asahiclean AK225 diichloropentafluoropropane; manufactured by Asahi Glass Co., Ltd.
  • the catheter base material prepared above was immersed in this mixed solution for 10 seconds, pulled up at a speed of 5 mm / sec, and dried at 60 ° C. for 30 minutes to prepare a catheter.
  • the prepared catheter was confirmed using a laser microscope (objective lens 150 times), a patchy structure was formed on the surface (Fig. 1).
  • Example 2 A catheter was prepared in the same manner as in Example 1 except that rifampicin (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) was used instead of chlorhexidine acetate. When the prepared catheter was confirmed using a laser microscope (objective lens 150 times), a patchy structure was formed on the surface (Fig. 1).
  • Example 3 Benzalkonium prepared by purifying a precipitate obtained by mixing an aqueous solution of benzalkonium chloride (manufactured by Kanto Chemical Co., Inc.) and an aqueous solution of heparin sodium (manufactured by SPL) instead of chlorhexidine acetate.
  • a catheter was prepared in the same manner as in Example 1 except that heparin was used. When the prepared catheter was confirmed using a laser microscope (objective lens 150 times), a patchy structure was formed on the surface (Fig. 1).
  • Example 4 A catheter was prepared in the same manner as in Example 1 except that minocycline hydrochloride (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) was used instead of chlorhexidine acetate. When the prepared catheter was confirmed using a laser microscope (objective lens 150 times), a patchy structure was formed on the surface (Fig. 1).
  • Example 1 A solution was prepared by dissolving chlorhexidine acetate (manufactured by Tokyo Kasei Co., Ltd.) in Asahiclean AK225 (manufactured by Asahi Glass Co., Ltd.) so as to have a concentration of 0.5 w / v%.
  • Asahiclean AK225 manufactured by Asahi Glass Co., Ltd.
  • the catheter base material prepared above was immersed in this solution for 10 seconds, pulled up at a speed of 5 mm / sec, and dried at 60 ° C. for 30 minutes to prepare a comparative catheter.
  • the prepared catheter was confirmed using a laser microscope (objective lens 150 times), the surface was uniformly covered.
  • Comparative Example 2 A comparative catheter was prepared in the same manner as in Comparative Example 1 except that rifampicin (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) was used instead of chlorhexidine acetate. When the prepared catheter was confirmed using a laser microscope (objective lens 150 times), the surface was uniformly covered.
  • Comparative Example 3 Benzalkonium prepared by purifying a precipitate obtained by mixing an aqueous solution of benzalkonium chloride (manufactured by Kanto Chemical Co., Inc.) and an aqueous solution of heparin sodium (manufactured by SPL) instead of chlorhexidine acetate.
  • a comparative catheter was prepared in the same manner as in Comparative Example 1 except that heparin was used. When the prepared catheter was confirmed using a laser microscope (objective lens 150 times), the surface was uniformly covered.
  • Comparative Example 4 A comparative catheter was prepared in the same manner as in Comparative Example 1 except that minocycline hydrochloride (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.) was used instead of chlorhexidine acetate. When the prepared catheter was confirmed using a laser microscope (objective lens 150 times), the surface was uniformly covered.
  • minocycline hydrochloride manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.
  • the puncture resistance was measured for the catheters of Examples 1 to 4 and the comparative catheters of Comparative Examples 1 to 4. Specifically, an inner needle is incorporated into a catheter having an outer diameter of 0.8 mm and an inner diameter of 1.1 mm, and a small tabletop tester EZ-1 manufactured by Shimadzu Corporation is used to form a polyethylene film with a thickness of 50 ⁇ m at an angle of 90 degrees. Puncture was performed while dripping water at a speed of 30 mm / min, and the maximum resistance value after passing 10 mm from the needle tip was measured and used as the body resistance. The results are shown in Table 1.
  • the antibacterial activity value was defined as the logarithm of the number obtained by subtracting the viable cell count after culturing of the catheters of Examples 1 to 4 or the comparative catheters of Comparative Examples 1 to 4 from the viable cell count after culturing the catheter base material. When the antibacterial activity value is 2.0 or more, it is judged to have antibacterial activity. The results are shown in Table 1.
  • the catheter of the example has excellent slipperiness, specifically, piercing property, and exhibits excellent antibacterial property as compared with the comparative catheter of the comparative example.

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JPH02234764A (ja) * 1989-01-18 1990-09-17 Becton Dickinson & Co 抗感染性および潤滑性医療用品ならびにそれらの製法
WO1993017746A1 (en) * 1992-03-11 1993-09-16 Board Of Regents, The University Of Texas System Antibacterial coated medical implants
WO1999018891A1 (en) * 1997-10-10 1999-04-22 Usbiomaterials Corporation Percutaneous biofixed medical implants
JP2008000287A (ja) * 2006-06-21 2008-01-10 Terumo Corp 医療用具コーティング用摺動性組成物および摺動性被膜保有医療用具
WO2008148786A1 (en) * 2007-06-04 2008-12-11 Coloplast A/S A method for manufacturing a patterned adhesive layer
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JP2013146504A (ja) * 2012-01-23 2013-08-01 Terumo Corp 医療用具およびその製造方法
JP2013192885A (ja) * 2012-03-22 2013-09-30 Terumo Corp 医療用具およびその製造方法
JP2014200974A (ja) * 2013-04-03 2014-10-27 テルモ株式会社 構造体およびこれを用いてなる内視鏡
US20170130096A1 (en) * 2015-10-28 2017-05-11 The Texas A&M University System Amphiphilic siloxane materials to reduce adhesion events in medical, marine and industrial applications
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JP2018023758A (ja) * 2016-08-02 2018-02-15 日立金属株式会社 ケーブル及び医療用中空管

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