WO2013137326A1 - Tube multicouche pour traitement médical - Google Patents

Tube multicouche pour traitement médical Download PDF

Info

Publication number
WO2013137326A1
WO2013137326A1 PCT/JP2013/057029 JP2013057029W WO2013137326A1 WO 2013137326 A1 WO2013137326 A1 WO 2013137326A1 JP 2013057029 W JP2013057029 W JP 2013057029W WO 2013137326 A1 WO2013137326 A1 WO 2013137326A1
Authority
WO
WIPO (PCT)
Prior art keywords
copolymer
ethylene
vinyl compound
tube
aromatic
Prior art date
Application number
PCT/JP2013/057029
Other languages
English (en)
Japanese (ja)
Inventor
荒井　亨
歩 塚本
Original Assignee
電気化学工業株式会社
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 電気化学工業株式会社 filed Critical 電気化学工業株式会社
Priority to KR1020147027431A priority Critical patent/KR20140138814A/ko
Priority to JP2014504964A priority patent/JP6106156B2/ja
Priority to CN201380012908.8A priority patent/CN104203296B/zh
Publication of WO2013137326A1 publication Critical patent/WO2013137326A1/fr

Links

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
    • A61L29/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • 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
    • A61L29/04—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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • 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
    • 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
    • A61M39/00—Tubes, tube connectors, tube couplings, valves, access sites or the like, specially adapted for medical use
    • A61M39/08—Tubes; Storage means specially adapted 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
    • 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
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • 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
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/08—Coatings comprising two or more layers

Definitions

  • the present invention relates to a medical tube excellent in softness, transparency, bending resistance (kink resistance), drug quantification and pump suitability.
  • medical tubes In general, in addition to flexibility, transparency, and bend resistance (kink resistance), medical tubes have drug quantification that can be transported quantitatively with little drug absorption and absorption, and ironing resistance suitable for pump circuits (shape recovery) And radiation resistance against gamma rays and electron beams for sterilization are required. Furthermore, it is required to have strength enough to withstand operation, moderate elongation elasticity and adhesiveness, so-called stiffness.
  • Conventional medical tubes are often manufactured using soft polyvinyl chloride materials. In recent years, disposable medical products have been made disposable, and incineration after use has been increasing in order to prevent biohazard.
  • a medical tube using soft PVC generates a chlorine compound as a gas at the time of incineration, so environmental load has been taken into consideration, and replacement of a medical tube made of soft PVC has been considered. Furthermore, there is also a demand for a non-soft vinyl-based medical tube that does not elute plasticizers such as phthalates.
  • Patent Document 1 A tube comprising a resin composition of 1,2 polybutadiene resin and hydrogenated styrene-butadiene block copolymer has been proposed (Patent Document 2).
  • This tube has a characteristic that it gives a molded article excellent in flexibility and does not generate toxic gas even when incinerated.
  • a molded product obtained using such a resin composition is disadvantageous in terms of cost as compared with soft vinyl chloride, and is not suitable for disposable use.
  • a polybutadiene-based resin has a double bond remaining in the polymer chain. Even with a hydrogenated styrene-butadiene block copolymer, a small amount of double bonds remain. Therefore, when these resins are used, the storage conditions and processing conditions must be restricted, and stabilizers must be added to prevent changes in tube properties during long-term storage, gelation and insolubilization during tube forming. Furthermore, in order to cope with gamma ray sterilization and electron beam sterilization, which are often employed in recent years, it is necessary to add a stabilizer, and the safety as a medical tube is not always satisfied.
  • Patent Documents 3 and 4 medical tubes using an ethylene-styrene copolymer have been proposed (Patent Documents 3 and 4).
  • the ethylene-styrene copolymer has flexibility, transparency, low absorption of chemicals, and ironing resistance (shape recovery, wear resistance, etc.) suitable for pump circuits. Since it does not have a double bond, it is chemically stable and has high radiation resistance against gamma rays and electron beams for sterilization. However, there is room for improvement in bending resistance, and since it has a certain self-adhesiveness, the shape of the tube can be restored by close contact between the inner walls when bent (when kinking occurs) or clamped with forceps.
  • a sufficiently soft ethylene-styrene copolymer has a heat resistance of only about 60 ° C., and the tubes may be blocked or clogged during storage. Therefore, a block copolymer containing ethylene-styrene copolymer chains and polystyrene chains (hereinafter referred to as a cross copolymer) has been proposed (Patent Documents 5 and 6), and a medical tube using the same has also been proposed. (Patent Document 7).
  • This cross-copolymer has heat resistance derived from the presence of polystyrene block chains and a unique branched structure.
  • the present invention has been made in view of the above circumstances, is a non-vinyl chloride resin material without elution of a plasticizer such as phthalate ester, and has flexibility, transparency, heat resistance, bending resistance (kink) resistance, It is an object of the present invention to provide a medical tube that is excellent in low absorption and absorption of a drug, suitability for a pump circuit, and chemical stability.
  • a plasticizer such as phthalate ester
  • the present invention includes at least a support layer and an inner layer, the support layer occupies 50% or more of the total thickness of the tube, and the resin used for the support layer is a cross-copolymer satisfying specific conditions. It is a multilayer tube.
  • the multilayer medical tube of the present invention is characterized by excellent flexibility, transparency, heat resistance, resistance to bending (kink), low absorption of drugs, suitability for pump circuits, and chemical stability.
  • the present invention comprises at least two layers including at least a support layer and an inner layer, and the support layer occupies at least 50% of the total thickness of the tube, and is preferably thicker from the viewpoint of the softness of the entire tube,
  • the total light measured with a sheet having a storage elastic modulus at 25 ° C. of 1 MPa or more and less than 30 MPa and a thickness of 1 mm is 70% or more, particularly preferably 90% or more.
  • an anionic polymerization step it is obtained by polymerization using an anionic polymerization initiator in the presence of this ethylene-aromatic vinyl compound-aromatic polyene copolymer and an aromatic vinyl compound monomer.
  • the weight average molecular weight of the ethylene-aromatic vinyl compound-aromatic polyene copolymer obtained in the coordination polymerization step is 30,000 to 200,000, preferably 30,000 to 150,000, and the molecular weight distribution (Mw / Mn ) Is 1.8 or more and 4 or less.
  • the sum of heats of crystal melting ( ⁇ H) observed from 0 ° C. to 150 ° C. of the cross-copolymer is 25 J / g or less.
  • the content of the ethylene-aromatic vinyl compound-aromatic polyene copolymer contained in the cross copolymer is in the range of 70% by mass to 95% by mass.
  • this medical multi-layer tube is excellent in flexibility, transparency, bending resistance (kink), low drug absorption, suitability for pump circuit, and chemical stability. Furthermore, it can be characterized by excellent heat resistance.
  • the storage elastic modulus at 25 ° C. is less than 1 MPa
  • the mechanical strength of the tube is insufficient, and the tube may be easily crushed and closed by an external force.
  • the softness of the tube itself is insufficient, the handling property is lowered, and the bending resistance may be deteriorated. If the total light transmittance measured with a sheet having a thickness of 1 mm is less than the above, the liquid level inside the tube and the visibility of bubbles may be reduced.
  • the storage elastic modulus at 100 ° C. is preferably 0.1 MPa or more and less than 3 MPa. If the storage elastic modulus at 100 ° C. is less than 0.1 MPa, the tube may be blocked during storage or transportation of the medical tube or during sterilization with ethylene oxide. In the case of 3 MPa or more, moldability is lowered, and there is a possibility that more severe conditions must be applied at the time of production.
  • the cross-copolymer is a copolymer obtained by anionic polymerization in the presence of an olefin-aromatic vinyl compound-aromatic polyene copolymer and aromatic vinyl compound monomer obtained by coordination polymerization.
  • the present cross-copolymer and its production process are described in WO 2000/37517, USP 6559234, or WO 2007/139116, the entire description of which is hereby incorporated by reference.
  • aromatic vinyl compound styrene and various substituted styrenes such as p-methylstyrene, m-methylstyrene, o-methylstyrene, ot-butylstyrene, mt-butylstyrene, pt- Examples include butyl styrene, p-chlorostyrene, and o-chlorostyrene.
  • styrene, p-methylstyrene, p-chlorostyrene, particularly preferably styrene is used.
  • olefins examples include ethylene and ⁇ -olefins having 3 to 20 carbon atoms, that is, propylene, 1-butene, 1-hexene, 4-methyl-1-pentene, and 1-octene.
  • cyclic olefins are also included in the category of olefins, and examples of the cyclic olefins include vinylcyclohexane, cyclopentene, and norbornene.
  • ethylene or a mixture of ethylene and an ⁇ -olefin, ie, propylene, 1-butene, 1-hexene, or 1-octene is used, and more preferably, ethylene is used.
  • the aromatic polyene used is a monomer having a carbon number of 10 to 30 and having a plurality of double bonds (vinyl groups) and one or more aromatic groups and capable of coordination polymerization.
  • An aromatic polyene in which one of (vinyl group) is used for coordination polymerization and a double bond left in a polymerized state can be anionically polymerized.
  • any one or a mixture of two or more of orthodivinylbenzene, paradivinylbenzene and metadivinylbenzene is preferably used.
  • the cross-copolymer most preferably used in the present invention is an ethylene-aromatic vinyl compound (hereinafter referred to as styrene) -aromatic polyene (hereinafter referred to as divinylbenzene) copolymer obtained by coordination polymerization, and A copolymer obtained by anionic polymerization in the presence of an aromatic vinyl compound (representatively referred to as styrene) monomer, and an ethylene-styrene-divinylbenzene copolymer chain (sometimes described as the main chain) Yes, it is a copolymer having a soft component) and a polystyrene chain (sometimes described as a side chain, a hard component).
  • styrene ethylene-aromatic vinyl compound
  • divinylbenzene divinylbenzene copolymer obtained by coordination polymerization
  • the cross-copolymer satisfying the conditions relating to the storage elastic modulus and transparency at 25 ° C. of the present invention needs to satisfy the conditions (1) to (4).
  • a cross-copolymer satisfying this condition can be produced based on the information described in the above-mentioned source (published patent publication) relating to the cross-copolymer.
  • the storage elastic modulus at 25 ° C. of the present cross-copolymer is the styrene content of the ethylene-styrene-divinylbenzene copolymer chain, which is its soft polymer chain component (soft segment), and the ratio of the soft component to the hard component.
  • the molecular fluidity of the entire cross-copolymer defined by the content of divinylbenzene component that binds the soft component chain and hard component chain, the molecular weight of ethylene-styrene-divinylbenzene copolymer chain or polystyrene chain, and the divinylbenzene content It is determined by various parameters (MFR value). It is not the intent of this specification to disclose this parameter, but the storage modulus is mainly as the styrene content of the ethylene-styrene-divinylbenzene copolymer chain increases and the crystallinity of the ethylene chain decreases or is softer.
  • this support layer occupies 50% or more of the tube layer thickness, its mechanical properties, and the functionality required for medical tubes (flexibility, transparency, heat resistance, low absorption of drugs, pump circuit, etc. This is an important layer for imparting suitability, chemical stability, and bending resistance.
  • the medical multilayer tube of the present invention has an inner layer in addition to the support layer.
  • the resin used in the inner layer is preferably a resin selected from polyolefin, hydrogenated styrene-diene block copolymer, syndiotactic 1,2-polybutadiene, urethane, or cross-copolymer, and these resin compositions
  • the storage elastic modulus at 25 ° C. is in the range of higher than 30 MPa and lower than or equal to 300 MPa
  • the total light transmittance measured with a sheet having a thickness of 1 mm is 75% or more, preferably 80%. That's it.
  • the inner layer is preferably at least 1% to 50% with respect to the thickness of the entire layer of the tube, and is preferably thinner from the viewpoint of the flexibility of the entire tube, preferably 1% with respect to the thickness of the entire layer of the tube. It is 30% or less and particularly preferably 1% or more and 10% or less.
  • the polyolefin includes an ethylene copolymer, a polypropylene copolymer, and a polybutene copolymer.
  • an ethylene- ⁇ olefin copolymer or a polypropylene copolymer is used.
  • a resin having a storage elastic modulus (25 ° C.) suitable for the present invention can be appropriately selected and used from the physical property tables of these copolymer resins provided by various companies.
  • the density is preferably 0.87 g / cm 3 or more and 0.91 g / cm 3 or less. Examples applied to medical tubes are described in Japanese Patent Application Laid-Open No. 2005-318949 and Japanese Patent No. 3251601.
  • a styrene-butadiene block copolymer or a styrene-isoprene block copolymer obtained by anionic polymerization is hydrogenated, and both SEBS and SEPS are used.
  • the block structure may be a diblock, triblock, multiblock, star block or taper block structure.
  • the block copolymer preferably exhibits a polystyrene-equivalent weight average molecular weight of not less than 30,000 and not more than 250,000 in order to develop physical properties and molding processability as a practical resin.
  • Examples of applying such a resin to a medical tube are described in, for example, Japanese Patent Application Laid-Open No. 2001-001432 and Japanese Patent No. 4179644.
  • Examples of syndiotactic 1,2-polybutadiene are described in JP-A No. 2003-102827 and JP-A No. 2005-253721.
  • the use of urethane is described, for example, in JP-A-05-084293.
  • a resin having a storage elastic modulus (25 ° C.) suitable for the present invention can be appropriately selected and used from the physical property tables of these resins provided by various companies. As described above, those described in WO2000 / 37517, USP65559234, or WO2007 / 139116 can be used as the cross copolymer.
  • polyolefin particularly ethylene- ⁇ olefin copolymer, polypropylene copolymer, hydrogenated styrene-diene block copolymer, and cross copolymer. This is because these resins have good adhesion to the cross-copolymer as a support layer, and therefore, it is not necessary to provide an adhesive layer, and the structure is simple and economically advantageous.
  • cross-copolymer when used for the inner layer, it is most preferable because it has good wear resistance, high infusion pump suitability, and low chemical adsorption.
  • the present cross-copolymer preferably satisfies at least the following conditions (A) and (B) and satisfies at least one of the conditions (C) and (D).
  • (A) obtained by a production method comprising a coordination polymerization step followed by a polymerization step consisting of an anionic polymerization step, and as a coordination polymerization step, using a single site coordination polymerization catalyst, an ethylene monomer, an aromatic vinyl compound monomer and Copolymerization of aromatic polyene, aromatic vinyl compound unit content of 8 mol% to 30 mol%, aromatic polyene unit content of 0.01 mol% to 0.2 mol%, the balance being ethylene unit content of ethylene -Aromatic vinyl compound-Aromatic polyene copolymer is synthesized.
  • an anionic polymerization step it is obtained by polymerization using an anionic polymerization initiator in the presence of this ethylene-aromatic vinyl compound-aromatic polyene copolymer and an aromatic vinyl compound monomer.
  • the ethylene-aromatic vinyl compound-aromatic polyene copolymer obtained in the coordination polymerization step has a weight average molecular weight of 30,000 to 200,000 and a molecular weight distribution ((Mw / Mn) of 1.8 to 4) It is.
  • the content of the ethylene-aromatic vinyl compound-aromatic polyene copolymer contained in the cross copolymer is 40% by mass or more and less than 70% by mass.
  • aromatic vinyl compound styrene and aromatic polyene are preferably divinylbenzene from the viewpoints of economy and physical properties.
  • the cross-copolymer satisfying the storage modulus range and transparency satisfies both the conditions (A) and (B) and satisfies either the condition (C) or (D). Can be obtained at Furthermore, according to the description of known literature as described above, it can be easily obtained by performing a few tests if necessary.
  • the cross-copolymer satisfying the conditions (1) to (4) used for the support layer 1) the styrene content of the ethylene-styrene-divinylbenzene copolymer chain is reduced, 2) Cross-copolymerization satisfying the storage elastic modulus range suitable for the inner layer of the present invention by increasing the crystallinity derived from 2) or decreasing the content of the ethylene-styrene-divinylbenzene copolymer chain, which is a soft component The coalescence can be easily manufactured. If the total heat of crystal melting ( ⁇ H) observed between 0 ° C. and 150 ° C.
  • the storage elastic modulus of the resin may be too higher than the above range.
  • the content of the ethylene-aromatic vinyl compound-aromatic polyene copolymer contained in the cross copolymer is less than 40% by mass.
  • the storage elastic modulus at 25 ° C. of the cross copolymer used for the inner layer is in the range of higher than 30 MPa and lower than or equal to 300 MPa, for example, it is compatible with the soft cross copolymer used for the support layer.
  • a sliding material such as silicone resin can be applied or kneaded.
  • the medical multilayer tube of the present invention can have an optional outer layer as required.
  • the outer layer is preferably at least 1% to 30% with respect to the thickness of the entire tube layer, and is preferably thinner from the viewpoint of the softness of the entire tube, preferably 1% with respect to the thickness of the entire tube layer. It is 10% or less.
  • a two-type three-layer structure in which the outer layer is composed of the same resin component as the inner layer is simple and preferable in terms of configuration. Providing this outer layer is preferable in that the adhesion between tubes is suppressed.
  • the support layer can be provided with appropriate embossments or irregularities to prevent the tubes from sticking to each other or to prevent slipping during handling.
  • the MFR value (200 ° C., weight 98N) of the raw material resin is not particularly limited, but is generally 1 g / 10 min or more and 100 g / 10 min or less. Considering multilayer tube forming by coextrusion method, it is preferable that the MFR values of the respective resins of the support layer and the inner layer are close, and the ratio of the MFR values of both is preferably within 1: 3, particularly preferably within 1: 2. is there.
  • the resin raw materials such as the cross-copolymer used in the present invention may be added with known additives usually used for the present application, such as antioxidants, stabilizers, and lubricants, if necessary.
  • the method for obtaining the composition of the cross copolymer used in the present invention and an additive or other resin is not particularly limited, and a known method can be used.
  • dry blending can be performed with a Henschel mixer, ribbon blender, super mixer, tumbler, etc.
  • melt mixing may be performed with a single or twin screw extruder, a Banbury mixer, a plast mill, a kneader, a roll, or the like.
  • it can also carry out in inert gas atmosphere, such as nitrogen.
  • the shape can be selected from powder, pellets, strands, chips, and the like.
  • the medical tube of the present invention can be obtained by a known technique such as multilayer extrusion molding or a coating method.
  • the shape, diameter, length and other shapes of the tube are selected according to the purpose of use and are not particularly limited.
  • the obtained tube is generally packaged and sterilized after joining with other parts such as a drip tube used for infusion.
  • ethylene oxide gas sterilization, ⁇ ray sterilization, or electron beam sterilization is selected.
  • the cross-copolymer used in the present invention is excellent in durability and exhibits high resistance to gamma rays and electron beams used for sterilization.
  • phosphorus antioxidants such as bis (2,6-di-tert-butyl-4-methylphenyl) pentaerythritol diphosphite, bis (2,4-di-tert-butylphenyl) )
  • Gamma ray or electron beam sterilization is possible even without a stabilizer such as pentaerythritol diphosphite.
  • ⁇ Raw resin> The raw material resins used in Examples and Comparative Examples are as follows.
  • the following cross-copolymer was produced by the production method described in WO2000 / 37517 or WO2007 / 139116, the entire contents of which are incorporated herein by reference, and the following composition was similarly determined by the method described in these publications. .
  • These cross copolymers include an ethylene-styrene-divinylbenzene copolymer chain obtained by anionic polymerization in the presence of an ethylene-styrene-divinylbenzene copolymer obtained by coordination polymerization and a styrene monomer. It is a copolymer having a polystyrene chain.
  • the cross-copolymer in order to define the cross-copolymer, the styrene content, divinylbenzene content, weight average molecular weight (Mw), molecular weight distribution (Mw / Mn) of the ethylene-styrene-divinylbenzene copolymer used, the cross-copolymer
  • Mw weight average molecular weight
  • Mw / Mn molecular weight distribution of the ethylene-styrene-divinylbenzene copolymer used, the cross-copolymer
  • the content of the ethylene-styrene-divinylbenzene copolymer, the molecular weight (Mw) of the polystyrene chain, and the molecular weight distribution (Mw / Mn) are shown.
  • ⁇ Crystal melting heat ( ⁇ H)> It was determined by DSC measurement. The measurement was performed under a nitrogen stream. That is, using 10 mg of the resin composition, measurement was performed from ⁇ 50 ° C. to 240 ° C. at a temperature rising rate of 10 ° C./min, and the melting point, the heat of crystal melting, and the glass transition point were obtained.
  • ⁇ Sheet preparation> As a sample sheet for measuring physical properties, a sheet having a predetermined thickness formed by a hot press method (temperature 180 ° C., time 3 minutes, pressure 50 kg / cm 2) was used.
  • ⁇ Tensile test> In accordance with JIS K-6251, the obtained sheet having a thickness of 1 mm was cut into a No. 2 1/2 type test piece shape, and using a Shimadzu AGS-100D type tensile tester at a tensile speed of 500 mm / min. Initial tensile elastic modulus, elongation at break, and strength at break were measured.
  • ⁇ Storage modulus> A sample for measurement (3 mm ⁇ 40 mm) is cut out from a film having a thickness of about 0.5 mm obtained by the above hot press method, and a dynamic viscoelasticity measuring device (Rheometrics RSA-III) is used. The measurement was made in the range of 50 ° C. to + 150 ° C., and the storage elastic modulus (E ′) at 25 ° C. or 100 ° C. was determined. Other measurement parameters are as follows. Measuring frequency 1Hz Temperature increase rate 4 ° C / min Measurement length 10mm The storage elastic modulus at 25 ° C. is an indicator of the softness of the tube and needs to be in the range of 1 MPa or more and less than 30 MPa. The storage elastic modulus at 100 ° C. is an index of the heat resistance of the tube, and is preferably in the range of 0.1 MPa or more and less than 3 MPa.
  • Examples 1 to 4 Using the cross-copolymers 1 to 5, a multilayer tube comprising a support layer / inner layer was prepared by coextrusion molding. All the multilayer tubes had an outer diameter of 3.6 mm, an inner diameter of 2.4 mm, and a tube thickness of 0.6 mm. Table 2 shows the ratio of the thickness of the support layer and the inner layer. The cross-copolymer 6 had poor transparency, and a tube was not prototyped. As Comparative Example 1, a single-layer tube not using an inner layer, as Comparative Example 2, a multilayer tube example in which the storage elastic modulus at 25 ° C.
  • Comparative Example 3 manufactured by an ethylene-styrene copolymer Table 3 shows the results of a single-layer tube, a single-layer tube made of 1,2 polybutadiene as Comparative Example 4, and a single-layer tube made of soft PVC as Comparative Example 4.
  • the tube of the example showed good softness, heat resistance, and transparency. Furthermore, although no stabilizer was added, it exhibited good gamma ray resistance and electron beam resistance, and passed the tests of pH, heavy metal, potassium permanganate reducing substance, and evaporation residue. Furthermore, it has a relatively small kink starting radius, is excellent in bending resistance and forceps resistance, has low drug adsorption, and is suitable for an infusion pump.
  • each measurement item was measured as follows.
  • ⁇ Softness of tube> A test tube cut to a length of 20 cm and a comparative soft PVC medical single-layer tube are touched by a blindfolded subject, and the one with a soft touch is selected. If the prototype tube was softer than the soft PVC single-layer tube for medical use, it was marked as ⁇ , when it was almost equivalent, it was marked as ⁇ , and when the prototype tube was clearly hard, it was marked as x.
  • ⁇ Transparency> A physiological saline solution was poured into the tube, and it was observed whether the liquid level, bubbles, etc. were visible with the naked eye.
  • test solutions for pH, heavy metal, potassium permanganate reducing substance, and evaporation residue were obtained as follows. Eluate test based on sterilized infusion set standard: A tube portion of 10 g was cut into about 1 cm length and boiled with 100 ml of distilled water for 30 minutes. Distilled water was added to make exactly 100 ml and used as a test solution. At the same time, boiling water alone was similarly boiled for 30 minutes to obtain a blank test solution.
  • ⁇ PH> Take 20 ml each of the test solution and the blank test solution, add 1.0 ml of a solution prepared by dissolving 1.0 g of potassium chloride in water to 1000 ml, and measure the pH change by the pH measurement method of the Japanese Pharmacopoeia General Test Method did. A pH difference of 2.0 or less was accepted.
  • ⁇ Reducing substance of potassium permanganate> Take 10 ml of the test solution in a stoppered Erlenmeyer flask, add 20.0 ml of 0.002 mol / l potassium permanganate solution and 1 ml of dilute sulfuric acid, seal tightly, stir and leave for 10 minutes, then 0.01 mol / l sodium thiosulfate solution (5 drops of indicator starch test solution). Separately, 10 ml of blank test solution is used and the same operation is performed. If the difference in 0.002 mol / l potassium permanganate liquid consumption between the test solution and the blank test solution was 2.0 ml or less, the test was accepted.
  • ⁇ Kink start radius> A 20 cm tube was bent to each radius of curvature, and the minimum radius of curvature at which the occurrence of bending of the tube was not confirmed after 1 minute was determined.
  • the kink start radius is preferably 10 mm or less.
  • the shape of the generated kink (bending) was observed. Observe the situation where crushing occurs relatively uniformly in a wide part of the tube, and in the order of goodness, ⁇ : wide kink occurs, then crushing occurs in a slightly narrower range ⁇ : relatively wide Kink generation, crushing occurred in a narrower range, and the tube was broken.
  • ⁇ Classified as acute-angle kink generation.
  • Nitroglycerin sorbability 60 ml of nitroglycerin injection solution (active ingredient 50 mg / 100 ml, Millisrol injection, Nippon Kayaku Co., Ltd.) was injected into 1 L of Japanese Pharmacopoeia physiological saline and gently stirred. Immediately, the sample was sampled with a syringe with a syringe needle to obtain a blank. The tube of the infusion set was closed with a flow rate adjusting clamp, and the drip tube was pierced through a rubber stopper. The lower half of the drip tube was filled with the solution by pumping the drip tube.
  • the clamp for adjusting the flow rate was gradually loosened, and the tube was filled with the solution, and then set on the infusion pump.
  • the flow rate was set to 36 ml / h, the flow rate adjusting clamp was opened, the switch was turned on, and infusion was started.
  • the solution flowing out from the tip was sampled over time, and the concentration was measured by high performance liquid chromatography.
  • the infusion was performed for 180 minutes, and the first 60 minutes were sampled every 5 minutes and thereafter every 15 minutes. If the density drop was within 10% compared to the blank density, the test was accepted.
  • Tube state after completion of pump infusion After completion of the above-mentioned pump flow rate stability, the squeezed portion of the tube was incised, and the surface state of the inner and outer surfaces, the change in tube diameter, and the presence or absence of cracks were observed.
  • the medical multi-layer tube of the present invention is a non-vinyl chloride resin material that does not elute plasticizers such as phthalates, and is flexible, transparent, heat resistant, soft, low drug absorption, infusion pump A medical tube with excellent aptitude, chemical stability and resistance to bending (kinks), low self-adhesiveness and excellent tube resilience (forceps resistance). Medical tubes such as infusion tubes, blood transfusion tubes, blood circuits It can also be suitably used for tubes in medical devices such as artificial blood vessels, hemodialyzers, blood component separators, and artificial lungs.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Pulmonology (AREA)
  • Vascular Medicine (AREA)
  • Biophysics (AREA)
  • Materials Engineering (AREA)
  • Composite Materials (AREA)
  • Chemical & Material Sciences (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Materials For Medical Uses (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • External Artificial Organs (AREA)

Abstract

L'invention fournit un tube multicouche pour traitement médical sans élution de plastifiant tel qu'un ester d'acide phtalique, ou similaire, consistant en un matériau de résine sans chlorure de vinyle, qui est excellent en termes de flexibilité, de transparence, de résistance à la chaleur, de faibles propriétés adsorption/absorption de médicament, d'adéquation avec une pompe à perfusion, de stabilité chimique et de résistance au pliage (tortillement), et qui en outre présente une faible auto-adhésion et d'excellentes propriétés de restauration de tube (résistance au serrage). Plus précisément, l'invention concerne un tube multicouche pour traitement médical qui contient au moins une couche support et une couche interne, la couche support représente 50% au moins de l'épaisseur de l'ensemble des couches du tube, et la résine mise en œuvre dans cette couche support consiste en un copolymère réticulé satisfaisant des conditions prédéfinies. Ce tube multicouche pour traitement médical est caractéristique en ce qu'il est excellent en termes de flexibilité, de transparence, de résistance à la chaleur, de faibles propriétés adsorption/absorption de médicament, d'adéquation avec une pompe à perfusion, de stabilité chimique et de résistance au tortillement, et qu'il présente en outre une faible auto-adhésion et d'excellentes propriétés de restauration de tube (résistance au serrage).
PCT/JP2013/057029 2012-03-14 2013-03-13 Tube multicouche pour traitement médical WO2013137326A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
KR1020147027431A KR20140138814A (ko) 2012-03-14 2013-03-13 의료용 다층 튜브
JP2014504964A JP6106156B2 (ja) 2012-03-14 2013-03-13 医療用多層チューブの製造方法
CN201380012908.8A CN104203296B (zh) 2012-03-14 2013-03-13 医疗用多层管

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012057052 2012-03-14
JP2012-057052 2012-03-14

Publications (1)

Publication Number Publication Date
WO2013137326A1 true WO2013137326A1 (fr) 2013-09-19

Family

ID=49161231

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2013/057029 WO2013137326A1 (fr) 2012-03-14 2013-03-13 Tube multicouche pour traitement médical

Country Status (4)

Country Link
JP (1) JP6106156B2 (fr)
KR (1) KR20140138814A (fr)
CN (1) CN104203296B (fr)
WO (1) WO2013137326A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106459327A (zh) * 2014-05-15 2017-02-22 电化株式会社 交联共聚物和其制造方法
KR20180098371A (ko) 2015-12-25 2018-09-03 덴카 주식회사 크로스 공중합체 및 그것을 사용한 의료용 단층 튜브
WO2021076990A1 (fr) * 2019-10-17 2021-04-22 Carefusion 303, Inc. Tube médical multicouche à adhérence améliorée

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0584293A (ja) * 1991-03-08 1993-04-06 Nissho Corp 医療用チユーブ
WO2000037517A1 (fr) * 1998-12-22 2000-06-29 Denki Kagaku Kogyo Kabushiki Kaisha Copolymere olefine/styrene/diene reticule, procede de production dudit copolymere et ses utilisations
JP2002011092A (ja) * 2000-04-27 2002-01-15 Terumo Corp カテーテルおよび医療用チューブ
JP2002322224A (ja) * 2001-02-21 2002-11-08 Denki Kagaku Kogyo Kk クロス共重合化オレフィン−芳香族ビニル化合物−ジエン共重合体
WO2003033254A1 (fr) * 2001-10-19 2003-04-24 Kuraray Co., Ltd. Produit stratifie et fourniture medicale comprenant ce produit stratifie
JP2004097600A (ja) * 2002-09-11 2004-04-02 Kuraray Co Ltd サクションカテーテル
JP2005318949A (ja) * 2004-05-06 2005-11-17 Terumo Corp 医療用チューブ
WO2006057370A1 (fr) * 2004-11-26 2006-06-01 Mitsui Chemicals, Inc. Tube médical
WO2007139116A1 (fr) * 2006-05-29 2007-12-06 Denki Kagaku Kogyo Kabushiki Kaisha Procédé pour la production de copolymères réticulés, copolymères réticulés obtenus par le procédé et utilisation de ceux-ci

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6803422B2 (en) * 1999-09-13 2004-10-12 Denki Kagaku Kogyo Kabushiki Kaisha Cross-copolymerized olefin/aromatic vinyl compound/diene copolymer and process for its production
CN101454365A (zh) * 2006-05-29 2009-06-10 电气化学工业株式会社 交叉共聚物的制造方法、得到的交叉共聚物及其用途

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0584293A (ja) * 1991-03-08 1993-04-06 Nissho Corp 医療用チユーブ
WO2000037517A1 (fr) * 1998-12-22 2000-06-29 Denki Kagaku Kogyo Kabushiki Kaisha Copolymere olefine/styrene/diene reticule, procede de production dudit copolymere et ses utilisations
JP2002011092A (ja) * 2000-04-27 2002-01-15 Terumo Corp カテーテルおよび医療用チューブ
JP2002322224A (ja) * 2001-02-21 2002-11-08 Denki Kagaku Kogyo Kk クロス共重合化オレフィン−芳香族ビニル化合物−ジエン共重合体
WO2003033254A1 (fr) * 2001-10-19 2003-04-24 Kuraray Co., Ltd. Produit stratifie et fourniture medicale comprenant ce produit stratifie
JP2004097600A (ja) * 2002-09-11 2004-04-02 Kuraray Co Ltd サクションカテーテル
JP2005318949A (ja) * 2004-05-06 2005-11-17 Terumo Corp 医療用チューブ
WO2006057370A1 (fr) * 2004-11-26 2006-06-01 Mitsui Chemicals, Inc. Tube médical
WO2007139116A1 (fr) * 2006-05-29 2007-12-06 Denki Kagaku Kogyo Kabushiki Kaisha Procédé pour la production de copolymères réticulés, copolymères réticulés obtenus par le procédé et utilisation de ceux-ci

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106459327A (zh) * 2014-05-15 2017-02-22 电化株式会社 交联共聚物和其制造方法
US20170145135A1 (en) * 2014-05-15 2017-05-25 Denka Company Limited Cross-copolymer and method for producing same
KR20180098371A (ko) 2015-12-25 2018-09-03 덴카 주식회사 크로스 공중합체 및 그것을 사용한 의료용 단층 튜브
CN108699185A (zh) * 2015-12-25 2018-10-23 电化株式会社 交叉共聚物及使用其的医疗用单层管
DE112016006045T5 (de) 2015-12-25 2018-10-25 Denka Company Limited Crosscopolymer und medizinischer einschichtiger schlauch, für den dieses verwendet wird
WO2021076990A1 (fr) * 2019-10-17 2021-04-22 Carefusion 303, Inc. Tube médical multicouche à adhérence améliorée

Also Published As

Publication number Publication date
KR20140138814A (ko) 2014-12-04
CN104203296B (zh) 2017-06-09
CN104203296A (zh) 2014-12-10
JPWO2013137326A1 (ja) 2015-08-03
JP6106156B2 (ja) 2017-03-29

Similar Documents

Publication Publication Date Title
DK2186859T3 (en) Tubes and medical device comprising this
CN102038607B (zh) 含有环状聚烯烃层的塑料容器
KR102623132B1 (ko) 수첨 블록 공중합체, 수지 조성물, 점착제, 접착제, 성형체, 액체 포장 용기, 의료용구, 의료용 튜브, 웨더 시일용 코너 부재 및 웨더 시일
US6977105B1 (en) Multilayered tube and medical supply comprising multilayered tube
JP5507540B2 (ja) チューブ及びそれを用いた医療用具
JP5908771B2 (ja) 医療用チューブ
JP4435934B2 (ja) 多層チューブ及び多層チューブからなる医療用具
US11078357B2 (en) Thermoplastic elastomer composition, extrusion molded article, and medical tube
JP6106156B2 (ja) 医療用多層チューブの製造方法
TWI752945B (zh) 樹脂組成物、熱封劑、液體包裝容器用薄膜、液體包裝容器、液體排出構件及醫療容器
JP2007002886A (ja) ガスケット用の熱可塑性エラストマー組成物及びガスケット
JP5058860B2 (ja) フィルム
JP5809276B2 (ja) シクロオレフィン系共重合体樹脂組成物
JP2012097146A (ja) シクロオレフィン系共重合体樹脂組成物
JP2007236781A (ja) 医療用チューブ
JP2008260797A (ja) ブロック共重合体及びそれを含む熱収縮性フィルム
JP2016106792A (ja) 医療用複室容器
WO2018225744A1 (fr) Composition élastomère thermoplastique
WO2018230614A1 (fr) Composition élastomère thermoplastique
JP4119920B2 (ja) 医療用複室容器
JP2018080248A (ja) 熱可塑性エラストマー組成物、それを用いた成形体及び医療用チューブ
TW201119862A (en) Polyolefin film and soft bag made thereby.

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: 13761566

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2014504964

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 20147027431

Country of ref document: KR

Kind code of ref document: A

122 Ep: pct application non-entry in european phase

Ref document number: 13761566

Country of ref document: EP

Kind code of ref document: A1