CN102791317B - Medical device and manufacturing method thereof - Google Patents

Abstract

The coating portion can be formed by a simple method to exhibit excellent wettability. A coating portion (12) is formed on the surface of a base material (11) of a medical device (10). The coating portion (12) has a first lubricating portion having higher lubricity when wet than the base material (11), and a second lubricating portion provided in a portion different from the first lubricating portion and at least a part of the outer surface of the coating portion (12), and having higher initial lubricity when wet than the first lubricating portion. The first lubricating portion contains a first lubricating material as a lubricating material having higher lubricity than the base material when wet, and the second lubricating portion contains a second lubricating material different from the first lubricating material.

Description

Medical device and manufacturing method thereof

technical field

The present invention relates to a medical device and a manufacturing method thereof.

Background technique

Conventionally, in medical devices for introducing into living bodies such as catheters, in order to suppress damage to the living body during introduction into the living body or to improve the operability of the operator, the surface of the base material of the medical device is coated with Cloth is a material with high lubricity when wet. As such a coating material, for example, various oils such as silicone oil, low-friction resins such as fluororesins and silicone resins, and the like are used.

In addition, in recent years, from the viewpoints of practicability, biocompatibility, etc., studies have been made on methods of improving the lubricity of the substrate surface when wet by coating a hydrophilic polymer on the surface of the substrate (for example, see Patent Document 1). Patent Document 1 discloses that the surface of a plastic substrate is coated with a solution containing a hydrophilic polymer such as polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), and then irradiated with radiation, whereby the A hydrophilic polymer is bonded to the surface of the plastic substrate. In addition, this Patent Document 1 discloses that PVP can be used as a preferable hydrophilic polymer from the viewpoint of binding properties to the substrate surface.

prior art literature

patent documents

Patent Document 1: Japanese Patent Laid-Open No. 2002-233568

The problem to be solved by the invention

However, when wet, the lubricity at the initial wetness greatly affects, for example, the operability at the time of initial introduction into the living body, and is likely to be related to the evaluation of the operability of the device. Therefore, the lubricity at the time of initial wetting is a particularly important factor in improving the operability of medical instruments, etc., and it is necessary to optimize it.

Then, the inventors of the present invention obtained, for example, the following knowledge: in the case of coating the substrate surface of a medical device with PVP, the adhesiveness to the substrate is good, but on the other hand, the lubricity at the initial wet It is not necessarily a good rise, and it may not be said to have excellent lubricity when it is first wet. In addition, it is not easy to realize a variety of performances as an excellent coating with one material, considering that advanced techniques, processes, etc., such as construction of new materials, are required.

Contents of the invention

The present invention was made in order to solve the above-mentioned problems, and its main object is to provide a medical device having excellent wettability by having a coating portion that can be assembled by a simple method, and a method for manufacturing the same.

means of solving problems

The inventors of the present invention have focused their attention on the fact that among materials that have lubricity when wet, such as hydrophilic polymers, the lubricity at the beginning of lubrication varies depending on each material, and specifically, the lubricity is fully exhibited after the start of wetting. The time required so far is different. And it discovered that the said subject can be solved by employ|adopting the following means based on this knowledge.

That is, the present invention is a medical device having a coating portion formed on the surface of a base material, wherein the coating portion has a first lubricating portion and a second lubricating portion, and the first lubricating portion is formed by the above-mentioned The base material is formed of a different material, and its lubricity when wet is higher than that of the base material, and the second lubricating part is formed of a material different from the base material, and is provided at a part different from the first lubricating part, and The coating portion is on at least a part of the outer surface, and has higher initial lubricity when wet than the first lubricating portion.

According to the above configuration, the second lubricating portion having higher initial lubricity when wet is exposed to the outside of the coating portion. Thus, when the present medical device is brought into contact with an aqueous system such as blood or body fluid, excellent lubricity can be imparted to the surface of the substrate by the second lubricating portion at the initial stage of wetting. Therefore, the medical instrument can exhibit initial lubricity on the outer surface of the second lubricating portion, and can exhibit an excellent lubricating effect when it is initially wetted. Therefore, when introducing this device into a living body, it can be inserted smoothly.

In addition, the present invention is a method of manufacturing a medical device, comprising: a first step of using a first solution containing a material different from that of the base material to form a wet lubricity ratio on the surface of the base material; The first lubricating part with a high base material; the second step, after the first step above, using a second solution containing a material different from the base material, in a part different from the first lubricating part and the medical device A second lubricating portion having a higher initial lubricity when wet than the first lubricating portion is formed on at least a part of the outer surface of the first lubricating portion.

According to the above-mentioned method, it is possible to manufacture a medical instrument in which the second lubricating portion with higher initial lubricity when wet is exposed to the outside of the coating portion. Therefore, when the medical device produced by the method of the present invention is brought into contact with an aqueous system such as blood or body fluid, excellent lubricity can be imparted to the surface of the substrate by the second lubricating portion at the initial stage of wetting. That is, the medical device produced by the above method can exhibit an excellent lubricating effect when it is initially wetted, and can be smoothly inserted when the device is introduced into the living body.

Description of drawings

FIG. 1 is a diagram showing an example of a coating portion of the present medical device.

Fig. 2 is a diagram for explaining an apparatus used in a slipperiness test.

Fig. 3 is a graph showing the results of a smoothness test for two-layer coating.

Fig. 4 is a graph showing the results of comparison between this coating part and single-layer coating.

Detailed ways

Hereinafter, the present invention will be described in detail with reference to the drawings as appropriate.

The coating part is arranged on the surface of the medical device, and has a first lubricating part and a second lubricating part, the lubricity of the first lubricating part when wet is higher than that of the base material, and the second lubricating part is provided on the same surface as the substrate. The first lubricating part is different from at least a part of the outer surface of the coating part. In addition, the initial lubricity of the second lubricating portion when wet is higher than that of the first lubricating portion.

(Arrangement form of the first lubricating part and the second lubricating part)

Regarding the configuration of the first lubricating portion and the second lubricating portion of the coating portion, firstly, one of them is an aspect in which at least a part of the outer surface of the coating portion is formed by the first lubricating portion and the second lubricating portion. At this time, by providing the first lubricating portion and the second lubricating portion on the surface of the substrate, a single-layer coating portion composed of the first lubricating portion and the second lubricating portion is formed.

A preferred aspect is that the first lubricating portion is disposed closer to the substrate side than the second lubricating portion, and a more preferable aspect is that the coating portion adopts an outermost layer having an outer surface constituting the coating portion and an intervening layer between the coating portion. In the structure of the intermediate layer present between the outermost layer and the surface of the base material, the outermost layer is formed by the second lubricating portion, and the intermediate layer is formed by the first lubricating portion.

FIG. 1 shows an example of the coating portion of the present medical device. As illustrated in FIG. 1 , this medical device 10 has a coating portion 12 on the surface of a base material 11 . The coating part 12 has the outermost layer 12a which comprises the outer surface, and the intermediate layer 12b which exists between the outermost layer 12a and the surface of the base material 11. And, in this instrument 10, at least a part of the outermost layer 12a is formed as the second lubricating portion, and the intermediate layer 12b is formed as the first lubricating portion. In this case, the second lubricating portion may cover a part of the first lubricating portion, but it is preferable that the second lubricating portion cover the entire first lubricating portion as shown in FIG. 1 . Thus, when the device 10 is brought into contact with blood, body fluid, etc., excellent initial lubricity can be imparted to the entire outer surface of the coating portion 12 by the lubricating material contained in the second lubricating portion.

In the case where the intermediate layer 12b is formed by a first lubricating portion and the outermost layer 12a is formed by a second lubricating portion, there may be other layers, such as containing a drug, between the intermediate layer 12b and the outermost layer 12a. 1, the outermost layer 12a is stacked in a state of being in contact with the intermediate layer 12b, or the outermost layer 12a contains the material contained in the outermost layer 12a and the material contained in the intermediate layer 12b. A transition layer (not shown) is stacked on the intermediate layer 12b. At this time, the outermost layer 12a is fixed on the intermediate layer 12b or the transition layer by chemical bonding, that is, preferably, the outermost layer 12a is not fixed on the surface of the substrate 11 by chemical bonding. This makes it possible to omit the treatment for fixing the outermost layer 12a to the intermediate layer 12b or transition layer (for example, introduction of functional groups, etc.), and to simplify the production of the coating portion 12 . In particular, in the structure shown in FIG. 1 , the first lubricating portion as the intermediate layer 12b is arranged at a position closer to the substrate 11 than the second lubricating portion as the outermost layer 12a. When the outermost layer 12a is formed, the lubricating effect when wet can be maintained by the first lubricating portion. Therefore, it is advantageous in that the continuity of the lubricating effect of the coating part 12 can be ensured and the production can be simplified.

(adhesive)

Regarding the adhesiveness of the first lubricating portion and the second lubricating portion to the base material, it is preferable that the adhesiveness of the first lubricating portion to the base material be higher than that of the second lubricating portion. More specifically, the lubricity of the substrate surface when the first lubricating part is arranged on the surface of the substrate when wet and the wettability of the substrate surface when the second lubricating part is arranged on the surface of the substrate are compared. When the lubricity is compared, the lubricity of the side where the second lubricating part is placed at the initial stage of wetting is high, and the lubricity of the side where the first lubricating part is placed after that is high, and it is preferable to adopt such a configuration. That is, in this coating part, the initial lubricity when wet is expressed by the second lubricating part, and the continuity (durability) of the lubricating effect is expressed by the first lubricating part. Thereby, multiple lubricating properties required as an excellent coating, that is, the initial lubricating properties and the persistence of the lubricating effect can be easily given, and further, when the device is inserted into the living body, it can be inserted into the living body smoothly and reliably. target site. Especially in the structure in which the outermost layer 12a is the second lubricating portion and the intermediate layer 12b is the first lubricating portion as shown in FIG. Since the lubricating effect can be continuously provided to the surface of the base material 11, it is preferable.

The intermediate layer 12b as the first lubricating portion can be bonded through a layer different from the intermediate layer 12b on the surface of the substrate, preferably as shown in FIG. The configuration of the contact mode. In this case, complicated processes for forming other layers can be omitted, and the production of the instrument 10 can be simplified.

In this case, regarding the thicknesses of the first lubricating portion as the intermediate layer 12b and the second lubricating portion as the outermost layer 12a, it is preferable to make the thickness of the first lubricating portion larger than the thickness of the second lubricating portion. Thereby, even in the case where the second lubricating portion is not formed in the outermost layer 12a, the lubricating effect on the base material surface can be sufficiently sustained by the first lubricating portion as the intermediate layer 12b.

As one form of making the lubricating performance of the second lubricating part higher than that of the first lubricating part at the initial stage of wetness, the lubricating material (first lubricating material) contained in the first lubricating part is made into a cross-linkable material, so that The second lubricating portion contains the first lubricating material. Furthermore, the density of the crosslink formed by the first lubricating material is lower than that of the first lubricating part in the second lubricating part, or the first lubricating material is made into a crosslinked structure in the first lubricating part and the density of the crosslinking in the second lubricating part is lower than that of the first lubricating part. In the section, the first lubricating material is not made into a cross-linked structure. Specifically, a crosslinking agent or, if necessary, a radical generator is contained in the first lubricating portion in addition to the first lubricating material. On the other hand, the crosslinking agent is not contained in the second lubricating part, or the content of the crosslinking agent in the second lubricating part is lower than that in the first lubricating part.

In a preferable aspect, the first lubricating part contains a first lubricating material, and the second lubricating part contains a second lubricating material different from the first lubricating material. Furthermore, by making the initial lubricity of the second lubricating material higher when wet than that of the first lubricating material, the initial wet lubricating performance of the second lubricating portion is expressed. In this case, it is preferable to make the adhesiveness of the first lubricating material to the base material higher than that of the second lubricating material. As a result, the first lubricating material exerts the continuous performance of the lubricating effect of the first lubricating part, and as a result, each of the first lubricating part and the second lubricating part can express a good lubricating effect more easily than the other. adhesion or initial lubricity.

For example, as a lubricating material, there is a material having high adhesiveness to the surface of a base material, capable of continuously exhibiting lubricating performance, and having low initial lubricating property when wet. Alternatively, conversely, there are materials that have high initial lubricity when wet but low adhesion to the substrate surface. In this regard, in this configuration, a plurality of lubricating materials complement each other with insufficient lubricating performance (initial lubricity, continuity of lubricating effect) in one lubricating material, so that it is possible to form a lubricating oil with both initial and lubricating properties through relatively simple processing. Continuous coating part of lubricity and lubricating effect.

In order to improve the adhesiveness of the first lubricating portion to the substrate, the first lubricating portion preferably contains the first lubricating material as a main component, and more preferably contains no second lubricating material or contains a small amount of the second lubricating material. This is because the presence of the second lubricating material in the first lubricating portion may reduce the adhesion of the first lubricating portion (intermediate layer 12 b ) to the base material 11 and reduce the sustainability of the lubricating effect.

The adhesiveness of the first lubricating material to the substrate is preferably expressed by being fixed on the surface of the substrate by chemical bonds such as covalent bonds. In this case, it is preferable to use a material that is at least more reactive than the second lubricating material as the first lubricating material.

The method of immobilizing the first lubricating material at this time is not particularly limited. For example, there is a method of bonding a functional group on the surface of the base material to a functional group of the lubricating material, or a method of graft-polymerizing a monomer of the lubricating material on the surface of the base material when the lubricating material is a polymer material. At this time, a new type of functional group that can be bonded to other functional groups is introduced into the first lubricating material and the part (substrate surface) to which the first lubricating material is bonded, and these functional groups can be bonded by various chemical reactions. Preferably, The method is: apply a solution containing the first lubricating material on the surface of the substrate, and then, by irradiation of radiation, plasma, ultraviolet rays, etc., the functional groups on the surface of the substrate are bonded to the functional groups of the lubricating material. According to this immobilization method, the chemical bonding between the first lubricating material and the surface of the substrate can be performed relatively easily.

On the other hand, the second lubricating material may or may not be fixed on the surface of the substrate or the first lubricating material. This is because even if the second lubricating material is not fixed on the surface of the base material or the first lubricating material, the lubricating effect on the surface of the base material can be maintained by the first lubricating material. In addition, there is no need to use a material with high adhesion to the base material as the second lubricating material, and a wide range of materials can be selected.

In the configuration in which the second lubricating portion contains the second lubricating material and exhibits initial lubricity by the second lubricating material, the second lubricating portion may contain the first lubricating material and other lubricating materials. A preferred embodiment is that the second lubricating portion does not contain a lubricating material other than the second lubricating material, or in a configuration containing the first lubricating material, the weight ratio of the second lubricating material to the first lubricating material is 1 above. Thereby, the initial lubricity when wet can be maintained at a high level. However, in order to suppress the sticky feeling when the operator touches it as much as possible, it is preferable to employ a configuration in which the second lubricating material is contained in the second lubricating portion constituting the outermost layer 12a without containing the first lubricating material.

In addition, when using a crosslinkable material as the first lubricating material and the second lubricating material, it is preferable to make the crosslinking density of the first lubricating portion higher than that of the second lubricating portion. More preferably, the first lubricating material is crosslinked and the second lubricating material is hardly crosslinked. Thereby, the hydrophilicity at the beginning of wetting of the second lubricating portion can be improved.

(first lubricating material and second lubricating material)

As the first lubricating material and the second lubricating material, materials different from the base material and having higher lubricity when wet than the base material can be used, and among them, hydrophilic polymers are preferably used. In the hydrophilic polymer, intermolecular crosslinks are formed by heat or light irradiation or the like. The cross-linked hydrophilic polymer absorbs water and swells (wets) upon contact with an aqueous system such as body fluid or physiological saline, and becomes a lubricating hydrogel. In such a hydrogel, the water absorption speed (water absorption speed) when it comes into contact with an aqueous system differs among different materials, and the initial lubricity when wet tends to be superior or inferior depending on the water absorption speed. That is, when in contact with an aqueous system, a hydrophilic polymer with a fast water absorption rate swells rapidly and exhibits lubricity immediately, and conversely, a hydrophilic polymer with a slow water absorption rate swells to exhibit sufficient lubricity It takes a long time to achieve good lubricity. In view of such a situation, in this coating part, a hydrophilic polymer (second lubricating material) having a faster water absorption rate is arranged on the outer surface of the coating part. As a result, the outer surface of the coating part rapidly swells when it comes into contact with the water system, and as a result, lubricity is rapidly expressed on the outer surface of the device.

Concerning the first lubricating material and the second lubricating material, specifically, the first lubricating material is preferably poly-N-vinyl lactam such as polyvinylpyrrolidone (PVP), ethylene ethyl ether maleic anhydride copolymer, etc. One or more of polyacrylamide-based polymers mainly composed of acrylamide and its derivatives, and more preferably PVP. Since PVP has a pyrrolidone ring, when there is a highly reactive functional group on the surface of the substrate, it can be easily bonded to the functional group on the surface of the substrate by activation by irradiation with ultraviolet light or the like.

In addition, as the second lubricating material, it is preferably one or more of polyethylene oxide (PEO), hydroxyethyl cellulose, carboxymethyl cellulose, starch, dextran, gelatin, etc., more preferably for PEOs.

A combination in which the first lubricating material is PVP and the second lubricating material is PEO is particularly preferred. When comparing the wet lubricity when PVP and PEO are formed on the surface of the substrate respectively, at the beginning of wetting, the side with PEO has good lubricity on the surface of the substrate, and then the side with PVP has good lubricity on the substrate. The lubricity of the surface is good. In particular, when comparing the lubricity of PVP at the initial stage of sliding (initial wetness) and the late stage of sliding (late stage of wetness), the late stage of sliding has a characteristic that the lubricity is higher. Therefore, as shown in FIG. 1, when PVP is bonded to the substrate surface and PEO with excellent initial lubricity is arranged on the outer surface of the coating part, the excellent adhesiveness of PVP is utilized, and PEO supplements the lack of initial lubricity of PVP.

In addition, the persistence of the lubricating effect in PEO is inferior to that of PVP. The reason for this is that PEO has lower reactivity than PVP, and as a result, the surface of the substrate and PEO are not immobilized by chemical bonding. With this in mind, it is considered that PEO cannot be fixed on PVP or even if it can be fixed its fixing power is low. In this regard, in the structure of FIG. 1, the state in which PVP is adhered to the surface of the substrate is maintained, so even if the continuity of the lubricating effect of the second lubricating part containing PEO decreases over time, it will The lubricating effect is continuously manifested on the surface of the substrate through PVP.

Furthermore, PEO and PVP are general-purpose materials and are readily available. In addition, although PEO and PVP are not biologically derived materials, they are already used for medical purposes, and they are also excellent in biosafety and biocompatibility. By using a variety of general-purpose materials with excellent biosafety/biocompatibility, this coating part can be produced by a relatively simple method without requiring advanced technology such as the construction of new materials, and the lubricating performance when wet Excellent, preferred at this point. In addition, compared with PVP, PEO has less stickiness when touched by the operator and has a good touch. Therefore, by arranging PEO on the outer surface of the coating part, the treatment of this instrument can be favorably performed.

In addition, when a hydrophilic polymer is used as the first lubricating material, it is preferable that the first lubricating portion contains a crosslinking agent in order to improve the adhesiveness between the first lubricating material and the surface of the substrate. On the other hand, the second lubricating portion may or may not contain a crosslinking agent. In addition, the content of the crosslinking agent in the first lubricating part and the second lubricating part may be appropriately determined, but if an excessive amount of the crosslinking agent is contained, the wettability at the time of wetting decreases, which is not preferable.

The crosslinking agent is not particularly limited, and for example, (1) a monomer having a plurality of vinyl groups in one molecule, (2) a substance having two or more glycidyl groups, (3) isocyanate compounds such as diisocyanate and triisocyanate, etc. , (4) At least any one of a radical initiator and the like. In addition, examples of (1) include neopentyl glycol diacrylate (NPGDA), polyalkylene glycol diacrylate (methacrylate) [(poly)ethylene glycol diacrylate (methacrylate) Acrylate), (poly)propylene glycol diacrylate (methacrylate)], alkanediol diacrylate (methacrylate), etc. As (2), polyalkylene glycol diglycidyl ether, neopentyl glycol diglycidyl ether, epoxidized soybean oil, etc. are mentioned, for example. Examples of (3) include diisocyanates such as diphenylmethane diisocyanate, toluene diisocyanate, and hexamethylene diisocyanate, or their adducts, furophhanate, biuret, and isocyanate. Modified body such as cyanurate. Examples of (4) include azo-based initiators such as azobisisobutyronitrile (AIBN), peroxide-based initiators, and the like, and are preferably those that generate a plurality of radicals per molecule. Among these, when using PVP or PEO as a lubricating material, it is more preferable to use a combination of neopentyl glycol diacrylate (NPGDA) and a radical generator (for example, AIBN).

(Medical Devices and Substrates)

As the medical device, as long as it is used in contact with living tissue, examples include tubes in living bodies such as blood vessels, digestive tracts, urinary catheters, and trachea, various catheters inserted into body cavities, guide wires, stents, internal organs, etc. Mirrors, contact lenses, artificial blood vessels, artificial joints, etc., but not limited to these devices.

Substrates, such as polyether polyamide block copolymers such as Pebax (registered trademark), polyolefins such as polyethylene and polypropylene, polyether ether ketone, nylon, polyester, polyester elastomer, polyimide, polyurethane Such as resin, metal and other components. Resins having polar groups such as polyether polyamide block copolymer, nylon, polyester, polyester elastomer, polyimide, polyurethane, and vinyl chloride are preferable. In addition, when an appropriate surface treatment is performed for immobilizing the first lubricating material, polyolefins such as polyethylene and polypropylene, polyetheretherketone, metals, and the like can be used.

(Manufacturing method of medical device)

The method for manufacturing a medical device according to the present invention includes a first step of forming a first lubricating portion having higher lubricity than the base material on the surface of the base material by using a first solution containing a material different from that of the base material. the second step, after the first step, using a second solution containing a material different from the base material, forming a wetted part on at least a part of the outer surface of the medical device at a part different from the first lubricating part; The second lubricating portion has higher initial lubricity than the first lubricating portion. Hereinafter, the manufacturing procedure of the coating part 12 shown in FIG. 1 is demonstrated using FIG. 1 suitably. Specifically, the coating portion 12 has a first lubricating portion as an intermediate layer 12b formed on the base surface, and a second lubricating portion as an outermost layer 12a formed on the outer surface of the coating portion 12 .

(first process)

In the first step, first, a first solution containing a first lubricating material as a material different from the base material is prepared. The solvent used to prepare the first solution may be used as long as it can dissolve the first lubricating material. For example, alcohols such as isopropanol, distilled water, and mixed solutions thereof are used. Next, the first solution is brought into contact with the surface of the substrate 11 . The form of contact is not particularly limited, and various methods such as coating, dipping, and spraying can be used, for example. In addition, before the first solution comes into contact with the surface of the substrate 11, surface treatment for improving the adhesion between the surface of the substrate and the first lubricating material may be implemented, specifically, for example, corona discharge treatment, plasma treatment, etc. , ultraviolet radiation treatment and the like.

Thereafter, in the presence of the first solution, the first lubricating material is adhered to the surface of the substrate 11 by, for example, ultraviolet irradiation. At this time, if a crosslinking agent and a radical generator are required to form the crosslinking of the first lubricating material, the first solution contains the crosslinking agent and the radical generator in advance. In addition, for example, for a lubricating material that can form crosslinking by irradiating ultraviolet rays in the absence of a crosslinking agent and a radical initiator like PVP, the crosslinking agent and radical initiator are also contained in the first solution in advance. agent, so that the adhesiveness between the first lubricating material and the surface of the substrate can be improved. As described above, the first lubricating portion as the intermediate layer 12 b is formed on the surface of the base material 11 .

(second process)

After the first process is completed, the second process is implemented next. In the second step, first, a second solution containing the first lubricating material or the second lubricating material, preferably the aforementioned second lubricating material, as a material different from the base material is prepared. The solvent of the second solution may be different from the solvent used for the preparation of the first solution, or may be the same solvent. Next, the second solution is brought into contact with the outer surface of the instrument 10, that is, the outer surface of the intermediate layer 12b (first lubricating portion), and then the lubricating material in the second solution is immobilized by ultraviolet irradiation or the like. At this time, by irradiation of ultraviolet light or the like, the lubricating material in the second solution is crosslinked to the same extent as the first lubricating material in the first lubricating part, and the crosslinking density is preferably higher than that in the first lubricating part. A state where the first lubricating material is low, or a state that is not crosslinked. In addition, the second solution may contain a crosslinking agent and a radical generator, or may not contain a crosslinking agent and a radical generator. As described above, the second lubricating portion as the outermost layer 12a is formed on the outer surface of the first lubricating portion.

As the first lubricating material and the second lubricating material, a combination of polyvinylpyrrolidone (PVP) and polyethylene oxide (PEO) is preferable. In addition, when the second solution contains the second lubricating material, the concentration of the second lubricating material, especially the PEO concentration in the second solution in the combination of PVP and PEO, is preferably 0.1% by weight or more and 1.0% by weight or less. By making this concentration 0.1% by weight or more, the amount of the second lubricating material contained in the outermost layer 12a can be set to be an amount sufficient to exhibit an excellent lubricating effect at the initial stage of wetting. Moreover, by making this concentration 1.0 weight% or less, the quantity of the 2nd lubricating material contained in the outermost layer 12a will not become too much, and the 2nd lubricating material will swell moderately when wet. More preferably, it is 0.1 weight% or more and 0.82 weight% or less, More preferably, it is 0.2 weight% or more and 0.55 weight% or less. In particular, when the concentration is 0.25% by weight or more and 0.5% by weight or less, excellent lubricity can be imparted to the substrate surface.

The thicknesses of the first lubricating part and the second lubricating part can be adjusted according to the number of coatings of the first solution and the second solution, and the concentration of the lubricating material in the solution. Therefore, in order to make the first lubricating part thicker than the second lubricating part, the concentration of the first lubricating material in the first solution is higher than the concentration of the second lubricating material in the second solution or the application of the first solution It is preferable that the number of times of application is greater than that of the second solution.

Example

Hereinafter, the present invention will be described with reference to specific examples, but the present invention is not limited to the following examples.

(1) Preparation of coating solution

A coating solution for coating the surface of a substrate of a medical device is prepared. Here, two types of PVP coating solution and PEO coating solution were prepared. The PVP coating solution uses a mixed solvent of isopropanol and distilled water at a ratio of 4:1 (by weight), to which polyvinylpyrrolidone (PVP, grade K-90, molecular weight: 360,000, manufactured by Wako Pure Chemical Industries), neopentyl Glycol diacrylate (NPGDA, manufactured by ALDRICH Corporation), azobisisobutyronitrile (AIBN, KISHIDA Chemical), and stirred, thereby preparing the coating solution. Concerning the concentration in the PVP coating solution, PVP was 0.82% by weight, and NPGDA was 15% by weight relative to the amount of PVP. Also, add a small amount of AIBN.

The PEO coating solution uses the same mixed solvent as the PVP coating solution, and polyethylene oxide (PEO, manufactured by SIGMA-ALDRICH) is added thereto and stirred to prepare the coating solution. The concentration of PEO in the PEO coating solution was 0.25% by weight.

(2) Coating of substrate

As a medical device, a catheter having a substrate made of Pebax (registered trademark) was used, and the surface of the substrate was coated with the above-mentioned two types of coating solutions (PVP coating solution, PEO coating solution). As a coating step, first, surface treatment of the substrate is performed by subjecting the surface of the substrate to corona discharge. Next, the PVP coating solution prepared in (1) above was coated on the surface of the substrate by dip coating, and thereafter, UV irradiation was performed for 90 seconds. Here, a series of treatments of dip coating with a PVP coating solution and subsequent UV irradiation were performed twice. Thereafter, the outer surface of the catheter was further coated with the PEO coating solution prepared in (1) above by a dip coating method, and UV irradiation was performed for 30 seconds. In this way, a catheter was obtained in which a PVP layer was formed on the surface of the base material and a PEO layer was formed on the outer side of the PVP layer (see FIG. 1 ). In addition, when the surface of the obtained catheter was touched by hand, it did not feel sticky, and the touch was good.

(3) Evaluation of lubricity when wet

(3-1) Smoothness test

As a slipperiness test for evaluating the wet lubricity of the coated catheter, the frictional resistance value was measured using the device 20 shown in FIG. 2 . As the device 20 , as shown in FIG. 2 , a device in which a rubber plate 22 is arranged in a hollow portion of a water tank 21 is used. In addition, the rubber plate 22 can be supported by a support shaft (not shown) in a state fixed at a predetermined position. The rubber plate 22 is made of natural rubber and has a thickness of 3 mm. By piercing (18G) the rubber sheet 22 vertically with a needle, a notch 23 penetrating the surface and the back surface of the rubber sheet 22 is provided thereon. Regarding the measurement of the frictional resistance value, first, a core material (made of metal) is inserted into the prepared sample 24 (catheter), and the sample 24 is passed through the notch 23 of the rubber plate 22, and is fixed in the filled tube. Water in the sink 21. At this time, the rubber plate 22 is fixed at a predetermined position in the water tank 21 by the support shaft. After that, the specimen 24 is reciprocated in the up and down direction with the position of the rubber plate 22 fixed, and the frictional resistance between the rubber plate 22 and the specimen 24 at this time is measured by a frictional resistance measuring device (digital dynamometer) 25. side. Let this measured value be the frictional resistance value [gf]. At this time, the measurement was performed by setting the stroke length to 10 cm and the stroke speed to 13 reciprocations/min.

(3-2) Preparation of Specimen

As samples for the smoothness test, four samples with different PEO concentrations in the PEO coating solution (PEO concentrations: 0.1% by weight, 0.25% by weight, 0.5% by weight, 0.82% by weight) (specimen numbers are 1 to 4, respectively). In addition, the PEO coating solution of the above (1) containing 37.5% by weight of NPGDA was prepared with respect to the PEO concentration, and a sample (specimen No. 5). In addition, sample numbers 1 to 5 are two-layer coatings in which a PVP layer is formed on the surface of a substrate and a PEO layer is further formed on the outside thereof.

In addition, as a comparative example, a sample was prepared in which one coating solution was applied to the surface of a base material by a dip coating method, and a single layer coating was formed by irradiating UV. Here, a sample (specimen No. 6) using a 1.0% by weight PEO coating solution, a sample (sample No. 7) using a 0.82% by weight PVP coating solution, and a sample containing 0.50% by weight PEO and 0.50 Three samples of a coating solution of % PVP (sample number 8). In addition, NPGDA was added to the coating liquid used in preparation of the specimens of specimen numbers 6 to 8. At this time, in sample number 6, the NPGDA concentration was 37.5% by weight relative to the PEO concentration, in sample number 7, the NPGDA concentration was 15% by weight relative to the PVP concentration, and in sample number 8, The NPGDA concentration was 37.5% by weight relative to the total concentration of PEO and PVP. In addition, a small amount of AIBN was added little by little to each solution. The compositions and the like of the eight samples are summarized in Table 1 below.

[Table 1]

(3-3) Lubricity evaluation when wet

The smoothness test of (3-1) above was performed on each sample. The smoothness test was performed after ethylene oxide gas sterilization (EOG sterilization). In addition, in the lubricity test, the stroke length and stroke speed of the reciprocating movement of the specimens were made the same among the specimens.

(3-4) Lubricity evaluation of two-layer coating

Fig. 3 shows the results of the slipperiness test on specimen numbers 1 to 4 coated with PEO and PVP in two layers.

As shown in Figure 3, first, as the initial lubricity when wet, the resistance values [gf] after 1 reciprocation to 5 reciprocations were 11 to 16 in sample number 1, and 11 to 16 in sample number 2. 7.5 to 9.5, 9.0 to 12 in sample number 3, and 15 to 19 in sample number 4. In addition, in any sample, as the number of reciprocations increases, the change in the resistance value becomes smaller, and the resistance value after 50 reciprocations is about 1.3 to 2.3 times the resistance value after 1 reciprocation. From this, it can be seen that specimen numbers 1 to 4 can continue to maintain the initial lubricity when wet, and the continuity (durability) of the lubricating effect is good.

In particular, in the sample No. 2 and the sample No. 3 in which the PEO concentration in the PEO coating solution was 0.25% by weight and 0.5% by weight, compared with other samples, it was seen that all the resistance values were smaller, and the As the number of reciprocations increases, the change in resistance value becomes smaller, and the sliding property is very good. Among them, in specimen number 2 in particular, the resistance value was the smallest among the four specimens from the beginning of the reciprocation (initial wetting) to the end, and the resistance value was substantially constant even when the reciprocation was repeated. From the above, it can be said that specimen No. 2 having a PEO concentration of 0.25% by weight has the best initial lubricity and durability when wet.

In addition, in sample number 5 in which NPGDA was included in the PEO coating solution, the transition of the resistance value was approximately the same as that of sample number 2, and each resistance value after 1 reciprocation to 50 reciprocations was in the range of 8 to 11. roughly constant in the range. It can be seen that the PEO layer may or may not contain NPGDA.

Furthermore, each sample was subjected to the above-mentioned smoothness test after EOG sterilization and then an accelerated deterioration test by heating (60° C., 1 month). As a result, in any sample, the resistance value after one reciprocation was substantially the same as that before the accelerated deterioration test, and the resistance value after 50 reciprocations was 1.5 times or less than the resistance value after one reciprocation. From this, it can be said that the product life of samples 1 to 4 is good.

(3-5) Comparison with single layer coating

Among specimen numbers 1 to 4 of two-layer coating, specimen number 2, which has particularly good surface lubricity when wet, was compared with specimen number 6 (PEO alone) and specimen number 7 (PVP alone) of single-layer coating. alone) and sample No. 8 (mixture of PEO and PVP) were compared. The result is shown in Figure 4. In addition, in FIG. 4 , the solid line represents the transition of the resistance value of specimen number 2, the dotted line represents the transition of the resistance value of specimen number 6, the single-dashed line represents the transition of the resistance value of specimen number 7, and the double-dashed line The transition of the resistance value of sample number 8 is shown. In addition, FIG. 4 shows test results after heat sterilization and before implementation of the accelerated deterioration test.

As shown in FIG. 4 , in PEO-only specimen No. 6 and mixed system specimen No. 8, the resistance value after 1 to 3 reciprocations was not so large as that of specimen No. 2. difference. However, in specimen numbers 6 and 8, the resistance value increased as the number of reciprocations increased, and after 50 reciprocations, it was about 1.3 times the resistance value after one reciprocation in specimen number 2. In contrast, it was about 4 times the resistance value after one reciprocation in sample numbers 6 and 8. From this, it can be said that in the single-layer coating of PEO or hybrid system (specimen Nos. 6 and 8), although the initial lubricity can be imparted to the medical device, it is not as good as the initial lubricity of specimen No. 2. In addition, it is also inferior to sample number 2 in terms of durability.

In the single-layer coating of PVP (specimen No. 7), the resistance value [gf] at the initial wetting was 18 after one reciprocation, which was higher than that of any of specimen Nos. 2, 6, and 8. big. Comparing this value with sample number 2, it is more than twice that of sample number 2. In addition, in specimen number 7, from the resistance values after 1 to 10 reciprocations, as the number of reciprocations increases, the resistance value decreases, and thereafter becomes approximately constant at 12 to 13. From this, it can be seen that in the single-layer coating of PVP, the wet initial lubricity is not so good, and it takes a long time to express the lubricity. In addition, the low initial lubricity of PVP is presumed to be due to the fact that in PVP, when water is absorbed between molecular chains in contact with water, the water absorption rate (water absorption rate) is slower than that of PEO. takes a long time.

In addition, for specimen number 7, after the resistance value became constant, the resistance value was smaller than specimen numbers 6 and 8, and larger than specimen number 2. From the above, it can be seen that the initial lubricity of specimen No. 7 coated with PVP in a single layer was inferior to that of specimen Nos. 6 and 8 in which the PEO-containing layer was formed on the outer surface, and on the contrary, it exhibited good lubricity thereafter. Lubricity. On the other hand, it can be seen that among specimen No. 7 and specimen No. 2, specimen No. 2 is good in both the initial lubricity and the continuity (durability) of the lubricating effect. In summary, compared to single-layer coating using at least one of PVP and PEO, the two-layer coating of the PVP layer and the PEO layer is superior in initial lubricity and durability. In addition, the surface of the obtained catheter has less stickiness and a better hand feeling than single-layer coating of PVP and single-layer coating of a mixed system of PVP and PEO.

Symbol Description

10...medical equipment, 11...substrate, 12...coating part, 12a...outermost layer, 12b...intermediate layer, 20...device, 21...water tank, 22...rubber plate, 23...grooving, 24...specimen, 25...frictional resistance tester.

Claims (13)

1. a medical device, it is the medical device being formed with coating portion on the surface of base material, it is characterized in that,

Described coating portion has the first lubrication portion and the second lubrication portion,

Described first lubrication portion is formed by the material different from described base material, and lubricity time moistening is higher than this base material,

Described second lubrication portion is formed by the material different from described base material, is arranged on the part different from described first lubrication portion and the going up at least partially of the outer surface in this coating portion, and initial lubricity time moistening is higher than described first lubrication portion.

2. medical device according to claim 1, wherein,

The first lubricant material is contained as the lubricant material higher than described base material of lubricity time moistening in described first lubrication portion,

Second lubricant material different from described first lubricant material is contained in described second lubrication portion.

3. medical device according to claim 2, wherein,

Described first lubricant material and described second lubricant material are hydrophilic polymer.

4. medical device according to claim 3, wherein,

Described first lubricant material is polyvinylpyrrolidone, and described second lubricant material is poly(ethylene oxide).

5. the medical device according to any one of claim 2 ~ 4, wherein,

Described first lubricant material is fixed on the substrate by chemical bonding, and described second lubricant material is not fixed on the substrate by chemical bonding.

6. the medical device according to any one of Claims 1 to 4, wherein,

Described first lubrication portion is higher than described second lubrication portion to the cementability of described base material.

7. the medical device according to any one of Claims 1 to 4, wherein,

When lubricity during moistening described in the surface configuration to described base material when the first lubrication portion is compared with lubricity during moistening described in the surface configuration to described base material when the second lubrication portion, high in the lubricity of described second this side of lubrication portion of moistening initial lower configuration, the lubricity configuring described first this side of lubrication portion is afterwards high.

8. the medical device according to any one of Claims 1 to 4, wherein,

The outermost layer that described coating portion has the outer surface forming this coating portion, the intermediate layer existed between this outermost layer and the surface of described base material,

Described outermost layer is formed by described second lubrication portion, and described intermediate layer is formed by described first lubrication portion.

9. medical device according to claim 8, wherein,

Described outermost layer to be stacked on this intermediate layer with the state layer connected with described intermediate layer or across the material contained by the material comprised contained by described outermost layer and described intermediate layer transition zone and be layered on described intermediate layer.

10. a manufacture method for medical device, is characterized in that, comprising:

First operation, uses the first solution containing the material different from base material, the first lubrication portion that the lubricity when the surface of described base material is formed moistening is higher than this base material;

Second operation, after described first operation, use the second solution containing the material different from described base material, in the part different from described first lubrication portion and the outer surface of this medical device at least partially on initial lubricity when the being formed moistening second lubrication portion higher than described first lubrication portion.

The manufacture method of 11. medical devices according to claim 10, wherein,

In described first solution containing the first lubricant material as the lubricant material higher than described base material of lubricity time moistening,

Containing second lubricant material different from described first lubricant material in described second solution.

The manufacture method of 12. medical devices according to claim 11, wherein,

Described first lubricant material is polyvinylpyrrolidone, and described second lubricant material is poly(ethylene oxide).

The manufacture method of 13. medical devices according to claim 11 or 12, wherein,

The concentration of described second lubricant material in described second solution is more than 0.2 % by weight and less than 0.55 % by weight.