JP2002095734A - Lubricative medical implement and its manufacturing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical implement which is rich in its surface durability and surface lubrication despite the property of its materials, and provide the manufacturing method of a medical implement which is rich in its surface durability and surface lubrication despite the property of its materials. SOLUTION: The surface material of this medical implement is composed of polymer having acid-base anhydride and polymer of a compound of vinyl lactam in addition to a cross-linking membrane formed by a compound having more than two active hydrogen and surface lubrication.

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, treatment and diagnosis are often performed by percutaneously inserting a catheter into the body, and accordingly, it is necessary to insert a catheter, a guide wire, or the like into a target site. Therefore, these medical devices are coated with a hydrophilic polymer to reduce the friction of the material surface in order to reduce damage to tissues such as blood vessels and to improve insertability into a target site.

As a method for coating a hydrophilic polymer, US Pat. No. 4,100,309 discloses a method for coating polyvinylpyrrolidone with isocyanate. JP-A-59-81341 discloses a method of coating a hydrophilic copolymer having a reactive functional group using an isocyanate.
No. 766 discloses a polyether via a polyisocyanate on a surface where at least one of an amino group, an imino group, a carboxyl group, and a mercapto group is present.
Methods for bonding copolymers such as polyamide and polysiloxane are disclosed. Further, WO90 / 0
International Publication No. 1344 discloses a method in which a polymer having a reactive functional group is applied to a substrate surface, and then a hydrophilic polymer having a reactive functional group capable of reacting with the reactive functional group is coated. . Furthermore, Japanese Patent Publication No. 33181/1989 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.

[0004] However, since two kinds of compounds, ie, an isocyanate compound and a hydrophilic polymer, must be uniformly coated, or a plurality of coating operations are required, the work is complicated, and the reactivity of isocyanate groups and the like is low. A compound having a high functional group easily reacts with impurities, and thus has problems such as difficulty in process control and harm to the human body. In addition, Tokuhei 1-550
No. 23, JP-B1-331
In the method disclosed in Japanese Patent Publication No. 81, a reactive functional group is required on the surface of the base material to be provided with lubricity,
There was a problem that the material to which lubricity could be imparted was limited.

[0005] On the other hand, regardless of the material of the base material constituting the medical device, there are provided a medical device having excellent surface lubricity when the surface of the base material is wet, and a simple manufacturing method of the medical device. JP-A-10-248918 and JP-A-10-248920 are disclosed. Any of the methods described above can easily impart high lubricity to the substrate surface.

[0006]

However, some medical devices are used, for example, friction between the catheter having surface lubrication and a coiled guide wire or mesh metal stainless steel having surface irregularities. May be very severe when viewed from the substrate surface. Even in such a case, the surface of the medical device needs to maintain good lubricity at a high level, but economical loss of lubricity is unavoidable in the above surface treatment method. From this, the present invention shows a method in which the lubricity of the substrate surface has a high degree of durability.

[0007]

Means for Solving the Problems The present inventors have conducted intensive studies to achieve the above object, and as a result, have found that a polymer having an acid anhydride group and a polymer of a vinyl lactam compound on the surface of a substrate constituting a medical device. Further, by forming a crosslinked film comprising a compound having two or more active hydrogens, a medical device having permanent lubricity when wet can be obtained regardless of the material of the base material constituting the medical device. Heading, the present invention has been reached.

That is, the present invention has a lubricating property having a crosslinked film formed from a polymer having an acid anhydride group and a polymer of a vinyl lactam compound on the surface of a substrate, and a compound having two or more active hydrogens. The medical device is characterized in that the weight ratio of the vinyl lactam compound polymer to the polymer having an acid anhydride group is preferably 0.01% to 5%. And, particularly preferably,
The polymer having an acid anhydride group has an acid anhydride group of 0.1 to
10 mol% reacts to form a crosslinked film. Also, the present invention provides a polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens on the surface of a substrate to form a crosslinked film on the surface of the substrate. The gist of the present invention is a method for producing a lubricating medical device characterized by being immersed therein.

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The details of the present invention will be described below.
The medical device according to the present invention is mainly used for indwelling or removing from the body. For example, an IVH catheter, a thermodilution catheter, an angiographic catheter, a vascular dilatation catheter,
Medical devices inserted or placed in blood vessels such as artificial blood vessels, shunt tubes, cannula, dilators, indwelling needles, guide wires, various sensors for measuring blood flow and blood gas concentration, urethra or urine such as urinary catheters Oral or nasal insertion or placement of medical devices inserted or placed in tubes, tracheostomy tubes, endotracheal tubes or other medical devices inserted or placed in trachea, tube feeding tubes, nutritional catheters, gastric tube tubes, etc. Examples of the indwelling medical device include an abdominal drainage tube, an artificial kidney, an artificial heart, an artificial valve, and an artificial lung.

The base material constituting these medical devices is not particularly limited, but a polymer material is preferable, and polyurethane, polyamide, polyester, polyvinyl chloride, polyethylene, polypropylene, silicone resin and the like are particularly preferable. It is. When lubricating a material other than a polymer material such as a metal, a polymer having a direct acid anhydride group and a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens are crosslinked on the material surface. Although it is also possible to crosslink after coating with the above-mentioned polymer material, it is more effective.

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 polymers such as maleic anhydride-ethylene copolymer, maleic anhydride-styrene copolymer, maleic anhydride-methylvinyl ether copolymer, polyacrylic anhydride, acrylic anhydride-styrene copolymer, etc. Methacrylic anhydride-based polymers such as acrylic anhydride-based polymers, polymethacrylic anhydride, and methacrylic anhydride-styrene copolymers are exemplified.

The molecular weight of the polymer having an acid anhydride group is not particularly limited.
Preferably 1000 to 500,000, more preferably 100
It is 0 to 100,000. When the molecular weight exceeds 1,000,000, the mixing state with the compound having two or more active hydrogens or the polymer of the vinyl lactam compound is not uniform, or the reactivity with the compound having two or more active hydrogens or the polymer of the vinyl lactam compound. Or when the solution is prepared and the substrate is treated, the solubility may be low and the treatment may not be easily performed.

[0013] The object of the present invention can be achieved if the number of acid anhydride groups in one molecule of the polymer having acid anhydride groups as reactive functional groups is at least two.
If the number of acid anhydride groups in the 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 or the lubricity when wet is maintained. It is preferable that the number of monomer units having an acid anhydride group in one molecule is large because the acidity may decrease. As the number of monomer units, for example, 5 or more, preferably 500 to 50,000,
More preferably, it is 100 to 10,000.

The vinyl lactam compound used in the present invention includes N-vinyl pyrrolidone, N-vinyl butyrolactam, N-vinyl caprolactam and the like. Polymers of the vinyl lactam compound include homopolymers and copolymers of these vinyl lactam compounds. It is a polymer comprising one or a mixture of a polymer and another vinyl monomer copolymerizable with a vinyl lactam compound. Vinyl lactam compound content in the polymer consisting of one or a mixture of other vinyl monomers copolymerizable with vinyl lactam compound,
It is at least 30 mol%, preferably at least 55%, more preferably at least 65%. The molecular weight of the polymer of the vinyl lactam compound is, for example, 10,000 to 5,000,000, preferably 1
It is between 10,000 and 5 million.

Such vinyl lactam compound polymers include, for example, poly-N-vinylpyrrolidone, N-vinylpyrrolidone-vinyl acetate copolymer, N-vinylpyrrolidone-hydroxyethyl acrylate copolymer, N-vinylpyrrolidone- A quaternized dimethylaminoethyl methacrylate copolymer may be mentioned, and polyN-vinylpyrrolidone is preferred.

The compound having two or more active hydrogens used in the present invention is a compound having at least two functional groups containing active hydrogen such as a hydroxyl group, an amino group and a thiol group in one molecule, Specific examples include polyols and polyamines.

The polyol in the present invention refers to a compound having at least two hydroxyl groups in one molecule, for example, ethylene glycol, propylene glycol, butylene glycol, glycerin, pentaerythritol, sorbitol, diglycerin, polyvinyl alcohol, diethylene glycol , Triethylene glycol, tetraethylene glycol, pentaethylene glycol, dipropylene glycol, tripropylene glycol, polyethylene glycol, polypropylene glycol, polybutylene glycol and the like, with polyalkylene glycol being particularly preferred.

The polyamine in the present invention is a low-molecular compound or a high-molecular compound having at least two amino groups in one molecule. Such examples include low molecular weight polyamines and high molecular weight polyamines.

Specific examples of low-molecular-weight polyamines include ethylenediamine, 1,3-diaminobutane, putrescine, cadaverine, hexamethylenediamine, octadecamethylenediamine, cardin, spermidine,
Aminopropyl cadaverine, theremin, spermine,
N, N-diethylethylenediamine, N, N, N′-triethylethylenediamine, 1,3-bis (2′-aminoethylamino) propane, tris (2-aminoethyl) amine, N-aminopropyl-2-morpholine, Phenylenediamine, piperazine, canabarmin, cardopentamine, N- (2-aminoethyl) ethanolamine, N,
N, N ', N'-tetramethylethylenediamine and the like can be mentioned.

Specific examples of high-molecular-weight polyamines include poly (alkylene polyamines) synthesized from amines and alkylenedihalides or epichlorohydrin (Encyclopedia of Polymer Science and Technology, vol. 10, p. 616). ), An alkyleneimine polymer obtained by ring-opening polymerization of an alkyleneimine such as ethyleneimine or propyleneimine (Encyclopedia of Polymer Science and Technology, Vol. 1, p. 734), polyvinylamine, polylysine, etc. No. Among these polyamines, poly (oxyethylene) diamine and polyethyleneimine are particularly preferably used because they are inexpensive and effective.

In the present invention, a polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens are reacted on a substrate surface to form a crosslinked film on the substrate surface. However, as a method of forming a cross-linked coating on the substrate surface, for example, a polymer having an acid anhydride group and a polymer of vinyl lactam compound,
Further, a method in which the substrate surface is brought into contact with a solution in which a compound having two or more active hydrogens is dissolved, and then the substrate surface is heated is preferable.

As a solvent for dissolving a polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens, any solvent may be used as long as it can dissolve them. For example, dioxane, tetrahydrofuran, ethyl acetate, acetone, methyl ethyl ketone, chloroform, nitromethane, benzene, toluene, xylene, dimethylformamide, dimethylacetamide, dimethylsulfoxide, methyl alcohol or ethyl alcohol, or even lower aliphatic alcohols such as propyl alcohol alone or Two or more types can be used in combination.

In order to obtain a solution in which a polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens are dissolved, a method in which these substances are dissolved at once with the above solvent, It can be obtained by any method such as a method of dissolving each substance and then mixing, or a method of dissolving any two kinds of substances and adding a solution of the remaining substance.

The polymer having an acid anhydride group, the polymer of a vinyl lactam compound, and the compound having two or more active hydrogens are preferably completely dissolved in a solution. It is preferable to remove the insolubilized material in advance by filtration or the like.

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 1%.
0% by weight, more preferably 0.5 to 5% by weight,
The polymer of the vinyl lactam compound in the solution has a weight ratio of 0.01 to the polymer having an acid anhydride group.
The concentration in the solution is, for example, ^10-5 % by weight or more, preferably ^10-4 to 1% by weight, and more preferably ^10-4 to ^10-1 % by weight. The concentration of the compound having two or more active hydrogens in the solution may be, for example, 0.1.
It is at least 001% by weight, preferably 0.005 to 10% by weight, more preferably 0.01 to 5% by weight.

If the concentration of the polymer having an acid anhydride group and the polymer of a vinyl lactam compound, and furthermore, the compound having two or more active hydrogens, is too low, the strength of the formed film tends to decrease. The thickness of the coating may be uneven.

Therefore, in order to form a uniform crosslinked film having appropriate strength, the polymer having an acid anhydride group reacts with 0.1 to 10 mol% of the acid anhydride group to form the crosslinked film. Preferably, it is formed. The surface of the substrate having a crosslinked film obtained in this concentration range can form lubricity having high durability when wet.

If the molecular weight of the polymer having an acid anhydride group and the polymer of a vinyl lactam compound and the compound having two or more active hydrogens are both large, the mixing state in a solution is deteriorated. Is preferably 5,000 or less. At this time, the compound having two or more active hydrogens preferably has a molecular weight of 5,000 or less.

A solution in which a polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens are dissolved is added with acetic acid, if necessary.
Acids such as sulfuric acid and p-toluenesulfonic acid, and bases such as triethylamine and pyridine may be added.

The solution prepared in this way is brought into contact with the surface of the substrate, for example, by immersing the substrate in the solution, by spraying the solution on the surface of the substrate, or by applying the solution to the surface of the substrate. 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, a polymer having an acid anhydride group and a polymer of a vinyl lactam compound by heating,
Furthermore, the compound reacts with a compound having two or more active hydrogens to form a film on the surface of the substrate. The heating operation may be performed at any of normal pressure and reduced pressure. The heating temperature and time are, for example, 30 ° C. or higher, preferably 50 to
180 ° C., more preferably 70 to 150 ° C., for 5 minutes to
48 hours, preferably 10 minutes to 24 hours, more preferably 30 minutes to 6 hours.

A substrate having on its surface a crosslinked film formed by the reaction of a polymer having an acid anhydride group with a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens, can be contacted with an aqueous medium as it is. Although it exhibits lubricity, once it is brought into contact with an aqueous medium and then dried, it immediately exhibits lubricity when it comes into contact with the aqueous medium again. After immersing the substrate having a crosslinked film on the surface in a solvent that can dissolve both the polymer having an acid anhydride group and the polymer of a vinyl lactam compound, and the compound having two or more active hydrogens, immersed in an aqueous medium This is preferable because lubricity when wet is improved. The mechanism by which lubricity is improved is not clear, but it forms 3
Solvents that can dissolve both types of molecules easily penetrate into the crosslinked film and swell the crosslinked film. For this reason, it is considered that the degree of freedom of the molecular chain is increased, and the water molecules are likely to enter the crosslinked film when brought into contact with the aqueous medium.

[0032]

Next, the present invention will be described specifically with reference to examples. Example 1, Comparative Examples 1 and 2, maleic anhydride-methyl vinyl ether copolymer having a molecular weight of about 69000 [ISP Co. Ltd.
5% by weight and poly N-vinylpyrrolidone having a molecular weight of 360,000 (manufactured by Wako Pure Chemical Industries, Ltd.) 3 × 10 ^-2 % by weight, and a polyethylene glycol having a molecular weight of 400 (manufactured by Maruzen Pharmaceutical Co., Ltd.) 0.06 A nylon 6 film (manufactured by Unitika) was immersed in a methyl ethyl ketone / methanol mixed solution in which the weight% was dissolved at room temperature for 1 hour, and then heated at 90 ° C. for 3 hours under reduced pressure. After heating, the nylon 6 film obtained was treated with the aforementioned methyl ethyl ketone /
It was immersed in a methanol mixed solvent for 30 minutes, dried, immersed in water for 24 hours, and then dried (Sample 1).

Next, the coefficient of friction of the sample 1 and the untreated nylon 6 film (Comparative Example 1, Sample 2) was measured by the following method. Each sample was first affixed to an aluminum plate and immersed in water, a 100 g weight with a collagen sheet attached to the lower surface was placed on each sample, and then the plate was gradually inclined to start moving the weight. The inclination angle (θ) was measured, and tan θ was calculated from the inclination angle to obtain a friction coefficient. Table 1 shows the results
Shown in

[0034]

[Table 1]

Regarding the durability of the surface lubricity of the sample 1,
After the tilt angle measurement test was performed 100 times, the tilt angle was measured again to obtain a friction coefficient, which was evaluated by comparison with an initial value. As a comparative sample, sample 3 prepared under exactly the same conditions as sample 1 except that poly-N-vinylpyrrolidone was not included
(Comparative Example 2) was used. The results are shown in Table 1. It is clear that a substrate having a crosslinked film formed from a polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens exhibits excellent sustainability of lubricity. .

Example 2, Comparative Example 3 Polyurethane (Pelesen, manufactured by Dow Chemical Co., Ltd.) was extruded at 180 ° C. to obtain a film having a thickness of about 400 μm. Next, a maleic anhydride-methyl vinyl ether copolymer having a molecular weight of about 69000 was used.
SPCo. Ltd.) 5% by weight and a molecular weight of 360,000 poly N-vinyl lactam (manufactured by Wako Pure Chemical Industries, Ltd.)
5 × 10 ^-3 % by weight, and 0.06% by weight of polyethylene glycol having a molecular weight of 400 (manufactured by Maruzen Pharmaceutical Co., Ltd.)
After immersing the obtained polyurethane film in an acetone / ethanol mixed solution in which
Heat at 0 ° C. for 24 hours. Subsequently, it was immersed in the above-mentioned acetone / ethanol mixed solvent for 10 minutes, dried, immersed in water for 24 hours, and then dried (sample 4). The coefficient of friction of the obtained sample 4 was measured in the same manner as in Example 1, and the coefficient of friction was 0.02 or less when wet.

Regarding the durability of the surface lubrication of Sample 4,
This was performed in the same manner as in Example 1. Comparative sample 5 was poly-N-
Except that vinylpyrrolidone was not included, it was produced under exactly the same conditions as Sample 4 (Comparative Example 3, Sample 5). Table 1 shows the results.

Example 3 Polyvinyl chloride (Esmedica, manufactured by Sekisui Chemical Co., Ltd.) was extruded at 170 ° C. to obtain a film having a thickness of about 400 μm. Next, 5% by weight of a maleic anhydride-methyl vinyl ether copolymer having a molecular weight of about 69000 (manufactured by ISP Co. Ltd.) and a molecular weight of 360,
000 poly N-vinyl lactam (manufactured by Wako Pure Chemical Industries, Ltd.) 1 × 10 ^-2 % by weight, and polyethylene glycol (molecular weight: 400) 0.0
The obtained polyvinyl chloride film was immersed in an acetone / methanol mixed solution in which 6% by weight was dissolved at room temperature for 1 minute, and then heated at 80 ° C. for 24 hours. This was further immersed in water for 24 hours and then dried (sample 6). The coefficient of friction of the obtained sample 6 was measured in the same manner as in Example 1, and it was found that the coefficient of friction when wet even after the durability test was 0.02.
It was below.

[0039]

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

Claims (4)

[Claims] A crosslinked coating formed from a polymer having an acid anhydride group and a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens on the surface of a substrate, and having lubricity. Medical equipment. 2. The weight ratio of the polymer of the vinyl lactam compound to the polymer having an acid anhydride group is 0.0
The medical device according to claim 1, wherein the content is 1% to 5%. 3. The medical device according to claim 1, wherein the polymer having an acid anhydride group has a crosslinked film formed by reacting 0.1 to 10 mol% of the acid anhydride group. Tools. 4. A polymer having an acid anhydride group, a polymer of a vinyl lactam compound, and a compound having two or more active hydrogens are reacted on a substrate surface to form a crosslinked film on the substrate surface. A method for producing a lubricating medical device, characterized by being immersed in water.