JP2008237523A - Production method of medical instrument and medical instrument - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a production method of a medical instrument capable of forming a highly durable lubricant surface on the surface of the medical instrument, and the medical instrument produced by the production method. <P>SOLUTION: The production method of the medical instrument, includes bringing a diisocyanate compound into contact with the surface of the medical instrument consisting of a polymeric material, and then bringing a mixture of polyalkylene oxide, polyurethane prepolymer, and polyalkylene glycol into contact therewith to apply lubricity to the surface of the medical instrument. This medical instrument is produced by the production method. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for manufacturing a medical device and a medical device, and more particularly, to a method for manufacturing a medical device in which lubrication is imparted to the surface of the medical device used by being inserted into the body, and the method. It relates to medical devices.

In medical devices that are inserted into the body, such as catheters and guidewires, a water-soluble polymer compound such as polyalkylene oxide is fixed on the surface in order to reduce frictional resistance with living tissue during insertion into the body. Therefore, it is known to treat so as to have lubricity when wet, and several methods for imparting this lubricity have been reported. For example, in Patent Document 1, after the surface of a medical device is brought into contact with a diisocyanate compound, a mixture obtained by adding a polyurethane prepolymer to a polyalkylene oxide is brought into contact with the surface of the medical device, thereby providing a highly durable lubricant. It is disclosed that an ionic surface can be formed.
JP 2005-287845 A

  However, although the above-described conventional method can provide a certain level of durability, there is a demand for a method for forming a lubricious surface with better durability. Accordingly, an object of the present invention is to provide a method of manufacturing a medical device that can form a lubricious surface having good durability on the surface of the medical device, and the medical device.

  The present invention relates to a medical device to which lubricity is imparted by bringing a diisocyanate compound into contact with the surface of the medical device made of a polymer material and then bringing a mixture of a polyalkylene oxide, a polyurethane prepolymer and a polyalkylene glycol into contact. It is a manufacturing method.

  Moreover, this invention is a medical device manufactured by the said manufacturing method.

  According to the manufacturing method of the present invention, there is an effect that it is possible to form a highly lubricious surface having a further improved durability even if the friction is repeated, that is, the lubricity is not further lowered. Further, according to the medical device of the present invention, a highly durable lubricating layer is formed on the surface thereof. There is an effect that high lubrication performance can be sufficiently maintained.

  In the method for producing a medical device of the present invention, the surface of the medical device made of a polymer material is brought into contact with a diisocyanate compound, and then the mixture of polyalkylene oxide, polyurethane prepolymer and polyalkylene glycol is brought into contact with the surface of the medical device. This is a method in which lubricity is imparted.

  The medical device to which the method according to the present invention can be applied is a medical device in which at least a surface to which lubricity is imparted is made of a polymer material. The polymer material is not particularly limited as long as it is usually used in the field of medical devices, but for example, heat such as polyolefin resin, fluororesin, polyester resin, polyamide resin, polyurethane resin, and polyvinyl chloride resin. Thermoplastic resins such as polyimide resins and epoxy resins; Thermoplastic elastomers such as olefin elastomers, styrene elastomers, vinyl chloride elastomers, polyester elastomers, polyamide elastomers, and urethane elastomers; and silicone rubber , Natural rubber, and rubber such as fluorine rubber.

  When the surface of the medical device is made of a resin that does not have a functional group such as a hydroxyl group that reacts with the diisocyanate compound, such as a polyolefin resin or a fluororesin, plasma irradiation should be performed in advance before bringing the surface of the medical device into contact with the diisocyanate compound. By applying, it is preferable to introduce a functional group that reacts with an isocyanate group such as an amino group or a hydroxyl group into the surface of the medical device.

  The conditions for plasma irradiation are not particularly limited. Usually, nitrogen gas and oxygen gas are used under conditions where the degree of vacuum is 39.9 Pa to 133.3 Pa, the output is 100 to 450 watts, and the time is 1 to 15 minutes. , Helium gas, argon gas, and / or neon gas is introduced. Moreover, you may irradiate atmospheric pressure plasma.

  In the present invention, the diisocyanate compound to be brought into contact with the surface of the medical device is a compound having two isocyanate groups in the molecule, and usually has a carbon number in the range of 2 to 13. Specific examples of the diisocyanate compound include ethylene diisocyanate, hexamethylene diisocyanate, xylene diisocyanate, toluene diisocyanate, diphenyl diisocyanate, naphthalene diisocyanate, phenylene diisocyanate, cyclohexylene diisocyanate, and 4,4'-diphenylmethane diisocyanate. Among these, 4,4'-diphenylmethane diisocyanate is preferable as the diisocyanate compound.

  If necessary, a small amount of triisocyanate, an addition compound of polyisocyanate and polyol, and the like can be used in combination with the diisocyanate compound. Examples of the triisocyanate include triphenylmethane triisocyanate and toluene isocyanate. Examples of the addition compound of polyisocyanate and polyol include an addition compound of tolylene diisocyanate and trimethylolpropane, an addition compound of hexamethylene diisocyanate and trimethylolpropane, and a trimer.

  The diisocyanate compound is preferably dissolved in a suitable solvent and brought into contact with the surface of the medical device. The solvent is not particularly limited as long as it does not react with the diisocyanate compound, and examples thereof include methylene chloride, ethyl acetate, acetone, chloroform, methyl ethyl ketone, and ethylene dichloride. The concentration of the diisocyanate compound in the solution is usually 0.5 to 50% by weight, preferably 5 to 30% by weight.

  The polyalkylene oxide used as a component of the mixture is a polymer having an alkylene oxide as a monomer. As the polyalkylene oxide, polyethylene oxide, polypropylene oxide, and a copolymer of ethylene oxide and propylene oxide are preferable, and polyethylene oxide is particularly preferable. The number average molecular weight of the polyalkylene oxide is usually in the range of 5,000 to 500,000.

  The polyalkylene oxide is preferably used after being dissolved in an appropriate solvent. The solvent is particularly preferably a non-aqueous solvent, and the same solvent as that used when dissolving the diisocyanate compound can be used. The concentration of polyalkylene oxide in the solution is usually 0.1 to 30% by weight, preferably 1 to 20% by weight.

  The polyurethane prepolymer that is a component of the mixture is obtained by reacting a polymer polyol, a diisocyanate compound and, if necessary, a chain extender in the presence or absence of a solvent, with one isocyanate group in the molecule. As described above, a polymer compound having two or more is preferable.

  Examples of the polymer polyol used for obtaining the polyurethane prepolymer include polyether polyol, polyester polyol, polycarbonate polyol, and polyester polycarbonate polyol. Among them, polyether polyol is preferably used. In the production of the polyurethane prepolymer, two or more of these polymer polyols may be used in combination.

  Examples of the polyether polyol used as the polymer polyol for obtaining the polyurethane prepolymer include polyethylene glycol, polypropylene glycol, and polytetramethylene glycol, and one or more of these can be used.

  As the diisocyanate compound used for obtaining the polyurethane prepolymer, the same compound as the diisocyanate compound to be brought into contact with the above-described medical device can be used.

  Examples of the chain extender component include low molecular weight compounds having a molecular weight of 300 or less having two or more active hydrogen atoms capable of reacting with an isocyanate group in the molecule. Specifically, ethylene glycol, propylene glycol, 1 Diols such as 1,4-butanediol, 1,6-hexanediol, 1,4-bis (β-hydroxyethoxy) benzene, 1,4-cyclohexanediol, bis- (β-hydroxyethyl) terephthalate, and xylylene glycol Triols such as trimethylolpropane; pentaols such as pentaerythritol; hydrazine, ethylenediamine, propylenediamine, xylylenediamine, isophoronediamine, piperazine and derivatives thereof, phenylenediamine, tolylenediamine, xylenediamine, Examples thereof include diamines such as dipic acid dihydrazide and isophthalic acid dihydrazide; amino alcohols such as aminoethyl alcohol and aminopropyl alcohol, and one or more of these can be used.

  The polyurethane prepolymer can be obtained by mixing the above-described components and reacting them in the presence or absence of an organic solvent under a temperature condition of 30 to 150 ° C., for example. Moreover, although the molecular weight of a polyurethane prepolymer is not specifically limited, 5000-20000 are preferable. Such a polyurethane prepolymer is commercially available, for example, as Coronate (trademark) 2491 (manufactured by Nippon Polyurethane Co., Ltd.), and may be used.

  The obtained polyurethane prepolymer may be added to the polyalkylene oxide solution and mixed. The addition amount is not particularly limited, but is preferably 30 to 50% by weight with respect to the polyalkylene oxide. In addition, when a polyurethane prepolymer is added to the polyalkylene oxide solution, the isocyanate group of the polyurethane prepolymer is prevented from reacting with the end group of the polyalkylene oxide and being deactivated. It is preferable to be immediately before contacting the surface.

  Examples of the polyalkylene glycol that is a component of the mixture include polyethylene glycol and polypropylene glycol. Among these, polyethylene glycol is preferable. Examples of the number average molecular weight of the polyalkylene glycol include 600 to 20000.

  The polyalkylene glycol is preferably used after being dissolved in an appropriate solvent. As this solvent, the same one as used when dissolving the polyurethane prepolymer can be used. The polyalkylene glycol is preferably blended so that the hydroxyl group is 0.01 to 1 equivalent with respect to the equivalent of the isocyanate group of the urethane prepolymer to be blended, so that the hydroxyl group is 0.01 to 0.2 equivalent. It is more preferable to blend in.

  In order to specifically carry out the present invention, the surface of a medical device is usually brought into contact with a solution in which a diisocyanate compound is dissolved by dipping, spraying, or other methods. The contact time is, for example, 5 to 60 seconds in the case of immersion.

  When the surface of the medical device is a polyolefin resin or a fluororesin, plasma irradiation is performed in advance before bringing the surface of the medical device into contact with the diisocyanate compound as described above.

  The solvent is then removed by air drying at room temperature. The time for removing the solvent is usually from 30 seconds to several tens of minutes. Subsequently, a solution in which a mixture of polyalkylene oxide, polyurethane prepolymer and polyalkylene glycol is dissolved is brought into contact with the surface of the medical device by dipping, spraying or other methods, and then air-dried at room temperature to remove the solvent. In the case of immersion, the immersion time is 5 to 60 seconds, and the time for removing the solvent is usually 30 seconds to several tens of minutes.

  Thereafter, the medical device is heated in the range of 40 to 80 ° C., preferably in the range of 50 to 70 ° C., and the polyalkylene oxide is fixed to the surface of the medical device. In this case, the processing time is usually 2 to 20 hours. After that, it is preferable to remove unreacted polyalkylene oxide, diisocyanate compound, and polyurethane prepolymer by washing with water.

  According to the present invention, when a polyalkylene oxide is brought into contact with the surface of a medical device brought into contact with a diisocyanate compound, a polyurethane prepolymer and a polyalkylene glycol are added to and mixed with the polyalkylene oxide. In comparison, the polyalkylene oxide is less likely to be detached from the surface of the medical device. That is, a highly durable lubricating surface is formed on the surface of the medical device. For this reason, the medical device to which lubricity is imparted by this method is unlikely to deteriorate even when the medical device is repeatedly rubbed. The reason why it is difficult to remove polyalkylene oxide from the surface of the medical device by adding polyalkylene glycol to the polyalkylene oxide is not necessarily clear, but the polyalkylene glycol is not between the polyurethane prepolymer and the polyalkylene oxide. It is presumed that the reaction is caused by bonding to fix the polyalkylene oxide.

  The medical device of the present invention is a medical device in which the surface is provided with lubricity when wet by the above-described method, and the lubricity is not easily deteriorated even when repeatedly rubbed. The type of medical device is not particularly limited. For example, catheters that are inserted or placed in the digestive tract orally or nasally, such as urinary catheters and suction catheters; thermodilution catheters (TDC), angiography Intravascular or intracardiac catheters, sheath introducers, aortic balloon pumping catheters (IABP), percutaneous coronary transvascular angioplasty balloon catheters (PTCA), microcatheters, thrombus aspiration catheters, stenosis penetrating catheters, etc. Catheters inserted or placed in the catheter; and further, a guide wire and the like. The shape of the medical device is not particularly limited as long as it is determined according to the type thereof, and examples thereof include a tube shape and a linear shape.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to these Examples.

<Example 1>
A tube (outside diameter 1.3 mm, inside diameter 0.9 mm, length 350 mm) obtained by extrusion-molding a polyamide-based elastomer (PEBAX ™ 5533) was converted into a methyl ethyl ketone solution of 4,4′-diphenylmethane diisocyanate (concentration: 20% by weight) and then pulled up and air-dried for 30 seconds. Next, this tube was prepared from polyethylene oxide having a molecular weight of 400,000 (concentration: 3% by weight) and a polypropylene glycol polyurethane prepolymer having a molecular weight of 8000 (Coronate (trademark) 2491, manufactured by Nippon Polyurethane Co., Ltd., 10% isocyanate group content). (Concentration: 0.35 wt%) and a polyethylene glycol having a molecular weight of 1000 (concentration: 0.06 wt%, hydroxyl group is 0.15 equivalent to the equivalent of the isocyanate group of the urethane prepolymer) in an acetonitrile solution of 10 After dipping for 2 seconds, it was air-dried for 2 minutes. Furthermore, this tube was heat-treated at 60 ° C. for 15 hours, then washed with water to remove unreacted polyethylene oxide, and the tube of Example 1 was obtained.

  Next, the durability test of lubricity was performed on the obtained tube of Example 1. First, a force gauge was attached to an actuator installed so that the driving direction was perpendicular to the ground so that the measurement terminal faced downward. Subsequently, the tube of Example 1 was connected to the measurement terminal of the force gauge and suspended, and the tube was immersed in a 37 ° C. water bath. Next, a position 120 mm from the lower end of the tube was sandwiched between two silicone rubber sheets (40 mm × 50 mm, thickness 10 mm) with the load adjusted to 80 gf (0.784 N). At this time, the orientation of the silicone rubber sheet was adjusted so that the longitudinal direction of the silicone rubber sheet and the tube coincided. Next, the actuator is moved upward at 8 mm / sec, and the stress measured by the force gauge (the friction stress that the tube receives from the silicone rubber sheet) is recorded every second for 15 seconds immediately after that, The average value was obtained. And the tube used for this measurement was used as it was, and the same measurement was repeated 20 times. As a result, the 5th friction stress was 45 mN, the 10th friction stress was 45 mN, and the 20th friction stress was 45 mN.

<Example 2>
Instead of polyethylene glycol having a molecular weight of 1000 (concentration: 0.06% by weight), polyethylene glycol having a molecular weight of 20000 (concentration: 0.50% by weight, 0.06 equivalent of the hydroxyl group relative to the equivalent of the isocyanate group of the urethane prepolymer) The tube of Example 2 to which lubricity was imparted was obtained in the same manner as in Example 1 except that (2) was added. The tube of Example 2 was subjected to a lubricity durability test in the same manner as Example 1. As a result, the 5th friction stress was 38 mN, the 10th friction stress was 39 mN, and the 20th friction stress was 38 mN.

<Comparative Example 1>
A tube of Comparative Example 1 to which lubricity was imparted was obtained in the same manner as Example 1 except that polyethylene glycol having a molecular weight of 1000 (concentration: 0.06% by weight) was not added to the acetonitrile solution. The tube of Comparative Example 1 was subjected to a lubricity durability test in the same manner as in Example 1. As a result, the 5th friction stress was 47 mN, the 10th friction stress was 49 mN, and the 20th friction stress was 54 mN.

  According to the present invention, it has been found that sufficient lubricity can be maintained even in the durability test of 20 times. For this reason, by adopting the above-described configuration, it was possible to form a highly durable lubricated surface on the surface of the medical device that hardly deteriorates the lubricity even if the friction is repeated.

Claims (2)

On the surface of medical devices made of polymer materials,
Contacting the diisocyanate compound, then
A method for producing a medical device to which lubricity is imparted by contacting a mixture of a polyalkylene oxide, a polyurethane prepolymer, and a polyalkylene glycol.   A medical device manufactured by the manufacturing method according to claim 1.