JPH05317411A - Medical equipment material - Google Patents

Abstract

PURPOSE:To eliminate elusion of impurities and adsorption of chemical components without deformation even subjected to sterilization by molding medical equipment material using a thermoplastic norbornene based resin excellent in heat resistance, low absortivity and low elusion property. CONSTITUTION:Medical equipment material is formed using a thermoplastic norbornene resin with 10.000-200.000 in average molecular weight on a polystyrene conversion basis and with less than 1wt.% in the content of a resin component of below 2.000 by a gel permeation chromatography analysis with toluene as solvent. The available method for molding is an injection molding, a blow molding method, an injection blow molding method, rotary molding method or the like. An example of the medical equipment material to be molded is a medical fluid container for injection, an ampule, a prefield syringe, a bag for transfusion or a solid chemical container. The medical equipment material thus obtained is excellent in heat resistance, moisture resistance and transparency and adsorption of chemicals and exudation of organic matters or the like are limited thereby eliminating the denaturalizing of any chemicals contacting it.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical device, and more particularly, to a medical device that does not deteriorate a drug that comes into contact therewith.

[0002]

2. Description of the Related Art Recently, medical devices are being replaced with disposable devices in order to prevent the secondary infection of viruses by repeated use. Further, for example, injectable drugs have also been used by suctioning with a syringe from a sterilized ampoule at the time of injection, but recently, a prefilled syringe in which the injectable drug has been previously inhaled in a syringe is distributed, After the injection, the syringe was discarded.

[0003] In medical chemical containers, it is necessary to have a certain level of transparency so that the contents can be easily seen. Conventionally, glass, polyethylene, polypropylene,
Polyvinyl chloride is used. However, the glass sometimes breaks, is heavy, and sometimes alkali ions and the like are eluted. In addition, it is sometimes difficult to dispose of it because it is difficult to burn it, or it is dangerous to dispose of debris. Polyethylene and polypropylene have poor heat resistance and cannot be steam sterilized.
The low-molecular organic components were sometimes eluted. Further, polyvinyl chloride is inferior in heat resistance, and chlorine may be eluted to alter the contents.

[0004]

DISCLOSURE OF THE INVENTION As a result of earnest research, the inventors of the present invention have found that a medical molded article made of a thermoplastic norbornene resin does not deform even when sterilized and does not elute impurities or adsorb chemical components. The present invention has been completed and the present invention has been completed.

[0005]

Thus, according to the present invention, there is provided a medical device comprising a thermoplastic norbornene-based resin, which does not deform even when sterilized and does not change the chemicals that come into contact due to elution of impurities or adsorption of chemical components. It

(Thermoplastic Norbornene Resin) The thermoplastic norbornene resin of the present invention is disclosed in JP-A-3-14882.
JP-A-3-122137, JP-A-4-63807
Known resins, such as ring-opening polymers of norbornene-based monomers, hydrogenated products thereof, addition-type polymers of norbornene-based monomers, addition of norbornene-based monomers and olefins. Type polymers and the like.

The norbornene-based monomer is also a monomer known in the above publications, JP-A-2-227424 and JP-A-2-276842, and examples thereof include norbornene, its alkyl, alkylidene and aromatic substituted derivatives. And halogens, hydroxyl groups of these substituted or unsubstituted olefins,
Polar group substituents such as ester group, alkoxy group, cyano group, amide group, imide group and silyl group, for example, 2-norbornene, 5-methyl-2-norbornene, 5,5-dimethyl-2-norbornene, 5- Ethyl-2-norbornene, 5-butyl-2-norbornene, 5-ethylidene-
2-norbornene, 5-methoxycarbonyl-2-norbornene, 5-cyano-2-norbornene, 5-methyl-5-methoxycarbonyl-2-norbornene, 5-phenyl-2-norbornene, 5-phenyl-5-methyl- 2-norbornene, 5-hexyl-2-norbornene, 5-octyl-2-norbornene, 5-octadecyl 2-norbornene, etc .; a monomer in which one or more cyclopentadiene is added to norbornene, a derivative similar to the above Substitutes, for example 1,4: 5,8-dimethano-
1,2,3,4,4a, 5,8,8a-2,3-cyclopentadienonaphthalene, 6-methyl-1,4: 5,8
-Dimethano-1,4,4a, 5,6,7,8,8a-octahydronaphthalene, 1,4: 5,10: 6,9-trimethano-1,2,3,4,4a, 5,5a , 6, 9,
9a, 10,10a-dodecahydro-2,3-cyclopentadienoanthracene, etc .; a polycyclic monomer that is a multimer of cyclopentadiene, a derivative or substituent similar to the above, for example, dicyclopentadiene, 2,3-dihydrodicyclopentadiene and the like; adducts of cyclopentadiene and tetrahydroindene and the like, derivatives and substitution products similar to the above, for example, 1,4-methano-1,4,4
a, 4b, 5,8,8a, 9a-octahydrofluorene, 5,8-methano-1,2,3,4,4a, 5,8,
8a-octahydro-2,3-cyclopentadienonaphthalene and the like; and the like.

In the present invention, when the norbornene-based monomer is polymerized, other copolymerizable cycloolefins and the like can be used in combination within a range that does not substantially impair the effects of the present invention. Can be Specific examples of the copolymerizable cycloolefin in the case of ring-opening polymerization include, for example, cyclopentene, cyclooctene, 5,6.
Examples thereof include compounds having one or more reactive double bonds such as dihydrodicyclopentadiene.

The polymerization of the norbornene type monomer may be carried out by a known method. Generally, TiCl ₄ , WC is used as a polymerization catalyst.
Polymerization is carried out by combining a transition metal compound such as l ₆ , MoCl ₅ , VCl ₅ , NiCl ₂ and PdCl _{2 with} an alkyl compound of a typical metal such as Al, Li, Na and Mg.
If necessary, a known method such as Ni or Pd may be used.
By hydrogenating the above as a catalyst, a hydrogenated product of a thermoplastic norbornene resin can be obtained.

In the conventionally known polymerization method, the transition metal derived from the polymerization catalyst remains in the polymer. Medical equipment
Upon contact with a living body or a drug, it is not preferable that the remaining transition metal elutes, and it is preferable that the transition metal does not substantially remain in the medical device. As a method for obtaining such a polymer, the pore volume is 0.5 cm ³ / g or more, preferably 0.1.
Hydrogenation of the polymer using a heterogeneous catalyst in which a hydrogenation catalyst metal such as nickel is carried on an adsorbent such as alumina having a specific surface area of 7 cm ³ / g or more, preferably 250 m ² / g or more, The transition atom derived from the polymerization catalyst can be reduced to 1 ppm or less by treating the resin solution with such an adsorbent to adsorb metal atoms or repeatedly washing the resin solution with acidic water and pure water. ..

The method for producing the heterogeneous catalyst may be carried out according to a known method, such as JP-B-50-15474 and JP-B-49-3.
No. 2187, Japanese Patent Publication No. 49-11312, Japanese Patent Publication No. 51-
According to No. 48479, etc., depending on the conditions of drying and firing,
The adsorption capacity of the carrier may be controlled. For example, in the case of a heterogeneous catalyst in which nickel is supported on activated alumina, the concentration is 10
Aluminum hydroxide powder is suspended in a 20% nickel sulfate or nickel nitrate aqueous solution at a concentration of 10 to 20% and hydrolyzed with sodium hydroxide to support nickel hydroxide on the surface of aluminum hydroxide. This powder is collected by filtration and extruded to harden,
Calcination at 450 ° C, contact with hydrogen at 100-200 ° C to reduce the surface, and 80-120 ° C in the presence of oxygen.
By heating the metal surface to oxidize it to form an oxide film, a nickel catalyst supported on activated alumina can be obtained. Although the surface of nickel is covered with nickel oxide, the nickel oxide becomes nickel by reduction in the hydrogenation reaction system and functions as a catalyst.

[0012] Extrusion conditions, the temperature and pressure, etc. of the firing, since the fine structure of the activated alumina is changed, the pore volume of 0.5 cm ³ / g or more, preferably 0.7 cm ³ / g or more, preferably The conditions are selected so that the specific surface area is 250 m ² / g or more. In addition, when hydrogenation is performed at a high temperature, the thicker the oxide film is, the more heat resistant it is. Therefore, the temperature, time, oxygen concentration, etc. of the oxidation may be adjusted to select preferable conditions. The fired product thus obtained may be crushed to obtain a heterogeneous catalyst.

When a transition metal chloride is used as a transition metal compound of a general polymerization catalyst, the chlorine atom is usually 2
Remains above ppm. It is preferable that chlorine atoms also do not remain in medical devices like transition metal atoms,
It is preferable to remove. As a method for removing, transition metal atoms can be removed by the same treatment, and the residual amount can be reduced to 1 ppm or less.

The glass transition temperature of the thermoplastic norbornene resin used in the present invention is preferably 105 ° C. or higher,
More preferably 120 ° C or higher, particularly preferably 130 ° C
That is all. Some sterilization methods do not require heating, such as γ-ray irradiation, but the simplest sterilization methods are methods that require heating, particularly boiling and steam sterilization. In sterilization by boiling, there is no problem if the glass transition temperature of the thermoplastic norbornene-based resin is 105 ° C. or higher, but in steam sterilization, the required heat resistance differs depending on the temperature setting during sterilization. The most common steam sterilization is the method at 121 ° C using an autoclave. In order to prevent deformation by steam sterilization, a glass transition temperature of 130 ° C. or higher is preferable. In general,
The glass transition temperature of the thermoplastic norbornene-based resin increases as the number of monomers having a large number of rings is used. For example, a hydrogenated product of a ring-opening polymer of ethyl tetracyclododecene, which is a tetracyclic compound, usually has a temperature of 130 ° C or higher. However, in the case of hydrogenated norbornene ring-opening polymer, which is a bicyclic compound, it is usually 30
It is about ℃. On the other hand, the glass transition temperature of the addition type polymer of norbornene is 300 ° C. or higher, and measurement may not be possible in some cases. If the glass transition temperature is too high, injection molding may be difficult. Therefore, a monomer or comonomer may be selected to produce a thermoplastic thermoplastic norbornene-based resin having a glass transition temperature according to the purpose.

The number average molecular weight of the thermoplastic norbornene resin used in the present invention is 10,000 to 200,000 in terms of polystyrene measured by GPC (gel permeation chromatography) method using a toluene solvent.
It is 0, preferably 20,000 to 100,000, more preferably 25,000 to 50,000. If the number average molecular weight is too small, the mechanical strength will be poor, and if it is too large, the moldability will be poor. The content of the resin component having a polystyrene reduced molecular weight of 2,000 or less by a high performance liquid chromatography analysis using toluene as a solvent in the thermoplastic norbornene resin is 1% by weight or less, preferably 0.5% or less. When the amount of the low molecular weight component is large, the medical device may be eluted by contact with a living body or a drug.

When the thermoplastic norbornene-based resin is hydrogenated, the hydrogenation rate is 90% or more, preferably 95% or more, and more preferably 99% or more from the viewpoint of heat deterioration resistance and light deterioration resistance. To do.

(Compounding agent) The thermoplastic norbornene-based resin is substantially free from changes in shape such as deformation by steam sterilization treatment which is often used for medical equipment, but it is turbid and transparent depending on treatment conditions. May deteriorate. In order to prevent this, it is preferable to add a compounding agent that is incompatible with the thermoplastic norbornene-based resin and use it as a resin composition. An organic compound or an inorganic filler may be used as long as it can be finely dispersed until transparency is exhibited.

The inorganic filler has an average particle size of 1 μm.
The following is particularly preferable to be 0.5 μm or less, and more preferably 0.2 μm or less. Further, it is preferably transparent and water-insoluble. For example, silica, alumina, glass, etc. made into ultrafine powder having the above particle size can be mentioned.

The organic compound is preferably a high molecular compound which does not easily change the drug by being dissolved in the drug which comes into contact with the medical device of the present invention, and has a glass transition temperature of 40 for fine dispersion. A rubbery polymer having a temperature of ℃ or less is preferable. Note that the block copolymerized rubbery polymer or the like may have two or more glass transition temperatures. In that case, the lowest glass transition temperature may be 40 ° C. or lower.

Examples of the polymer compound used as a compounding agent include emulsion- or solution-polymerized styrene-butadiene rubber, random or block styrene-butadiene copolymer such as high styrene rubber, and hydrogenated products thereof. Isoprene rubber, hydrogenated product thereof; chloroprene rubber, hydrogenated product thereof; saturated polyolefin rubber such as ethylene / propylene copolymer, ethylene / α-olefin copolymer, propylene / α-olefin copolymer; ethylene / Propylene / diene copolymer, α-
Diene-based polymers such as olefin / diene copolymers, diene copolymers, isobutylene / isoprene copolymers, isobutylene / diene copolymers, halides thereof,
Hydrogenated products of diene polymers or their halides;
Acrylonitrile / butadiene copolymer, hydrogenated product thereof; vinylidene fluoride / trifluoroethylene copolymer, vinylidene fluoride / hexafluoropropylene copolymer, vinylidene fluoride / propylene hexafluoride / tetrafluoroethylene copolymer Fluorine rubbers such as polymers and propylene / tetrafluoroethylene copolymers; special urethane rubber, silicone rubber, polyether rubber, acrylic rubber, chlorosulfonated polyethylene rubber, epichlorohydrin rubber, propylene oxide rubber, ethylene acrylic rubber, etc. Rubber; copolymer of norbornene-based monomer and ethylene or α-olefin, terpolymer of norbornene-based monomer and ethylene and α-olefin, ring-opening polymer of norbornene-based monomer, norbornene-based monomer Ring-opening polymers of polymers such as hydrogenated products Incompatible with the thermoplastic norbornene-based resin which is the main component of the resinous composition of the humic polymer; styrene / butadiene / styrene / rubber, styrene / isoprene / styrene / rubber, styrene / ethylene / butadiene / styrene / Aromatic vinyl monomers such as rubber
Random copolymers of conjugated dienes, their hydrogenated products;
A linear or radial block copolymer of styrene / butadiene / styrene / rubber, styrene / isoprene / styrene / rubber, styrene / ethylene / butadiene / styrene / rubber aromatic vinyl monomers / conjugated dienes
In addition to styrene-based thermoplastic elastomers such as hydrogenated products thereof, urethane-based thermoplastic elastomers, polyamide-based thermoplastic elastomers, 1,2-polybutadiene-based thermoplastic elastomers, vinyl chloride-based thermoplastic elastomers, fluorine-based thermoplastic elastomers, etc. A thermoplastic elastomer, a rubbery polymer having a glass transition temperature of 20 ° C. or lower, a cyclohexyl group, an isobornyl group,
Tricyclo [4.3.0.1 ^2,5 ] decan-3-yl group, tricyclo [4.3.0.1 ^2,5 ] -7-decene-
Poly (meth) acrylate resin having a cyclic substituent such as 3-yl group; copolymer of styrene and (meth) acrylate such as octyl acrylate, hexyl acrylate butyl acrylate, poly (aminocarbonyltetramethylenecarbonylaminomethylene- Polyamide resins such as 1,3-cyclohexylenemethylene); poly [oxycarbonyl (1,3-phenylene) carbonyloxymethylene (tricyclo [4.3.0.1 ^2,5 ]-
3,8-diyl) methylene] and other polyester resins;
Polybutylene oxide, poly [oxy (2-methyl-
2-hydroxytrimethylene) oxy (1,4-phenylene) isopropylidene (1,4-phenylene)] and other polyether resins; poly [oxycarbonyloxy (2-methyl-1,4-cyclohexylene] isopropylidene ( 3-methyl-1,4-cyclohexylene)] and other polycarbonate resins; polyurethane resins; and other polymeric compounds.

Among these, copolymers of aromatic vinyl monomers and conjugated diene monomers, hydrogenated products thereof,
Also, the norbornene-based rubbery polymer which is incompatible with the thermoplastic norbornene-based resin of the present invention has good dispersibility with the thermoplastic norbornene-based resin and is preferable. The copolymer of the aromatic vinyl-based monomer and the conjugated diene-based monomer may be a block copolymer or a random copolymer. From the viewpoint of weather resistance, it is more preferable that the portion other than the aromatic ring is hydrogenated. Specifically, styrene / butadiene block copolymers, styrene / butadiene / styrene / block copolymers, styrene / isoprene / block copolymers, styrene / isoprene / styrene / block copolymers, and hydrogenated products thereof. , Styrene / butadiene / random copolymer and the like.

Further, when the resin of the present invention is molded into a chemical container, it is necessary that the resin be transparent enough to confirm the amount and state of the contents. For that purpose, it is preferable that the compounding agent has a small difference in refractive index from the thermoplastic norbornene-based resin to which the compounding agent is added. When a mixture having a large difference in refractive index is mixed, it becomes opaque so that the amount of the content becomes invisible when added in a large amount. On the other hand, if the amount is too small, turbidity prevention in steam sterilization becomes insufficient.

When a compounding agent is added to the thermoplastic norbornene resin, the transparency generally decreases, but the transparency varies depending on the resin, the compounding agent, and the compounding ratio, and when molded to a thickness of 1 mm, a wavelength range of 450 to 700 nm is obtained. The light transmittance in the range is usually 40% or more, preferably 50% or more, more preferably 60% or more. In the case where the compounding agent forms and is dispersed as microdomene, 0.3 μm or less, particularly 0.
If the microdomains of 2 μm or less are formed, the compounding agent has a diameter smaller than the wavelength of visible light, and light is less likely to scatter, so that the transparency is excellent.

Further, the smaller the difference in refractive index between the compounding agent and the thermoplastic norbornene-based resin, the more excellent the transparency is. When the compounding amount is 5% by weight to 0.5% by weight, preferably 0.2 or less,
More preferably 0.1 or less, particularly preferably 0.05 or less, particularly preferably 0.02 or less, and the compounding amount is 0.1.
If it is less than 5% by weight, it is 0.3 or less, more preferably 0.2.
The ratio is particularly preferably 0.1 or less, particularly preferably 0.05 or less.

Different types of thermoplastic norbornene resins have different refractive indices. For example, in rubbery polymers, the ratio of monomers may be changed, or the number of unsaturated bonds in the main chain may be changed by hydrogenation or the like. With, it is possible to continuously change the refractive index. It is preferable to select a rubbery polymer having an appropriate refractive index according to the refractive index of the thermoplastic norbornene-based resin used.

(Compounding) In the present invention, the thermoplastic norbornene resin is 90 to 99.99% by weight, preferably 95.
To 99.98% by weight, more preferably 99 to 99.95.
% By weight, particularly preferably 99.5 to 99.9% by weight, and 10 to 0.01% by weight of the compounding agent, preferably 5 to 0.02% by weight, more preferably 1 to 0.05% by weight, particularly preferably 0.5 to 0.1% by weight is added and dispersed in a thermoplastic norbornene resin. If the amount added is too large, the transparency, glass transition temperature, and heat resistance of the resin will decrease. If the amount added is too small, the effect of compounding the compounding agent cannot be obtained.

The addition method is not particularly limited as long as the compounding agent is a method in which the compounding agent is sufficiently dispersed in the thermoplastic norbornene resin. For example, when a rubbery polymer is used as a compounding agent, a method of kneading the resin temperature in a molten state with a mixer, a biaxial kneader, or the like, a coagulation method of dissolving and dispersing in a suitable solvent,
There is a method of removing the solvent by a casting method or a direct drying method.

When kneading, the resin temperature is Tg + 50.
Sufficient shearing is applied at a temperature of ℃ to Tg + 150 ℃.
If the resin temperature is too low, the viscosity will be high, making it difficult to knead. If the resin temperature is too high, the resin and the rubbery polymer will be deteriorated, and the two cannot be kneaded well due to the difference in viscosity and melting point.

When the type and amount of the compounding agent are adjusted, the resin becomes transparent to the extent that the amount of the content can be confirmed when the resin is molded into a chemical container. In order to improve transparency, it is preferable that the compounding agent becomes a micro domain and is dispersed in the thermoplastic norbornene-based resin. In the case of organic compounds,
If the compounding amount is large, it may not be a microdomain, but for example, in the case of a rubbery polymer, it is 0.8 to 0.01.
A micro domain can be obtained by adding the composition in a weight percentage. Further, when the compounding amount is small or when the compounding agent is not added, steam sterilization by an autoclave or the like may cause the resin to become cloudy and lose transparency.

For example, Labo Plastomill (made by Toyo Seiki)
When using, the number of rotations is 20
When the kneading is carried out at a feed rate of about 30 rpm and a residence time of about 1 to 10 minutes, a rubbery polymer usually forms microdomains having a diameter of 0.3 μm or less in a thermoplastic norbornene resin. Can be dispersed. Usually, in a twin-screw kneader, L / D is 25 or more,
It is preferably 30 or more and the residence time is about 1 to 10 minutes. The longer the residence time, the easier it is to form microdomains, but since the resin or rubbery polymer is likely to deteriorate, the resin to be used, the rubbery polymer, and the combination of the devices used for kneading, preliminary kneading, It is necessary to decide the number of rotations and the residence time that match the combination.

When the rubbery polymer is used as a compounding agent, the microdomains have a substantially spherical shape, and the variation in particle size among particles is small. Usually, the diameter is 0.3 μm or less, preferably 0.2 μm or less. With this particle size, as will be described later, the decrease in transparency of the thermoplastic norbornene-based resin composition due to the addition of the rubbery polymer is small, and there is no problem. Also in the case of other compounding agents, it is preferable that the microdomains have a substantially spherical shape, and that there is no variation in particle diameter between particles, and the diameter is 0.3 μm or less, particularly 0.2 μm.
The following is preferable. Even if the micro domain is not spherical, it is preferable that the smallest sphere capable of confining the micro domain has a diameter of 0.3 μm or less, particularly 0.2 μm or less.

(Additives) If desired, various additives may be added to the thermoplastic norbornene-based resin used in the present invention. The additives used in the resin are those that are compatible with the resin, such as phenol-based and phosphorus-based antioxidants,
Antistatic agents, UV absorbers, lubricants, etc. When a sheet is formed by the solution casting method, addition of a leveling agent is also preferable in order to reduce the surface roughness. As the leveling agent, for example, a fluorine-based nonionic surfactant, a special acrylic resin-based leveling agent, a silicone-based leveling agent such as a coating leveling agent can be used, and among them, those having good compatibility with a solvent are preferable. However, since these may be eluted from the resin, it is preferable that the additive has a large molecular weight, and the addition amount is small.

For example, the antioxidant has a relatively small molecular weight and is easily eluted, but the molecular weight is 600 or more, preferably 7
If the antioxidant is 00 or more, elution can be prevented,
3000 ppm or less, preferably 1000 ppm or less,
More preferably, if it is added in an amount of 500 ppm or less, the antioxidant hardly elutes.

As the antioxidant having a molecular weight of 600 or more,
Pentaerythrityl-tetrakis [3- (3,5-di-
t-butyl-4-hydroxyphenyl) propionate], 1,3,5-trimethyl-2,4,6-tris (3,5-di-t-butyl-4-hydroxybenzyl)
Benzene, tris (3,5-di-t-butyl-4-hydroxybenzyl) isocyanurate, 3,9-bis [1,1-dimethyl-2- [β- (3-t-butyl-4)
-Hydroxy-5-methylphenyl) propionyloxy] ethyl] -2,4,8,10-tetraoxaspiro [5.5] undecane, 1,6-hexanediol-bis [3- (3,5-di- t-butyl-4-hydroxyphenyl) propionate], 2,2-thio-diethylenebis [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionate], N, N′-hexamethylenebis (3,5-di-t-butyl-4-hydroxy-hydrocinnamide), 1- [2- [3- (3,5-di-
t-butyl-4-hydroxyphenyl) propionyloxy] ethyl] -4- [3- (3,5-di-t-butyl-4-hydroxyphenyl) propionyloxy]-
2,2,6,6-tetramethylpiperidine and the like can be mentioned.

In order to prevent the occurrence of turbidity during steam sterilization, the thermoplastic norbornene-based resin contains a partial etherified product and / or a partial esterified product of a polyhydric alcohol in an amount of 5 to 0.01% by weight, preferably 2 to 0. 0.05% by weight,
Particularly preferably, 1.0 to 0.1% by weight may be added. Addition can prevent the occurrence of turbidity during steam sterilization, as in the case of adding the compounding agent.

Examples of the partially esterified product obtained by esterifying a part of the alcoholic hydroxyl group of the polyhydric alcohol include glycerin monostearate, glycerin monolaurate, glycerin monobehenate and diester known in JP-A-63-275654. Glycerin monostearate, glycerin distearate, glycerin dilaurate, pentaerythritol monostearate, pentaerythritol monolaurate, pentaerythritol monobeherate, pentaerythritol distearate, pentaerythritol dilaurate, pentaerythritol tristearate, dipentaerythritol Examples include distearate.

Examples of the partially etherified product obtained by etherifying a part of the alcoholic hydroxyl group of the polyhydric alcohol include 3- (octyloxy) -1,2-propanediol and 3- (decyloxy) -1,2-propane. Diol, 3- (lauryloxy) -1,2-propanediol, 3- (4-nonylphenyloxy) -1,2-propanediol, 1,6-dihydroxy-2,2-di (hydroxymethyl)- 7- (4-nonylphenyloxy) -4-oxoheptane, ether compound obtained by reaction of condensate of p-nonylphenol and formaldehyde and glycidol, ether compound obtained by reaction of condensate of p-octylphenol and formaldehyde and glycidol Of p-octylphenol and dicyclopentadiene And ether compounds obtained by the reaction of glycidol and the like. Among these, those having a molecular weight of 500 to 2000, particularly 800 to 1500 are preferable. When using additives with low molecular weight,
When the addition amount is large, it is preferable to add a small amount of one having a large molecular weight because it is easily eluted. If the amount added is small,
The effect of preventing turbidity due to steam sterilization is small.

(Molding) The method for molding the thermoplastic norbornene resin of the present invention is not particularly limited. Depending on the purpose, an injection molding method, a blow molding method, an injection blow molding method, a rotational molding method, a vacuum molding method, an extrusion molding method, a calender molding method, a solution casting method and the like are possible.

The heat resistance, chemical resistance, dielectric properties and rigidity of the molded product of the thermoplastic norbornene resin when the compounding agent of the present invention is blended are substantially the same as those of the molded product of the thermoplastic norbornene polymer which is not added. Is.

Further, the thermoplastic norbornene-based resin of the present invention absorbs little chemicals. In particular, there is little adsorption of compounds having polar groups such as alcohols, amines, esters, amides, ethers, carboxylic acids, and amino acids, and the thermoplastic norbornene-based resin of the present invention exudes organic substances and the like. Since it does not occur, the chemicals that come into contact do not deteriorate.

(Medical Equipment) The medical equipment of the present invention includes, for example, liquid medicine containers for injection, ampoules, prefilled syringes, infusion bags, solid medicine containers, eye drop containers, drip solution containers, and the like. Powder or solid chemical container; food container; sample container such as sampling test tube for blood test, blood collection tube, sample container; sterilization container such as medical material such as scalpel, forceps, gauze and contact lens;
Medical equipment such as syringes; laboratory equipment such as beakers, petri dishes, flasks; optical parts such as plastic lenses for medical examinations; medical infusion tubes, piping, joints, valves and other piping materials; denture bases, artificial hearts, artificial roots, etc. Artificial organs and their parts; In particular, in the case of drug bottles, prefilled syringes, sealed drug bags, eye drop containers, ampoules, vials, drip drug containers, etc. that store drugs, especially liquid drugs, for a long period of time, compare with conventional resin products. In addition to transparency and physical properties, there are no impurities, etc. eluting from the resin, and since it does not adsorb chemicals, it has the favorable property that the quality of chemicals is small.

[0042]

EXAMPLES The present invention will be described more specifically below with reference to Reference Examples, Examples, and Comparative Examples.

Reference Example 1 20 parts by weight of ethyltetracyclododecene, 200 parts by weight of cyclohexane, and 2.0 parts of 1-hexene under nitrogen substitution.
Parts by weight, 15 parts by weight of a triethylaluminum 15% by weight toluene solution and 5.0 parts by weight of triethylamine are added, and the mixture is kept at 20 ° C. and stirred with 80 parts by weight of ethyltetracyclododecene and a 20% by weight titanium tetrachloride toluene solution 9 0.0 parts by weight was added continuously over 60 minutes. Then, after reacting for 1 hour, 5.0 parts by weight of ethyl alcohol and 2.0 parts by weight of water were added to stop the reaction. After the reaction solution was heated to 40 ° C. to hydrolyze the catalyst, 3 parts by weight of calcium sulfate and 6 parts of cyclohexane were used.
0 parts by weight was added to remove excess water. The deposited metal-containing precipitate was removed by filtration to obtain 371 parts by weight of a transparent polymer solution containing an ethyltetracyclododecene ring-opening polymer.

Reference Example 2 750 parts by weight of a polymer solution obtained by repeating Reference Example 1 was mixed with 1 part of Ni-diatomaceous earth catalyst (N113, manufactured by JGC Chemical Co., Ltd.).
5 parts by weight was added, placed in a pressure resistant reactor, hydrogen was introduced, and a hydrogenation reaction was carried out at a pressure of 50 kg / cm ² and a temperature of 200 ° C. for 3 hours. After completion of the reaction, cyclohexane 700
1 part by weight was added for dilution, the catalyst was removed by filtration, and a solution of ethyl tetracyclododecene ring-opening polymer hydrogenated product 13
50 parts by weight were obtained.

550 parts by weight of this solution was poured into 1500 parts by weight of isoproyl alcohol with stirring to coagulate the hydrogenated product of the ring-opening polymer. The solidified ring-opening polymer hydrogenated product was collected by filtration, and isopropyl alcohol 300
After washing twice with parts by weight, 5to in a rotary vacuum dryer
It was dried at rr and 120 ° C. for 48 hours to obtain 52 parts by weight of a hydrogenated product of an ethyltetracyclododecene ring-opening polymer.

This ring-opening polymer hydrogenated product had a number average molecular weight of 28,000 and a weight average molecular weight of 5 in terms of polystyrene by gel permeation chromatography.
8,000, hydrogenation rate 99.8% or more, glass transition temperature 142 ° C., molecular weight 2,000 by finger scanning calorimetry
The content of the following resin components was 0.1%.

A 10% by weight solution of the hydrogenated product of the ring-opening polymer in cyclohexane was analyzed by atomic absorption spectrometry. As a result, the atomic weight of titanium in the hydrogenated product of the ring-opening polymer was 4 ppm, the atomic weight of nickel was 1.8 ppm, and the atomic weight of aluminum was 2 ppm. ．
It was 21 ppm. In addition, 100 mg of this hydrogenated product of a ring-opening polymer was burned in a Dorman combustion device, absorbed in 5 ml of pure water, and analyzed by ion chromatography. As a result, the amount of chlorine atoms was 2.7 ppm.

Reference Example 3 800 parts by weight of a 97% by weight solution of the ring-opening polymer hydrogenated product obtained in Reference Example 2 in cyclohexane was charged with 4.5 parts by weight of activated alumina (Neo-Bead D, manufactured by Mizusawa Chemical Co., Ltd.), and an inner diameter of 10c.
It was passed through a column having a length of m and a length of 100 cm for a residence time of 100 seconds and circulated for 24 hours. The hydrogenated product of the ring-opening polymer was solidified by pouring into 2500 parts by weight of isopropyl alcohol while stirring. The solidified ring-opened polymer hydrogenated product was collected by filtration, and isopropyl alcohol 43
After washing twice with 0 parts by weight, 5 t in a rotary vacuum dryer
After drying at 120 ° C. for 48 hours, 78 parts by weight of a hydrogenated product of an ethyl tetracyclododecene ring-opening polymer was obtained.

The hydrogenated product of this ring-opening polymer showed no difference in molecular weight and glass transition temperature from those of Reference Example 2, but the titanium atomic weight was 1 ppm (detection limit) or less, and the nickel atomic weight was 0.1 ppm ( Below detection limit), aluminum atomic weight 0.21ppm, chlorine atomic weight 0.37p
It was pm.

REFERENCE EXAMPLE 4 Ring-opening polymer of ethyl tetracyclododecene obtained in Reference Example 3 99.8 parts by weight of a rubber-like polymer (Tuftec H1052 manufactured by Asahi Kasei Corporation, glass transition temperature 0 ° C. or lower)
0.2 parts by weight, 0.05 parts by weight of an antioxidant, Irganox 1010 manufactured by Ciba-Geigy Co., Ltd. were added, and a twin-screw kneader (TEM-35B manufactured by Toshiba Machine Co., Ltd., screw diameter 37 m) was added.
m, L / D = 32, screw rotation speed 250 rpm, resin temperature 265 ° C., feed rate 10 kg / hour), and extruded into pellets.

Example 1 Using the pellets obtained in Reference Example 4, injection molding (molding pressure 350 tons, resin temperature 280 ° C., mold temperature 100 ° C.),
A cylindrical transparent container with a diameter of 200 mm, a height of 130 mm and an average thickness of 3 mm and 100 mm x 50 mm x 2.0 mm.
About 10 test pieces were prepared.

When the total light transmittance of the test piece was measured, it was 9
The transparency was good at 0.2%, and the turbidity was measured and found to be 0.1%. LB in the molded container
Medium (1 wt% bactotryptone, 0.5 wt% yeast extract, 1 wt% NaCl, glucose 0.
300 ml of 1% by weight aqueous solution was adjusted to pH 7.5), 6 g of agar, and one piece of a test piece was put therein, capped with aluminum foil, and steam sterilized at 121 ° C. for 30 minutes.

After the treatment, the temperature was kept at 37 ° C. for 3 days, but no fungal growth was observed.

The transparent container after the treatment had a good appearance, and no turbidity, cracking, or deformation due to heat was visually confirmed. The turbidity measured after removing the LB medium solidified by agar from the test piece taken out from the container was 0.27%, and the total light transmittance was 89.7%.

Further, the test piece was immersed in an aqueous sodium carbonate solution having a pH of 9, a hydrochloric acid having a pH of 4, and ethanol for 48 hours, and then the appearance was observed, but no change was observed, and neither turbidity nor total light transmittance was changed.

Distilled water (200 g) was put into a hard glass flask, covered with a hard glass lid, steam sterilized at 120 ° C. for 1 hour, cooled to room temperature, and allowed to stand for 24 hours to collect distilled water. did.

Further, the test piece was ultrasonically cleaned in distilled water for 20 minutes and then dried at 40 ° C. for 10 hours. This test piece was cut into 10 mm width, 20 g was put into a hard glass flask, and 200 g of distilled water was added. With a lid made of hard glass, steam sterilization was carried out at 120 ° C. for 1 hour, and after cooling to room temperature, it was left standing for 24 hours to collect distilled water.

From the difference in the analysis results by the atomic absorption method of these two kinds of distilled water, the ion chromatography, the combustion-nondispersion infrared gas analysis method, etc., the elution amount from the test piece was obtained. 0.1 ppm (detection limit)
Below, the elution amount of nickel atoms is 0.01 ppm (detection limit) or less, and the elution amount of aluminum atoms is 0.01 ppm
(Detection limit) or less, chlorine atom elution amount was 0.02 ppm (detection limit) or less, and total organic carbon amount was 2 ppm (detection limit) or less.

The test piece was subjected to an eluate test according to the 12th revision of the Japanese Pharmacopoeia “Plastic Test Method for Infusion Solution”. Effervescence disappeared within 3 minutes, pH difference was -0.03, UV absorption was 0.007, potassium permanganate reducing substance was 0.1.
It was 15 ml and was found to have characteristics suitable for medical use.

Example 2 The hydrogenated product of the ring-opening polymer of Reference Example 3 was pelletized and molded in the same manner as in Example 1 without adding the rubbery polymer and the antioxidant.

The total light transmittance of the test piece after molding was 90.8.
%, The transparency was good, and the measured turbidity was 0.06%.

2% by weight of agar was added to the LB medium to obtain 12
Sterilize by steam sterilization at 1 ° C for 30 minutes to gel it, and put 300 ml of it into a molded container before solidifying, and let it stand at room temperature for 6 minutes.
After leaving for a while, cap with aluminum foil and gamma ray 25k
It was sterilized by irradiation with Gy.

After the treatment, the temperature was kept at 37 ° C. for 3 days, but no fungal growth was observed.

The transparent container after the treatment had a good appearance, and no turbidity, cracking, or deformation was visually confirmed. The turbidity and total light transmittance measured after removing the LB medium solidified by agar from the test piece taken out of the container showed no change compared with those before the treatment.

Also, as in Example 1, no change due to immersion in each liquid was observed, the titanium atom elution amount measured in the same manner as in Example 1 was 0.1 ppm (detection limit) or less, and the nickel atom elution amount was 0.01 ppm (detection limit) or less, aluminum atom elution amount is 0.01 ppm (detection limit) or less, chlorine atom elution amount is 0.02 ppm (detection limit) or less,
The total organic carbon content was 2 ppm (detection limit) or less.

As a result of the eluate test, foaming disappeared within 3 minutes, pH difference was -0.03, ultraviolet absorption was 0.006, and potassium permanganate reducing substance was 0.13 ml, which was suitable for medical use. It was found to have characteristics.

Comparative Example 1 Polystyrene (Idemitsu Styrol HT53, glass transition temperature 100 ° C.) was injection molded in the same manner as in Example 1 at a resin temperature of 220 ° C. and a mold temperature of 40 ° C.

When steam sterilization was carried out in the same manner as in Example 1, it was greatly deformed and could not be used. Further, after steam sterilization, the total light transmittance could not be measured because it was cloudy and opaque and was not plate-shaped.

Example 3 100 parts by weight of the hydrogenated product of the ring-opening polymer obtained in Reference Example 3 was added to pentaerythrityl-tetrakis [3- (3,5-di-t].
-Butyl-4-hydroxyphenyl) propionate]
(Ciba Geigy antioxidant, Irganox 101
0, molecular weight 1177.7) 0.05 part by weight is added,
Pellets were manufactured by kneading with a twin-screw extruder.

Molding was performed in the same manner as in Example 1 except that the above pellets were used instead of the pellets obtained by kneading the rubbery polymer.

The total light transmittance of the test piece after molding was 90.1.
%, The transparency was good, and the measured turbidity was 0.08%. Further, LB medium was added and sterilized in the same manner as in Example 2, but no fungal growth was observed, and the transparent container after the treatment had a good appearance and no cloudiness, cracking, or deformation was visually observed. No change was observed in the total light transmittance and turbidity of the test piece.

Titanium atom elution amount is less than 0.1 ppm (detection limit), nickel atom elution amount is less than 0.01 ppm (detection limit), aluminum atom elution amount is 0.01 ppm.
(Detection limit) or less, chlorine atom elution amount was 0.02 ppm (detection limit) or less, and total organic carbon amount was 2 ppm (detection limit) or less.

The above kneaded pellets were subjected to an eluate test according to the Japanese Pharmacopoeia 12th revision “Plastic test method for infusion”. Effervescence disappeared within 3 minutes, pH difference was -0.05, ultraviolet absorption was 0.007, potassium permanganate reducing substance 0.13 ml, and it was found that it has properties suitable for medical use. It was

Example 4 Pentaerythrityl-tetrakis [3- (3,5-di-
t-butyl-4-hydroxyphenyl) propionate] instead of octadecyl-3- (3,5-di-t-
Pellets were obtained in the same manner as in Example 3 except that butyl-4-hydroxyphenyl) propionate (antioxidant manufactured by Ciba Geigy, Irganox 1076, molecular weight 530.9) was used, and the above was used instead of the pellets in which the rubbery polymer was kneaded. Molding was performed in the same manner as in Example 1 except that the above pellets were used.

The total light transmittance of the molded test piece is 90.0.
%, The transparency was good. The turbidity was measured and found to be 0.06%. Although sterilized in the same manner as in Example 2, no fungal growth was observed, the appearance of the transparent container after the treatment was good, and no cloudiness, cracking, or deformation was visually confirmed, and No change was observed in light transmittance and turbidity.

Titanium atom elution amount is 0.1 ppm (detection limit) or less, nickel atom elution amount is 0.01 ppm (detection limit) or less, aluminum atom elution amount is 0.01 ppm
(Detection limit) or less, chlorine atom elution amount was 0.02 ppm (detection limit) or less, and total organic carbon amount was 2 ppm.

Example 5 A condensate of nonylphenol and formaldehyde (average condensation number of nonylphenol component: 5.
0) and a glycidol ether compound (repeating unit 1 derived from nonylphenol obtained by the reaction of glycidol
Pellets were prepared and injection-molded in the same manner as in Example 1 except that 0.3 parts by weight of the average molecular weight of 1,590) were added and glycidol was bonded at an average of 1.2 molecules per unit.

The total light transmittance of the molded test piece is 88.0.
%, The transparency was good. The turbidity was measured and found to be 0.90%. It was sterilized in the same manner as in Example 1, but no growth of fungi was observed, the appearance of the container after the treatment was good, no cloudiness, cracking, or deformation was visually confirmed, and the total light of the test piece was not observed. The transmittance was 87.5% and the turbidity was 1.1%.

Titanium atom elution amount is less than 0.1 ppm (detection limit), nickel atom elution amount is less than 0.01 ppm (detection limit), aluminum atom elution amount is 0.01 ppm.
(Detection limit) or less, chlorine atom elution amount was 0.02 ppm (detection limit) or less, and total organic carbon amount was 2 ppm (detection limit) or less.

Example 6 The resin obtained in Reference Example 3 was injection molded (clamping pressure 350 tons,
Resin temperature 280 ℃, mold temperature 100 ℃), outer diameter 18m
m, an inner diameter of 14 mm, and a length of 110 mm, a syringe cylinder for an internal capacity of 10 ml was prepared. The syringe cylinder was ultrasonically cleaned in distilled water for 20 minutes and then dried at 40 ° C. for 10 hours. Using a high-pressure steam sterilizer, 20 at 120 ℃
Steam sterilized for minutes. No change was observed in the shape of the syringe cylinder.

[0081] This syringe cylinder three, close the tip with a Teflon stopper, and held in the holder by the front end portion downwards, respectively, vitamin concentrations 800 ppm B ₂
An aqueous solution, a methamphetamine hydrochloride aqueous solution with a concentration of 300 ppm, and a tranexamic acid aqueous solution with a concentration of 1000 ppm were used 10 times.
ml was put and the rear end was tightly closed with a Teflon stopper. After leaving it in the dark at room temperature for 30 days, it was analyzed by high performance liquid chromatography, and as a result, the vitamin B ₂ concentration was about 790 pp.
m, the methamphetamine hydrochloride concentration was about 300 ppm, and the tranexamic acid concentration was about 990 ppm.

Example 7 A syringe cylinder was molded and sterilized in the same manner as in Example 6 except that the pellet obtained in Reference Example 4 was used in place of the resin obtained in Reference Example 3, but no change in shape was observed. It was Further, as in Example 5, various aqueous solutions were added, and the mixture was allowed to stand for 30 days and analyzed. As a result, the vitamin B ₂ concentration was about 800 pp.
m, the methamphetamine hydrochloride concentration was about 300 ppm, and the tranexamic acid concentration was about 990 ppm.

Example 8 The pellet obtained in Reference Example 4 was injection blow-molded at a resin temperature of 280 ° C. and a mold temperature of 120 ° C. to obtain an outer diameter of 25 mm and a height of 6.
A bottle having a 0 mm content volume of 20 ml was prepared.

After ultrasonic cleaning in distilled water for 20 minutes, thoroughly drying and steam sterilization at 120 ° C. for 30 minutes,
20 ml of a vitamin B ₂ aqueous solution having a concentration of 800 ppm was put therein, and the container was sealed with a Teflon stopper. After standing at room temperature in the dark for 30 days, the aqueous solution was analyzed by high performance liquid chromatography. As a result, the concentration of vitamin B ₂ was 800 ppm, and almost no change was observed.

[0085]

From these results, the chemical container of the present invention has excellent heat resistance, moisture resistance and transparency, less adsorption of chemicals, less exudation of organic substances and the like, and does not deteriorate the chemicals that it comes into contact with.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ima Natsume 1-2-1 Yokou, Kawasaki-ku, Kawasaki-shi, Kanagawa Nihon Zeon Co., Ltd. Research and Development Center

Claims (10)

[Claims] 1. A medical device comprising a thermoplastic norbornene-based resin. 2. The medical device according to claim 1, wherein the thermoplastic norbornene-based resin has a glass transition temperature of 105 ° C. or higher. 3. The thermoplastic norbornene-based resin has a polystyrene-reduced number average molecular weight of 1 as determined by gel permeation chromatography analysis using toluene as a solvent.
The content of the resin component of 20,000 to 200,000 and 2,000 or less is 1% by weight or less.
Or the medical device according to 2. 4. The medical device according to claim 1, 2 or 3, wherein the thermoplastic norbornene resin contains 0.01 to 10% by weight of a compounding agent which is incompatible with the thermoplastic norbornene resin. 5. The medical device according to claim 1, wherein the thermoplastic norbornene-based resin does not contain a single metal atom of 1 ppm or more in the resin. 6. The medical device according to claim 1, wherein the thermoplastic norbornene-based resin does not contain a chlorine atom concentration of 1 ppm or more in the resin. 7. The medical device according to claim 1, wherein the thermoplastic norbornene-based resin contains an antioxidant having a molecular weight of 600 or more and 3,000 ppm or less. 8. The thermoplastic norbornene-based resin contains 0.01 to 5% by weight of a partially etherified product and / or partially esterified product of a polyhydric alcohol. The medical device according to 6 or 7. 9. The medical device according to claim 1, 2, 3, 4, 5, 6, 7, or 8, wherein the medical device is a drug container. 10. The medical device according to claim 9, wherein the container is filled with a chemical and then sterilized together with the container.