JP2000157627A - Medical tools and molding materials - Google Patents

Abstract

(57) [Problem] To provide a medical device which is excellent in flexibility, blood compatibility, heat resistance, gas barrier property, water vapor barrier property and the like and has no sticking property. SOLUTION: The medical device of the present invention is a composition containing a block copolymer (a) containing an isobutylene-based polymer segment and a vinyl aromatic compound-based polymer segment and a specific thermoplastic resin (b). Consists of here,
(B) is selected from a polyolefin-based resin and an ethylene-vinyl alcohol copolymer resin. (A)
The weight ratio of / (b) is in the range of 10/90 to 95/5.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a flexible, blood-compatible, heat-resistant material comprising a block copolymer containing an isobutylene polymer segment and a vinyl aromatic compound polymer segment. It relates to a medical device having excellent properties. The present invention also relates to a molding material for producing the medical device.

[0002]

2. Description of the Related Art Conventionally, flexible and inexpensive soft vinyl chloride resin has been widely used as a molding material for medical devices such as catheters and medical tubes such as blood circuits. However, a large amount of a low-molecular-weight plasticizer such as DOP (dioctyl phthalate) is added to a soft vinyl chloride resin, and the problem of bleed-out of the plasticizer has been pointed out from the viewpoint of safety. In recent years, disposable medical devices have been promoted. However, medical devices using a vinyl chloride resin generate harmful gases when incinerated, and thus have problems such as environmental pollution. Furthermore, medical devices made of soft vinyl chloride resin are inferior in heat resistance and radiation resistance,
Since high-pressure steam sterilization and γ-ray sterilization cannot be performed, E
Although OG (ethylene oxide gas) sterilization is performed, there is a concern that the residual EOG may adversely affect patients.

Japanese Patent Application Laid-Open No. 4-159344 discloses a resin composition which provides a molded product suitable for medical use, which is disclosed in olefin resin, hydrogenated styrene-butadiene block copolymer and styrene-isoprene block copolymer. A resin composition comprising a hydrogenated polymer has been proposed. Also, JP-A-5-212104, JP-A-5-212104
JP-A-269201 and JP-A-5-310868 propose that a medical device is produced by molding a vinyl aromatic compound-isobutylene block copolymer.

[0004]

The resin compositions comprising the above-mentioned olefin resin, hydrogenated styrene-butadiene block copolymer and hydrogenated styrene-isoprene block copolymer are used for medical tubes, medical tubes, For the purpose of using as a medical device such as a balloon,
The balance between heat resistance (durability of high-pressure steam sterilization) and flexibility is not sufficient. Further, the resin composition is insufficient in the balance between flexibility and gas barrier properties for the purpose of use for medical balloons and the like. From these facts, the resin composition has many applications. Further, a molded article having a single-layer structure composed of the above-mentioned vinyl aromatic compound-isobutylene block copolymer has strong adhesiveness. Therefore, the range in which the molded article can be used as a medical device is not necessarily wide.

Accordingly, the present invention provides a medical device which is excellent in flexibility, blood compatibility, heat resistance, gas barrier property, water vapor barrier property and the like and has no sticking property, and a molding material which provides the medical device. That is the task.

[0006]

According to the present invention, there is provided a molding material for a medical device, which comprises a block copolymer containing an isobutylene polymer segment and a vinyl aromatic compound polymer segment. (A) and

(B-1) a polyolefin resin, and

(B-2) Ethylene-vinyl alcohol copolymer resin

[0009] At least one type of thermoplastic resin (b) selected from the group consisting of (a) and (b) having a weight ratio of 1
The problem is solved by providing a molding material comprising the composition (I) containing the composition in a ratio falling within the range of 0/90 to 95/5.

Further, according to the present invention, the above-mentioned object is solved by providing a medical device characterized by comprising the above-mentioned composition (I).

Further, according to the present invention, the above-mentioned problems are
The problem is solved by providing a medical device comprising a multilayer (II) having at least one layer containing the block copolymer (a).

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The block copolymer (a) used in the present invention contains an isobutylene-based polymer segment and a vinyl aromatic compound-based polymer segment. The isobutylene-based polymer segment is a segment composed of an addition polymer of isobutylene alone or a mixed monomer mainly containing isobutylene. On the other hand, the vinyl aromatic compound-based polymer segment is a segment composed of an addition polymer of a vinyl aromatic compound alone or a mixed monomer mainly containing the same. Here, examples of the vinyl aromatic compound include styrene, methylstyrene, dimethylstyrene, trimethylstyrene, chlorostyrene, dichlorostyrene, trichlorostyrene, t-butylstyrene,
Examples include methoxystyrene, α-methylstyrene, β-methylstyrene, chloromethylstyrene, and the like. In constructing each segment, it is possible to copolymerize a small amount of other monomers in addition to isobutylene and the vinyl aromatic compound, as long as the intended performance is not significantly impaired. Examples of the other monomer include vinyl ethers such as vinyl methyl ether, N-vinylcarbazole, β-pinene, 8,9-p-menthen, dipentene, methylene norbornene, and 2-methylenetetrahydrofuran.

In the block copolymer (a) used in the present invention, the arrangement of the isobutylene-based polymer segment and the vinyl aromatic compound-based polymer segment is not particularly limited, and a desired one can be appropriately selected. . Accordingly, in the usable block copolymer (a), when the isobutylene-based polymer segment and the vinyl aromatic compound-based polymer segment are represented by “B” and “A,” respectively, the diblock represented by the formula AB A block copolymer; a triblock copolymer represented by the formula ABA or BAB; a formula (AB) _k , A- (BA) _m ,
A multi-block copolymer represented by B- (AB) _n (k, m and n each represent an integer of 2 or more); formulas A (-B) _p , B (-A) _q (p and q is 3
And a star block copolymer represented by the following integers). Among these, a triblock copolymer represented by the formula ABA is particularly preferred.

The number average molecular weight of the block copolymer (a) to be used is not limited, but may be 500
It is generally preferred to be in the range of 0 to 400,000. Further, the content ratio of the isobutylene-based polymer segment and the vinyl aromatic compound-based polymer segment in the block copolymer (a) is represented by the weight ratio of isobutylene-based polymer segment / vinyl aromatic compound-based polymer segment, Generally, it is preferable to be in the range of 95/5 to 20/80. In the present invention, only one type may be used as the block copolymer (a),
Also, two or more kinds may be used in combination.

The method for producing the block copolymer (a) is not necessarily limited. For example, the general formula:
C (—R ¹ ) (— R ² ) —X (wherein, R ¹ and R ² each represent an alkyl group, an aryl group or an aralkyl group, and X represents an acyloxy group, an alkoxyl group, a hydroxyl group or a halogen atom. A) a polymerization operation of isobutylene (which may be a mixed monomer mainly composed of isobutylene) using an initiator system comprising a compound (1) containing at least one group represented by the formula (1) in a molecule and a Lewis acid; It can be produced by performing a polymerization operation of a vinyl aromatic compound (may be a mixed monomer mainly composed of a vinyl aromatic compound) stepwise.

The compound (1) includes an ether having a tertiary carbon atom bonded to an oxygen atom, a halogenated hydrocarbon having a tertiary carbon atom bonded to a halogen atom, a tertiary alcohol, and a tertiary alcohol. Esters of alcohol and carboxylic acid are included. Specific examples of the ester of the tertiary alcohol and the carboxylic acid include 2-acetoxy-2-phenylpropane and 2-propionyloxy-
Α-cumyl esters such as 2-phenylpropane and the like. Specific examples of the ether having a tertiary carbon atom bonded to an oxygen atom include 1,4-bis (1-
Α-cumyl ether such as methoxy-1-methylethyl) benzene. Specific examples of the halogenated hydrocarbon having a tertiary carbon atom bonded to the halogen atom include 2-chloro-2-phenylpropane,
4-bis (1-chloro-1-methylethyl) benzene,
1,3,5-tris (1-chloro-1-methylethyl)
Α-cumyl chloride such as benzene; 2-chloro-2,
4,4-trimethylpentane; 2,6-dichloro-2,
4,4,6-tetramethylheptane and the like.
Specific examples of the above tertiary alcohol include 1,4-bis (1-hydroxy-1-methylethyl) benzene,
2,6-dihydroxy-2,4,4,6-tetramethylheptane and the like.

The Lewis acids include metal halides
Is preferably used. Specific examples of the metal halide
As boron trichloride, boron trifluoride,
Boron halide compounds such as diethyl ether complex of iodine
Products: titanium tetrachloride, titanium tetrabromide, titanium tetraiodide, etc.
Titanium halide compounds: tin tetrachloride, tin tetrabromide, tetra
Tin halide compounds such as tin iodide; aluminum trichloride
Aluminum, alkyldichloroaluminum, dialkylchloro
Aluminum halide compounds such as aluminum
Halogenated aluminum such as antimony chloride and antimony pentafluoride
Halogenated compounds such as tungsten pentachloride
Nustene compounds; halogenated molybdenum such as molybdenum pentachloride
Libdenum compound; tantalum halide such as tantalum pentachloride
And the like. As Lewis acid,
Use metal alkoxides such as traalkoxy titanium
You can also. The amount of Lewis acid to be used is
General formula derived from (1): -C (-R ¹) (-R²) -X
In the range of 1 to 100 times the number of moles of the group represented by
A ratio that is a number of moles is preferable.

In the above-mentioned polymerization method, in the above-mentioned production method for obtaining the block copolymer (a), isobutylene (or a mixed monomer mainly composed of isobutylene) is used.
At least once and the polymerization operation of a vinyl aromatic compound (or a mixed monomer mainly composed of a vinyl aromatic compound) at least once are performed in an arbitrary order and number of times. An isobutylene-based polymer segment is formed by the former polymerization operation, and a vinyl aromatic compound-based polymer segment is formed by the latter polymerization operation.
That is, first, in the presence of a polymerization initiator system comprising the compound (1) and a Lewis acid, a predetermined monomer that gives one of an isobutylene-based polymer segment and a vinyl aromatic compound-based polymer segment is polymerized. As a result, a desired polymer segment structure is formed (first polymer segment).
After that, a predetermined monomer that gives the other polymer segment is added and the polymerization reaction is continued to form a structure composed of an isobutylene polymer segment and a vinyl aromatic compound polymer segment ( Second polymerization operation). Subsequently, if necessary, such a polymerization operation is further performed an arbitrary number of times. In this manner, a block copolymer structure having a desired arrangement of polymer segments can be formed. In each polymerization operation, it is preferable to set conditions so that the conversion of the monomer is substantially 100%.

The above polymerization reaction can be carried out in an organic solvent. As the organic solvent, a solvent used for ordinary cationic polymerization can be used, and specifically, a saturated aliphatic hydrocarbon such as hexane, heptane, cyclohexane, and methylcyclohexane; and an aromatic solvent such as benzene, toluene, and xylene Group hydrocarbons; single solvents such as halogenated hydrocarbons such as methyl chloride, ethyl chloride, methylene chloride, ethylene dichloride, and chlorobenzene; and mixed solvents thereof. In the polymerization system, if necessary, esters such as ethyl acetate; amines such as triethylamine and pyridine; amides such as dimethylacetamide; THF
Ethers such as (tetrahydrofuran) and dioxane;
Sulfoxides such as dimethyl sulfoxide; acetone,
An organic Lewis base such as a ketone such as methyl ethyl ketone can be present. When the organic Lewis base is used, the amount of the organic Lewis base used is usually based on the number of moles of the group represented by the general formula: -C (-R ¹ ) (-R ² ) -X derived from the compound (1). Is a ratio that results in the number of moles within a range of 0.1 to 100 times. The above-mentioned polymerization reaction is preferably carried out under a condition in which the amount of moisture is small from the viewpoint of preventing a side reaction. Therefore, chemical substances such as monomers and organic solvents that are charged in a large amount to the polymerization reaction system are subjected to a dehydration treatment in advance using a physical adsorption type dehydrating agent such as molecular sieves and aluminum oxide as necessary. It is preferable to keep it.

The polymerization temperature in the above polymerization method is not necessarily limited, but it is usually -150 ° C.
The temperature can be appropriately selected from the range of + 50 ° C. The polymerization reaction is preferably carried out in a solution state in the above-mentioned organic solvent under sufficient stirring conditions while controlling the temperature.

After the completion of a predetermined polymerization operation, the above polymerization reaction can be stopped by adding a protic compound such as methanol, ethanol or water as a reaction terminator to the reaction system. Separation and purification of the block copolymer (a) from the obtained reaction mixture can be performed according to a method employed in ordinary cationic polymerization. For example, the reaction mixture after the termination of the polymerization is washed with an aqueous liquid such as water or an alkaline aqueous solution to remove a Lewis acid or the like, and then reprecipitated in a poor solvent such as methanol, or by introducing steam to remove the solvent. The predetermined block copolymer (a) can be separated and obtained by a method such as azeotropic removal.

The thermoplastic resin (b) used in the present invention is at least one selected from the group consisting of a polyolefin resin (b-1) and an ethylene-vinyl alcohol copolymer resin (b-2). is there.

As the polyolefin resin (b-1), known resins can be used, but polyethylene resins or polypropylene resins are preferred. Specific examples of preferable polyolefin resins include homopolypropylene, random polypropylene, block polypropylene, low-density polyethylene, linear low-density polyethylene, medium-density polyethylene, high-density polyethylene, and ethylene-α-olefin copolymer (ethylene-propylene). Copolymer), an ethylene-vinyl acetate copolymer, an ethylene-methacrylic acid copolymer or an ionomer thereof,
Examples thereof include an ethylene-acrylic acid copolymer or an ionomer thereof, and an ethylene-ethyl acrylate copolymer. One type may be used alone, or two or more types may be used in combination. The melt viscosity of the polyolefin resin (b-1) was 230 ° C. under a load of 2 according to ASTM D-1238.
The melt flow rate (MFR) measured at 160 g is preferably in the range of 0.1 to 500, and more preferably in the range of 0.5 to 200.

Further, ethylene-vinyl alcohol copolymer resin (hereinafter referred to as "EVOH") which is component (b-2)
Referred to as) mainly ethylene units _(-CH 2 -CH
₂ -) and vinyl alcohol units _(-CH 2 -CH (O
H)-). The EVOH used in the present invention is not particularly limited,
For example, known materials used for molding applications can be mentioned. However, the content of ethylene units in EVOH is
From the viewpoint of high barrier properties against gas, liquid and the like and good moldability, the content is preferably in the range of 10 to 99 mol%, more preferably in the range of 20 to 75 mol%, and 25 More preferably, it is in the range of ６０60 mol%, particularly preferably in the range of 25 to 50 mol%. EVOH is typically a saponified ethylene-fatty acid vinyl ester copolymer, as described later. In the case of a saponified ethylene-fatty acid vinyl ester copolymer, EVOH is a saponified fatty acid vinyl ester unit. The degree is preferably 50 mol% or more, and more preferably 90 mol%, from the viewpoint of high barrier properties and thermal stability of the obtained EVOH.
It is more preferably at least 95 mol%, further preferably at least 95 mol%, particularly preferably at least 98 mol%. EVOH melt flow rate (temperature 21
ASTM D12 under the conditions of 0 ° C. and a load of 2.16 kg.
38) is preferably in the range of 0.1 to 100 g / 10 min, and more preferably in the range of 0.5 to 50 g / 10 min from the viewpoint of good moldability. More preferably, it is particularly preferable that it is within the range of 1 to 20 g / 10 minutes. The intrinsic viscosity of EVOH is preferably in the range of 0.1 to 5 dl / g at a temperature of 30 ° C. in a mixed solvent composed of 85% by weight of phenol and 15% by weight of water, and 0.2 to 2 dl. / G is more preferably within the range.

The EVOH may contain other structural units in addition to ethylene units and vinyl alcohol units in a small amount (preferably 10 mol% or less based on all the structural units). Other structural units include α-olefins such as propylene, isobutylene, 4-methylpentene-1, 1-hexane, and 1-octene; vinyl acetate, vinyl propionate, vinyl versatate, vinyl pivalate, Carboxylic acid vinyl esters such as valeric acid vinyl ester, capric acid vinyl ester, and benzoic acid vinyl ester; unsaturated carboxylic acids such as itaconic acid, methacrylic acid, acrylic acid, and maleic anhydride or derivatives thereof (eg, salts, esters, nitriles) Amides, anhydrides and the like); vinylsilane compounds such as vinyltrimethoxysilane; unsaturated sulfonic acids or salts thereof; and units derived from monomers such as N-methylpyrrolidone. Also EV
OH may have a functional group such as an alkylthio group at the terminal.

The method for producing EVOH is not particularly limited. For example, an ethylene-fatty acid vinyl ester copolymer is produced according to a known method, and then saponified to produce a desired EVOH. Can be manufactured. Ethylene-fatty acid vinyl ester-based copolymer is, for example, a monomer mainly composed of ethylene and a fatty acid vinyl ester, methanol, ter
It is obtained by polymerizing under pressure in an organic solvent such as t-butyl alcohol and dimethyl sulfoxide using a radical polymerization initiator such as benzoyl peroxide and azobisisobutyronitrile. As the fatty acid vinyl ester, vinyl acetate, vinyl propionate, vinyl versatate, vinyl pivalate, vinyl valerate, vinyl caprate, and the like can be used. Is preferred. In the saponification of the ethylene-fatty acid vinyl ester copolymer, an acid catalyst or an alkali catalyst can be used. EVOH
As (b-2), one type may be used alone,
Two or more kinds may be used in combination.

The composition (I) according to the present invention comprises a block copolymer (a) and a thermoplastic resin (b) comprising (a) / (b)
In a weight ratio of 10/90 to 95/5. When the content of the block copolymer (a) is less than this range, the flexibility of the medical device comprising the composition (I) becomes insufficient. On the other hand, when the content of the block copolymer (a) is larger than this range, the molded article made of the composition (I) has an inferior adhesive property and is not suitable as a medical device. The weight ratio of (a) / (b) in the composition (I) is within the above range, depending on the kind of the target medical device, required performance, etc., such as anti-adhesion property, flexibility, blood compatibility and the like. It can be selected as appropriate while taking into account the balance of overall performance.
It is preferably in the range of 0/90 to 90/10,
More preferably, it is in the range of 10/90 to 80/20.

The composition (I) according to the present invention has the above-mentioned block copolymer (a) and the above-mentioned block copolymer (a) within the range not impairing the effects of the present invention for the purpose of imparting desired performance to the obtained medical device. Another polymer material (c) may be contained in addition to the thermoplastic resin (b). Examples of the other polymer material (c) include thermoplastic resins other than the thermoplastic resin (b), and elastomers other than the block copolymer (a). Specific examples of other thermoplastic resins that can be used include known thermoplastic resins such as a functional group-containing polyolefin such as an ethylene-glycidyl methacrylate copolymer. Specific examples of other usable elastomers include hydrogenated polyisoprene, hydrogenated polybutadiene, styrene-ethylene / butylene-styrene block copolymer, styrene-ethylene / butylene block copolymer, and styrene-ethylene / propylene. -Known elastomers such as styrene block copolymer, styrene-ethylene / propylene block copolymer, butyl rubber, ethylene propylene rubber (EPR, EPDM, etc.), polybutene, polyisobutylene, methacrylate-butadiene-styrene copolymer (MBS) Is mentioned. When using other polymer materials as described above, only one type may be used, or two or more types may be used. The composition (I) may contain an organic or inorganic additive as long as its physical properties are not significantly impaired. Examples of the additive include processing aids such as higher aliphatic carboxylic acids such as stearic acid and derivatives thereof, process oils, and liquid polyisobutylene; mica, carbon black, silica, glass fiber, carbon fiber, calcium carbonate, talc. Lubricants such as higher fatty acid amides and silicone oils; antioxidants; ultraviolet absorbers; pigments and the like. As a countermeasure for gel generation / prevention, hydrotalcite-based compounds, hindered phenols, hindered amine-based heat stabilizers, phosphite-based stabilizers, metal salts of higher aliphatic carboxylic acids (eg, calcium stearate, magnesium stearate, etc.) It may be effective to add 0.01 to 1% by weight of the composition (I) to the composition (I). In addition, by blending an alkali metal compound, it may be effective to make the composition (I) contain 10 to 500 ppm of an alkali metal ion such as a lithium ion, a sodium ion, and a potassium ion. As the alkali metal compound,
Monovalent metal aliphatic carboxylate, aromatic carboxylate,
Examples thereof include phosphates and metal complexes, and specific examples include sodium acetate, potassium acetate, sodium phosphate, lithium phosphate, sodium stearate, and potassium stearate.

The composition (I) is prepared by mixing the block copolymer (a), the thermoplastic resin (b) and, if desired, other optional components according to a known general mixing method. Can be manufactured. The mixing can be performed, for example, by kneading the respective components using a kneading device such as a continuous extrusion kneader such as a single screw extruder or a twin screw extruder; or a kneading device such as a batch kneader. In view of the above, it is preferable to use a twin-screw extruder. The kneading temperature is not generally defined because a suitable range depends on the type of each component to be mixed. However, generally, the kneading temperature of the block copolymer (a), the thermoplastic resin (b), etc. It is a temperature above the melting point and within a range that does not cause deterioration of these components. In many cases, specifically between 150 ° C. and 3
It is preferably in the range of 20 ° C, more preferably in the range of 160 ° C to 280 ° C. After the mixing as described above, a molding material for a medical device comprising the composition (I) of the present invention can be obtained in the form of a solid having an arbitrary shape and dimensions such as a pellet. However, the molding material of the present invention is not limited to those in the form of solids, and the molding material in the molten state obtained in the step of mixing the above components is not directly taken out without taking out as a solid. It can also be subjected to a medical device molding process.

The molding material comprising the composition (I) in the present invention can be used for a medical device having an arbitrary shape by a usual molding method such as an extrusion molding method, an injection molding method, a blow molding method, a compression molding method, and a thermoforming method. Can be molded into For example, as a molding method for producing a medical tube, a method such as extrusion molding, injection molding, or blow molding, which is a usual tube molding method, can be adopted. In addition, as a molding method in the case of forming a balloon member of a medical tube, after extruding into a tube having a thickness of about 10 to 500 μm, the outer peripheral direction of the tube is heated by air or the like in a mold while heating the tube. To form a desired balloon shape.

Now, the multilayer body (II) according to the present invention comprises:
At least one of the layers contains the above block copolymer (a). The layer containing the block copolymer (a) may be composed of the block copolymer (a) alone, and may contain the block copolymer (a) and another polymer material (d) and / or the above-mentioned organic compound. Alternatively, it may be composed of a composition comprising an inorganic additive, but the weight ratio ((a) / (d)) between the block copolymer (a) and the polymer material (d) in the layer is It is preferable to be in the range of 5/95 to 100/0 from the viewpoint of flexibility, gas barrier properties and the like. Further, the content of the block copolymer (a) in the entire multilayer body (II) is preferably in the range of 3 to 95% by weight from the viewpoint of flexibility, gas barrier properties and the like. The polymer material (d) may be either the thermoplastic resin (b) or the polymer material (c) as described above. In addition, the block copolymer (a)
The composition consisting of and other polymer materials (d) and / or additives can be prepared by mixing the components in the same manner as described for the composition (I).

The multilayer body (II) comprises a block copolymer (a)
May be included. The layer may be made of the thermoplastic resin (b) and / or the polymer material (c) as described above, or may be made of other materials such as metal, paper, and fabric.

The layer configuration of the multilayer body (II) is not particularly limited, and a suitable layer configuration can be appropriately adopted according to the use as a medical device. Therefore, the multilayer body (I
In the medical device consisting of I), the layer constitution of the multilayer body (II) is diversified. For example, the layer containing the block copolymer (a) is represented by “E1,” “E2,” and “E3,” and the like. Are represented by “F1” and “F2”, E1
/ F1 or E1 / E2 two-layer structure; F1 / E1 / F
2, three-layer structures such as E1 / E2 / F1, E1 / E2 / E3 and the like. In the two-layer structure and the three-layer structure, an adhesive layer may be interposed between the layers. In the multilayer body (II) of the present invention, the surface layer is formed of a thermoplastic resin such as a polypropylene resin or a non-adhesive material such as the composition (I) for the purpose of preventing sticking when used as a medical device. It is preferable to form with. Also,
When the medical device can come into contact with blood at the time of use, it is preferable to adopt a layer configuration in which a layer that can come into contact with blood is formed from a material having excellent blood compatibility.

In the medical device comprising the multilayer body (II), the constituent materials of each layer are formed by a multilayer extrusion molding method, a multilayer injection molding method, a multilayer blow molding method, a multilayer compression molding method, or the like according to a desired layer configuration, shape, and the like. Manufacture in any shape by subjecting to known molding and processing methods such as lamination molding method with other materials, multilayer sheet and film molding method by coating method, multilayer sheet and film molding method by transfer method, multilayer dipping molding method can do. For example, as a molding method in the case of manufacturing a medical multilayer tube, a common multilayer tube molding method, a multilayer extrusion molding method, a multilayer injection molding method, a multilayer blow molding method, a laminate molding method with other materials,
A multilayer tube molding method by a coating method or the like can be employed. In addition, as a molding method for producing a medical multilayer sheet / film, a general multilayer sheet / film is used.
Multi-layer extrusion, multi-layer injection, multi-layer blow molding, multi-layer compression, lamination with other materials, multi-layer sheet / film forming by coating, multi-layer sheet by transfer -A film forming method, a multilayer dipping forming method, or the like can be employed.

The medical device comprising the composition (I) of the present invention and the medical device comprising the multilayer body (II) of the present invention include a wide variety of medical devices. Among them, a preferred example is a medical tube. . As a medical tube, for example,
Gastrointestinal catheters (nutrition catheters, gastroesophageal catheters, intestinal catheters, biliary catheters, etc.), respiratory catheters (suction catheters, intratracheal catheters, oxygen administration catheters, solaric catheters, etc.), urinary catheters (Indwelling bladder catheter, urinary catheter, nephrostomy catheter, transurethral balloon catheter, ureteral stent J-type catheter, etc.), vascular catheter (arteriovenous indwelling catheter, open heart catheter, endovascular diagnosis) Catheter, heart catheter, etc.), vascular dilatation catheter, suction beak,
Indwelling infusion catheter, indwelling drainage catheter,
Examples include a balloon catheter, a blood tube, and an infusion tube. These include a catheter having a balloon, and the balloon member can also be formed from a medical device comprising the composition (I) of the present invention and the multilayer body (II) of the present invention. Further, the medical device comprising the composition (I) of the present invention and the medical device comprising the multilayer body (II) of the present invention also include a medical sheet / film, an infusion bag and the like.

The medical device comprising the composition (I) of the present invention and the medical device comprising the multilayer body (II) of the present invention have not only an appropriate flexibility but also good blood compatibility.
For example, in the case of a catheter having a blood contact site, adhesion of blood components such as platelets and fibrin can be suppressed to a low level even when the catheter is placed in a vein for one week. Further, since the medical device of the present invention has high heat resistance and withstands autoclave sterilization, the adoption of this sterilization method eliminates the problem of residual ethylene oxide gas. Furthermore, since the medical device of the present invention is excellent in gas barrier properties and water vapor barrier properties, this advantage is particularly effectively exhibited when used as a catheter having a balloon portion.

[0037]

The present invention will be described more specifically with reference to the following examples.

The number average molecular weight (Mn) and weight average molecular weight / number average molecular weight (Mw / Mn) of the block copolymer obtained in the reference example and used in the examples were determined by GPC (manufactured by Shimadzu Corporation). Further, the polystyrene segment content of the block copolymer was determined by spectral analysis obtained using NMR (manufactured by JEOL Ltd.).

The performance of the composition was evaluated by the following method (1).
To (6).

(1) Flexibility (hardness) Using a composition (molding material for medical device), compression molding is performed at 210 ° C. to produce a sheet having a thickness of 1 mm, and a plurality of the sheets are stacked to obtain a thickness. JIS K
Hardness was measured by a rubber hardness meter (A type) based on 6301. Similarly, a sheet having a thickness of 1 mm was prepared by compression molding at 210 ° C. in the same manner as described above, and a plurality of the sheets were stacked to a thickness of 12 mm or more, and the hardness was measured based on ASTM D. These hardness measurement results were used as an index of the flexibility of the medical device manufactured from the molding material.

(2) Anti-sticking property Using the composition (molding material for medical device), compression molding was performed at 210 ° C. to produce a sheet having a thickness of 1 mm.
The evaluation was made on two levels: “good (）)” (the sticking feeling was low and within a practically acceptable range) and “bad (x)” (the sticking feeling was so strong that it could not withstand practical use). This was used as an index of the anti-sticking property of the medical device manufactured from the molding material.

(3) Mechanical properties A sheet having a thickness of 1 mm was prepared from the composition (molding material for medical device), and a dumbbell-shaped test piece specified in JIS-3 was punched from the sheet. , JIS K6301
A tensile test is performed according to the following formula, and the tensile strength (kgf / cm
² ) and tensile elongation (%) were determined. These were used as indicators of the mechanical properties of the medical device manufactured from the molding material.

(4) Heat resistance (high-pressure steam sterilization durability) A sheet having a thickness of 1 mm was prepared from the composition (molding material for medical devices), and a dumbbell specified in JIS-3 was prepared from this sheet. Specimens were punched out. The test piece was subjected to high-pressure steam sterilization (115 ° C., 30 minutes). JIS K63
01 and a tensile strength (kgf /
cm ² ) and tensile elongation (%) were determined. The smaller the change in the tensile strength and tensile elongation from the value before the high-pressure steam sterilization, the better the heat resistance (high-pressure steam sterilization durability) of the medical device manufactured from the molding material is evaluated. can do.

(5) Oxygen Barrier Property A 200 μm thick film was produced by injection molding using the composition (molding material for medical devices). About this film, a gas permeability measuring device (“GTR-
10 "), oxygen pressure 2.5 kg / cm ² , temperature 3
Oxygen permeability coefficient (PO ₂ ) at 5 ° C. (unit: c)
c · 20 μm / m ² · day · atm). It can be evaluated that the smaller the value of the oxygen permeability coefficient, the better the oxygen barrier properties of the medical device manufactured from the molding material.

(6) Water Vapor Barrier Property The water vapor permeability of the composition (molding material for medical device) was measured by JI
It was measured based on SZ0208. That is, a predetermined amount of a hygroscopic agent (calcium chloride) was put in an aluminum moisture-permeable cup, and a thickness of 20 μm was prepared from the composition by compression molding.
Seal the cup opening with a film of 40 ° C, 90%
By measuring the weight every 24 hours in an atmosphere of RH, the water vapor transmission coefficient of the composition (unit: g · mm / m
² · 24hrs) was determined. It can be evaluated that the smaller the value of the water vapor transmission coefficient, the better the water vapor barrier property of the medical device manufactured from the molding material.

Reference Example 1 In a reactor equipped with a stirrer, methylene chloride 80 dehydrated and purified with molecular sieves 4A was used.
0 ml and 1,200 ml of methylcyclohexane were charged, and 0.97 g (4.2 mmol) of 1,4-bis (1-chloro-1-methylethyl) benzene, 2,6-di-t
1.74 g (9.1 mmol) of -butylpyridine, 0.66 g (8.4 mmol) of pyridine and 210 g of isobutylene were added, and titanium tetrachloride 1 was added at -78 ° C.
2.3 g (65 mmol) was added to start polymerization, and after polymerization for 4 hours, 1.74 g of 2,6-di-t-butylpyridine
(4.7 mmol) and styrene (90 g) were added, and the mixture was further polymerized for 4 hours to obtain a polystyrene-polyisobutylene-polystyrene triblock copolymer (hereinafter, referred to as “block copolymer (1)”). Obtained. The number average molecular weight of the obtained block copolymer (1) was 7,000, Mw / Mn was 1.24, and the polystyrene segment content was 29.5% by weight.

Reference Example 2 In a reactor equipped with a stirrer, methylene chloride 80 dehydrated and purified using molecular sieves 4A was used.
0 ml and 1200 ml of methylcyclohexane were charged, and 1.94 g (8.4 mmol) of 1,4-bis (1-chloro-1-methylethyl) benzene, 0.98 g (9.1 mmol) of 2,6-dimethylpyridine, and pyridine 1 .30 g (16.4 mmol) and isobutylene 2
10 g each, and titanium tetrachloride at -78 ° C.
3 g (65 mmol) was added to start polymerization, and after polymerization for 3 hours, 0.5 g of 2,6-dimethylpyridine (4.7 mm
ol) and 90 g of styrene, and the mixture was further polymerized for 2 hours to give polystyrene-polyisobutylene-
A polystyrene triblock copolymer (hereinafter, referred to as “block copolymer (2)”) was obtained. The number average molecular weight of the obtained block copolymer (2) was 37000, Mw / Mn was 1.25, and the polystyrene segment content was 29.8% by weight.

Example 1 A block copolymer (1) obtained in Reference Example 1 and commercially available polypropylene (MFR: 11
g / 10 minutes (230 ° C., 2.16 kg)) [“MA-
3 "(trade name, manufactured by Mitsubishi Chemical Corporation) with a weight ratio of block copolymer (1) / polypropylene of 80/20.
And kneaded at 210 ° C. with a kneader to obtain a composition. By performing the above-mentioned various measurements on the obtained composition (molding material for medical devices), the flexibility, anti-sticking properties, mechanical properties, heat resistance, oxygen barrier properties and water vapor barrier of the medical devices were evaluated. . Table 1 shows the obtained measurement results.

Example 2 A composition was prepared in the same manner as in Example 1 except that the weight ratio of the block copolymer (1) / polypropylene was changed to 20/80. Various measurements were made on the molding material) to evaluate the flexibility, anti-sticking properties, mechanical properties, heat resistance, oxygen barrier properties and water vapor barrier of the medical device. Table 1 shows the obtained measurement results.

Example 3 The block copolymer (2) obtained in Reference Example 2 and a commercially available polyethylene (MFR: 20 g)
/ 10 minutes (190 ° C., 2.16 kg)) [“Ace Polyethylene HD Showrex F6200V” (trade name),
Manufactured by Showa Denko KK) and a block copolymer (2) /
The polyethylene was blended at a weight ratio of 70/30, and kneaded at 210 ° C. with a kneader to obtain a composition.
By performing the above-mentioned various measurements on the obtained composition (molding material for medical devices), the flexibility, anti-sticking properties, mechanical properties, heat resistance, oxygen barrier properties and water vapor barrier of the medical devices were evaluated. . Table 1 shows the obtained measurement results.

Example 4 A composition was prepared in the same manner as in Example 3 except that the weight ratio of the block copolymer (2) / polyethylene was changed to 30/70. By performing various measurements on molding materials)
Medical device flexibility, anti-sticking properties, mechanical properties, heat resistance,
The oxygen barrier property and the water vapor barrier were evaluated. Table 1 shows the obtained measurement results.

Example 5 The block copolymer (2) obtained in Reference Example 2 and a commercially available ethylene-vinyl alcohol copolymer resin (ethylene content: 44 mol%; MFR: 5.
5 g / 10 min (190 ° C., 2.16 kg)) [“EVAL EP-E105” (trade name), manufactured by Kuraray Co., Ltd.) and a block copolymer (2) / ethylene-vinyl alcohol copolymer The resin was blended at a weight ratio of 80/20 and kneaded at 210 ° C. with a kneader to obtain a composition. By performing the above-described various measurements on the obtained composition (molding material for medical device), the flexibility of the medical device,
The anti-sticking properties, mechanical properties, heat resistance, oxygen barrier properties and water vapor barrier were evaluated. Table 1 shows the obtained measurement results.

Example 6 The weight ratio of the block copolymer (2) / ethylene-vinyl alcohol copolymer resin was set to 50.
A composition was prepared in the same manner as in Example 5 except that the composition was changed to / 50, and various measurements were performed on the composition (molding material for medical devices), whereby the flexibility, anti-sticking property, and mechanical properties of the medical devices were measured. Physical properties, heat resistance, oxygen barrier properties and water vapor barrier were evaluated. Table 1 shows the obtained measurement results.
Shown in

Comparative Example 1 Various measurements were carried out in the same manner as in Example 1 except that the same type of polypropylene as that used in Example 1 was used alone. Table 1 shows the obtained measurement results.

(Comparative Examples 2 to 4) The same type of block copolymer (1) as used in Example 1 and a polystyrene-hydrogenated polyisoprene-polystyrene triblock copolymer [“Septon 2007” (trade name) (Hereinafter, referred to as “block copolymer (A)”) or polystyrene-hydrogenated polyisoprene-polystyrene triblock copolymer [“Hybler 7125”
(Trade name), manufactured by Kuraray Co., Ltd.] (hereinafter referred to as “block copolymer (B)”), and various measurements were performed in the same manner as in Example 1. Table 1 shows the obtained measurement results.

[0056]

[Table 1]

In the column of "thermoplastic resin" in Table 1,
“PP”, “PE” and “EVOH” are “polypropylene”, “polyethylene” and “ethylene-
"Vinyl alcohol copolymer resin".

As is clear from Table 1, the molding materials of the medical device of the present invention in Examples 1 to 6 are flexible, anti-sticking, mechanical physical properties, heat resistance (high pressure steam sterilization durability), oxygen barrier. It has properties suitable for medical devices because of its excellent properties and water vapor barrier flexibility. On the other hand, in the case of the polypropylene alone of Comparative Example 1, the Shore D hardness was 68, indicating that the flexibility was insufficient. It can be seen that the polystyrene-polyisobutylene-polystyrene triblock copolymer alone of Comparative Example 2 lacks anti-sticking properties. In addition, in the case of the polystyrene-hydrogenated polyisoprene-polystyrene triblock copolymers of Comparative Examples 3 and 4, all of them lack heat resistance and have insufficient oxygen barrier properties and water vapor barrier properties. In addition, in the case of the polystyrene-hydrogenated polyisoprene-polystyrene triblock copolymer of Comparative Example 4, it can be seen that the anti-sticking property is still insufficient.

(Examples 7 to 12) The composition obtained in Example 1, the composition obtained in Example 2, the composition obtained in Example 3, the composition obtained in Example 4, The composition obtained in Example 5 or the composition obtained in Example 6 was extruded into a tube by using a single screw extruder at a temperature of 210 ° C., and was extruded into a tube. Intravascular indwelling part outer diameter 0.8 mm) was prepared (Example 7,
8, 9, 10, 11 and 12). This was placed in the jugular vein of a rabbit for 7 days, taken out, fixed with glutaraldehyde and osmium oxide, and the attached thrombus was observed with the naked eye and an electron microscope. As a result, 6% (Example 7), 4% (Example 8), 7% (Example 9), 5% (Example 10), 7% of each catheter surface
Fibrin and platelets adhered to (Example 11) and 8% (Example 12).

Comparative Example 5 A catheter made of soft vinyl chloride (manufactured by Nippon Sherwood; length: 30 cm, outer diameter of the indwelling portion of the blood vessel: 0.8 mm) was placed in the jugular vein of a rabbit for 7 days.
After removal, the cells were fixed with glutaraldehyde and osmium oxide, and the attached thrombus was observed with the naked eye and an electron microscope. As a result, fibrin and platelets were attached to about 30% of the surface of the catheter.

The results of the blood compatibility test on the medical devices (catheters) of the present invention of Examples 7 to 12 were compared with the results of tests on the medical devices (catheters) of Comparative Example 5 other than the present invention. In addition, the molding material of the present invention (the compositions of Examples 1 to 6) that provides the same has a small amount of fibrin and platelets adhered to the surface, and has excellent blood compatibility.

(Examples 13 to 18) The composition obtained in Example 1, the composition obtained in Example 2, the composition obtained in Example 3, the composition obtained in Example 4, Using the composition obtained in Example 5 or the composition obtained in Example 6,
Using a single screw extruder, set the temperature to 210 ° C,
It was extruded into a tube at 0 μm. The tubular material was formed into a desired balloon shape by inflating it in the outer peripheral direction with air in a mold while heating it at 110 ° C. (Examples 13, 14, 15, 16, 17, and 18 respectively). In each case, the formation of the balloon portion was easy.

(Example 19) The composition obtained in Example 5 was disposed in an intermediate layer, and commercially available polypropylene (MFR:
11 g / 10 min (230 ° C., 2.16 kg)) [“MA
-3 "(trade name, manufactured by Mitsubishi Chemical Corporation) is co-extruded to form an inner layer and an outer layer, and the outer layer is 12 mm in diameter, the inner diameter is 8 mm, and the inner layer thickness is 0.05 mm. A three-layer tube having an intermediate layer thickness of 1.9 mm and an outer layer thickness of 0.05 mm was produced. The extrusion temperature of the composition was 210 ° C., and the extrusion temperature of polypropylene was 210 ° C. The obtained tube was transparent and rich in flexibility, and had sufficient physical properties as a medical tube. The resulting three-layer tube had sufficient adhesiveness between the layers, was transparent and flexible, and was practically usable as a medical tube.

Example 20 The composition obtained in Example 5 was disposed in an intermediate layer, and a commercially available polyethylene (MFR: 2
0 g / 10 min (190 ° C., 2.16 kg)) (“Ace Polyethylene HD Showrex F6200V” (trade name), manufactured by Showa Denko KK) so that the composition and polyethylene are arranged on both surface layers. Are co-extruded and molded to a total thickness of 1 mm, a surface layer thickness of 0.05 mm, and an intermediate layer thickness of 0.1 mm.
An 8-mm three-layer sheet was produced. The extrusion temperature of the composition was 210 ° C, and the extrusion temperature of polyethylene was 180 ° C. The resulting three-layer sheet had sufficient adhesiveness between the layers, was transparent and flexible, and was practically usable as a medical sheet or film.

[0065]

Industrial Applicability The medical device and the molding material thereof of the present invention have sufficient flexibility without adding a plasticizer, and have higher safety than a medical device made of a soft vinyl chloride resin. Further, the medical device and the molding material thereof of the present invention have sufficient heat resistance to withstand high-pressure steam sterilization without fear of generating harmful gas by incineration and contaminating the environment, and have blood compatibility. Excellent (antithrombotic).
Further, the medical device and the molding material thereof are excellent in gas barrier properties and water vapor barrier properties. Therefore,
The medical device of the present invention can be particularly preferably used as a medical tube such as an indwelling intravascular catheter and an endotracheal tube.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) B32B 27/32 C08L 23/02 C08L 23/02 23/26 23/26 29/04 C 29/04 53 / 0053/00 A61J 1/00 331A (72) Inventor Nobuyuki Utagawa 1621 Sakurazu, Kurashiki-shi, Okayama Pref. Kuraray Co., Ltd. (72) Inventor Yukihiro Fujieda 1621 Sakurazu, Kurashiki-shi, Okayama Pref. Reference) 4C081 AB32 AC08 BA02 BA04 BB02 BB03 BB07 BB08 BC02 BC03 CA022 CA052 CA121 CB051 CC01 CC02 DA03 DC03 DC04 DC12 EA03 4F100 AK03A AK04A AK04J AK07A BB08A02J03 BB08X BB12X BB14X BB15X BB22X BB23X BE03X BP02X BP03W FD010 FD020 FD030 GB01 GF00

Claims (3)

[Claims] 1. A molding material for a medical device, comprising: a block copolymer (a) containing an isobutylene-based polymer segment and a vinyl aromatic compound-based polymer segment; and (b-1) a polyolefin-based resin; (B-2) at least one thermoplastic resin (b) selected from the group consisting of ethylene-vinyl alcohol copolymer resins,
A molding material comprising a composition containing (a) / (b) in a weight ratio of 10/90 to 95/5. 2. A block copolymer (a) containing an isobutylene polymer segment and a vinyl aromatic compound polymer segment, (b-1) a polyolefin resin, and (b-2) ethylene-vinyl alcohol At least one thermoplastic resin (b) selected from the group consisting of copolymer resins,
A medical device comprising a composition containing (a) / (b) in a weight ratio of 10/90 to 95/5. 3. A medical device comprising a multilayer having at least one layer containing a block copolymer containing an isobutylene-based polymer segment and a vinyl aromatic compound-based polymer segment.