JP2001000531A - Medical device with lubricity - Google Patents

Abstract

(57) [Summary] [PROBLEMS] To provide a medical device having lubricating properties which may be brought into contact with a living tissue, a body fluid, or blood by being inserted into a human body or the like. SOLUTION: A hydrophilic material having a lubricating surface is made of a third material.
It is fixed to a substrate by using a compound containing a grade nitrogen atom and / or a mixture thereof. The compound containing a tertiary nitrogen atom may be a polyether-type polyurethane, and further, a tertiary nitrogen atom may have a tertiary nitrogen atom in the main chain of the polyether-type polyurethane.
It can be chosen that a first-class nitrogen atom is present.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improvement of a medical device that may be brought into contact with a living tissue, a body fluid, or blood when inserted into a human body.

[0002]

2. Description of the Related Art Medical devices include those that are inserted into tissues or body cavities of the human body, such as blood vessels, trachea, and urethra, and guidewires and stylets that are used together with the insertion procedure.
There is a problem in that the insertion causes a foreign body reaction or causes a thrombus to adhere to the medical device or tissue adhesion. Therefore, in order to avoid medical problems when inserting a medical device, it is necessary to reduce damage due to contact with tissues and mucous membranes,
It has been pointed out that it is necessary to use a low friction material for the medical device as a measure for the medical device. Therefore, for example, fluororesin or high-density polyethylene is used. In addition, in order to impart lubricity to the medical device, a method of applying glycerin, olive oil, silicone oil, or the like to the surface of the medical device substrate at the time of insertion is used. However, this not only has the disadvantage of poor sustainability of its effects, but also has a low toxicity, and there are some reports that there were adverse events to human tissues. There is also. In addition, by roughening the surface of the base material and reducing the contact area, a means for reducing the frictional force can be taken. However, although it is a simple means, it is far from providing medically satisfactory performance. . In recent years, means for forming a layer using a hydrophilic material on the surface of a medical device to impart low friction when wet have been studied. For example, immobilization of polyvinylpyrrolidone using isocyanate (US Pat. No. 4,100,309, Japanese Patent Publication No. 59-19582), formation of an unreacted isocyanate group on the surface of a medical device, and formation of a hydrophilic polymer capable of covalently bonding to this group. Reaction method (JP-A-59-81341), a method using a polyurethane in which a coating solution of isocyanate, polyol and poly (ethylene oxide) is applied and reacted on the surface (JP-A-4-227671), active hydrogen (Japanese Patent Publication No. 1-55023), a method of covalently bonding a reactive functional group on the substrate surface to a maleic anhydride-based polymer (Japanese Patent Publication No. 1-31811). , Functional groups are introduced on the polyurethane surface by coating A method for immobilizing on the surface of the hydrophilic polymer by work (W
D90 / 01344), and a method for forming a lubricating material to which peeling resistance has been imparted by an ultraviolet grafting method (Japanese Patent Application Laid-Open No. 9-3)
13594). However, in order to impart stable lubricating properties by these methods, there is a disadvantage that many steps and time are required. In addition, most lubricating materials produced by a relatively simple method have only temporary effects, and none are satisfactory in medical practice. In particular, this tendency was remarkable for hydrophobic materials having low reactivity such as silicone polymers.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a simple method without introducing a complicated pretreatment after introducing a reactive functional group onto a surface of a medical device substrate by using a hydrophilic material as a lubricating component. Is applied directly to the substrate to provide a high degree of adhesion, and thus the lubricity is not temporary,
An object of the present invention is to provide a medical device capable of sufficiently providing an effect suitable for a medical purpose.

[0004]

[Technical Means for Solving the Problems] In order to solve the above-mentioned problems, the present inventors have conducted intensive studies and found that the use of a compound containing a tertiary nitrogen atom reduces the number of steps as compared with the conventional proposal. It was found that a medical device having both anticoagulant properties and lubricity can be proposed by a simple method. The medical device is a catheter used for a vascular system, a guide wire, a stylet, a sheath, and a medical device that comes into contact with tissue or blood at the time of insertion, such as a device involving a procedure of inserting from the urethra such as a urinary catheter. Although the effect is remarkable, it is also effective for those having a long shape and those used for complex procedures. Also, the base material may be a metal such as stainless steel, nickel-titanium alloy, tungsten alloy, and the polymer may be polyolefin, polyvinyl chloride, polystyrene, polyacrylate, polyacrylonitrile, polyurethane, polyamide, polyester, polycarbonate, cellulose, silicone. Etc.
Further, it may be a single material such as ceramic or a composite material. Next, the means for imparting lubricity to the base material of the medical device will be described in more detail. First, a compound and / or mixture layer containing a tertiary nitrogen atom is formed on the base material to form a base material. And a functional group reactive with both the tertiary nitrogen atom and the hydrophilic material in a single compound.
A method of bonding a tertiary nitrogen atom to a hydrophilic material through a compound layer having at least three tertiary nitrogen atoms and / or a mixture containing a tertiary nitrogen atom-containing compound and / or a mixture on a substrate. A method of forming a substance layer having a reactivity or a mixture property with a grade nitrogen atom, and forming a hydrophilic material layer having a reactivity with a tertiary nitrogen atom on the layer. There is a method of forming a layer in which a compound and / or mixture containing a tertiary nitrogen atom and a hydrophilic material are mixed. Means for forming each of the above-mentioned layers on the surface of the base material include various methods such as dipping and spraying, and is not particularly limited. There are various compounds and / or mixtures containing the tertiary nitrogen atom. For example, the tertiary amino group-containing diol is prepared using a tertiary amino group-containing diol as disclosed in Japanese Patent No. 2663186 or Japanese Patent No. 2615698. Polyurethane and polyurethane urea can be used, but are not limited to these, and other materials may be used as long as they contain a tertiary nitrogen atom. Preferably, it is a polyether-type polyurethane containing a tertiary nitrogen atom structure in the main chain. As the tertiary nitrogen-reactive group, alkyl halides and sulfates are widely known as generally used for imparting dyeability and improving adhesiveness. It is not limited to this. However, it is more preferable to use a compound having a chloromethylstyrene structure or a compound having an isocyanate group or an epoxy group. Various materials can be used as the hydrophilic material having lubricity. For example, a polymer comprising acrylamide or a derivative thereof, polyvinylpyrrolidone, polyvinyl alcohol, a polymer having a polyethylene glycol chain, various sugars and polysaccharides, cellulose or a derivative thereof, a phospholipid, a maleic anhydride polymer, and the like can be used. Most preferably, a vinyl copolymer or a maleic anhydride copolymer having a polyvinylpyrrolidone and chloromethylstyrene structure can be used. When forming a mixed layer of the tertiary nitrogen atom and the hydrophilic material, any material may be used as long as a solvent capable of dissolving or mixing each material can be used. A vinyl copolymer having a chloromethylstyrene structure and / or a quaternary ammonium salt and / or acrylamide and / or a polyoxyethylene structure, and further a maleic anhydride copolymer can be used.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The medical device according to the present invention has been described in detail as described above. Hereinafter, as an example, a production example of a tertiary nitrogen-containing polyurethane and a chloromethylstyrene structure will be described. A production example of the contained vinyl copolymer will be described, but it is needless to say that the present invention is not limited to this as already described in detail.

First, an example of preparing a tertiary nitrogen-containing polyurethane (hereinafter referred to as "Preparation Example 1") is described. For example, a 4,4-diphenylmethane diisocyanate is placed in a 1000 mL four-neck separable flask. 41,
25 g and 95 mL of dioxane are added and heated to 60 ° C. with stirring. A solution prepared by dissolving 55 g of polytetramethylene ether glycol having a number average molecular weight of 1010 in 55 mL of dioxane was added to the solution, and 0,546 g of dibutyltin dilaurate dissolved in 5 mL of dioxane was added as a catalyst, followed by stirring for 2 hours. . An additional 425 mL of dioxane was added to the reaction mixture, and N-methyldiethanolamine 9, 82 g and 1,4
-A solution prepared by dissolving 2,48 g of butanediol in 95 mL of dioxane was added dropwise over 30 minutes,
React at 65 ° C for 4 hours. Thereafter, the reaction solution is added to a large amount of distilled water to precipitate the polymer. The precipitate is washed with water / methanol and dried at 60 ° C. to obtain a polyurethane containing a tertiary nitrogen atom in the main chain.

Next, an example of the preparation of a vinyl copolymer having a chloromethylstyrene structure (hereinafter referred to as "Preparation Example 2") will be described. In a three-necked flask, 5,82 g of dimethylaminoethyl methacrylate quaternary is placed. Compound, 2
3,81 g of methoxypolyethylene glycol methacrylate, 0.61 g of chloromethylstyrene, and 0.11312 g of 2,2′-azobisisobutyronitrile as a polymerization initiator are added, and 75 mL of ethanol is further added. The temperature of the reaction system is set to 60 ° C. in a nitrogen atmosphere.
And then react at 70 ° C. for 15 hours.
Then, after reprecipitation purification with diethyl ether,
Dry at ℃ to obtain a slightly yellowish candy-like vinyl copolymer.

[0008] Then, the embodiments of the present invention will be sequentially described with reference to Production Example 1 and Production Example 2, but as described above, the invention is not limited thereto. In evaluating the lubricity, the static friction coefficient was measured using a portable friction meter HEIDON Tribogear Muse 94i manufactured by Shinto Kagaku.

[0009]

Example 1 5% of the polyurethane obtained in Production Example 1
After dip coating a urethane sheet (Pelecene 2363 80AE) using a tetrahydrofuran solution,
Dry at room temperature for 16 hours. Thereafter, dip coating was performed with a 1% solution of 4,4′-diphenylmethane diisocyanate in methyl ethyl ketone, followed by drying at room temperature for 16 hours. Heat treatment was performed at 1 ° C. for 1 hour. We invade this into physiological saline,
When the coefficient of static friction was measured, it was 0,05 or less.
Then, the measurement was carried out by immersion in physiological saline for one month, but no decrease in the coefficient of static friction was observed.

[0010]

Example 2 A 10% glycerol aqueous solution of polyglycidyl ether was used in place of 4,4′-diphenylmethane diisocyanate in Example 1, and the other procedures were the same. Similar results were obtained.

[0011]

Example 3 A 5% tetrahydrofuran solution of the vinyl copolymer obtained in Production Example 2 was used in place of polyvinylpyrrolidone in Example 1, and the other procedures were the same. Similar results were obtained.

[0012]

Example 4 A base material was coated with a 5% tetrahydrofuran solution of the tertiary nitrogen-containing polyether-type polyurethane obtained in Preparation Example 1, and 5% of the vinyl copolymer obtained in Preparation Example 2 When coated with a tetrahydrofuran solution and heat-treated at 110 ° C. for 3 hours, the coefficient of static friction was 0.05 or less, indicating sufficient lubricity.

[0013]

Example 5 A silicone sheet was coated with a coating solution prepared by adding 0 and 3 g of the polyether polyurethane obtained in Preparation Example 1, 2.8 g of a 25% silicone solution, and 16 g of a tetrahydrofuran solution. Immediately thereafter, coating was performed with a 5% solution of the polyether polyurethane obtained in Preparation Example 1 in tetrahydrofuran.
Dry at 50 ° C. for 1 hour. The underlayer thus prepared was dip-coated with a 1% solution of 4,4′-diphenylmethane diisocyanate in methyl ethyl ketone. Further, after coating with a chloroform solution of 3% polyvinylpyrrolidone and drying at room temperature for several hours,
Let dry for hours. After immersing the thus-prepared coat film in distilled water, the coefficient of static friction was measured.

[0014]

Example 6 The same result was obtained by using a tetrahydrofuran solution of a methyl vinyl ether / maleic anhydride copolymer instead of polyvinylpyrrolidone in Example 5, and using the same procedure.

[0015]

Seventh Embodiment FIG. 1 is a partially enlarged sectional view of a tube showing an example of the embodiment. That is, according to the same procedure as in Example 5, the inner cavity (2) of the 3 Fr silicone tube (1) of 16 Fr size was treated to provide the coat film (3),
A stainless steel spring type guide wire of 1, 32 mm (0, 052 inch) is passed through and wound around a 10 cm tube, and both ends of the guide wire are 500 m.
It was alternately pulled at a speed of m / min with a moving amount of 10 cm. As a result, in contrast to the case where no pulling could be performed without the above treatment, no attempt was made with this treatment, but 50 attempts were made, but the tensile resistance of about 0, 98 N (100 gf) remained unchanged throughout. Was.

[0016]

Example 8 A silicone sheet was coated with 4 g of a 25% silicone solution, 4 g of an epoxy-containing styrene copolymer, and 1 g of a tetrahydrofuran solution containing the polyether-type polyurethane obtained in Preparation Example 1, and air-dried. At 150 ° C. for 1 hour. Thereafter, a 1% solution of 4,4′-diphenylmethane diisocyanate in methyl ethyl ketone was dip-coated. Further, it was coated with a chloroform solution of 3% polyvinylpyrrolidone, dried at room temperature for several hours, and then dried at 60 ° C. for 3 hours. The samples thus produced also had a static friction coefficient of 0.05 or less.

[0017]

Example 9 The same result was obtained when the same procedure was followed except that a nylon was used as the base material, and instead of polyvinylpyrrolidone in Example 8, a tetrahydrofuran solution of a methylvinyl ether maleic anhydride copolymer was used. Obtained.

[0018]

Example 10 A urethane sheet was prepared using a coating liquid prepared by mixing a 5% tetrahydrofuran solution of the polyether polyurethane obtained in Preparation Example 1 and a 5% tetrahydrofuran solution of a methyl vinyl ether maleic anhydride copolymer in a ratio of 3: 7. Was coated and dried. Thereafter, the sample immersed in 3% aqueous ammonia for 1 hour and washed with distilled water had a coefficient of static friction of 0.05 or less.
Although this sample was immersed in a physiological saline solution for one month, the coefficient of static friction did not change from that before the immersion.

[0019]

According to the present invention, human health is maintained,
Or the techniques needed to restore health,
It is possible to obtain a medical device which can be performed without damaging blood or the like and which can provide a sufficient medical effect, relatively easily, and maintains excellent performance of the medical device for a long time. Therefore, it also has the advantage of reducing the cost burden on the patient.

[Brief description of the drawings]

FIG. 1 is a partially enlarged sectional view of a tube showing an example of an embodiment.

[Explanation of symbols]

 1. Tube 2. Lumen 3. Coat film

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Eiko Yoshida 2-5-2-5 Chigasaki-minami, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture (72) Inventor Manabu Kubota 2-5-25-2 Chigasaki-minami, Tsuzuki-ku, Yokohama-shi, Kanagawa F Terms (reference) 4C081 AC06 AC08 BA03 BB05 CA021 CA031 CA041 CA062 CA081 CA091 CA161 CA201 CA211 CA212 CA231 CA271 CD021 CF111 CG03 CG05 DA03 DC03 DC04 DC05 DC14 EA06

Claims (3)

[Claims] A hydrophilic material having a lubricating surface is made of a third material.
Medical device characterized in that it is fixed to a substrate using a compound containing a nitrogen atom of a grade and / or a mixture thereof. 2. The medical device according to claim 1, wherein the tertiary nitrogen-containing compound is a polyether-type polyurethane. 3. The medical device according to claim 1, wherein a tertiary nitrogen atom is present in the main chain of the polyether type polyurethane.