JP5477071B2 - Medical device with lubricity when wet - Google Patents

Description

  The present invention relates to a medical device having lubricity when wet, and more particularly to a technique for imparting excellent lubricity to the surface of a medical device on which a polyurethane layer containing a contrast agent is formed.

  Conventionally, medical devices such as catheters and guide wires for guiding such catheters have been widely used in the medical field. These medical devices such as catheters and guidewires are inserted into blood vessels, digestive tracts, ureters, trachea, bile ducts, other body cavities or tissues, so that they are securely inserted to the target site without damaging the tissues. What we can do is needed. In addition, a low-friction hydrophilic coating is provided on the surface of the medical device so that it does not damage the mucous membrane or the like due to friction while it is placed in the tissue. It is required to impart lubricity.

  In order to meet such a requirement, Japanese Patent Publication No. 1-333181 (Patent Document 1) describes a reactive functional group present on the surface of a base material constituting a medical device, and a maleic anhydride polymer substance. A medical device has been proposed in which the surface exhibits lubricity when wet by covalent bonding.

  JP-A-3-236683 (Patent Document 2) discloses a maleic anhydride copolymer half ester obtained by partially cross-linking the surface of a base material constituting a medical device (medical in-vivo insertion device) with diisocyanate. A medical device has been proposed in which wettability is expressed in the presence of water by coating with the derivative. However, a resin layer (resin film) containing a contrast agent may be formed on the surface of the base material of these medical devices so as to enable imaging in the presence of X-rays. Even if the above-mentioned coating is applied to a medical device having a resin layer containing a contrast agent, although initially exhibiting lubricity, the sliding resistance greatly increases due to repeated sliding, and the lubricity tends to decrease. There was a need for improvement in terms of durability.

Japanese Examined Patent Publication No. 1-33311 JP-A-3-236854

  Here, the present invention has been made against the background of the above circumstances, and the solution to the problem is durability that expresses lubricity when wet and does not easily deteriorate even when repeatedly slid. It is to provide an excellent medical device.

  As a result of various studies to solve the above problems, the present inventors have found that the lubricating performance is greatly reduced due to the contrast agent contained on the surface of the base material of the medical device. Then, after forming a urethane polymer layer on the outer peripheral surface of the medical device containing such a contrast agent, water or body fluid is formed by coating a solution containing a maleic anhydride polymer and a polyisocyanate. It has been found that excellent surface lubricity is exhibited at the time of contact with and that the lubricity is not easily lowered even when sliding repeatedly.

  The present invention has been made based on such knowledge, and the feature thereof is that a urethane polymer layer is provided on the outer peripheral surface of a medical device on which a resin layer containing a contrast agent is formed. The maleic anhydride polymer layer is further laminated on the outer peripheral surface of the urethane polymer layer by coating a solution containing a maleic anhydride polymer and a polyisocyanate. The medical device has lubricity when wet.

  In a preferred embodiment of the medical device according to the present invention, the maleic anhydride polymer is a methyl vinyl ether maleic anhydride copolymer half-esterified product.

  Furthermore, in another preferable aspect of the medical device according to the present invention, the urethane polymer layer is formed using a solution containing a urethane polymer and a polyisocyanate.

  In addition, in a preferred embodiment of the medical device according to the present invention, the polyisocyanate is diphenylmethane diisocyanate.

  In another preferred aspect of the medical device according to the present invention, the resin layer containing the contrast agent is a polyurethane layer containing barium sulfate.

  In addition, as a medical device which concerns on this invention, a guide wire and a catheter can be mentioned, for example.

  Thus, in the medical device according to the present invention, a urethane polymer layer is first formed on the outer peripheral surface of the medical device on which a resin layer containing a contrast agent is formed, and the urethane polymer is further formed. By coating a solution containing maleic anhydride polymer and polyisocyanate on the outer peripheral surface of the layer, the maleic anhydride polymer layer is laminated, so that it not only has lubricity when wet. Even by repeated sliding, good lubricity is maintained and the durability is excellent.

It is an axis perpendicular section explanatory view showing a guide wire as an example of a medical instrument according to the present invention. It is explanatory drawing of the surface lubricity test in an Example. It is a graph which shows the result of the surface lubricity test in an Example.

  The medical device in the present invention is a medical device whose surface needs to be lubricated. For example, a PTCA balloon catheter, a PTA balloon catheter, a contrast catheter, a catheter introduction tube, a catheter such as a microcatheter, and a guide wire are used. Can be mentioned. Hereinafter, in order to clarify the present invention more specifically, embodiments of the present invention will be described with reference to the drawings.

  First, FIG. 1 schematically shows a guide wire 10 as an example of a medical device according to the present invention in a cross-sectional form perpendicular to the axis. Here, 12 is a core wire made of a metal base material such as Ni—Ti, and a resin layer 14 containing a contrast agent 13 is formed on the outer peripheral surface of the core wire 12. Here, as contrast agent 13 contained in resin layer 14, publicly known contrast agents, such as barium sulfate and tungsten, can be mentioned.

  In the present invention, the urethane polymer layer 16 is formed on the outer peripheral surface of the resin layer 14 containing the contrast agent 13, and the maleic anhydride polymer layer 18 is further formed on the outer peripheral surface. Each is laminated with a predetermined thickness. As a result, the maleic anhydride polymer layer 18 as the hydrophilic coating film is prevented from being peeled off by repeated sliding, and the lubricity when wet is advantageously maintained.

  More specifically, in the guide wire 10 of the present embodiment, the urethane-based polymer layer 16 is a film containing a urethane-based polymer, for example, by coating a solution in which the urethane-based polymer is dissolved. It is formed.

  Here, examples of the urethane-based polymer include a urethane-based thermosetting elastomer and a urethane-based thermoplastic elastomer (TPU). Among them, the urethane-based polymer has rubber elasticity at room temperature and is easy to process. From the viewpoint, TPU is preferably employed. Examples of such a commercially available TPU include Peresen 2363-80AE manufactured by Dow Chemical Company, and Milactolan E380 manufactured by Nippon Miractolan.

  As the solvent for dissolving the urethane polymer, those capable of dissolving the urethane polymer are used. For example, acetone, methyl ethyl ketone, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, tetrahydrofuran, a mixed solvent thereof or the like And can be appropriately selected depending on the urethane polymer used.

  Moreover, it is desirable that the solution in which the urethane polymer is dissolved contains polyisocyanate in addition to the urethane polymer. By adding the polyisocyanate, the variation in sliding resistance for each production lot is reduced as compared with the case of using only the urethane polymer, and the production stability of the medical device is enhanced. Examples of the polyisocyanate include isocyanates having two or more isocyanate groups, such as diphenylmethane diisocyanate (MDI), toluene diisocyanate, xylylene diisocyanate, isophorone diisocyanate, hexamethylene diisocyanate, and dicyclohexylmethane diisocyanate. The mixing ratio of the urethane polymer and polyisocyanate is appropriately set depending on the type of the urethane polymer and polyisocyanate used, and is usually 3: 0 to 3: 1, more preferably 3 on a weight basis. : 0.5-3: 1.5.

  The maleic anhydride-based polymer layer 18 laminated on the outer peripheral surface of the urethane-based polymer layer 16 is a coating that forms the outermost peripheral surface of the medical device, and is a maleic anhydride-based polymer and a polyisocyanate. Formed by coating a solution containing The maleic anhydride-based polymer imparts excellent lubricity to the surface of the medical device, and by adding polyisocyanate, the maleic anhydride-based polymer layer 18 is strengthened and has durability against repeated sliding. The effect that it is advantageously increased is obtained.

  Here, examples of maleic anhydride polymers include methyl vinyl ether / maleic anhydride copolymer, ethylene / maleic anhydride copolymer, 1-octadecene / maleic anhydride copolymer, styrene / maleic anhydride copolymer. A polymer can be mentioned. Among these, a half-esterified product of a methyl vinyl ether maleic anhydride copolymer, particularly a methyl vinyl ether represented by the following chemical formula (I), can form a strong film and has excellent compatibility with an organic solvent. Maleic anhydride copolymer monoethyl ester (MVE) is preferably used.

〔式（Ｉ）中、ｎ＝１２０００〜１３０００〕

[In formula (I), n = 12000-13000]

  On the other hand, as the polyisocyanate, those similar to the polyisocyanate added to the solution containing the urethane polymer can be used.

  As the solvent for dissolving these maleic anhydride polymer and polyisocyanate, the same solvents as those for the urethane polymer described above are appropriately selected according to the maleic anhydride polymer and polyisocyanate used. Is done.

  Further, the mixing ratio of the maleic anhydride polymer and the polyisocyanate can be appropriately set depending on the types of the maleic anhydride polymer and the polyisocyanate to be used, and is generally 4: 1 to 1: 2 on a weight basis. The ratio of

  By the way, when manufacturing the guide wire 10 shown in FIG. 1, for example, the following method is advantageously employed.

<First Step> Formation of Urethane Polymer Layer 16 First, a urethane polymer is dissolved in a solvent to prepare a urethane polymer solution (a coating solution for forming a urethane polymer layer). At this time, the concentration of the urethane-based polymer is preferably about 1 to 5 w / v%. If the thickness is less than 1 w / v%, the thickness of the coating is not sufficient, and if it exceeds 5 w / v%, the viscosity of the solution becomes too high, and a coating having a uniform thickness may be formed. May be difficult. Then, the urethane polymer layer 16 is surrounded around the resin layer 14 by immersing a medical device (here, the guide wire 10) in which the resin layer 14 containing the contrast agent 13 is formed in the urethane polymer solution. Are integrally laminated. The dipping operation is usually performed at room temperature for 1 to 60 seconds, and then is preferably left at room temperature for 0.5 to 2 hours to dry the coating.

  In addition, when adding a polyisocyanate to a urethane polymer solution, in consideration of the reactivity of the polyisocyanate, after sufficiently dissolving the urethane polymer in a solvent, immediately before immersing the medical device in the solution It is desirable to add and mix polyisocyanate to the urethane polymer solution.

<Second Step> Formation of Maleic Anhydride Polymer Layer 18 A maleic anhydride polymer solution is prepared by dissolving a maleic anhydride polymer in a solvent. At this time, the concentration of the maleic anhydride polymer is preferably about 1 to 5 w / v%. If the thickness is less than 1 w / v%, the thickness of the coating is not sufficient, and if it exceeds 5 w / v%, the viscosity of the solution becomes too high, and a coating having a uniform thickness may be formed. May be difficult.

  Next, a polyisocyanate is added to and mixed with the maleic anhydride polymer solution to prepare a coating solution for forming a maleic anhydride polymer layer containing the maleic anhydride polymer and the polyisocyanate. . At this time, the concentration of the polyisocyanate is appropriately set so as to have a predetermined blending ratio according to the concentration of the maleic anhydride polymer.

  Then, the medical device (here, the guide wire 10) in which the urethane polymer layer 16 is formed is immersed in a maleic anhydride polymer layer forming solution containing a maleic anhydride polymer and polyisocyanate. As a result, the maleic anhydride polymer layer 18 is integrally laminated around the urethane polymer layer 16. The dipping operation is usually performed at room temperature for 1 to 60 seconds, and then left at room temperature for 1 to 60 minutes to evaporate the solvent and dry the film.

<Third step>
After the maleic anhydride polymer layer 18 is provided, heat treatment is performed to promote the crosslinking reaction and increase the bonding strength between the layers. Such heat treatment is usually performed at 30 to 60 ° C. and 30 to 60 RH for 2 to 4 hours.

<4th process>
Thereafter, the medical device is dipped in water at room temperature for 2 to 4 hours to perform a hydrophilic treatment, and is dried by heating at 30 to 60 ° C. for 1 to 3 hours.

  In the medical device obtained as described above, the urethane polymer layer 16 is formed between the resin layer 14 containing the contrast agent 13 and the maleic anhydride polymer layer 18 which is the outermost layer. Therefore, not only has lubricity when wet, but also by repeated sliding, good lubricity is maintained and durability is excellent.

  The specific configuration of the present invention has been described in detail by taking the guide wire 10 as an example, but this is only an example.

  For example, any medical device other than the guide wire 10 can be applied as long as the surface of the medical device requires lubricity, such as a PTCA balloon catheter, a PTA balloon catheter, a contrast catheter, a catheter introduction tube, a micro tube. It can also be applied to catheters such as catheters. Moreover, if the resin layer 14 containing the contrast medium 13 is formed on the outer peripheral surface of the medical device, the material of the base material body of the medical device is not limited in any way, and the metal of the above example is used. In addition, for example, it may be made of a polymer material such as polyurethane, polytetrafluoroethylene, polyester, polyamide, PVC, polyacrylate, polystyrene, latex or the like.

  In the above specific example, the urethane polymer layer 16 and the maleic anhydride polymer layer 18 are formed by dipping that immerses the medical device in the polymer solution, but the spray method, spin coating method, roll It is also possible to employ a known film forming method such as a coating method.

  In addition, although not enumerated one by one, the present invention can be carried out in a mode to which various changes, modifications, improvements, etc. are added based on the knowledge of those skilled in the art. All are included within the scope of the present invention without departing from the spirit of the present invention.

  Examples of the present invention will be shown below, and the present invention will be more specifically clarified. However, the present invention is not limited to the contents of such examples.

<Example 1>
(1) First, as a medical device, a guide wire (0.035 inch, stiff made by Zima) in which a polyurethane layer containing barium sulfate as a contrast agent is formed in advance on the surface of a Ni-Ti core wire is prepared. Wipe with ethanol.
(2) A urethane polymer (Pelecene 2363-80AE manufactured by Dow Chemical Co., Ltd.) was dissolved in a THF solvent to prepare a 3 w / v% urethane polymer solution.
(3) MDI was added to this urethane polymer solution so that it might become 1 w / v%, and it stirred for 1 minute, and prepared the coating solution for urethane polymer layers.
(4) Immediately after the preparation, a guide wire was immersed in this coating solution for 1 second and dried at room temperature for 1 hour to form a urethane polymer layer.
(5) Next, MVE (manufactured by ISP, GANTREZ AN-169 converted to half monoethyl ester in THF solvent. In the above chemical formula (I), n = 12681) was dissolved, and 2.5 w / v% A MVE solution was prepared.
(6) MDI was added to this MVE solution so that it might become 2.5 w / v%, and it stirred for 1 minute, and prepared the coating solution for maleic anhydride type polymer layers.
(7) Immediately after preparation, a guide wire having a urethane polymer layer formed thereon is immersed in this coating solution for 1 second and dried at room temperature for 1 minute to laminate a maleic anhydride polymer layer as a hydrophilic film. did.
(8) Then, it heated and humidified at 40 degreeC and 50% RH for 4 hours.
(9) Further, after being immersed in room temperature water for 3 hours, it was heated at 54 ° C. for 3 hours.
(10) The guide wire thus obtained was subjected to a surface lubricity test described later, and the obtained results are shown in Table 1 and FIG.

<Example 2>
The same procedure as in Example 1 was performed except that MDI was not added to the coating solution for the urethane-based polymer layer and the step (3) of Example 1 was not performed.

<Example 3>
In the step (1) of Example 1 above, as a guide wire, a guide wire (0.035 inch, stiff manufactured by Zima) in which a polyurethane layer containing tungsten as a contrast agent is formed on the surface of a Ni-Ti core wire in advance. In the step (2) of Example 1 above, MIRCATRAN E380 manufactured by Nippon Milactolan was used as the urethane polymer, and the concentrations of MVE and MDI were used in the steps (6) and (7) of Example 1 above. Were the same as in Example 1 except that each was 2 w / v%.

<Comparative Example 1>
(1) As a medical device, a guide wire (0.035 inch, stiff made by Zima) in which a polyurethane layer containing barium sulfate as a contrast agent is formed on the surface of a Ni-Ti core wire is prepared, and the surface is made of ethanol. Wiped.
(2) A 2.5 W / v% MVE solution was prepared by dissolving MVE (a half monoethyl ester of Gantretz AN-169 manufactured by ISP) in a THF solvent.
(3) MDI was added to this MVE solution so that it might become 2.5 w / v%, and it stirred for 1 minute, and prepared the coating solution for maleic anhydride type polymer layers.
(4) Immediately after preparation, a guide wire having a urethane polymer layer formed thereon is immersed in this coating solution for 1 second, dried at room temperature for 1 minute, and a maleic anhydride polymer layer as a hydrophilic film is laminated. did.
(5) Then, it heated and humidified at 40 degreeC and 50% RH for 4 hours.
(6) Further, after being immersed in room temperature water for 3 hours, it was heated at 54 ° C. for 3 hours.
(7) The guide wire obtained as described above was subjected to a surface lubricity test which will be described later, and the obtained results are shown in Table 1 and FIG.

<Comparative example 2>
In the process (3) of Comparative Example 1, the same procedure as in Comparative Example 1 was performed except that the concentration of MDI was 5 w / v%.

<Comparative Example 3>
In the step (1) of Comparative Example 1, a guide wire (0.035 inch, stiff manufactured by Zima) in which a polyurethane layer containing tungsten as a contrast agent is formed on the surface of a Ni-Ti core wire in advance as a guide wire. Used in the same manner as Comparative Example 1 except that the concentration of MDI was changed to 5 w / v% in the step (3) of Comparative Example 1 above.

<Surface lubricity test>
The surface lubricity test was performed using a test apparatus shown in FIG. In FIG. 2, A is a container, B is a jig, and C is a weight. Instron 5565 type was used as a tensile tester. A guide wire cut to a length of about 15 cm was placed at a predetermined position of the container A filled with physiological saline, and the upper part thereof was fixed to a tensile tester. Next, 100 g of weight C was placed on the jig B (the surface was polyurethane), and a load was applied to the guide wire. After that, using a tensile tester, it is repeatedly raised and lowered at a speed of 8 mm / s and a width of 20 mm, and the initial, the sliding resistance after 20 times, 40 times, 60 times, 80 times and 100 times are measured 5 times each. The average values and standard deviations are shown in Table 1 below. The frictional resistance value (gf) was half of the sum of the rising stress and the falling stress.

  As is clear from the results of Table 1 and FIG. 3, Examples 1 to 3 in which a urethane polymer layer was formed between a resin layer containing a contrast agent and a maleic anhydride polymer layer according to the present invention. 3, it can be seen that the sliding resistance value is greatly reduced as compared with Comparative Examples 1 to 3 in which the urethane polymer layer is not formed, and the lubricity is good. In addition, it is recognized that even if the number of sliding times increases, an increase in sliding resistance value is suppressed and the durability is excellent.

  In addition, Example 1 in which MDI was used to form the urethane polymer layer had a smaller standard deviation than Example 2 in which MDI was not used, and variation in sliding resistance was suppressed. .

DESCRIPTION OF SYMBOLS 10 Guide wire 12 Core wire 13 Contrast agent 14 Resin layer 16 Urethane type polymer layer 18 Maleic anhydride type polymer layer

Claims (5)

On the outer peripheral surface of the medical device on which a resin layer containing a contrast agent is formed, a urethane polymer layer formed using a solution containing a urethane polymer and polyisocyanate is provided,
Further, when wet, the maleic anhydride polymer layer is laminated on the outer peripheral surface of the urethane polymer layer by coating a solution containing a maleic anhydride polymer and a polyisocyanate. A medical device with lubricity. The medical device having lubricity when wet according to claim 1, wherein the maleic anhydride polymer is a methyl vinyl ether maleic anhydride copolymer half-esterified product. The polyisocyanate is a medical device having a lubricious when wet according to claim 1 or 2 is a diphenylmethane diisocyanate. The resin layer containing a contrast agent, a medical device having a lubricious when wet of claim 1-3, wherein the polyurethane layer containing barium sulfate. The medical device having lubricity when wet according to any one of claims 1 to 4 , which is a guide wire or a catheter.

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