JP2011224132A - Medical connector/shaft assembly, or method of manufacturing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an (easily insertable) medical connector/shaft assembly which has high joint strength between the catheter shaft and the connector and is superior in insertability of a guide wire into the connector.SOLUTION: In the medical connector/shaft assembly, a core pin includes: an insertion part with an outer diameter almost same as the inner diameter of the lumen of a catheter shaft containing a reactive functional group; and a projection part adjacent to and connected with the insertion part without level difference at least at the adjacence portion, and in that in a state in which the insertion part of the core pin is inserted into the proximal part of the lumen of the catheter shaft and the projection part is disposed in a manner to project adjacent to the proximal side from the proximal part of the lumen of the catheter shaft, polyamide-based resin composition is insert-molded to form a connector part which is integrated with the shaft catheter.

Description

  The present invention relates to a medical connector / shaft assembly used in a medical institution such as a hospital, or a manufacturing method thereof.

  In recent years, minimally invasive endovascular surgery that percutaneously inserts a catheter into a blood vessel to treat a vascular lesion has become the mainstream. For example, embolization performed for hepatocellular carcinoma or arteriovenous malformation tumor Intravascular surgery, which is called intravascular surgery, selectively inserts the tip of the catheter to or near the affected area, then injects an angiographic agent, and injects a granular embolic substance or metal coil such as gelatin sponge or polyvinyl alcohol granules to embolize the affected area. This is a technique that necroses the tumor. In this way, for the administration of the contrast medium to the thin blood vessel and the injection of the embolic substance or the metal coil, a catheter having a flexible diameter corresponding thereto is used. The catheter includes, for example, a catheter shaft including an inner layer having lubricity, a reinforcing layer made of a resin wire and / or a metal wire provided on the outer side, and an outer layer having flexibility provided on the outer side. It is mainly composed of connectors for injecting and administering contrast media.

  In particular, it is desired that the injection of a contrast medium and an embolizing substance can be performed correctly with high operability so that a predetermined position in the living body can be accurately reached without damaging a blood vessel wall or a living organ in the middle of insertion.

  In addition, the required performance includes ease of operation such as insertion and withdrawal of a catheter into a blood vessel and the like through a guide wire without stress, and pressure resistance when injecting a contrast medium or an embolic material. .

  As one element of this operability, the guide wire insertion property, in which the guide wire is smoothly inserted into the connector, is very important in the initial operation. Various types of guidewires have been commercialized, such as a type with a rigid tip or a flexible type according to the lesion, a type with the tip bent at 90 °, and a J type. In order for these guide wires to be smoothly inserted into the connector, the point is that the connector lumen and the catheter lumen are integrated with no step.

  In addition, the connector is required to have high rigidity, transparency that allows the used drug and embolic material to be easily visually confirmed, and chemical resistance to a contrast medium and the like. This type of connector is often integrated with a catheter shaft using a relatively rigid and transparent resin material molded product.

  As a connector, for example, Patent Document 1 proposes a medical hub characterized by comprising a resin alloy with aromatic polycarbonate and polyester.

  However, this type of material is excellent in chemical resistance, transparency, sterilization resistance, and heat resistance, but has no affinity with a catheter shaft having a flexible outer layer, and therefore is integrated by an adhesive.

  However, as a result of the inventor's confirmation, there is a slight step between the catheter shaft and the connector due to the integration using the adhesive. It turned out to be one.

  In addition, for the purpose of preventing the generation of a step, the present inventor performed insert molding using the resin listed in Patent Document 1 as the material of the connector, so that the catheter shaft is formed flexibly so as not to damage the blood vessel. Since the melting point difference with the resin material used for the resin is large, it is also related to the fact that it is formed to be thin, and bubbles and softening deformation are generated on the shaft surface, making it difficult to stably produce good products. .

  On the other hand, in Patent Document 2, a connector having an outer cylindrical portion formed on the front end side and an inner cylindrical portion positioned in the outer cylindrical portion, and an inner end of the inner cylindrical portion having an annular recess and an edge. Is disclosed. Although the pullout resistance of the catheter is improved by the physical anchor effect of the structure, it is considered that there is a problem in the pressure resistance at the time of contrast medium administration.

JP 2000-197707 A JP 2000-245851 A

  In view of the above problems, the present invention provides a medical connector / shaft assembly having a high bonding strength between a catheter shaft and a connector and excellent in insertion property of a guide wire into a connector (easy insertion property), and a manufacturing method thereof. The purpose is that.

  In view of such a situation, as a result of intensive studies, the present inventors have determined that a catheter shaft containing a reactive functional group has an insertion portion having an outer diameter substantially the same as the inner diameter of the lumen. A core pin having a protrusion adjacent to the insertion portion and connected to the insertion portion without having a step at least in the adjacent portion is inserted into the proximal portion of the lumen of the catheter shaft. In a state in which is inserted in a manner that protrudes adjacent to the proximal side from the proximal portion of the lumen of the catheter shaft, the polyamide resin composition is insert-molded to form a connector portion and integrated with the shaft A medical connector / shaft assembly is provided. According to this, the joint strength between the catheter shaft and the connector is high, and further, the step between them can be reduced, and the guide wire insertion property can be greatly improved.

In addition, the amine value of the polyamide-based resin composition is 4.7 × 10 ⁻⁶ mol / g or more and 6.7 × 10 ⁻⁶ mol / g or less, and the medical connector / shaft assembly is characterized in that Provided. According to this, the joint strength between the catheter shaft and the connector can be further improved.

  Further, the catheter shaft is a composite shaft including a reinforcing layer composed of a metal wire and / or a resin wire, and an outer layer disposed on the outer periphery of the reinforcing layer, and further, lubricity disposed on the inner periphery of the reinforcing layer. The medical connector / shaft assembly is a composite shaft comprising an inner layer having

  In addition, the medical connector / shaft assembly is provided in which the reactive functional group in the catheter shaft containing the reactive functional group is a carboxyl group. According to this, the affinity with the polyamide-based resin composition is promoted, and the bonding strength between the catheter shaft and the connector can be further improved.

  The reactive functional group in the catheter shaft containing the reactive functional group is derived from one or more resin compositions selected from polyamide, polyamide elastomer, polyurethane elastomer, and polyester elastomer. A medical connector / shaft assembly is provided.

The acid value of the resin composition constituting the catheter shaft containing the reactive functional group is 3.7 × 10 ⁻⁶ mol / g or more and 7.7 × 10 ⁻⁶ mol / g or less. The medical connector / shaft assembly is characterized. According to this, it becomes possible to improve the joint strength between the catheter shaft and the connector while reducing the deterioration of the appearance.

  Further, with respect to the catheter shaft containing a reactive functional group, an insertion portion having an outer diameter substantially the same as the inner diameter of the lumen in the lumen thereof, a step adjacent to the insertion portion and at least an adjacent portion thereof Without inserting the core pin having the protrusion connected to the insertion portion, the insertion portion is inserted into the proximal portion of the lumen of the catheter shaft, and the protrusion is proximal from the proximal portion of the lumen of the catheter shaft. A method of manufacturing a medical connector / shaft assembly, characterized in that a polyamide resin composition is insert-molded to form a connector portion and integrated with a shaft in a state where the polyamide-based resin composition is arranged so as to protrude adjacently. Provided. According to this, it is possible to manufacture a medical connector / shaft assembly that has a high bonding strength, further reduces the step between the catheter shaft and the connector, and greatly improves the insertion property of the guide wire.

  The medical connector of the present invention is excellent in the bonding strength between the catheter shaft and the connector, and further has no step between the shaft lumen and the connector lumen. It is possible to provide a medical connector having excellent properties.

1 is a side view of a medical connector / shaft assembly of the present invention. FIG. It is a side view of an insert molding device. Example of insert mold

  The present invention relates to a catheter shaft containing a reactive functional group, an insertion portion having an outer diameter substantially the same as the inner diameter of the lumen, an insertion portion adjacent to the insertion portion, and at least an adjacent portion thereof. A core pin having a protrusion connected to the insertion portion without a step is inserted into the proximal portion of the lumen of the catheter shaft, and the protrusion is proximal from the proximal portion of the lumen of the catheter shaft. A connector / shaft assembly for medical use, characterized in that a connector portion is formed by insert molding of a polyamide-based resin composition in a state of being protruded adjacent to the side and integrated with a shaft It is.

  FIG. 1 shows a schematic view of an example of the medical connector / shaft assembly 1 of the present invention having a connector 2 and a catheter shaft 3. The medical connector / shaft assembly 1 has a flexible tube (strain relief 4) provided as necessary.

  Moreover, in FIG. 2, FIG. 3, the side surface schematic of an insert molding apparatus and an example of a shaping | molding die are shown, respectively. The main structure of the insert molding apparatus is an insert molding die 5, an insert injection molding machine 6, and a hopper dryer 7 (used to simultaneously dry the supplied resin if necessary). Further, as shown in FIG. 3, the insert mold 5 is loaded with the catheter shaft 3 into which the core pin 8 for maintaining the lumen of the catheter shaft is inserted.

1. Insert molding Insert molding in the present invention is performed, for example, by filling a resin mold injected through a gate into a molding die holding a catheter shaft into which a core pin is inserted and cooling it into a connector shape. Can do. The insert molding is divided into a vertical type and a horizontal type. Features of the vertical insert molding include that the surface of the molding die can be mounted upward, that a plurality of shaft parts can be easily positioned, and that space is saved. The operating mechanism is divided into a hydraulic type and an electric type, but it is desirable to be an electric type considering the use in a clean room. In addition, the screw diameter related to the injection amount is appropriately selected according to the size and number of connector molded products.

  The core pin inserted into the catheter shaft includes an insertion portion having an outer diameter substantially the same as the inner diameter of the catheter shaft lumen, and an insertion portion adjacent to the insertion portion and having no step at least in the adjacent portion. It has a structure having connected protrusions (the insertion part and the protrusion may be separable). Here, “having no step” means that, for example, the diameter is continuously changed without being stepped even when the diameter is the same before and after or the diameter is different between before and after. In addition, the core pin insertion portion is inserted into the proximal portion of the lumen of the catheter shaft, and the protruding portion is arranged so as to protrude adjacent to the proximal side from the proximal portion of the lumen of the catheter shaft. , Insert molding, forming the connector part and integrating with the shaft (mainly the insertion part of the core pin maintains the lumen of the catheter shaft, while the protrusion is on the connector formed by insert molding. Forming a lumen against it). Also, the core pin is usually removed after molding and used as a medical connector / shaft assembly. By performing insert molding using the core pin in this manner, a medical connector / shaft assembly can be stably produced that can secure a lumen without a step and can be prevented from being caught when a guide wire is inserted. It becomes possible. The mold may be nested so that it can be used for small-volume, high-mix production, or may be embossed so that the outer surface of the connector has a matte shape.

2. Polyamide resin composition In the present invention, the resin material that is injected into the mold at the time of insert molding and constitutes the medical connector needs to be composed of a polyamide-based resin composition. In particular, in the present invention, the insert molding using a specific core pin is performed to improve the insertability of a guide wire or the like. However, a polyamide-based resin composition is used as a resin to be injected at the time of insert molding. By using in combination with a catheter shaft containing, it becomes possible to develop the bonding strength required between the catheter shaft and the connector even in a system that does not use an adhesive.

  Also in the polyamide-based resin composition, a transparent polyamide-based resin composition is particularly preferable, and the glass transition temperature of the resin composition related to transparency is 100 ° C. or higher and 200 ° C. or lower, particularly 105 ° C. or higher and 195 ° C. or lower, It is preferably 110 ° C. or higher and 190 ° C. or lower. When the glass transition temperature is less than 100 ° C., the transparency of the molded product is impaired, and the guide wire visibility is impaired. On the other hand, if the glass transition temperature exceeds 200 ° C., the insert molding temperature becomes high, which causes foaming and thermal deformation of the catheter shaft surface, which is not desirable. Moreover, when obtaining transparency, it is preferable to comprise an aromatic polyamide elastomer.

  Further, from the viewpoint of holding the shaft lumen after insert molding, the molding shrinkage rate of the resin composition is, for example, 0.1% or more, 1.0% or less, particularly 0.2% or more. 0.9% or less, more preferably 0.3% or more and 0.8% or less. By selecting the molding shrinkage rate, an integrally molded product having mold releasability and holding the shaft lumen can be manufactured. If the mold shrinkage is less than 0.1%, the mold releasability is impaired. On the other hand, if the molding shrinkage ratio exceeds 1.0%, the lumen of the catheter shaft is reduced and the guide wire insertion property and the guide wire sliding property are deteriorated.

  Furthermore, the elastic modulus of the resin composition is preferably, for example, 1500 MPa or more and 2500 MPa or less, particularly 1700 MPa or more, 2300 MPa or less, and more preferably 1900 MPa or more and 2100 MPa or less from the viewpoint of imparting pressure resistance of the connector. If the elastic modulus is less than 1500 MPa, the connector may be damaged, deformed, and the shaft may come off at high injection pressures. On the other hand, if the elastic modulus is greater than 2500 MPa, the connector may be damaged at the time of impact, which is not preferable.

The amine value of the polyamide resin treated for the purpose of end-capping is, for example, 4.7 × 10 ⁻⁶ mol / g or more, 6.7 × 10 ⁻⁶ mol / g or less, particularly 4.9 × 10 ^−6. It is preferable that they are mol * g or more and 6.5 * 10 < ^-6 > mol / g or less, Furthermore, it is 5.1 * 10 < ^-6 > mol / g or more and 6.3 * 10 < ^-6 > mol / g or less. If the amine value is less than 4.7 × 10 ⁻⁶ mol / g, the bonding strength between the resin composition and the shaft at the time of insert molding may not be sufficiently obtained, which is not preferable. On the other hand, if the amine value is larger than 6.7 × 10 ⁻⁶ mol / g, it tends to be colored during molding, which may cause a decrease in yield, which is not preferable.

  The MFR of the polyamide resin composition is preferably 10 g / 10 min or more and 100 g / 10 min or less, more preferably 15 g / 10 min or more and 90 g / 10 min or less, and particularly preferably 20 g / 10 min or more and 80 g / 10 min or less. When the MFR is less than 10 g / 10 min, it is necessary to inject at a high pressure at the time of insert molding, which is not preferable because the catheter shaft may be deformed. Further, if the MFR is 100 g / 10 min or more, resin leakage between the molds is likely to occur during insert molding, which may cause a reduction in productivity such as cleaning each time.

3-1. Structure of Catheter Shaft As the catheter shaft used in the present invention, various types of structures such as a single-layer shaft structure and a composite shaft structure can be used. The catheter shaft can be sized according to the device, but preferably has an inner diameter of 0.30 mm or more and 2.40 mm or less, and an outer diameter of 0.42 mm or more and 2.60 mm or less, particularly an inner diameter of 0.40 mm or more and 2.10 mm or less. The outer diameter is preferably 0.52 mm or more and 2.30 mm or less, further the inner diameter is 0.50 mm or more and 1.80 mm or less, and the outer diameter is 0.70 mm or more and 2.00 mm or less. By setting the inner and outer diameters of the catheter shaft within the above ranges, insert molding can be stably performed, and it is preferably used as a medical catheter, for example, when inserted into a blood vessel. Can do. In addition, a flexible tube (strain relief 4) may be covered to relieve stress during the twisting operation of the surgeon between the shaft and the connector.

  The catheter shaft of the composite shaft structure includes a composite layer including a reinforcing layer made of a metal wire and / or a resin wire, an outer layer disposed on the outer periphery of the reinforcing layer, and further on an inner periphery of the reinforcing layer. It is possible to use a composite shaft that includes an inner layer having lubricity. As a method for forming a medical tube having such a composite shaft structure, for example, a method of coating with an adhesive, a method of coating an outer layer by heat fusion using a heat shrinkable tube, an outer layer in an airtight state Examples of the method include coating. Alternatively, a method of forming a reinforcing layer by applying a braid or a coil using the above strands after passing the core wire through the lumen with the above tube as an inner layer is appropriately selected.

  Further, the tip portion may be formed so that the rigidity thereof is more flexible than the rigidity of the hand portion. In addition, the total length of the catheter is appropriately selected when performing the integral molding. For example, the length is 300 mm or more and 1700 mm or less, preferably 400 mm or more and 1600 mm or less, more preferably 500 mm or more and 1500 mm or less.

3-2. Composition of catheter shaft The catheter shaft used in the present invention is characterized by containing a reactive functional group. In 3-1 above, it was shown that the catheter shaft can have a single layer shaft structure, a composite shaft structure, etc., but the portion containing the reactive functional group is the outer surface when the insert molding is performed. It is preferable to arrange | position. That is, it is preferable that the resin composition constituting the single layer in the single-layer shaft structure or the resin composition forming the outer layer in the composite shaft structure contains a reactive functional group.

The reactive functional group is not particularly limited, but is a hydroxyl group (—OH), a carboxyl group (—COOH), a carbonyl group (—C═O), a carboxylate group (—COOR), a carboxylate group ( -COONa), isocyanate group (-NCO-), amine group _(-NH 2), amido (-NHCO-) is preferred. In particular, it preferably has a carboxyl group that promotes affinity with the polyamide resin composition.

The acid value of the resin composition is, for example, 3.7 × 10 ⁻⁶ mol / g or more, 7.7 × 10 ⁻⁶ mol / g or less, particularly 4.2 × 10 ⁻⁶ mol / g or more, and 7. It is preferably 2 × 10 ⁻⁶ mol / g or less, more preferably 4.7 × 10 ⁻⁶ mol / g or more and 6.7 × 10 ⁻⁶ mol / g or less. If the acid value is less than 3.7 × 10 ⁻⁶ mol / g, the bonding strength between the polyamide-based resin composition and the connector when insert-molded may not be sufficiently obtained, such being undesirable. On the other hand, when the acid value is larger than 7.7 × 10 ⁻⁶ mol / g, foaming is likely to occur on the shaft surface during molding, which may cause a decrease in appearance, which is not preferable.

  On the other hand, as a specific resin composition constituting the catheter shaft containing such a reactive functional group, any one of polyamide, polyamide elastomer, polyurethane elastomer, polyester elastomer, or a combination of two or more thereof is used. It is preferable to use one.

  As the polyamide-based resin, for example, nylon 6, nylon 64, nylon 66, nylon 610, nylon 612, nylon 9, nylon 6 having a molecular structure in which an amide bond is bonded to an aliphatic structure or an alicyclic structure. / 66, polyamide 66/12, nylon 46, nylon 11, nylon 12 and the like.

  Examples of polyamide elastomers include nylon 6, nylon 64, nylon 66, nylon 610, nylon 612, nylon 46, nylon 9, nylon 11, nylon 12, N-alkoxymethyl modified nylon, hexamethylenediamine-isophthalic acid condensation polymer. Typical examples include block copolymers in which various aliphatic or aromatic polyamides such as a metaxyloyldiamine-adipic acid condensation polymer are used as hard segments, and polymers such as polyester and polyether are used as soft segments. It is a concept including a polymer alloy (polymer blend, graft polymerization, random polymerization, etc.) of the polyamide and a resin rich in flexibility, a softening of the polyamide with a plasticizer or the like, and a mixture thereof. As a material suitably used, polyamide elastomer (PAE) is preferable from the viewpoint of processability and flexibility, and for example, PEBAX manufactured by Arkema Co., Ltd. is exemplified.

  Examples of a suitably used polyurethane elastomer material include Tecoflex, Tecothane manufactured by Lubrizol, and Pandex manufactured by DIC Bayer Urethane.

  Furthermore, the polyester elastomer is typically a block copolymer of a saturated polyester such as polyethylene terephthalate or polybutylene terephthalate and a polyether or polyester. In addition, the polymer alloy or the saturated polyester may be used as a plasticizer. It is a concept that includes a softened material and a mixture thereof. Examples of materials that can be suitably used include Hytrel manufactured by Toray Deyupon and Perprene manufactured by Toyobo.

  Moreover, in order to improve the visibility of the catheter under X-ray fluoroscopy, the substance which has a radiopaque property with respect to the said resin composition may be included. Any radiopaque material may be used as long as it has sufficient radiopacity, for example, barium sulfate, bismuth trioxide, bismuth subcarbonate, basic bismuth carbonate, bismuth tungstate, powder Tungsten, powdered tantalum, or a combination thereof. Furthermore, pigments may be appropriately blended for imparting design properties.

  Further, a hydrophilic coating can be applied to the outer surface of the catheter shaft in order to facilitate insertion into a blood vessel or a guide catheter. However, the length of the hydrophilic coating can be determined according to the purpose of use of the catheter. The kind of the hydrophilic coating does not limit the effect of the present invention, and the cellulosic polymer material (for example, hydroxypropyl cellulose), the polyethylene oxide polymer material (polyethylene glycol), and the maleic anhydride polymer material. (For example, maleic anhydride copolymers such as methyl vinyl ether maleic anhydride copolymer), acrylamide polymer materials (for example, polyacrylamide), water-soluble nylon, polyvinylpyrrolidone, and other hydrophilic polymers can be suitably used. The coating method is not limited.

3-3. Reinforcing layer The form of the reinforcing layer used in the present invention is not particularly limited. For example, the reinforcing layer can be formed of a braid, a coil, or a combination thereof. The material used for the braid or the coil is not particularly limited, but a metal strand, a synthetic resin strand, or the like is used.

  As metal wires, stainless steel, spring steel, oil tempered wire, copper, tungsten, nickel, titanium, piano wire, Ni-Ti alloy, Ni-Ti-Co alloy, Ni-Al alloy, Cu-Zn alloy, Cu Various metal strands such as a superelastic alloy such as a Zn—X alloy (for example, X = Be, Si, Sn, Al, Ga) and an amorphous alloy are used. Of these materials, stainless steel is preferred for reasons such as workability, economy, and lack of toxicity.

  As the wire shape of the metal wire, a round wire, a flat wire, an elliptical shape, a deformed wire made of a triangular wire, or the like can be used. The thickness of the strand is preferably 5 μm or more and 100 μm or less in order to stably process the reinforcing layer.

  Examples of synthetic resin wires include polyethylene terephthalate, polyethylene naphthalate, polybutylene terephthalate, polyester such as polymethylene terephthalate, polyolefin such as polyethylene and polypropylene, rigid polyvinyl chloride, polyamide, polyimide, polystyrene, thermoplastic polyurethane. , Polycarbonate, acrylic resin, polymethyl methacrylate, polyacetal, polyarylate, polyoxymethylene, high-tensile polyvinyl alcohol, fluororesin, polyvinylidene fluoride, polytetrafluoroethylene, saponified ethylene-vinyl acetate, polysulfone, polyethersulfone, polyether Aromatic polymers such as ether ketone, polyphenylene oxide, polyphenylene sulfide and Kevlar Such as aramid, a polymer alloy containing any of these, carbon fibers, glass fibers and the like. As the line shape, a round line, a rectangular line, an elliptical shape, an irregular line composed of a triangular line, or the like is appropriately used. The thickness of the strand is preferably 5 μm or more and 100 μm or less in order to stably process the reinforcing layer.

3-4. Inner layer Although it does not specifically limit as a resin composition which comprises the inner layer (particularly it has lubricity) used for this invention, An olefin resin, a polyamide resin, a silicone resin, a fluororesin Etc. are preferable.

  Preferred examples of the olefin resin include high density polyethylene, low density polyethylene, polymethylpentene (TPX), polypropylene, and modified polyethylene.

  In addition, as fluororesin, polytetrafluoroethylene (PTFE), tetrafluoroethylene-perfluoroalkyl vinyl ether copolymer (PFA), tetrafluoroethylene-hexafluoropropylene copolymer (FEP), ethylene-tetrafluoroethylene copolymer Copolymer (ETFE), polychlorotrifluoroethylene (PCTFE), ethylene-tetrafluoroethylene-hexafluoropropylene copolymer (EFEP), vinylidene fluoride-tetrafluoroethylene-hexafluoropropylene copolymer (THV), polyfluoride Examples thereof include vinylidene (PVDF) and vinylidene fluoride-hexafluoropropylene copolymer (FKM), and two or more kinds of blends may be appropriately carried out.

  As a technique for increasing the adhesive strength between the inner layer, the reinforcing layer and the outer layer, although not particularly limited, for example, sodium etching treatment using a chemical treatment solution such as sodium salt-ammonia solution, flame treatment step for melting the resin surface, corona discharge treatment, Methods such as plasma treatment and excimer laser treatment can be employed.

4). Catheter The medical connector / shaft assembly of the present invention can be used as, for example, a microcatheter, a thrombus aspiration catheter, a guiding catheter, a contrast catheter or a penetration catheter.

5). Measurement Various data in this specification were measured by the following methods.

(Shaft inner diameter measurement)
The composite shaft inner diameter (mm) was measured using a pin gauge set EP-3A manufactured by Eisen Co., Ltd.

(Amine number measurement by potentiometric titration)
4 g of polyamide resin composition injected by insert molding and 80 mL of m-cresol (manufactured by Wako Pure Chemical Industries, Ltd.) are mixed, and stirred and dissolved at room temperature for 12 hours and further at 60 ° C. for 2 hours to obtain AT-500N manufactured by Kyoto Electronics Industry Co., Ltd. Then, potentiometric titration was performed with a 0.01 mol / l perchloric acid methanol solution, and an amine value (× 10 ⁻⁶ mol / g) was calculated.

(Acid value measurement by potentiometric titration)
4 g of the resin composition (resin composition for the outer layer) constituting the catheter shaft and 80 mL of benzyl alcohol (manufactured by Wako Pure Chemical Industries, Ltd.) were mixed and stirred and dissolved at 175 ° C. for 1 hour. Using AT-500N manufactured by Kyoto Electronics Industry, Potentiometric titration was performed with a 0.1 mol / l KOH alcohol solution, and the acid value (× 10 ⁻⁶ mol / g) was calculated.

(Appearance test)
Check the created medical connector / shaft assembly visually, ◎ if there is no defect, ◎ if very small foaming is confirmed in some samples, medical connector, or A case where a part of the shaft was deformed was indicated as x.

(Bonding strength measurement)
Using a Strograph EII manufactured by Toyo Seiki Seisakusho Co., Ltd., the connector and the shaft were sandwiched at a load cell of 50 N and a distance between chucks of 50 mm, respectively, and the bonding strength between the medical connector and the shaft was measured at a chuck speed of 100 mm / min. The stress value at break (N) was defined as the bonding strength.

(MFR measurement)
MFR measurement was performed using a melt indexer manufactured by Toyo Seiki Seisakusho Co., Ltd. at a load of 2.16 kgf and a set temperature of 230 ° C. The weight of resin discharged per 10 minutes was defined as MFR (g / 10 min).

(Guide wire insertion test)
A guide wire having a shape bent at 90 ° between 1.0 and 1.5 mm from the tip (Conquest, total length 175 cm, tip diameter 0.23 mm, hand diameter 0.36 mm manufactured by Asahi Intec Corporation) from the tip, Inserted manually from the proximal end of the medical connector / shaft assembly, this guide wire was inserted to the end of the shaft, and ○ was not inserted.

(Pressure resistance measurement (drug injection test))
Using a drug injector (MarkV ProVis manufactured by Nippon Medrad Co., Ltd.), a contrast medium (Oipamilon 370 iodine content 370 mg / mL manufactured by Konica Monoluta Co., Ltd.) at a pressure of 1200 psi from the connector proximal end of the medical connector / shaft assembly is 10 mL / second. And the pressure resistance between the medical connector and the shaft was evaluated. At this time, the distal end of the medical connector / shaft assembly was released. In addition, as an index of pressure resistance, the contrast agent was successfully injected without any problem. ◎ Although it was successfully injected, when the joint of the medical connector / shaft was confirmed after the test, it felt wet. Was marked with ◯, and when the shaft was dropped or the connector was broken during the injection of the contrast medium, it was marked with x.

  Specific examples and comparative examples according to the present invention are described in detail below, but the present invention is not limited to the following examples.

Example 1
A catheter shaft (composite shaft structure) having an inner diameter of 0.51 mmΦ, a tip outer diameter of 0.70 mmΦ, a hand outer diameter of 0.90 mmΦ, and a total length of 1600 mm was prepared. The resin composition constituting the outer layer of the catheter shaft was polyamide 12 (Rilsan AESN-OTL manufactured by Arkema Co., hereinafter referred to as PA12), and its acid value was 5.0 × 10 ⁻⁶ mol / g. It was. A taper-shaped protrusion having an outer diameter of 4.3 mmΦ with a straight tube-shaped insertion portion having an outer diameter of 0.53 mmΦ and a maximum outer diameter portion adjacent to the insertion portion without a step with respect to the insertion shaft ( That is, the outer diameter of the protrusion adjacent to the insertion portion is 0.53 mmΦ, and the core pin has a tapered shape from this to the maximum outer diameter portion of 4.3 mmΦ. Amorphous polyamide as a material constituting the connector portion, which is inserted into the proximal portion of the cavity and the protruding portion protrudes adjacent to the proximal side of the lumen of the catheter shaft adjacent to the proximal side (Grilled amide TR, manufactured by EMS Grevory Co., Ltd., glass transition temperature 110 ° C., elastic modulus 1900 MPa, MFR 40 g / 10 min, hereinafter referred to as T-PA) It is insert molded with insert molding machine (manufactured by Nissei Plastic Industrial Co., THM-7 type clamping force 7t). In addition, the core pin was removed and used as a test sample. There was no change in the shaft inner diameter after molding, the shaft appearance was good and ◎, and the shaft joint strength was 26N. When the guide wire insertion property was confirmed, it was easy to insert into the connector. Further, when the pressure resistance of the connector was confirmed, the shaft was not broken or damaged.

(Example 2)
Other than using polyamide elastomer A (PEBAX3533, acid value 3.7 × 10 ⁻⁶ mol / g, hereinafter referred to as PAE-A) manufactured by Arkema as a resin composition constituting the outer layer of the catheter shaft. In the same manner as in Example 1, insert molding was performed. There was no change in the inner diameter of the shaft after molding, the appearance of the shaft was good, and the shaft joining strength was 22N. When the guide wire insertion property was confirmed, it was easy to insert into the connector. Further, when the pressure resistance of the connector was confirmed, the shaft was not broken or damaged.

(Example 3)
A polyurethane elastomer (Tecoflex EG-72D manufactured by Lubrizol, acid value of 7.7 × 10 ⁻⁶ mol / g, hereinafter sometimes referred to as PUE-A) is used as a resin composition constituting the outer layer of the catheter shaft. Except that, insert molding was carried out in the same manner as in Example 1. There was no change in the inner diameter of the shaft after molding, the appearance of the shaft was good, and the shaft joining strength was 20N. When the guide wire insertion property was confirmed, it was easy to insert into the connector. Further, when the pressure resistance of the connector was confirmed, the shaft was not broken or damaged.

Example 4
Other than using a polyester elastomer (Hytrel 7277 manufactured by Toray DuPont, acid value 6.0 × 10 ⁻⁶ mol / g, hereinafter referred to as PETE) as the resin composition constituting the outer layer of the catheter shaft. In the same manner as in Example 1, insert molding was performed. There was no change in the inner diameter of the shaft after molding, the appearance of the shaft was good, and the shaft joining strength was 15N. When the guide wire insertion property was confirmed, it was easy to insert into the connector. Further, when the pressure resistance of the connector was confirmed, the shaft was not broken or damaged.

(Example 5)
Other than using polyamide elastomer B (PEBAX2533, acid value 3.4 × 10 ⁻⁶ mol / g, hereinafter referred to as PAE-B, manufactured by Arkema) as a resin composition constituting the outer layer of the catheter shaft. In the same manner as in Example 1, insert molding was performed. There was no change in the inner diameter of the shaft after molding, the appearance of the shaft was good, and the shaft joint strength was 10N. When the guide wire insertion property was confirmed, it was easy to insert into the connector. When the connector pressure resistance was confirmed, it could be injected without any problem, but when the medical connector / shaft junction was confirmed after the test, it was felt as wet.

(Example 6)
As a resin composition constituting the outer layer of the catheter shaft, polyurethane elastomer B (Tecoflex EG-85A manufactured by Lubrizol, acid value 9.0 × 10 ⁻⁶ mol / g, hereinafter sometimes referred to as PUE-B) may be used. In the same manner as in Example 1, insert molding was performed. Although there was no change in the inner diameter of the shaft after molding, very small foaming was confirmed on a part of the surface of the shaft after molding. On the other hand, the shaft bonding strength was 9N. When the guide wire insertion property was confirmed, it was easy to insert into the connector. When the connector pressure resistance was confirmed, it could be injected without any problem, but when the medical connector / shaft junction was confirmed after the test, it was felt as wet.

(Comparative Example 1)
Polycarbonate (manufactured by Bayer Co., Ltd., Macrolon LTG 3123, glass transition temperature 150 ° C., amine number 0.0 × 10 ⁻⁶ mol / g, elastic modulus 2200 MPa, hereinafter may be referred to as PC) is used as a material constituting the connector part. Except that, insert molding was performed in the same manner as in Example 1. The inner diameter of the shaft after molding decreased to 0.47 mmΦ, and foaming and deformation were confirmed on the surface of the shaft. The shaft joint strength was 5N. Since the sample was deformed, there were steps and gaps, and evaluation of guide wire insertion property and connector pressure resistance was not performed.

(Comparative Example 2)
An acetal resin as a material constituting the connector part (Delin 900P, manufactured by Deupon, glass transition temperature -60 ° C., amine value 0.0 × 10 ⁻⁶ mol / g, elastic modulus 3000 MPa, hereinafter referred to as POM) The insert molding was carried out in the same manner as in Example 1 except that was used. At first glance, it seemed that there was no defect in the appearance, but the shaft inner diameter was lowered to 0.46 mmΦ, causing deformation, and the appearance test was x. The shaft joint strength was 7N. When the guide wire insertion property was confirmed, it could not be inserted into the connector due to a decrease in the inner diameter. Further, when the pressure resistance of the connector was confirmed, the shaft was detached, and the result was x.

(Comparative Example 3)
The same catheter shaft as that used in Example 1 and a connector manufactured separately using T-PA were butted through a core material (0.52 mmΦ), and then a two-component curable adhesive (manufactured by Sekisui Fuller) A sample was prepared by bonding. There was no change in the inner diameter of the shaft after joining, the appearance of the shaft was good, and the shaft joining strength was 16N. When the guide wire insertion property was confirmed, it could not be inserted into the connector due to the step between the shaft and the connector. Further, when the pressure resistance of the connector was confirmed, the shaft was not broken or damaged.

  The experimental results are summarized in Table 1. From the results of each Example and Comparative Example in Table 1, by inserting the polyamide resin composition as a material constituting the connector portion into the catheter shaft containing the reactive functional group, insert molding between the catheter shaft and the connector is performed. It can be seen that it is possible to provide a medical connector that is excellent in bonding strength, has no step between the shaft lumen and the connector lumen, and has excellent guide wire insertion into the connector during surgery and pressure resistance during drug injection. In addition, it can be seen that in improving the bonding strength, by setting the acid value of the catheter shaft containing a reactive functional group within a specific range, a more excellent medical connector / shaft assembly can be provided.

1. 1. Medical connector / shaft assembly Connector 3. 3. Catheter shaft 4. Strain relief Insert mold 6. 6. Insert injection molding machine 7. Hopper dryer Core pin

Claims (15)

The catheter shaft containing a reactive functional group has an insertion portion having an outer diameter substantially the same as the inner diameter of the lumen, a step adjacent to the insertion portion, and at least a portion adjacent to the insertion portion. Without inserting a core pin having a protrusion connected to the insertion portion into the proximal portion of the lumen of the catheter shaft, the protrusion being adjacent to the proximal portion of the lumen of the catheter shaft. A connector / shaft assembly for medical use, wherein a polyamide resin composition is insert-molded to form a connector portion and integrated with a shaft in a state of being arranged in a projecting manner. The amine value of the polyamide-based resin composition is 4.7 × 10 ⁻⁶ mol / g or more and 6.7 × 10 ⁻⁶ mol / g or less (mol / g). The medical connector / shaft assembly as described. The medical connector / shaft assembly according to any one of claims 1 and 2, wherein the polyamide-based resin composition has an MFR of 10 g / 10 min or more. The medical connector / shaft assembly according to any one of claims 1 to 3, wherein the polyamide-based resin composition has a tensile elastic modulus of 1500 MPa or more and 2500 MPa or less. The medical connector / shaft assembly according to any one of claims 1 to 4, wherein the polyamide resin composition has a molding shrinkage of 0.3% or more and 1.0% or less. Solid. The medical connector / shaft assembly according to any one of claims 1 to 5, wherein a glass transition temperature of the polyamide-based resin composition is 100 ° C or higher and 190 ° C or lower. The said catheter shaft is a composite shaft containing the reinforcement layer which consists of a metal strand and / or a resin strand, and the outer layer arrange | positioned on the outer periphery of this reinforcement layer, The any one of Claims 1-6 characterized by the above-mentioned. A medical connector / shaft assembly according to claim 1. 8. The medical connector / shaft assembly according to claim 7, wherein the catheter shaft is a composite shaft further including an inner layer having lubricity disposed on an inner periphery of the reinforcing layer. The medical connector / shaft assembly according to any one of claims 1 to 8, wherein the reactive functional group in the catheter shaft containing the reactive functional group is a carboxyl group. The reactive functional group in the catheter shaft containing the reactive functional group is derived from one or more resin compositions selected from polyamide, polyamide elastomer, polyurethane elastomer, and polyester elastomer. The medical connector / shaft assembly according to any one of 1 to 9. The acid value of the resin composition constituting the catheter shaft containing the reactive functional group is 3.7 × 10 ⁻⁶ mol / g or more and 7.7 × 10 ⁻⁶ mol / g or less. The medical connector / shaft assembly according to claim 1. The medical connector / shaft assembly according to any one of claims 1 to 11, wherein the joint strength between the catheter shaft and the medical connector is 10 N or more. The medical connector / shaft assembly according to any one of claims 1 to 12, wherein the first catheter shaft is any one of a microcatheter, a thrombus aspiration catheter, and a guiding catheter. The catheter shaft containing a reactive functional group has an insertion portion having an outer diameter substantially the same as the inner diameter of the lumen, a step adjacent to the insertion portion, and at least a portion adjacent to the insertion portion. Without inserting a core pin having a protrusion connected to the insertion portion into the proximal portion of the lumen of the catheter shaft, the protrusion being adjacent to the proximal portion of the lumen of the catheter shaft. A method of manufacturing a medical connector / shaft assembly, wherein the polyamide-based resin composition is integrated by insert molding after being arranged in a projecting manner. 15. The method of manufacturing a medical connector / shaft assembly according to claim 14, wherein the polyamide resin composition is simultaneously insert-molded into at least two molds.

Images