JP3428824B2 - Medical instrument - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a medical device and a method for manufacturing the same. More specifically, the present invention relates to a medical device which exhibits lubricity on its surface when contacted with a body fluid or a physiological aqueous system condition, and a method for producing the same. More specifically,
The present invention relates to a medical device which exhibits lubricity on its surface when inserted into a body for treatment or diagnosis and brought into contact with a body fluid or a physiological aqueous system condition.

[0002]

2. Description of the Related Art When a general medical device made of plastics, metal, ceramics or the like is inserted into the body and comes into strong contact with living tissue, tissue injury such as mucous membrane damage or blood vessel damage occurs. Specifically, catheters, guide wires,
When an endoscope, rectal thermometer probe, etc. is inserted into the lumen of a blood vessel or digestive system to the target site, various tissue injuries such as mucous membrane damage and blood vessel damage occur, resulting in patient pain and treatment period. Directly connected to the extension of. Moreover, the insertion resistance at the time of insertion is large, and the medical device may not be advanced to the target site. Therefore, in order to reduce such various injuries and insertion resistance, conventionally, a low-friction material has been used for the base material, oils that impart lubricity to the surface have been coated, and hydrophilic heavy materials have been used. Coating coalescence,
Further, a hydrophilic polymer has been immobilized on the surface by using a chemical bond such as a covalent bond or an ionic bond.

Specific examples of the low friction material include polyethylene, polyacetal, fluororesin and the like, and oils imparting lubricity include silicone oil, olive oil, glycerin and the like. As a method of fixing the hydrophilic polymer on the material surface, a method of fixing polyvinylpyrrolidone or the like using an isocyanate group is disclosed in JP-B-59-19.
Japanese Patent Laid-Open No. 59-8134 discloses a method of fixing two or more hydrophilic polymers using an isocyanate group.
JP-A-59-193766 discloses a method of fixing polyethylene oxide using an isocyanate group.
No. However, the low friction material cannot sufficiently prevent the tissue damage, and the method using oil or hydrophilic polymer cannot maintain the lubricity permanently. Furthermore, since a highly reactive substance (isocyanate group or the like) is used to fix it on the surface, there is a concern about its toxicity when it remains. Further, in the method using oil and the method using hydrophilic polymer, the manufacturing method thereof is complicated because of the large number of steps.

[0004]

As described above, in the conventional method for imparting lubricity to the surface of the medical device, the manufacturing method is complicated and the lubricity cannot be maintained permanently. However, since a highly reactive substance is used, the safety may not be maintained in some cases, which is a problem.

Therefore, it is an object of the present invention to provide a medical device which can maintain its effect permanently and ensure safety by a method simpler than coating.

[0006]

The above object can be achieved by the following constitution. (1) When contacted with body fluids or physiological water-based conditions,
Contact with water, where lubricity develops on at least part of its surface
In therapeutic or diagnostic medical devices used by touching ,
Cover the resin substrate or non-resin substrate that forms the medical device.
The covered resin layer and the lubricity developing portion are molded by thermoforming , and the base or the base is coated during the thermoforming.
Chemical bond at the interface between the resin layer
Medical device characterized by comprising Te. (2) The medical device according to (1), wherein the lubricity-developing site is made of a polyalkylene oxide at least partially cross-linked. (3) The lubricity manifesting site is an amino group or a carboxyl group
Group, thiol group, epoxy group, aldehyde group
Modified polyalkylene oxa Lee Dodea having Kano functional group
The medical device according to (1) or (2) . (4) Other than resin base or resin forming the medical device
The resin surface of the resin layer coated on the substrate is
Modified with acid or glycidyl (meth) acrylate
The medical device according to any one of (1) to (3), which is a resin . (5) The medical device according to any one of (1) to (4), wherein the lubricity-developing site further contains a contrast agent . (6) The contrast agent is tungsten, barium sulfate, or oxy.
Either bismuth silicate or sodium iodide
Medical instrument according to any one of wherein there (1) to (5).

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The material used for at least a part of the portion exhibiting lubricity according to the present invention is different from the conventional coating material or the material using a polymer reaction utilizing a chemical bond. It can be thermoformed. That is,
It has a thermoplastic property. The material is not particularly limited as long as it is a thermoplastic resin that exhibits lubricity by taking in water or the like when it is contacted with a body fluid or physiological water system conditions, but a hydrophilic thermoplastic resin is preferable. Furthermore, polyalkylene oxides such as polyethylene oxide and polypropylene oxide are suitable. A preferable polyalkylene oxide has an atomic ratio of C and O in the repeating unit of 3 or less, for example, ethylene oxide has a C / O ratio of 2 and polypropylene oxide has a C / O ratio of C / O.
The O ratio is 3 and the dioxolane has a C / O ratio of 1.5.
In particular, polyethylene oxide, a copolymer thereof, or a mixture thereof is preferable. However, since they may not have sufficient strength when dried or when they contain water depending on the application, it is more preferable to partially crosslink them in order to increase the strength without impairing the function. The crosslinking method is preferably one using a peroxide, but is not particularly limited. The cross-linking rate is preferably such that the volume expansion rate becomes three times or more in actual use in physiological saline, body fluids and the like.

The molecular weight of the polyalkylene oxide in the uncrosslinked state is 5,000 to 5,000,000, preferably 20,000 to 1.00.
0,000, especially 1 for polyethylene oxide
00,000 to 500,000 is preferable. Further, the material used for at least a part of the portion exhibiting lubricity of the present invention may be a polyalkylene oxide such as polyethylene oxide or a modified polyalkylene oxide.
For example, a modified polyalkylene oxide having one end or both ends modified with an amino group, a carboxyl group, a thiol group, an epoxy group, an aldehyde group or the like is exemplified.

Further , the material of the resin surface constituting the medical device for which lubricity is desired to be expressed is constituted by a material modified with a substance having a functional group capable of reacting with a proton such as maleic anhydride or glycidyl (meth) acrylate. When the material expressing lubricity is modified polyethylene oxide having a proton donating group such as an amino group, a carboxyl group, or a thiol group, a chemical bond occurs at the interface during thermoforming, resulting in stronger adhesion and safety. It becomes possible to supply highly reliable medical devices.

The material used for at least a part of the portion exhibiting lubricity according to the present invention does not have to be a single material, and can be used as a mixture with other materials, especially other resins. For example, cross-linked polyethylene oxide is an olefin resin such as polyethylene, polypropylene, modified polyolefin, polystyrene, polyvinyl chloride, polycarbonate, acrylonitrile / butadiene / styrene copolymer, ethylene / vinyl acetate copolymer,
It is also preferable to use it as a mixture with polyamide, polyethylene terephthalate or the like. Furthermore, the mixing ratio is not particularly limited. The content of crosslinked polyalkylene oxide is preferably 5 to 95% by weight, particularly 2
0 to 80% by weight.

[0011] Tungsten as contrast agent in the material of the surface to be expressed lubricity of the present invention, barium sulfate, bismuth subcarbonate, may be mixed fine powder such as sodium iodide, the mixing ratio is limited Preferably not more than 50% by weight, more preferably 45 to 20% by weight
And As a result, a medical device having a contrasting property and a highly lubricious surface can be obtained.

The thermoforming of the present invention is not particularly limited, but may be extrusion molding, multi-layer extrusion molding, profile extrusion molding, injection molding, multicolor injection molding, insert injection molding, press molding, vacuum press molding and the like. It is suitable. Any thermoforming is a usual forming method, and it is not necessary to use a special forming machine or to perform a special forming method. That is, in the case of a crystalline resin, it is preferable to mold at a temperature about 10 to 40 ° C. higher than the melting point, and in the case of an amorphous resin, molding at a temperature about 80 to 150 ° C. higher than the glass transition temperature. A hollow material such as a catheter can be extruded, and when it is desired to obtain lubricity only on the outermost surface of the catheter, it can be coextruded with the resin of the base material.
It can also be applied to a member molded by injection molding such as a rectal thermometer probe. Furthermore, in order to impart lubricity only to the outermost surface of the probe, two colors (multicolor) are used.
Injection molding and insert injection molding are suitable. When a thin dish-shaped molded product is obtained, press molding or vacuum press molding can be used. Furthermore, if a multilayer sheet having a lubricious material on the surface is previously obtained by coextrusion molding, a press-molded product having lubricity only on the outermost surface can be obtained. Alternatively, it has been thermoformed in advance 2
It is also preferable to combine two or more members with an adhesive resin or an adhesive. In all of these molding methods, the part that develops lubricity is formed sufficiently thicker than the material that uses a polymer reaction that utilizes a coating method or chemical bond, so there is no risk of peeling during operation of the medical device. It can be expected to maintain a permanent function.

[0013] The medical device of the present invention, blood, lymph, saliva, tears, gastric fluid, body fluids or physiological saline, including urine, etc.,
It is a device that is used by contacting with a physiological water system such as a buffer solution with adjusted ion concentration, and by contacting them, lubricity is developed on the surface, and the medical device is inserted to the target site. It is possible to improve operability such as easy and to reduce tissue damage. This medical device is for treatment or diagnosis used as described above, and the medical device is not particularly limited, but is suitable for catheters, guide wires, endoscopes, rectal thermometer probes, etc. .

[0014]

EXAMPLES Examples of the present invention are shown below, but the present invention is not limited to the medical devices, materials and molding methods described in the examples.

[0015] (Example 1) crosslinked polyethylene oxide with (Sumitomo Seika Co., Ltd. AQUACALK) to the outer layer, and a maleic anhydride-modified polyethylene (Mitsubishi Petrochemical Co., Ltd. MODIC) on the inner layer 2
Co-extrusion molding from a layer die at a die temperature of 105 ° C. and an outer diameter of 4.
A catheter made of a multi-layer tube having a diameter of 0 mm and an inner diameter of 2.0 mm was obtained. Cut the tube at right angles to the long axis and cut
When observing the layer composition with a projector, the thickness of each layer is about 0.5 m.
It was m. Also, the interface was well adhered. When the prepared tube was inserted into a simulated blood vessel made of polyvinyl chloride tube with an inner diameter of 6 mm filled with physiological saline in a loop shape with a radius of 50 mm (see Fig. 1) (insertion distance 500 mm, insertion speed 50 mm / m
in, 37 ° C.) was measured with a tensile tester.
The results are shown in Table 1. After repeating insertion and removal 100 times, no peeling was observed and the lubricity was maintained. In addition, the eluate test using the "Disposable catheter for arteriovenous indwelling"
Table 1 also shows the results of p.71-273, published by Yakuhin Jikhosha, 1991.

[0016] (Example 2) modified polyethylene oxide (Dai-ichi Kogyo Seiyaku Co., Ltd. Paogen, modified P which is modified by reaction with a polycarboxylic acid
EO) and tungsten fine powder as a contrast agent (particle size of about 3 to
4 μm) was melt-kneaded to a content of 45% by weight to obtain a material having contrast properties. With this as the outermost layer, maleic anhydride modified polyethylene (Bondyne HX8290 manufactured by Sumitomo Chemical Co., Ltd.) is used as the intermediate layer (adhesive layer), urethane (Miractran P395 manufactured by Nippon Miractolane Co., Ltd.) is used as the innermost layer, and the total length is 1800 mm, The tip diameter is 0.0
6mm, diameter of the rear end is 0.25mm and 120m from the front
A 51% Ni Ni—Ti alloy having a taper shape of m toward the tip was entirely coated to obtain an angiographic catheter. The whole wire is 1800mm,
The diameter was about 0.8 mm. This was changed to a vinyl chloride tube having an inner diameter of 1 mm in FIG. 1, and the same test as in Example 1 was conducted. The results are shown in Table 1. After inserting and pulling out 100 times, no peeling or marked increase in resistance value was observed, and the lubricity was maintained. In addition, an eluate test was conducted in the same manner as in Example 1, but the results met the criteria (Table 1).

[0017] were molded same catheter (Comparative Example 1) maleic anhydride-modified polyethylene (Mitsubishi Petrochemical Co., Ltd. MODIC) alone Example 1. The resistance value when the tube was inserted into the simulated blood vessel was measured in the same manner as in Example 1, and the results are shown in Table 1.

[0018] except that not used (Comparative Example 2) polyethylene oxide crosslinked to the raw material (Sumitomo Seika Chemicals Co., Ltd. AQUACALK) to give a catheter in the same manner as in Example 2. The resistance value when the tube was inserted into the simulated blood vessel was measured in the same manner as in Example 1, and the results are shown in Table 1.

[0019] to give the probes except that not used (Comparative Example 3) polyethylene oxide crosslinked to the raw material (Sumitomo Seika Chemicals Co., Ltd. AQUACALK) in the same manner as in Example 3. The resistance value when the tube was inserted into the simulated anus was measured in the same manner as in Example 3, and the results are shown in Table 2.
It was shown to.

[0020] without using (Comparative Example 4) modified polyethylene oxide of Example 4 (Dai-ichi Kogyo Seiyaku Co., Ltd. Paogen), and tungsten fine powder of maleic anhydride modified polyethylene (manufactured by Sumitomo Chemical Co., Ltd. Bondine HX8290) melting The material was kneaded to obtain a material having a contrast property. Using this as an outer layer, an angiographic catheter was obtained in the same manner as in Example 4. Similarly, the resistance values of insertion and withdrawal were measured, and the results are shown in Table 1.

[0021] (Example 3) Styrene-based elastomer (manufactured by Mitsubishi Chemical Corporation Rabalon ME6301) an inner layer, an intermediate layer (adhesive layer) to the maleic anhydride-modified polyethylene (MODIC E-200H manufactured by Mitsubishi Chemical Corporation), both the outer layer A glove for anal palpation was obtained by multi-layer blow molding using terminal amine PEO (PEO amine # 6000 manufactured by Kawaken Fine Chemical Co., Ltd.).
The surface of this glove was not lubricated in the dry state, but the surface lubricity was developed by immersing it in physiological saline, and no lubricant such as jelly or oil was required for actual use. Met.

[0022] (Comparative Example 5) both terminal amine PEO (Kawaken Fine Chemicals Co., Ltd. PE
A glove for anal palpation was obtained in the same manner as in Example 3 except that O amine # 6000) was not used. No lubricity was observed on the surface of this glove in either a dry state or a wet state, and a lubricant such as jelly or oil was required for actual use.

[0023]

[0024] Note) ABS copolymer: acrylonitrile-butadiene-
Styrene copolymer

It can be seen that each of the examples has a smaller resistance value than the comparative example and is provided with lubricity.

[0026]

INDUSTRIAL APPLICABILITY As described above, the present invention provides a medical device in which at least a part of the surface thereof exhibits lubricity when contacted with a body fluid or physiological water system conditions, and at least the lubricity-expressing site is present. Since it is a medical device characterized by being partially thermoformed, like the conventional method,
Lubricity could be imparted to the medical device surface much more easily than by applying oil or coating a lubricious material. In addition, its function is maintained permanently, there is no peeling, etc., and it also complies with the prescribed eluate test and is excellent in safety.

[Brief description of drawings]

FIG. 1 is a schematic view of a simulated blood vessel for evaluating the lubricity of the medical device of the present invention.

[Explanation of symbols]

1 simulated blood vessels

─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yasunobu 1500 Inoguchi, Nakai-cho, Ashigaragami-gun, Kanagawa Terumo Corporation (72) Inventor Naoki Ishii 1500, Inoguchi, Nakai-cho, Ashigagami-gun, Kanagawa Terumo Corporation (72) Inventor Taku Aoike 1500 Inoguchi, Nakai-cho, Ashigarashami-gun, Kanagawa Terumo Corporation (56) References JP-A-4-210064 (JP, A) JP-A-4-227671 (JP, A) JP-A-1-195863 (JP, A) JP-A-61-45775 (JP, A) JP-A-60-259269 (JP, A) JP-A-5-503439 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) ) A61L 24/00-33/18

Claims (4)

(57) [Claims] 1. Lubricity is exhibited on at least a part of the surface of a body fluid or when contacted with it under physiological aqueous conditions.
In therapeutic or diagnostic medical devices used in contact with body fluids or physiological water systems , the resin surface is a substance having a functional group capable of reacting with protons.
And a resin layer coated on the modified consists materials medical device on a substrate other than the resin substrate or a resin to form a small
At least partly crosslinked polyalkylene oxide
Is an amino group, carboxyl group, thiol group, epoxy
Group having a functional group of either a aldehyde group or an aldehyde group
The lubricity-developing part made of a polyalkylene oxide is molded by thermoforming, and at the time of the thermoforming, the base or the resin layer coated on the base is chemically bonded at the interface between the lubricity-developing part. And medical equipment. 2. A resin surface of the coated resin layer on the substrate other than the resin substrate or a resin to form the medical device is, in claim 1 is a resin which is modified with maleic anhydride or glycidyl (meth) acrylate The listed medical device. 3. A medical device according to claim 1 or 2 wherein the lubricity expression site, characterized in that further comprising a contrast agent. Wherein said contrast agent is tungsten, medical instrument according to any one of claims 1 to 3, characterized in that any of a barium sulfate, bismuth subcarbonate, sodium iodide.