JP2012000240A - Medical tool having surface lubricity in wetting - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical tool for permanently exhibiting excellent surface lubricity during use by firmly immobilizing various polymeric base materials and a surface lubricating layer with a simple method.SOLUTION: The medical tool includes: a base material layer comprising a polymeric material at least on the surface; compounds each of which is carried by at least a part of the base material layer and has a plurality of thiol groups in a molecule; and surface lubricating layers each of which covers the compound having the plurality of thiol groups in the molecule and comprises hydrophilic polymers with a reactive functional group. The medical tool has the surface lubricity in wetting, where the compounds having the thiol groups are carried by the base material layer by radiating ionized gas plasma containing nitrogen and also the surface lubricating layers are joined with the base material layers by reacting the compounds having the thiol groups with the hydrophilic polymers with the reactive function group.

Description

  The present invention relates to a medical device whose surface has lubricity when wet.

  Medical devices such as catheters, guide wires, and indwelling needles that are inserted into a living body are required to exhibit excellent lubricity in order to reduce tissue damage such as blood vessels and improve operability for the operator. For this reason, a method of coating the surface of a substrate with a hydrophilic polymer having lubricity has been developed and put into practical use. In such a medical device, it is a problem in terms of maintaining safety and operability that the hydrophilic polymer is eluted and separated from the surface of the base material.

  In order to prevent such a problem, Patent Document 1 discloses that a water-soluble or water-swellable polymer is dissolved in a solvent in which a base material of a medical device swells to prepare a polymer solution, and the medical solution is added to the medical solution. A medical device is disclosed in which a surface lubricant layer is formed on the surface of the substrate by dipping and swelling the substrate of the device, and further cross-linking or polymerizing the polymer on the surface of the substrate.

  Even by the method described in Patent Document 1, the surface lubricating layer can be fixed to the base material to a certain degree. In particular, when the substrate itself swells with a hydrophilic polymer solution, the substrate polymer and the hydrophilic polymer forming the surface lubrication layer form an interpenetrating network structure, which enables extremely strong fixation. . On the other hand, when the base polymer is difficult to swell by the hydrophilic polymer solution, the hydrophilic polymer forming the surface lubricating layer is fixed to the base material only by the effect of insolubilization by crosslinking or polymerizing, and an interpenetrating network structure There is a higher risk that the surface lubricating layer will be peeled off compared to the polymer base material that forms. For this reason, there is a need for a coating method that can more firmly immobilize the hydrophilic polymer on the surface of the hardly swellable polymer substrate.

  As a method for firmly fixing a large amount of hydrophilic polymer on the surface of a polymer substrate, Patent Document 2 discloses that a polymer material forming a substrate layer has a first higher-order structure in the molecule, and the first And a first functional group provided at at least one end of the higher-order structure of the second higher-order structure capable of interacting with the first higher-order structure in the molecule. A medical device characterized by having a structure and a second functional group provided at at least one end of the second higher-order structure and capable of hydrogen bonding with the first functional group is disclosed. .

JP-A-8-33704 JP 2007-289299 A

  However, the method described in Patent Document 2 has a problem that the combination of the base polymer and the hydrophilic polymer is limited.

  Accordingly, the object of the present invention is to solve the above-mentioned problems of the prior art, and to fix various polymer base materials and surface lubrication layers firmly by a simpler method, thereby providing an excellent surface during use. It is to provide a medical device that permanently exhibits lubricity.

  In order to achieve the above object, the present invention provides (1) a base material layer having at least a surface made of a polymer material, and a compound having a plurality of thiol groups in the molecule supported on at least a part of the base material layer. And a surface lubricating layer made of a hydrophilic polymer having a reactive functional group that covers the compound having a plurality of thiol groups in the molecule, wherein the compound having the thiol group contains nitrogen. The surface lubricant layer is bonded to the base material layer by reacting the compound having the thiol group and the hydrophilic polymer having the reactive functional group, which are supported on the base material layer by irradiating It is a medical device whose surface has lubricity when wet.

  Moreover, this invention for achieving the said objective is (2) Irradiating the ionized gas plasma containing nitrogen to the said base material layer surface, Then, the solution which melt | dissolved the said compound which has the said thiol group is applied to the base material layer surface. It is a medical device as described in said (1) by which the compound which has the said thiol group is carry | supported by the base material layer by apply | coating.

  Furthermore, the present invention for achieving the above object is (3) by applying a solution in which the compound having the thiol group is dissolved to the surface of the base material layer, and then irradiating with ionized gas plasma containing nitrogen, The medical device according to (1) or (2), wherein the compound having the thiol group is supported on a base material layer.

  Furthermore, the present invention for achieving the above object is as follows: (4) After irradiating the substrate layer surface with a solution in which the compound having the thiol group is dissolved, irradiating the ionized gas plasma containing nitrogen, followed by heating It is a medical device as described in said (2) or (3) by which the compound which has the said thiol group is carry | supported by the base material layer by processing.

  According to the medical device of the present invention, various polymer base materials and surface lubrication layers can be firmly fixed by a simpler method to permanently exhibit excellent surface lubricity during use. Can do.

It is the fragmentary sectional view which represented typically the lamination structure of the surface of typical embodiment of the medical device which the surface has lubricity at the time of the wetness of this invention. FIG. 2 is a partial cross-sectional view schematically illustrating a configuration example having a different surface layer configuration as an application example of the embodiment of FIG. 1. It is a schematic diagram of the surface lubricity maintenance evaluation test apparatus (friction measuring machine) used in Example 1 and Comparative Example 1. It is drawing which shows the surface lubricity maintenance evaluation test result (n = 3) of the polyethylene tube (1) (sample) obtained in Example 1. FIG. It is drawing which shows the surface lubricity maintenance evaluation test result (n = 3) of the comparative polyethylene tube (1) (sample) obtained in the comparative example 1.

  In the present invention, at least a surface of a base material layer made of a polymer material (hereinafter, also simply referred to as “polymer base material layer” or “base material layer”) and supported on at least a part of the base material layer, A compound having a plurality of thiol groups in the molecule (also referred to as —SH: mercapto group, sulfhydryl group, or hydrosulfur group) (hereinafter, also simply referred to as “thiol compound”), and a plurality of thiols in the molecule And a surface lubricating layer made of a hydrophilic polymer having a reactive functional group that covers the compound having a group, and the compound having the thiol group is irradiated with ionized gas plasma containing nitrogen (hereinafter simply referred to as “plasma treatment”). The surface lubricating layer is formed by reacting the compound having the thiol group with the hydrophilic polymer having the reactive functional group. Base material Are attached, the surface when wetted to provide a medical device having lubricity.

  Usually, polymer materials such as polyamide and polyethylene do not have a functional group that reacts with a thiol group. Therefore, in the case of the surface of the base material layer made of the polymer material as described above, the surface lubricant layer is firmly attached to the base material layer via the thiol compound because it cannot react with the thiol compound simply by applying the thiol compound. It is impossible to immobilize.

  On the other hand, as in the present invention, by irradiating ionized gas plasma containing nitrogen, the surface lubricating layer can be firmly bonded (immobilized) to the base material layer via the thiol compound.

  As described above, the mechanism for firmly bonding (immobilizing) the base material layer to the surface lubricating layer via the thiol compound is not clear, but is presumed as follows. The present invention is not limited by the following estimation. That is, in the medical device of the present invention, by performing ionized gas plasma irradiation containing nitrogen on the surface of the base material layer before applying the thiol compound, from a polymer material having no reactive functional group such as polyamide or polyethylene. Even if it is a base material layer which becomes, functional groups, such as a carboxyl group, a hydroxyl group, and a peroxide, can be introduce | transduced into the surface. As a result, the wettability with respect to the solution in which the thiol compound is dissolved is increased, and the thiol compound can be uniformly applied to the surface of the base material layer, and the functional group on the surface of the base material layer reacts with the thiol group of the thiol compound. By doing so, the thiol compound can be firmly fixed on the surface of the base material layer. And as above-mentioned, in addition to the said functional group, an amino group can be introduce | transduced to the base-material layer surface by containing nitrogen in ionization gas. As a result, hydrogen bonds and polar interaction work between the amino group and the thiol compound, and the thiol compound is stably held on the surface of the base material layer, thus promoting the reaction between the thiol compound and a functional group such as peroxide. Thus, the thiol compound can be more efficiently immobilized on the surface of the base material layer. Alternatively, by applying a nitrogen-containing ionized gas plasma after applying a thiol compound to the surface of the base material layer, in addition to the effect of introducing functional groups on the base material layer surface as described above, the thiol compound itself is activated. Thus, the reaction between the thiol compound and the surface of the base material layer and the polymerization between the thiol compounds can be promoted, and as a result, the thiol compound can be firmly fixed on the surface of the base material layer. Moreover, since the thiol compound according to the present invention has a plurality of thiol groups, there are residual thiol groups that do not contribute to supporting (immobilization) on the surface of the base material layer. This residual thiol group reacts with a reactive functional group (for example, an epoxy group, an isocyanate group, etc.) of the hydrophilic polymer to form a surface lubricating layer. Thus, according to the present invention, the surface lubricating layer can be firmly fixed to the surface of the base material layer made of various polymer materials through a thiol compound by a simple method, and an excellent surface during use. The lubricity can be demonstrated permanently.

  DESCRIPTION OF EXEMPLARY EMBODIMENTS Hereinafter, exemplary embodiments to which the invention is applied will be described with reference to the accompanying drawings.

  FIG. 1 is a partial cross-sectional view schematically showing a laminated structure of a surface of a medical device whose surface is lubricious when it is wet according to a representative embodiment of the present invention (hereinafter also simply referred to as a medical device). . FIG. 2 is a partial cross-sectional view schematically showing a configuration example having a different surface laminated structure as an application example of the present embodiment. In addition, each appendix in FIG.1 and FIG.2 represents the following, respectively. 1 is a base material layer; 1a is a base material layer core; 1b is a polymer surface layer; 2 is a compound having a plurality of thiol groups in the molecule (thiol compound); 3 is a surface Lubricant layer; and 10 respectively represent medical devices whose surfaces are lubricious when wet.

  As shown in FIG. 1 and FIG. 2, in the medical device 10 of this embodiment, at least the surface is supported by a base material layer 1 made of a polymer material and at least a part of the base material layer 1 (in the figure, The compound (thiol compound) 2 having a plurality of thiol groups in the molecule and the compound 2 having a plurality of thiol groups in the molecule are shown. And a surface lubricating layer 3 made of a hydrophilic polymer having a reactive functional group covering the substrate, and the compound 2 having the thiol group is supported on the base layer 1 by irradiating ionized gas plasma containing nitrogen ( The surface lubricating layer 3 is bonded to the base material layer 1 via the thiol compound 2 by reacting the compound 2 having the thiol group and the hydrophilic polymer having the reactive functional group. Are connected.

  Hereinafter, the medical device of this embodiment is demonstrated in detail for every structural member.

(1) Base material layer 1
The base material layer 1 constituting the medical device of the present embodiment has at least a surface made of a polymer material.

(1a) Configuration of Base Material Layer 1 The base material layer 1 is “at least the surface is made of a polymer material” as long as at least the surface of the base material layer 1 is made of a polymer material. The whole (all) is not limited to what is composed (formed) of a polymer material. Therefore, as shown in FIG. 2, a polymer material that is more flexible than a reinforcing material such as a metal material is formed on the surface of the base layer core portion 1a formed of a hard reinforcing material such as a metal material or a ceramic material. Coating (coating) by an appropriate method (a conventional method such as dipping, spraying, coating, printing, etc.) or a metal material of the base layer core portion 1a and a polymer material of the surface polymer layer 1b Are combined (appropriate reaction treatment) to form the surface polymer layer 1b is also included in the base material layer 1 of the present invention. Therefore, the base layer 1a is a multilayer structure in which different materials are laminated in multiple layers, or a structure (composite) in which members formed of different materials for each part of a medical device are connected. Also good. Further, a different middle layer (not shown) may be formed between the base material layer core portion 1a and the surface polymer layer 1b. Furthermore, regarding the surface polymer layer 1b, a multilayer structure in which different polymer materials are laminated in multiple layers, or a structure (composite) in which members formed of different polymer materials for each part of a medical device are connected. It may be.

(1b) Configuration of the base material layer core portion 1a The material that can be used for the base material layer core portion 1a is not particularly limited, and is an optimum base depending on the use such as a catheter, a guide wire, an indwelling needle or the like. What is necessary is just to select suitably the reinforcement material which can fully express the function as the material layer core part 1a. For example, various stainless steel (SUS) such as SUS304, SUS316L, SUS420J2, SUS630, gold, platinum, silver, copper, nickel, cobalt, titanium, iron, aluminum, tin and nickel-titanium alloy, cobalt-chromium alloy, zinc- Examples include various metal materials such as tungsten alloys and the like, inorganic materials such as various ceramic materials, and metal-ceramic composites, but are not limited thereto.

(1c) Configuration of Base Material Layer 1 to Surface Polymer Layer 1b The polymer material that can be used for the base material layer 1 to the surface polymer layer 1b is not particularly limited. For example, nylon 6, nylon 11, Polyamide resins such as nylon 12 and nylon 66 (both are registered trademarks), polyethylene resins such as linear low density polyethylene (LLDPE), low density polyethylene (LDPE), high density polyethylene (HDPE), and polypropylene resins Polyolefin resin, epoxy resin, urethane resin, diallyl phthalate resin (allyl resin), polycarbonate resin, fluorine resin, amino resin (urea resin, melamine resin, benzoguanamine resin), polyester resin, styrene resin, acrylic resin, polyacetal resin, vinyl acetate Resin, pheno Resin, vinyl chloride resin, silicone resin (silicon resin), and the like. These may be used individually by 1 type and may use 2 or more types together. What is necessary is just to select the polymeric material optimal as polymeric base materials, such as a catheter, a guide wire, and an indwelling needle which are use applications, as said polymeric material suitably.

(1d) Structure of middle layer In addition, the material that can be used for the middle layer (not shown) is not particularly limited, and may be appropriately selected depending on the intended use. Examples include various metal materials, various ceramic materials, and organic-inorganic composites, but are not limited thereto. Hereinafter, “base material layer 1 having at least a surface made of a polymer material” is also simply referred to as “polymer base material layer 1” or “base material layer 1”.

(2) Compound 2 having a plurality of thiol groups in the molecule
A compound (hereinafter simply referred to as “thiol compound”) 2 having a plurality of thiol groups in a molecule constituting the medical device of the present embodiment is supported on at least a part of the surface of the polymer base material layer 1. .

  Here, it is assumed that the thiol compound 2 is supported on at least a part of the surface of the base material layer 1 in medical devices such as catheters, guide wires, and indwelling needles that are used, and these medical devices are not necessarily used. It is not necessary for all surfaces (the entire surface) to have lubricity when wet, and thiol compounds only on the surface part (some or all) where the surface is required to have lubricity when wet This is because it is sufficient that 2 is supported.

  The “supporting” referred to here is a state in which the thiol compound 2 is immobilized in a state where it is not easily released from the surface of the base material layer 1.

  The thiol compound 2 is not particularly limited as long as it is a compound having a plurality of thiol groups in the molecule, but when it reacts with the polymer material on the surface of the base material layer 1 and is firmly fixed by plasma treatment and subsequent heat treatment, etc. In addition, the thiol group remaining on the outermost surface of the thiol compound 2 is easily exposed so that the remaining thiol group and the reactive functional group of the hydrophilic polymer of the surface lubricating layer 3 are likely to react. desirable. From this viewpoint, the thiol compound 2 may be a compound having two or more thiol groups in one molecule, but preferably 2 to 10 thiol groups in one molecule, more preferably 3 to 6 thiol groups. It is a compound that has.

  From this viewpoint, the thiol compound may be linear, branched, or cyclic. For example, 1,2-ethanedithiol, 1,2-propanedithiol, 1,3-propanedithiol, 1,4- Butanedithiol, 2,3-butanedithiol, 1,5-pentanedithiol, 1,6-hexanedithiol, 1,8-octanedithiol, 3,6-dioxa-1,8-octanedithiol, bis (2-mercaptoethyl) ) Ether, bis (2-mercaptoethyl) sulfide, 1,2-benzenedithiol, 1,4-benzenedithiol, 1,4-bis (mercaptomethyl) benzene, toluene-3,4-dithiol, 1,5-di Mercaptonaphthalene, 4,4'-biphenyldithiol, 4,4'-thiobisbenzenethiol, tetra Compounds having two thiol groups in the molecule such as tylene glycol bis (3-mercaptopropionate), 1,3,5-benzenetrithiol, tris-[(3-mercaptopropionyloxy) -ethyl] -isocyanurate (TEMPIC), triazine trithiol, trimethylolpropane tris (3-mercaptopropionate) (TMMP) and other compounds having three thiol groups in the molecule, pentaerythritol tetrakis (mercaptoacetate), pentaerythritol tetrakis (3- Mercaptopropionate), pentaerythritol tetrakis (3-mercaptobutyrate) and other compounds having four thiol groups in the molecule, dipentaerythritol hexakis (3-mercaptopropionate) and other thiol groups in the molecule Compound 6 having, and can be suitably exemplified and their derivatives and polymers. These may be used individually by 1 type and may use 2 or more types together. Preferably, when the thiol group is immobilized on the surface of the base material layer 1, a structure in which the remaining thiol group is easily exposed on the outermost surface so that the remaining thiol group and the reactive functional group of the hydrophilic polymer are likely to react with each other. -Tris-[(3-mercaptopropionyloxy) -ethyl] -isocyanurate, which is a compound having a stable molecular skeleton, good affinity with the surface of the base material layer 1 and having 3 to 6 thiol groups (TEMPIC), dipentaerythritol hexakis (3-mercaptopropionate).

  Moreover, in this embodiment, it is not restrict | limited at all to the thiol compound illustrated above, Other thiol compounds can also be utilized if the effect of this invention can be expressed effectively.

(2a) Thickness of the thiol compound 2 The thickness of the thiol compound 2 constituting the medical device of the present embodiment is not particularly limited, and the surface lubricating layer 3 can be firmly fixed to the surface of the base material layer 1, It is only necessary to have a thickness capable of permanently exhibiting excellent surface lubricity during use. Usually, the thickness is 10 μm or less, preferably 1 μm or less. Moreover, as long as it can function effectively as a so-called molecular adhesive, even if the monomolecular film layer of the thiol compound is formed on the surface of the base material layer 1 (= the thiol compound is one molecule in the thickness direction). Good. Furthermore, from the viewpoint that the medical device such as a catheter, a guide wire, and an indwelling needle can be made thinner by reducing the thickness of the thiol compound 2, even if the surface of the base material layer 1 is impregnated with the thiol compound 2 Good.

(2b) Fixing method of thiol compound 2 In the medical device of the present invention, the thiol compound 2 is fixed to the base material layer 1 by irradiating ionized gas plasma containing nitrogen (plasma treatment).

  As a specific form for immobilizing the thiol compound 2 on the base material layer 1, (i) before applying a solution containing a compound having a thiol group to the base material layer surface, nitrogen is applied to the base material layer surface. The form which carry | supports the compound which has the said thiol group on a base material layer by irradiating the ionized gas plasma to contain is mentioned. Specifically, before applying a solution (thiol compound solution) in which the thiol compound is dissolved to the surface of the base material layer 1 (before applying the thiol compound), the surface of the base material layer 1 is previously plasma-treated to improve the surface. After activation, the thiol compound solution is applied to react the thiol compound 2 and the surface of the base material layer 1 (bond / fix). In this form, functional groups such as a carboxyl group, a hydroxyl group, and a peroxide are introduced to the surface of the base material layer 1 by performing ionized gas plasma irradiation containing nitrogen. Thereby, the wettability with respect to the thiol compound solution is increased, and the thiol compound 2 can be uniformly applied to the surface of the base material layer 1, and the functional group on the surface of the base material layer 1 reacts with the thiol group of the thiol compound 2. By doing so, the thiol compound 2 can be firmly fixed to the surface of the base material layer 1. And by adding nitrogen to ionized gas as mentioned above, in addition to the said functional group, an amino group can be introduce | transduced into the base material layer 1 surface. Thereby, since a hydrogen bond and a polar interaction work between an amino group and the thiol compound 2 and the thiol compound 2 is stably held on the surface of the base material layer 1, a functional group such as thiol compound 2 and peroxide And the thiol compound 2 can be more efficiently immobilized on the surface of the base material layer 1.

  In the form (i), a heat treatment or the like may be performed after the thiol compound solution is applied. After applying the thiol compound solution, it is possible to accelerate the reaction between the surface of the base material layer 1 and the thiol compound 2 or to polymerize the thiol compound 2 itself by heat treatment or the like. For this reason, the thiol compound can be more firmly fixed to the surface of the base material layer by the heat treatment or the like.

  Also, (ii) a solution in which a compound having a thiol group is dissolved is applied to the surface of the substrate layer, and then the compound having a thiol group is supported on the substrate layer by irradiating ionized gas plasma containing nitrogen. A form is mentioned. Specifically, after the thiol compound solution is applied to the surface of the base material layer 1 (after the application of the thiol compound), the plasma treatment is performed to react (immobilize) the thiol compound 2 and the surface of the base material layer 1. It is a form to be made. In this form, in addition to the effect of introducing a functional group on the surface of the base material layer 1 as described above, the thiol compound 2 itself is activated to react the thiol compound 2 with the surface of the base material layer 1 or the thiol compound. As a result, the thiol compound 2 can be firmly immobilized on the surface of the base material layer 1.

  In the form (ii), heat treatment or the like may be performed after irradiation with ionized gas plasma containing nitrogen. After the plasma treatment, the reaction between the surface of the base material layer 1 and the thiol compound 2 or the polymerization of the thiol compound 2 itself can be promoted by heat treatment or the like. For this reason, the thiol compound can be more firmly fixed to the surface of the base material layer by the heat treatment or the like.

  Further, a mode in which the plasma treatment before the application of the thiol compound of (i) and the plasma treatment after the application of the thiol compound of (ii) are used together, that is, (iii) the substrate layer surface is irradiated with ionized gas plasma and has the thiol group The compound-dissolved solution is applied to the surface of the base material layer, and again irradiated with ionized gas plasma, thereby supporting the compound having the thiol group on the base material layer. At this time, at least one of the above two ionized gas plasmas is supported. One of the forms is an ionized gas plasma containing nitrogen. Specifically, by applying a plasma treatment to the surface of the base material layer 1 before applying the thiol compound, after modifying and activating the surface, the thiol compound solution is applied, and then the plasma treatment is performed again. The thiol compound 2 and the surface of the base material layer 1 are reacted (immobilized), and at this time, at least one of the two ionized gas plasmas is an ionized gas plasma containing nitrogen. In this form, taking into account the fixing strength of the thiol compound on the surface of the base material layer, the above two ionized gas plasmas (the ionized gas plasma treatment before applying the thiol compound solution to the base material layer, the thiol compound solution applied) In the ionized gas plasma treatment after the treatment, it is preferable to perform in advance an ionized gas plasma treatment containing nitrogen before applying the thiol compound solution to the base material layer. More preferably, the ionized gas plasma treatment containing nitrogen is performed both before and after application of the thiol compound solution. This form is excellent in that the thiol compound 2 can be fixed very firmly on the surface of the base material layer 1 and the surface lubricating layer can be uniformly bonded (fixed) with uniform strength over the entire surface of the base material layer. ing. In particular, when the two ionized gas plasmas are both ionized gas plasmas containing nitrogen, the above effect can be further achieved.

  Also in this case, heat treatment or the like may be performed after the plasma treatment is performed again. By such heat treatment, it is possible to promote the reaction between the surface of the base material layer 1 and the thiol compound 2 or the polymerization of the thiol compound 2 itself. For this reason, the thiol compound can be more firmly fixed to the surface of the base material layer by the heat treatment or the like.

  Since the thiol compound has a plurality of thiol groups, there are residual thiol groups that do not contribute to supporting (immobilization) on the surface of the base material layer. This residual thiol group reacts with a reactive functional group (for example, an epoxy group, an isocyanate group, etc.) of the hydrophilic polymer described later to form a surface lubricating layer. In this way, the surface lubrication layer can be firmly fixed to the surface of the base material layer made of various polymer materials through a thiol compound by a simple method, and the excellent surface lubricity during use is permanent. Can be demonstrated.

  Hereinafter, the form (iii) using the forms (i) and (ii) together will be described. In the following embodiment, the ionized gas plasma treatment containing nitrogen is performed in both the ionized gas plasma treatment before applying the thiol compound solution to the base material layer and the ionized gas plasma treatment after applying the thiol compound solution. As described above, it is not necessary to perform both, and at least one of them may be subjected to ionized gas plasma treatment not containing nitrogen. Here, with “ionized gas plasma treatment not containing nitrogen”, the same operation and conditions can be applied except that the following plasma treatment does not contain nitrogen.

(2b-1) Plasma treatment before application of thiol compound In this embodiment, before applying the thiol compound solution to the base material layer 1 (before application of the thiol compound), ionized gas plasma containing nitrogen on the surface of the base material layer 1 in advance. Is irradiated. Thereby, the surface of the base material layer 1 can be modified and activated, and the wettability of the surface of the base material layer 1 with respect to the thiol compound solution can be improved, so that the thiol compound solution is uniformly applied to the surface of the base material layer 1. Can do. The ionized gas plasma treatment can be performed on a thin and narrow inner surface of a medical device such as a catheter, a guide wire, or an indwelling needle.

  Before irradiating the surface of the base material layer 1 with ionized gas plasma containing nitrogen, it is preferable to clean the surface of the base material layer 1 in advance by an appropriate method. Even when the thiol compound application is performed without performing the plasma treatment prior to the application of the thiol compound as in the form (ii) above, the cleaning treatment is performed before the application of the thiol compound solution. Is desirable.

  There are no particular restrictions on the pressure conditions in the plasma treatment prior to the application of the thiol compound, which can be under reduced pressure or atmospheric pressure, but can be irradiated with plasma gas from any angle and requires a vacuum device. The apparatus can be downsized, space-saving, low-cost system configuration can be realized, and it is economically preferable. Further, the plasma irradiation nozzle is irradiated with the plasma gas while rotating around the object to be processed such as a guide wire, so that the entire periphery of the object to be processed can be uniformly subjected to the plasma processing.

  Examples of the ionized gas that can be used for the plasma treatment before the application of the thiol compound include helium, neon, argon, krypton, carbon dioxide, carbon monoxide, water vapor, oxygen, and hydrogen. At this time, the ionized gas may be used alone or in the form of two or more mixed gases.

  Here, the ionized gas contains nitrogen. By including nitrogen in the ionized gas, as described above, there is an advantage that the thiol compound can be more efficiently immobilized on the surface of the base material layer. Here, the content of nitrogen in the ionized gas is not particularly limited as long as it has an effect as described above.

  The irradiation time in the plasma treatment before application of the thiol compound is 10 minutes or less, preferably 0.1 second to 5 minutes, and more preferably 1 second to 3 minutes. The lower limit of the plasma irradiation time is not particularly limited, but when it is less than 0.1 seconds, it is possible to secure a time sufficient to sufficiently increase the wettability (modification, activation) of the surface of the base material layer 1. This may be difficult, and formation of a thin film of the thiol compound may be difficult. On the other hand, when the plasma irradiation time exceeds 10 minutes, the activation of the surface of the base material layer 1 becomes excessive, so that the breakage and recombination of the polymer material on the surface of the base material layer 1 (recombination or cross-linking of the molecular structure) May occur excessively.

  The temperature of the workpiece (base material layer 1 before application of the thiol compound) in the plasma treatment before application of the thiol compound is lower than the melting point of the polymer material on the surface of the base material layer 1 and the base material layer 1 is deformed. The temperature is not particularly limited as long as it is not in the temperature range, and it may be heated or cooled to high or low temperature in addition to normal temperature. From an economical viewpoint, a temperature (5 to 35 ° C.) that does not require a heating device or a cooling device is preferable.

  The plasma treatment conditions prior to the application of the thiol compound are not particularly limited as long as the irradiation conditions such as the applied current and gas flow rate are appropriately determined according to the area of the object to be processed, and the plasma irradiation apparatus and ionized gas type to be used. It is not something.

  The plasma irradiation apparatus (system) that can be used for plasma treatment before thiol compound coating is not particularly limited. For example, a plasma generation tube that introduces gas molecules and excites them to generate plasma. A plasma irradiation apparatus (system) having an electrode for exciting gas molecules in the plasma generation tube and configured to emit plasma from one end of the plasma generation tube can be exemplified. There is no limit to this. For example, an ionized gas plasma irradiation apparatus (system) suitable for irradiation to a catheter, a guide wire, an indwelling needle, etc., particularly a plasma irradiation apparatus (system) at atmospheric pressure can be used from those already on the market. . Specifically, a plasma irradiation device made by TRI-STAR TECHNOLOGIES: DURADYNE (trade name or trade name), a plasma irradiation device made by DIENER ELECTRONIC: PLASMABEAM, etc. can be used, but it is not limited thereto.

(2b-2) Application of thiol compound The method for applying the thiol compound solution to the polymer base material layer 1 is not particularly limited, and is a coating / printing method (coating method), dipping method (dipping method), or spraying. Conventionally known methods such as a method (spray method), a spin coat method, and a mixed solution impregnated sponge coat method can be applied.

  In the following, after immersing the polymer base material layer 1 in the thiol compound solution, drying and applying the thiol compound solution to the surface of the polymer base material layer 1, plasma treatment is performed, and heat treatment is performed. This will be described in detail by taking as an example a form in which the thiol compound 2 is immobilized on the surface of the molecular substrate layer 1. However, the present invention is not limited to these formation methods. In the case of this form, the medical base material layer 1 is immersed in a thiol compound solution, and the inside of the system is depressurized and degassed, so that medical devices such as catheters, guide wires, injection needles and the like are narrow and narrow. It is also possible to accelerate the application of the thiol compound 2 by allowing the solution to rapidly penetrate the inner surface.

  In the case where the thiol compound 2 is immobilized only on a part of the surface of the polymer base material layer 1, the thiol compound solution is applied (immersed and dried) only on a part of the polymer base material layer 1. The thiol compound 2 can be immobilized on a desired surface portion of the polymer base material layer 1 by irradiating ionized gas plasma containing nitrogen again and further performing heat treatment or the like as necessary. .

  When it is difficult to immerse only a part of the surface of the polymer base material layer 1 in the thiol compound solution, the surface portion of the polymer base material layer 1 on which the thiol compound 2 is not immobilized in advance is attached / detached (attached / detached) After protecting (covering, etc.) with an appropriate member or material possible, after immersing the base material layer 1 in a thiol compound solution and drying it, again performing ionized gas plasma irradiation containing nitrogen, After performing heat treatment as necessary, the protective member (material) on the surface portion of the polymer base material layer 1 that does not immobilize the thiol compound 2 is removed, so that the desired surface portion of the base material layer 1 is removed. The thiol compound 2 can be immobilized. However, in the present invention, there is no limitation to these immobilization methods, and the thiol compound 2 can be immobilized by appropriately using conventionally known methods. For example, when it is difficult to immerse only a part of the base material layer 1 in the thiol compound solution, other coating methods (for example, an application method or a spray method) are applied instead of the dipping method. Also good. However, due to the structure of the medical device 10, both the outer surface and the inner surface of the cylindrical device need to have lubricity when wet (see the configuration of FIGS. 1 and 2). ) Is superior in the dipping method (dipping method) in that both the outer surface and the inner surface can be coated at once.

  The concentration of the thiol compound solution used when immobilizing the thiol compound 2 is not particularly limited. From the viewpoint of uniformly coating the desired thickness, the concentration of the thiol compound in the thiol compound solution is preferably 0.001 to 20 wt%, more preferably 0.01 to 10 wt%. When the concentration of the thiol compound is less than 0.001 wt%, a sufficient amount of the thiol compound cannot be immobilized on the surface of the base material layer 1, and the surface lubricating layer 3 can be firmly fixed to the base material layer 1. It can be difficult. In addition, when the concentration of the thiol compound exceeds 20 wt%, the viscosity of the thiol compound solution may be too high, and the thiol compound having a uniform thickness may not be immobilized. It may be difficult to quickly coat the narrow and narrow inner surface of the tool. However, even if it is out of the above range, it can be sufficiently utilized as long as it does not affect the operational effects of the present invention.

  Examples of the solvent used in the thiol compound solution include water, methanol, ethanol, isopropanol, ethylene glycol and other alcohols, acetone, methyl ethyl ketone and other ketones, ethyl acetate and other esters, chloroform and other halides, Examples include alkanes such as butane and hexane, ethers such as tetrahydrofuran (THF) and butyl ether, aromatics such as benzene and toluene, amides such as N, N-dimethylformamide (DMF), and the like. There is no limitation to these. These may be used alone or in combination of two or more.

  The drying conditions for the thiol compound solution are not particularly limited. That is, since medical devices such as catheters, guide wires, and indwelling needles that are the subject of the present invention are extremely small and do not take much time to dry, natural drying is sufficient. From this viewpoint, the drying temperature of the thiol compound solution under the drying conditions is preferably 20 to 150 ° C, more preferably 20 to 130 ° C. The drying time is preferably 1 second to 1 hour, more preferably 1 to 30 minutes. When the drying time is less than 1 second, plasma energy is absorbed by evaporation of the remaining solvent, etc. by performing plasma treatment after application of the thiol compound in an undried state, and activation of the surface of the base material layer 1 and the thiol compound (For example, increase the surface energy of the base material layer 1 or create functional groups (active sites or active sites) by exciting or ionizing elements of the surface of the base material layer 1 or thiol compounds). This may be difficult, and there is a possibility that a bonding portion with the surface of the base material layer cannot be secured sufficiently. On the other hand, when drying time exceeds 1 hour, the further effect by drying exceeding the said time cannot be acquired, and it may be uneconomical.

  The pressure condition at the time of drying is not limited at all, and it can be performed under normal pressure (atmospheric pressure), or under pressure or reduced pressure.

  As the drying means (apparatus), for example, an oven, a vacuum dryer, or the like can be used. However, in the case of natural drying, the drying means (apparatus) is not particularly necessary.

(2b-3) Plasma treatment after application of thiol compound In this embodiment, the thiol compound solution is applied to the surface of the base material layer 1 and then irradiated with ionized gas plasma containing nitrogen again. Also by such plasma treatment, the thiol compound 2 itself can be activated to bond (react) the thiol compound 2 and the surface of the base material layer 1 so that the thiol compound 2 can be firmly fixed. In addition, the thiol compound 2 itself can be polymerized by the plasma treatment.

  The plasma treatment after application of the thiol compound of this embodiment can be performed under the same conditions as the plasma treatment before application of the thiol compound described above, and can be performed using the same plasma irradiation apparatus as the plasma treatment before application of the thiol compound. In addition, it is preferable that the plasma treatment conditions after application of the thiol compound of the present embodiment are in a preferable range described in the plasma treatment before application of the thiol compound, but the same conditions as the plasma treatment before application of the thiol compound are required. There is no.

(2b-4) Heat treatment when immobilizing the thiol compound 2 When immobilizing the thiol compound 2 on the surface of the base material layer 1, after performing the plasma treatment after the application of the thiol compound, further by heat treatment, etc. It is also possible to promote the reaction between the surface of the base material layer 1 and the thiol compound 2 or the polymerization of the thiol compound 2 itself.

  Such heat treatment is not particularly limited as long as the reaction (polymerization) of the thiol compound can be accelerated, and may be appropriately determined according to the temperature characteristics (heat resistance) of the polymer material on the surface of the base material layer 1.

  Therefore, the lower limit of the heat treatment temperature (set temperature of a heating apparatus such as a heating furnace) is not less than a temperature at which the reaction (polymerization) of the thiol compound can be accelerated, preferably not less than 40 ° C., more preferably not less than 50 ° C. If the temperature is lower than the temperature at which the reaction (polymerization) of the thiol compound can be accelerated, the desired reaction (polymerization) is not sufficiently promoted, and the heat treatment takes a long time and is uneconomical, or the reaction by heat treatment (polymerization) May not be able to achieve the desired effect.

  Moreover, as an upper limit of heat processing temperature, it is below melting | fusing point-5 degreeC temperature of the polymeric material of the base material layer 1 surface, Preferably it is melting | fusing point-10 degreeC or less. In the case of a temperature higher than the melting point of the polymer material on the surface of the base layer 1 -5 ° C, the reaction (polymerization) is sufficiently accelerated, but depending on the temperature distribution inside the heating apparatus such as a heating furnace, the set temperature In some cases, part of the surface of the base material layer 1 may be melted or deformed.

  Further, some polymer materials used for the surface of the base material layer 1 are taken as an example, and the heat treatment temperature range is exemplified below, but the heat treatment temperature range of the present embodiment is not limited to these. . For example, when the polymer material on the surface of the base material layer 1 is various nylons (nylon 6, 11, 12, 66, etc.), the heat treatment temperature is 40 to 150 ° C., preferably 60 to 140 ° C. When the polymer material on the surface of the base material layer 1 is various polyethylenes (LDPE, LLDPE, HDPE, etc.), the heat treatment temperature is 40 to 85 ° C, preferably 50 to 80 ° C.

  The heat treatment time is not particularly limited as long as the reaction (polymerization) of the thiol compound can be accelerated, but it is desirable to heat-treat for 15 minutes to 24 hours, preferably 30 minutes to 12 hours. . When the heating time is less than 15 minutes, there is a possibility that the reaction (polymerization) may not be sufficiently performed, the amount of unreacted thiol compound may be increased, and a bonding portion with the surface of the base material layer 1 is secured. In addition, there is a possibility that the strength compensation effect due to polymerization of the thiol compound 2 itself cannot be sufficiently exhibited. On the other hand, when the heating time exceeds 24 hours, it is uneconomical because a further effect by heating exceeding the above time cannot be obtained.

  However, regarding the above heat treatment temperature and time, when the plasma treatment after application of the thiol compound is performed under a low vacuum, for example, the temperature of the object to be treated rises during the plasma treatment, and the heat treatment is conducted during the plasma treatment. In some cases, the same reaction (polymerization) may be performed, and it may be desirable to appropriately determine the plasma treatment conditions.

  The pressure condition during the heat treatment is not limited at all, and it can be performed under normal pressure (atmospheric pressure), or under pressure or reduced pressure.

  Moreover, when superposing | polymerizing thiol compounds, you may use additives, such as a thermal-polymerization initiator, adding a timely appropriate quantity to a thiol compound solution so that this polymerization can be accelerated | stimulated. As the heating means (device), for example, an oven, a dryer, a microwave heating device, or the like can be used.

  Examples of methods other than the heat treatment for promoting the reaction or polymerization of the thiol compound include UV irradiation and electron beam irradiation, but are not limited thereto.

  After immobilizing the thiol compound 2, the excess thiol compound can be washed with an appropriate solvent to leave only the thiol compound immobilized on the surface of the polymer substrate layer 1.

(3) Surface lubrication layer 3
The surface lubricating layer 3 constituting the medical device of the present embodiment is made of a hydrophilic polymer having a reactive functional group that covers the surface of the thiol compound 2.

  Here, the hydrophilic polymer having a reactive functional group constituting the surface lubricating layer 3 (hereinafter, also simply referred to as “hydrophilic polymer”) is formed so as to cover the surface (the whole) of the thiol compound 2. Just do it. However, when the thiol compound 2 is formed on the entire surface of the base material layer 1 including the surface portion required to have lubricity when wet, the surface of the thiol compound 2 is lubricated when wet. The surface lubricating layer 3 may be formed only on the surface portion (some or all of the surface portions) that are required to have the property.

(3a) Thickness of the surface lubrication layer 3 As the thickness of the surface lubrication layer 3 constituting the medical device of this embodiment, a thickness capable of permanently exhibiting excellent surface lubricity during use is used. There is no particular limitation as long as it has. The thickness of the surface lubricating layer 3 when not swollen is preferably in the range of 0.5 to 5 μm, more preferably 1 to 5 μm, and even more preferably 1 to 3 μm. When the thickness of the surface lubricating layer 3 when not swollen is less than 0.5 μm, it is difficult to form a uniform film, and the surface lubricity may not be sufficiently exhibited when wet. On the other hand, when the thickness of the non-swelled surface lubricating layer 3 exceeds 5 μm, the thick surface lubricating layer swells, so that when the medical device 10 is inserted into a blood vessel or the like in a living body, When passing a portion having a small clearance from the medical device (for example, inside a peripheral blood vessel), internal tissues such as blood vessels may be damaged, or it may be difficult to pass the medical device.

(3b) Hydrophilic polymer The hydrophilic polymer having a reactive functional group constituting the surface lubricating layer 3 is not particularly limited. For example, a monomer having a reactive functional group in the molecule and a hydrophilic monomer It can be obtained by copolymerizing the body.

(3b-1) Monomer having a reactive functional group The monomer having a reactive functional group is not particularly limited as long as it has reactivity with a thiol group. Specific examples include monomers having an epoxy group such as glycidyl acrylate and glycidyl methacrylate, monomers having an isocyanate group such as acryloyloxyethyl isocyanate in the molecule, and the like. Above all, the reactive functional group is an epoxy group because of its excellent reactivity with thiol groups, the reaction is accelerated by heat, and it is insolubilized by forming a crosslinked structure to easily form a surface lubricating layer. A monomer having an epoxy group, such as glycidyl acrylate and glycidyl methacrylate, which can be used and is relatively easy to handle, is preferable. Hydrophilic polymers using monomers with epoxy groups are more reactive than those with monomers having isocyanate groups in the molecule when they are reacted by heating (heating treatment). The speed is moderate (appropriate speed). Therefore, when reacting by heating operation, etc., when reacting with a thiol compound or crosslinking reaction between reactive functional groups, it reacts immediately and gels or hardens to increase the crosslinking density of the surface lubrication layer and lubricity. Since the reaction rate is moderate (appropriate rate) to such an extent that it is possible to suppress and control the decrease in the pH, it can be said that the handleability is good. These monomers having reactive functional groups may be used alone or in combination of two or more.

(3b-2) Hydrophilic monomer The hydrophilic monomer is not particularly limited as long as it exhibits lubricity in body fluids and aqueous solvents. Specific examples include monomers having side chains of acrylamide and derivatives thereof, vinylpyrrolidone, acrylic acid and methacrylic acid and derivatives thereof, sugars, and phospholipids. For example, N-methylacrylamide, N, N-dimethylacrylamide, acrylamide, acryloylmorpholine, N, N-dimethylaminoethyl acrylate, vinylpyrrolidone, 2-methacryloyloxyethylphosphorylcholine, 2-methacryloyloxyethyl-D-glycoside, 2-Methacryloyloxyethyl-D-mannoside, vinyl methyl ether, hydroxyethyl methacrylate and the like can be suitably exemplified. From the viewpoint of ease of synthesis and operability, N, N-dimethylacrylamide is preferred. These hydrophilic monomers may be used individually by 1 type, and may use 2 or more types together.

(3b-3) Preferred form of hydrophilic polymer In order to develop good lubricity, monomers having reactive functional groups gather to form a reactive domain, and hydrophilic monomers gather. And a block or graft copolymer forming a hydrophilic domain. With such a block or graft copolymer, good results can be obtained in the strength and lubricity of the surface lubricating layer.

  The production method (polymerization method) of these hydrophilic polymers is not particularly limited. For example, a living radical polymerization method, a polymerization method using a macromonomer, a polymer initiator such as a macroazo initiator is used. It can be produced by applying conventionally known polymerization methods such as conventional polymerization methods and polycondensation methods.

(3c) Formation method of surface lubricating layer 3 (bonding form between base material layer 1 and surface lubricating layer 3)
In the present embodiment, the base material layer 1, the thiol compound 2, and the surface lubricating layer 3 are provided, and the thiol compound 2 is fixed to the base material layer 1 by irradiating the ionized gas plasma containing nitrogen as described above. Furthermore, the surface lubricating layer 3 is bonded to the base material layer 1 by reacting the remaining thiol group of the thiol compound with the reactive functional group of the hydrophilic polymer. .

  Therefore, when the surface lubricating layer 3 is formed, the base material layer 1 on which the thiol compound 2 is immobilized is immersed in a solution in which the hydrophilic polymer is dissolved (hereinafter also abbreviated as “hydrophilic polymer solution”). After that, the surface lubricating layer 3 is formed by reacting the reactive functional group (for example, epoxy group) of the hydrophilic polymer and the remaining thiol group of the thiol compound 2 by drying and heat treatment. At the same time, the surface lubricating layer 3 can be bonded (fixed) to the base material layer 1. In addition, in the state which the base material layer 1 which fix | immobilized the thiol compound 2 was immersed in the hydrophilic polymer solution, the inside of a system was pressure-reduced and it was made to degas | defoam, and medical devices, such as a catheter, a guide wire, and a syringe needle, were The formation of the surface lubricating layer 3 may be promoted by allowing the solution to quickly penetrate into the narrow and narrow inner surface.

  In the case where the surface lubricating layer 3 is formed only on a part of the thiol compound 2, only a part of the thiol compound 2 immobilized on the base material layer 1 is immersed in the hydrophilic polymer solution and then heated. By performing the treatment or the like, the surface lubricating layer 3 made of a hydrophilic polymer can be formed on a desired surface portion of the thiol compound 2.

  When it is difficult to immerse only a part of the thiol compound 2 immobilized on the base material layer 1 in the hydrophilic polymer solution, the surface portion of the thiol compound 2 that does not form the surface lubricating layer 3 in advance is attached or detached. (Protection / desorption) After protecting (covering, etc.) with an appropriate member or material, the surface lubricating layer 3 is obtained after the thiol compound 2 immobilized on the base material layer 1 is immersed in the hydrophilic polymer solution. The surface lubricating layer 3 made of a hydrophilic polymer is formed on a desired surface portion of the thiol compound 2 by removing a protective member (material) from the surface portion of the thiol compound 2 that does not form a thiol compound 2 and then performing a heat treatment or the like. Can do. However, in the present invention, the formation method is not limited to these forming methods, and the surface lubricating layer 3 can be formed by appropriately using conventionally known methods.

  In place of the method (immersion method or dipping method) of immersing the base material layer 1 with the thiol compound 2 immobilized in the hydrophilic polymer solution, for example, a coating / printing method, a spraying method (spraying method), Conventionally known methods such as a spin coat method and a mixed solution impregnated sponge coat method can be applied.

  Further, the method of reacting the thiol compound with the hydrophilic polymer is not particularly limited, and for example, a conventionally known method such as heat treatment, light irradiation, electron beam irradiation, or radiation irradiation can be applied. it can.

  In the following, the thiol compound 2 immobilized on the base material layer 1 is immersed in a hydrophilic polymer solution, and the hydrophilic polymer solution (coating solution) is coated (coated) on the surface of the thiol compound 2 and then heated. A detailed description will be given by taking as an example a form in which the surface lubricating layer 3 is formed by reacting the residual thiol group of the thiol compound with the reactive functional group of the hydrophilic polymer by the operation. However, the present invention is not limited to these coating and reaction processing operations.

(3c-1) Concentration of hydrophilic polymer solution The concentration of the hydrophilic polymer solution used when forming the surface lubricating layer 3 is not particularly limited. From the viewpoint of uniformly coating the desired thickness, the concentration of the hydrophilic polymer in the hydrophilic polymer solution is 0.1 to 20 wt%, preferably 0.5 to 15 wt%, more preferably 1 to 10 wt%. %. When the concentration of the hydrophilic polymer solution is less than 0.1 wt%, it may be necessary to repeat the dipping operation a plurality of times in order to obtain the surface lubricating layer 3 having a desired thickness. There is. On the other hand, when the concentration of the hydrophilic polymer solution exceeds 20 wt%, the viscosity of the hydrophilic polymer solution may become too high to coat a uniform film, and the catheter, guide wire, injection needle, etc. It can be difficult to quickly coat the narrow, narrow inner surface of a medical device. However, even if it is out of the above range, it can be sufficiently utilized as long as it does not affect the operational effects of the present invention.

(3c-2) Solvent used for the hydrophilic polymer solution In addition, examples of the solvent used for dissolving the hydrophilic polymer include N, N-dimethylformamide (DMF), chloroform, acetone, tetrahydrofuran (THF). ), Dioxane, benzene and the like, but are not limited thereto. These may be used alone or in combination of two or more.

(3c-3) Reaction conditions (heating conditions) when forming the surface lubricating layer 3
In addition, when the surface lubricating layer 3 is formed, the present invention reacts the reactive functional group (for example, epoxy group) of the hydrophilic polymer with the remaining thiol group of the thiol compound 2 by heat treatment or the like. The lubricating layer 3 is bonded to the base material layer 1.

  Conditions for the heat treatment (reaction conditions) are not particularly limited as long as the reaction between the reactive functional group of the hydrophilic polymer and the remaining thiol group of the thiol compound 2 can proceed (promote). What is necessary is just to determine suitably according to the temperature characteristic (heat resistance) of this polymeric material.

  Therefore, the lower limit of the heat treatment temperature (set temperature of a heating device such as a heating furnace) is preferably at least the temperature at which the reaction between the reactive functional group of the hydrophilic polymer and the remaining thiol group of the thiol compound 2 can be promoted. It is 40 ° C or higher, more preferably 50 ° C or higher. If the temperature is lower than the temperature at which the reaction between the reactive functional group of the hydrophilic polymer and the remaining thiol group of the thiol compound 2 can be promoted, the desired reaction is not sufficiently promoted, and the heat treatment takes a long time and is uneconomical. Alternatively, the desired reaction due to the heat treatment may not proceed and the desired effect may not be obtained.

  Moreover, as an upper limit of heat processing temperature, it is below melting | fusing point-5 degreeC temperature of the polymeric material of the base material layer 1 surface, Preferably it is melting | fusing point-10 degreeC or less. In the case of a temperature higher than the melting point of the polymer material on the surface of the base material layer -5 ° C, the desired reaction is sufficiently promoted, but depending on the temperature distribution inside the heating apparatus such as a heating furnace, the temperature is higher than the set temperature. In some cases, a part of the surface of the base material layer 1 may be melted or deformed.

  Further, some polymer materials used for the surface of the base material layer 1 are taken as an example, and the heat treatment temperature range is exemplified below, but the heat treatment temperature range of the present embodiment is not limited to these. . For example, when the polymer material on the surface of the base material layer 1 is various nylons (nylon 6, 11, 12, 66, etc.), the heat treatment temperature is 40 to 150 ° C., preferably 60 to 140 ° C. When the polymer material on the surface of the base material layer 1 is various polyethylenes (LDPE, LLDPE, HDPE, etc.), the heat treatment temperature is 40 to 85 ° C, preferably 50 to 80 ° C.

  The heat treatment time is not particularly limited as long as the reaction between the reactive functional group of the hydrophilic polymer and the remaining thiol group of the thiol compound 2 can be promoted, but 15 minutes to 15 hours, It is preferably 30 minutes to 10 hours. When the heating time is less than 15 minutes, the reaction hardly proceeds and the unreacted hydrophilic polymer may increase, and it may be difficult to maintain the surface lubricity for a long period of time. On the other hand, when heating time exceeds 15 hours, the further effect by heating is not acquired and it is uneconomical.

  The pressure condition during the heat treatment is not limited at all, and it can be performed under normal pressure (atmospheric pressure), or under pressure or reduced pressure. In addition, when the reactive functional group of the hydrophilic polymer is an epoxy group, a tertiary amine compound such as a trialkylamine compound or pyridine can be used to promote the reaction with the remaining thiol group of the thiol compound 2. A suitable amount of a reaction catalyst such as the above may be added to the hydrophilic polymer solution in a timely manner. As the heating means (device), for example, an oven, a dryer, a microwave heating device, or the like can be used.

  In addition to the heat treatment, examples of the method for promoting the reaction between the reactive functional group of the hydrophilic polymer and the remaining thiol group of the thiol compound 2 include light, electron beam, and radiation, but are not limited thereto. Is not to be done.

  After the surface lubricating layer 3 is formed, the excess hydrophilic polymer is washed with an appropriate solvent to leave only the hydrophilic polymer in which the surface lubricating layer 3 is firmly fixed to the base material layer 1. It is also possible.

  The surface lubricating layer 3 thus formed absorbs water at the patient's body temperature (30 to 40 ° C.) and exhibits lubricity.

(4) Use of the medical device 10 of the present invention The medical device 10 having a lubricious surface when wet according to the present invention is an instrument used in contact with body fluid, blood, etc., and is an aqueous system such as body fluid or physiological saline. The surface has lubricity in the liquid, and the operability can be improved and the damage to the tissue mucosa can be reduced. Specific examples include catheters, guide wires, indwelling needles, and the like used in blood vessels, but the following medical devices are also shown.

  (4a) Catheters that are inserted or placed in the digestive organs orally or nasally, such as gastric tube catheters, feeding catheters, tube feeding tubes, and the like.

  (4b) Oxygen catheters, oxygen canulas, endotracheal tube tubes and cuffs, tracheostomy tube tubes and cuffs, intratracheal suction catheters, and other catheters that are inserted or placed in the trachea or trachea orally or nasally.

  (4c) Catheters inserted or placed in the urethra or ureter, such as urethral catheters, urinary catheters, urethral balloon catheter catheters and balloons.

  (4d) Catheters inserted or placed in various body cavities, organs, tissues such as suction catheters, drainage catheters, rectal catheters.

  (4e) Indwelling needles, IVH catheters, thermodilution catheters, angiographic catheters, vasodilator catheters and catheters inserted or placed in blood vessels such as dilators or introducers, or for these catheters Guide wire, stylet, etc.

  (4f) Artificial trachea, artificial bronchi, etc.

  (4g) Medical devices for extracorporeal circulation treatment (artificial lung, artificial heart, artificial kidney, etc.) and their circuits.

[Example 1]
After ultrasonically washing a hollow tube (inner diameter 0.68 mm, outer diameter 0.87 mm) of polyethylene (linear low density polyethylene; Nipolon-Z (registered trademark) ZF-260, manufactured by Tosoh Corporation) in acetone, Using a plasma irradiation apparatus (DURADYNE, manufactured by TRI-STAR TECHNOLOGIES), nitrogen mixed argon ion gas plasma treatment was performed at atmospheric pressure for 25 seconds (plasma treatment before thiol compound application). At this time, the plasma treatment was performed using a gas in which nitrogen gas and argon gas were mixed at 1:50 (= volume ratio of nitrogen gas: argon gas).

  THF of tris-[(3-mercaptopropionyloxy) -ethyl] -isocyanurate (TEMPIC) (manufactured by SC Organic Chemical Co., Ltd.) in which a polyethylene tube subjected to plasma treatment before application of the thiol compound was adjusted to a concentration of 5% by weight After immersing in the solution and drying at room temperature, the mixture was again irradiated with nitrogen-mixed argon ion gas plasma under atmospheric pressure for 25 seconds (plasma treatment after application of the thiol compound). At this time, the plasma treatment was performed using a gas in which nitrogen gas and argon gas were mixed at 1:50 (= volume ratio of nitrogen gas: argon gas). Thereafter, TEMPIC was immobilized on the polyethylene tube surface by heating in an oven at 80 ° C. for 5 hours. Further, the TEMPIC-immobilized polyethylene tube was ultrasonically washed in THF to remove excess TEMPIC that was not immobilized on the tube surface. This formed (immobilized) the thiol compound 2 which consists of TEMPIC which covers the whole surface of the base material layer 1 (polyethylene tube).

  Block copolymer [p (DMAA-b-GMA)] having polydimethylacrylamide (DMAA) as the hydrophilic domain and polyglycidyl methacrylate (GMA) as the reactive domain (DMAA: GMA (molar ratio) = 11.5: 1) ) Is dissolved in a THF solution (block copolymer solution) at a ratio of 3.5% by weight. After immersing the polyethylene tube on which TEMPIC is immobilized, it is dried at room temperature and reacted in an oven at 80 ° C. for 5 hours. A lubricating layer was formed. Thereby, the thickness (when not swollen) made of the block copolymer (hydrophilic polymer) is 2 μm so as to cover the surface of the thiol compound 2 made of TEMPIC immobilized on the surface of the base material layer 1 (polyethylene tube). A surface lubricating layer 3 was formed (polyethylene tube (1)).

[Comparative Example 1]
A polyethylene tube (polymer substrate layer 1) similar to that in Example 1 was ultrasonically cleaned in acetone, then immersed in the same block copolymer solution as in Example 1, dried at room temperature, and then in an oven at 80 ° C. By reacting for 5 hours, the surface lubricating layer 3 having a thickness of 2 μm (when not swollen) made of the block copolymer (hydrophilic polymer) was formed so as to cover the surface of the base material layer 1 (polyethylene tube) ( Comparative polyethylene tube (1)).

[Evaluation of surface lubricity]
For the polyethylene tube (1) obtained in Example 1 and the comparative polyethylene tube (1) obtained in Comparative Example 1, the friction measuring machine (manufactured by Trinity Labs, Handy Tribo) shown in FIG. Master TL201) 20 was used to evaluate surface lubricity maintenance.

  That is, a stainless steel rod 13 (diameter 0.63 mm) passed through each polyethylene tube 16 was stuck in the petri dish 12 and immersed in water at a height that the entire polyethylene tube 16 was immersed. The petri dish was placed on the friction measuring machine 20 shown in FIG. 3 and the sliding resistance value was measured when the tube surface was repeatedly slid 25 times under the following conditions. At this time, the polyethylene tube (1) obtained in Example 1 and the comparative polyethylene tube (1) obtained in Comparative Example 1 were each tested three times, and the results are shown in FIGS. 4 and 5, respectively. .

<Measurement conditions of sliding resistance value>
Speed: 1,000mm / min
Load: 50g
Travel distance: 25mm
Terminal: Polyethylene cylindrical terminal (φ20mm, R1mm)
As shown in FIGS. 4 and 5, the polyethylene tube (1) obtained in Example 1 is more resistant to sliding 25 times than the comparative polyethylene tube (1) obtained in Comparative Example 1. The sliding resistance value could be kept low, and the durability of the surface lubricating layer was good.

1 ... base material layer,
1a ... base material layer core part,
1b ... polymer surface layer,
2 ... thiol compound,
3 ... surface lubrication layer,
10 ... medical tools,
11 ... water,
12 ... Petri dish,
13 ... stainless steel rod,
14 ... Polyethylene cylindrical terminal,
15 ... Weight,
16 ... polyethylene tube (sample),
20: Friction measuring machine.

Claims (4)

A base material layer having at least a surface made of a polymer material;
A compound having a plurality of thiol groups in the molecule carried on at least a part of the substrate layer;
A surface lubricating layer made of a hydrophilic polymer having a reactive functional group and covering a compound having a plurality of thiol groups in the molecule,
The compound having the thiol group is supported on the substrate layer by irradiation with ionized gas plasma containing nitrogen, and the compound having the thiol group and the hydrophilic polymer having the reactive functional group A medical device in which a surface lubricating layer is bonded to a base material layer by reacting, and the surface has lubricity when wet.   The substrate layer surface is irradiated with ionized gas plasma containing nitrogen, and then a solution in which the compound having the thiol group is dissolved is applied to the substrate layer surface, whereby the compound having the thiol group is applied to the substrate layer. The medical device according to claim 1, which is carried.   By applying a solution in which the compound having the thiol group is dissolved to the surface of the base material layer and then irradiating ionized gas plasma containing nitrogen, the compound having the thiol group is supported on the base material layer. The medical device according to claim 1 or 2.   After applying a solution in which the compound having a thiol group is dissolved to the surface of the substrate layer, the substrate layer is loaded with the compound having the thiol group by irradiating the ionized gas plasma containing nitrogen and then performing a heat treatment. The medical device according to claim 2 or 3, wherein:

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