JPH10248919A - Medical device and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To impart surface lubricity at a time of wetting regardless of the material quality of a base material and to also impart excellent surface lubricity regardless of the base material constituting a medical device. SOLUTION: This medical device is formed by providing a crosslinked coating film formed from a polymer having an acid anhydride group and polyamine on the surface of a base material and has lubricity at a time of wetting. The polymer having the acid anhydride group and polyamine are reacted on the surface of the base material to form the crosslinked coating film and the surface of the base material has lubricity at a time of wetting.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical device exhibiting excellent surface lubricity when wet, and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, treatments and diagnoses are frequently performed by inserting a catheter into the body percutaneously, and accordingly, it is necessary to insert a catheter, a guide wire, or the like into a target site. Therefore, low-friction materials are used on the surface of these medical devices for the purpose of reducing tissue damage such as blood vessels and the like, and improving the ease of insertion into target sites. It is coated with lubricant, low friction resin, hydrophilic polymer, etc. For example, low friction has been achieved by applying silicone oil, olive oil, glycerin, or the like, or coating a silicone resin or a fluorine resin. However, in these methods, the lubricant and the low-friction resin may be separated and eluted from the surface of the base material, and there is a problem in safety and durability of lubrication. As a method for coating a hydrophilic polymer, U.S. Pat. No. 4,100,309 discloses a method for coating polyvinylpyrrolidone using isocyanate. Also, JP-A-59-8134
No. 1 discloses a method of coating a hydrophilic copolymer having a reactive functional group using an isocyanate.
JP-A-193766 discloses a method of coating polyethylene oxide with an isocyanate.
No. 023 discloses a polyether via a polyisocyanate on a surface on which at least one or more of an amino group, an imino group, a carboxyl group and a mercapto group are present.
Methods for bonding copolymers such as polyamide and polysiloxane are disclosed. Further, WO90 / 0
No. 1344 discloses a method in which a polymer having a reactive functional group is applied to the surface of a substrate, and then a hydrophilic polymer having a reactive functional group capable of reacting with the reactive functional group is coated. Furthermore, it is Japanese Patent Publication 1-3318
No. 1 discloses a method of imparting lubricity by covalently bonding a reactive functional group present on the surface of a substrate to a maleic anhydride-based polymer.

[0003]

The method for imparting surface lubricity as described above requires uniform coating of two kinds of compounds, an isocyanate compound and a hydrophilic polymer, or requires a plurality of coating operations. For,
The work is complicated, and a compound having a highly reactive functional group such as an isocyanate group easily reacts with impurities, so that there is a problem that process control is difficult or harmful to the human body. Was. Further, in the method disclosed in Japanese Patent Publication No. 1-55023 and the method disclosed in Japanese Patent Publication No. 1-33181, a reactive functional group is required on the surface of the base material to be provided with lubricity. For this reason, there has been a problem that materials capable of imparting lubricity are limited.

An object of the present invention is to solve the above problems,
An object of the present invention is to provide a medical device having excellent surface lubricity when wet and to provide a simple method of manufacturing a medical device capable of imparting excellent surface lubricity irrespective of the material of a base material constituting the medical device. .

[0005]

Means for Solving the Problems The present inventors have made intensive studies to achieve the above object, and as a result, by cross-linking a polymer having an acid anhydride group with a polyamine on the surface of a base material constituting a medical device, The present inventors have found that a medical device having lubricity when wet can be obtained irrespective of the material of the base material constituting the medical device, and arrived at the present invention. In other words, the present invention has a crosslinked coating formed from a polymer having an acid anhydride group and a polyamine on the surface of a base material, and has a medical device characterized by having lubricity when wet, and has an acid anhydride group. The gist of the present invention is a method for producing a medical device having lubricity when wet, characterized by reacting a polymer and a polyamine on the surface of a substrate to form a crosslinked film on the surface of the substrate.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

[0007] The medical device of the present invention is one that is mainly placed in the body or withdrawn from the body. For example, an IVH catheter, a thermodilution catheter, an angiographic catheter, a vascular dilatation catheter, and a die Medical instruments such as lators, indwelling needles, and guidewires that are inserted or placed in blood vessels, urinary catheters and other urethra or ureters inserted and placed in the trachea, such as tracheostomy tubes and endotracheal tubes And medical devices to be inserted or placed orally or nasally such as indwelling medical devices, tube feeding tubes, feeding catheters, gastric tube tubes, and the like.

[0008] The base material constituting these medical devices is not particularly limited, but a polymer material is preferable.
Polyurethane, polyamide, polyester, polyvinyl chloride, polyethylene, polypropylene, silicone resin and the like are particularly suitable. When imparting lubricity to a material other than a polymer material such as a metal, a polymer having an acid anhydride group and a polyamine can be directly crosslinked at the material surface, but the polymer is coated with a polymer material as described above. It is more effective to crosslink after the formation.

In the present invention, the polymer having an acid anhydride group is a polymer or a copolymer containing at least two or more monomer units having an acid anhydride group in one molecule. , Maleic anhydride-ethylene copolymer,
Maleic anhydride-styrene copolymer, maleic anhydride-
Maleic anhydride polymers such as methyl vinyl ether copolymers, polyacrylic anhydrides, acrylic anhydride polymers such as acrylic anhydride-styrene copolymers, and anhydrides such as polymethacrylic anhydride and methacrylic anhydride-styrene copolymers Methacrylic acid polymers and the like can be mentioned.

[0010] The molecular weight of the polymer having an acid anhydride group is not particularly limited.
Preferably it is 500,000 or less, more preferably 100,000 or less. When the molecular weight exceeds 1,000,000, the mixed state with the polyamine is not uniform, the reactivity with the polyamine is reduced, and the solubility becomes low when the solution is prepared and the base material is processed. It can be difficult to do.

The number of acid anhydride groups in one molecule which the polymer having acid anhydride groups has as a reactive functional group is 2
If the number is more than one, the object of the present invention can be achieved,
If the number of acid anhydride groups in one molecule is small, the reaction to form a crosslinked film takes a long time, and if the reaction conditions are mild, the strength of the crosslinked film is not sufficient, and the lubricity when wet is obtained. It is preferable that the number of monomer units having an acid anhydride group in one molecule is large because the durability may be reduced. The number of monomer units is, for example, 5 or more, preferably 50 or more, and more preferably 100 or more.

The polyamine used in the present invention is a compound having at least two amino groups in one molecule, for example, ethylenediamine, propylenediamine,
Examples thereof include diamines such as hexamethylene diamine, polyethylene glycol diamine, and polypropylene glycol diamine, urea, polyvinylamine, aminoacetalized polyvinyl alcohol, polyethyleneimine, and reaction products of diamine and epichlorohydrin.

Examples of the reactive functional group possessed by the polyamine include an amino group, an isocyanate group, an epoxy group, and a hydroxyl group. The amino group is preferable because it can be reacted at room temperature. 1 that polyamine has
The number of reactive functional groups in the molecule is not particularly limited, but when the polymer having an acid anhydride group to be used has three or more reactive functional groups, it has two reactive functional groups. Polyamines are preferred. When both the polymer having an acid anhydride group and the polyamine have three or more reactive functional groups, the strength of the crosslinked film is high, but the density of the crosslink is too high, and good lubricity may not be obtained. . In order to obtain good lubricity, one having one of a polymer having an acid anhydride group and a polyamine having two reactive functional groups in one molecule may be used, but the polyamine has a reactive functional group. It is preferable to have two.

In the present invention, a polymer having an acid anhydride group is reacted with a polyamine on the surface of a substrate to form a crosslinked film on the surface of the substrate. For example, a method in which the surface of a substrate is contacted with a solution in which a polymer having an acid anhydride group and a polyamine are dissolved, and then the surface of the substrate is dried is preferable.

As a solvent for dissolving a polymer having an acid anhydride group and a polyamine, for example, dioxane, tetrahydrofuran, ethyl acetate, acetone, methyl ethyl ketone, chloroform, nitromethane, benzene, toluene, xylene, dimethylformamide, dimethylacetamide, dimethylacetamide Sulfoxide and the like can be used.

The concentration of the polymer having an acid anhydride group in the solution is, for example, 0.1% by weight or more, preferably 0.2 to
10.0 wt%, more preferably 0.5 to 5.0 wt%, and the concentration of the polyamine in the solution is, for example, 0.001 wt% or more, preferably 0.005 to 1 wt%.
It is 0.0% by weight, more preferably 0.01 to 5.0% by weight. If the concentration of the polymer having an acid anhydride group and the polyamine in the solution is too low, the strength of the formed film tends to decrease, and if the concentration is too high, the thickness of the film may be uneven.

The molar ratio of the acid anhydride group of the polymer having an acid anhydride group in the solution to the reactive functional group of the polyamine is, for example, the ratio of acid anhydride group / reactive functional group is 10 or more, preferably 25 or more. The number is more preferably 50 or more.
When the reactive functional group is excessive in relation to the acid anhydride group, the reactivity decreases, and it takes a long time to form a crosslinked film, so that the acid anhydride group is used in excess to the reactive functional group. Is preferred. In addition, when the acid anhydride groups and the reactive functional groups are close to equivalent amounts, after performing a cross-linking reaction, unreacted acid anhydride groups and reactive functional groups are reduced, so that it is difficult to obtain good lubricity. There is. However, when the number of reactive functional groups is small relative to the acid anhydride group, the strength of the crosslinked film is reduced and the possibility of falling off occurs. Therefore, the molar ratio of the acid anhydride group is, for example, / The number of reactive functional groups is 10,000 or less, preferably 5000 or less, and more preferably 1000 or less.

From the above points, the molar ratio of the acid anhydride group of the polymer having an acid anhydride group in the solution to the reactive functional group of the polyamine is such that acid anhydride group: reactive functional group = 10: 1.
It is preferably from 10000 to 10000: 1. At this time, the molar ratio of the acid anhydride group of the polymer having an acid anhydride group to the reactive functional group of the polyamine in the obtained crosslinked film was 10%.
That is all.

If the molecular weight of both the polymer having an acid anhydride group and the polyamine used is large, the mixing state in the solution becomes poor, so that at least one of the compounds has a molecular weight of 5,000.
The following is preferred. At this time, it is preferable that, of the polymer having an acid anhydride group and the polyamine, a compound having less reactive functional groups has a molecular weight of 5,000 or less. When the molecular weight of the compound having a large number of reactive functional groups is small, the distance between the reactive functional groups becomes short, and thus the reactivity may be reduced.

The solution in which the polymer having an acid anhydride group and the polyamine are dissolved may contain acetic acid, sulfuric acid, p-
An acid such as toluenesulfonic acid or a base such as triethylamine or pyridine may be added.

The method of bringing the solution prepared in this manner into contact with the surface of the substrate includes immersing the substrate in the solution,
A method of spraying the solution on the surface of the substrate, a method of applying the solution on the surface of the substrate, and the like can be appropriately selected. The method of immersing the substrate in the solution is particularly preferable because the control of the contact time is easy. The time for immersing the substrate in the solution is 10 seconds to 2 seconds.
4 hours, preferably 30 seconds to 2 hours. After the solution is brought into contact with the substrate surface and dried, the polymer having an acid anhydride group reacts with the polyamine to form a film on the substrate surface. When drying, heating is preferable because the reaction speed is increased. The heating operation is
It may be performed at any of normal temperature and reduced pressure. The heating temperature and time are, for example, 30 ° C. or more, preferably 50 to 180 ° C.
5 ° C., more preferably 70 to 150 ° C., for 5 minutes to 48 hours, preferably 10 minutes to 24 hours, more preferably 3 to 48 hours.
0 minutes to 6 hours.

A substrate having on its surface a crosslinked film formed by a reaction between a polymer having an acid anhydride group and a polyamine shows lubricity when it comes into contact with an aqueous medium as it is, but after once contacting with an aqueous medium, By drying, when it comes into contact with the aqueous medium again, it immediately exhibits lubricity. Also, a substrate having a crosslinked film on the surface,
After dipping in a solvent capable of dissolving both the polymer having an acid anhydride group and the polyamine, dipping in an aqueous medium is preferable because lubricity when wet is improved. The mechanism by which the lubricity is improved is not clear, but a solvent capable of dissolving the two types of molecules forming the crosslinks easily penetrates into the crosslinked coating and swells the crosslinked coating. For this reason, it is considered that the degree of freedom of the molecular chain is increased, and the water molecules may easily enter the crosslinked film when brought into contact with the aqueous medium.

[0023]

Next, the present invention will be described specifically with reference to examples.

Example 1 Maleic anhydride-methyl vinyl ether copolymer having a molecular weight of about 69000 [ISP Co., Ltd.]
5% by weight and 1% by weight of polyethylene glycol diamine having a molecular weight of 4000 (manufactured by Sanyo Chemical Industries Co., Ltd.). A nylon 6 film (manufactured by Unitika Ltd.) is immersed in an acetone solution at room temperature for 1 hour, and then at 90 ° C. Heat under reduced pressure for 3 hours. After heating, the obtained nylon 6 film was immersed in water for 24 hours and then dried (sample 1). Separately, the nylon 6 film obtained after the heating was immersed in acetone for 90 minutes, dried, immersed in water for 24 hours, and dried again (Sample 2).

Next, the friction coefficients of the samples 1, 2 and the untreated nylon 6 film (sample 3) were measured by the following method. Sample 1, Sample 2, and Sample 3 were each immersed in water for 24 hours, dried, affixed to an aluminum plate, placed with a weight of 100 g, and gradually tilted the plate, and the tilt when the weight began to move Measure the angle (θ) and tan
θ was calculated and used as a friction coefficient. Further, after immersing each sample in water, the friction coefficient was measured in the same manner in a wet state. Table 1 shows the results. A film with a crosslinked film formed on the surface has a significantly reduced coefficient of friction when wet, and it is clear that the effect is greater when immersed in a solvent that dissolves both the polymer having acid anhydride groups and the polyamine before immersion in water. It is.

[0026]

[Table 1]

Example 2 Polyurethane [Thermedics, Ind.
c.) Tecoflex] was pressed at 200 ° C. using a press machine (manufactured by Hayashi Kikai Seisakusho) to obtain a sheet having a thickness of about 500 μm. Next, 2% by weight of a maleic anhydride-methyl vinyl ether copolymer having a molecular weight of about 69000 (manufactured by ISP Co., Ltd.) and 0.1% of polyethylene glycol diamine having a molecular weight of 1000 were used.
The obtained polyurethane sheet was immersed in a cyclohexanone solution in which the weight% was dissolved for 1 minute, and then dried at 70 ° C. This was further washed with cyclohexanone, immersed in physiological saline at 37 ° C. for 24 hours, and dried (sample 4). When the coefficient of friction of the obtained sample 4 was measured by the same method as in Example 1, the coefficient of friction when wet was 0.02.
It was below.

[0028]

The medical device of the present invention has excellent surface lubricity. Further, according to the method for producing a medical device of the present invention, a medical device having excellent surface lubricity when wet can be obtained by a simple method regardless of the material of the base material.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yumiko Ogura 23 Uji Kozakura, Uji-city, Kyoto Pref.

Claims (10)

[Claims] 1. A medical device having a crosslinked film formed from a polymer having an acid anhydride group and a polyamine on the surface of a substrate, and having lubricity when wet. 2. Either a polymer having an acid anhydride group or a polyamine has two reactive functional groups in one molecule, and the other has three or more reactive functional groups in one molecule. The medical device according to claim 1, wherein: 3. The medical device according to claim 2, wherein the polyamine has two reactive functional groups in one molecule. 4. The medical device according to claim 1, wherein the molecular weight of either the polymer having an acid anhydride group or the polyamine is 5,000 or less. 5. The polymer according to claim 2, wherein one of the polymer having an acid anhydride group and the polyamine has two reactive functional groups in one molecule and has a molecular weight of 5,000 or less. The medical device according to any one of claims 3 and 4. 6. The method according to claim 1, wherein the molar ratio of the reactive functional group of the polymer having an acid anhydride group to the reactive functional group of the polyamine constituting the crosslinked film is 10 or more. The medical device according to any one of claims 2, 3, 4, and 5. 7. A method for producing a medical device having lubricity when wet, comprising reacting a polymer having an acid anhydride group with a polyamine on the surface of a substrate to form a crosslinked film on the surface of the substrate. 8. A wet lubricating property characterized by reacting a polymer having an acid anhydride group with a polyamine on the substrate surface to form a crosslinked film on the substrate surface and then immersing the substrate in an aqueous medium. A method for producing a medical device, comprising: 9. A solvent capable of reacting a polymer having an acid anhydride group with a polyamine on the surface of a substrate to form a crosslinked film on the surface of the substrate and then dissolving both the polymer having an acid anhydride group and the polyamine. A method for producing a medical device having lubricity when wet, wherein the device is further immersed in an aqueous medium after immersion in water. 10. The molar ratio of the reactive functional group of the polymer having an acid anhydride group to be reacted on the surface of the substrate and the reactive functional group of the polyamine is 10: 1 to 10,000: 1. 7. The method for manufacturing a medical device according to claim 8.