WO2022210132A1 - 容器 - Google Patents

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Publication number
WO2022210132A1
WO2022210132A1 PCT/JP2022/013308 JP2022013308W WO2022210132A1 WO 2022210132 A1 WO2022210132 A1 WO 2022210132A1 JP 2022013308 W JP2022013308 W JP 2022013308W WO 2022210132 A1 WO2022210132 A1 WO 2022210132A1
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WO
WIPO (PCT)
Prior art keywords
container
housing member
wall surface
less
cyclic olefin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2022/013308
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English (en)
French (fr)
Japanese (ja)
Inventor
太一 澤口
洋輔 原内
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zeon Corp
Original Assignee
Zeon Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zeon Corp filed Critical Zeon Corp
Priority to US18/549,168 priority Critical patent/US20240158565A1/en
Priority to EP22780347.5A priority patent/EP4317311A4/en
Priority to CN202280015925.6A priority patent/CN116916871A/zh
Priority to JP2023511039A priority patent/JPWO2022210132A1/ja
Publication of WO2022210132A1 publication Critical patent/WO2022210132A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L65/00—Compositions of macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • A61M5/3129—Syringe barrels
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F232/00—Copolymers of cyclic compounds containing no unsaturated aliphatic radicals in a side chain, and having one or more carbon-to-carbon double bonds in a carbocyclic ring system
    • C08F232/08—Copolymers of cyclic compounds containing no unsaturated aliphatic radicals in a side chain, and having one or more carbon-to-carbon double bonds in a carbocyclic ring system having condensed rings
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/04—Reduction, e.g. hydrogenation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G61/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G61/02—Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes
    • C08G61/04—Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes only aliphatic carbon atoms
    • C08G61/06—Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes only aliphatic carbon atoms prepared by ring-opening of carbocyclic compounds
    • C08G61/08—Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes only aliphatic carbon atoms prepared by ring-opening of carbocyclic compounds of carbocyclic compounds containing one or more carbon-to-carbon double bonds in the ring
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00—Use of organic ingredients
    • C08K5/04—Oxygen-containing compounds
    • C08K5/13—Phenols; Phenolates
    • C08K5/134—Phenols containing ester groups
    • C08K5/1345—Carboxylic esters of phenolcarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D165/00—Coating compositions based on macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain; Coating compositions based on derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/178—Syringes
    • A61M5/31—Details
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/10—Definition of the polymer structure
    • C08G2261/22—Molecular weight
    • C08G2261/228—Polymers, i.e. more than 10 repeat units
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
    • C08G2261/33—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain
    • C08G2261/332—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain containing only carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
    • C08G2261/33—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain
    • C08G2261/332—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain containing only carbon atoms
    • C08G2261/3324—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain containing only carbon atoms derived from norbornene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/30—Monomer units or repeat units incorporating structural elements in the main chain
    • C08G2261/33—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain
    • C08G2261/332—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain containing only carbon atoms
    • C08G2261/3325—Monomer units or repeat units incorporating structural elements in the main chain incorporating non-aromatic structural elements in the main chain containing only carbon atoms derived from other polycyclic systems
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/40—Polymerisation processes
    • C08G2261/41—Organometallic coupling reactions
    • C08G2261/418—Ring opening metathesis polymerisation [ROMP]
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
    • C08G2261/70—Post-treatment
    • C08G2261/72—Derivatisation
    • C08G2261/724—Hydrogenation

Definitions

  • the present invention relates to a container, particularly a container used for containing proteins.
  • a container with a housing member formed using a material containing resin is used in a wide range of applications in daily life.
  • various containers such as syringes and infusion bags are used for the purpose of containing protein-containing formulations and the like.
  • Patent Document 1 In order to reduce such non-specific adsorption of proteins, improvement of containers has been conventionally performed. Specifically, in Patent Document 1, by making the zeta potential of the surface of the container containing the sample the same polarity as the substance contained as the sample, the substance non-specifically adsorbs to the surface of the container. Techniques for preventing this have been proposed.
  • the above-described conventional container has room for improvement in terms of reducing non-specific adsorption of proteins to the inner wall surface of the containing member.
  • an object of the present invention is to provide a container in which non-specific adsorption of proteins to the inner wall surface of a housing member is reduced.
  • the inventor of the present invention conducted intensive studies with the aim of solving the above problems. Then, the present inventors have developed a container comprising a housing member formed by molding a molding material containing a resin, wherein the zeta potential and surface free energy dispersion term components at pH 7.0 of the inner wall surface of the housing member are each predetermined. The inventors have found that non-specific adsorption of proteins to the inner wall surface of the housing member can be reduced by using a container having a value less than the above value, and have completed the present invention.
  • an object of the present invention is to advantageously solve the above-described problems, and a container according to the present invention is a container provided with a housing member formed by molding a molding material containing resin, wherein the housing member
  • the zeta potential of the inner wall surface at pH 7.0 is less than -40.0 mV, and the dispersion term component of the surface free energy is less than 24.5 mJ/m 2 .
  • a container comprising a housing member formed by molding a molding material containing a resin, wherein the dispersion term components of the zeta potential and the surface free energy at pH 7.0 of the inner wall surface of the housing member are each less than a predetermined value.
  • the term "accommodating member formed by molding a molding material containing resin” means an accommodating member in which at least a portion of the inner wall of the accommodating member is made of the molding material.
  • the resin preferably contains at least one of a hydrogenated cyclic olefin ring-opening polymer and a copolymer of a cyclic olefin and a chain olefin. If the resin contains at least one of a hydrogenated cyclic olefin ring-opening polymer and a copolymer of a cyclic olefin and a chain olefin, nonspecific adsorption of proteins to the inner wall surface of the housing member can be further reduced. .
  • the molding material preferably contains at least one of an antioxidant and a light stabilizer.
  • the total content of the antioxidant and the light stabilizer is preferably 0.001 parts by mass or more and 1.8 parts by mass or less per 100 parts by mass of the resin. If the total amount ratio of the antioxidant and light stabilizer to the resin is within the above range, non-specific adsorption of protein to the inner wall surface of the housing member can be further reduced.
  • the "total content of antioxidant and light stabilizer per 100 parts by mass of resin" is, for example, dissolved in an appropriate solvent in the housing member of the container, and then subjected to high performance liquid chromatography (HPLC). can be used to measure the contents (% by mass) of the resin, antioxidant, and light stabilizer, respectively, and the calculation can be performed from these measured values.
  • FIG. 1 is a diagram showing a schematic configuration of an example of a syringe, which is a container according to the present invention
  • the container of the present invention is not particularly limited as long as it is intended to contain protein therein.
  • Specific examples of the container of the present invention include vials, infusion bags, cartridges, ampoules, bottles, tubes, chips, microwell plates, pouches, blister packs, syringes and the like.
  • the syringe includes, for example, an outer cylinder having a nozzle portion at its tip, a sealing member that seals the nozzle portion, a gasket that is slidably accommodated in the outer cylinder, and a gasket that is connected to the outer cylinder. and a pusher that moves in the longitudinal direction of the body.
  • FIG. 1 shows an example of the structure of the syringe.
  • the syringe 1 shown in FIG. 1 includes an outer cylinder 10, a sealing member 20 (a cap in FIG. 1), a gasket 30, and a plunger 40.
  • the outer cylinder 10 has a nozzle portion 12 at a tip portion 11 and a sealing member 20 is fitted to the nozzle portion 12 .
  • the gasket 30 is slidable inside the outer cylinder 10 in the longitudinal direction of the outer cylinder 10 , and the sliding of the gasket 30 can be performed by a pusher 40 connected to the gasket 30 .
  • the syringe 1 contains a content 50, and the content 50 is a space defined by a partial region 14 of the inner wall surface 13 of the outer cylinder 10, the sealing member 20, and the gasket 30. are housed in
  • the protein accommodated in the container is not particularly limited, and examples thereof include antibodies (chimeric antibodies, human antibodies, humanized antibodies, and domain antibodies thereof), and antigen-binding fragments thereof. are mentioned. These proteins may be in the form of a solution or in the form of a solid (such as a lyophilized powder).
  • More specific proteins include, for example, actin, actinin, aggrecan, biglycan, cadherin, clathrin, collagen, decorin, elastin, fibrinogen, fibronectin, heparan, keratin, laminin, mucin, myelin-associated glycoprotein, and myelin base.
  • sex protein myosin, spectrin, tropomyosin, troponin, tubulin, vimentin, vitronectin, ofatumumab (trade name “Azera (registered trademark)”), cetuximab (trade name “Erbitux (registered trademark)”), tocilizumab (trade name “ Actemra (registered trademark)”), bevacizumab (brand name “Avastin (registered trademark)”), canakinumab (brand name “Ilaris (registered trademark)”), golimumab (brand name “Simpony (registered trademark)”), ustekinumab (product name name "Stelara (registered trademark)”), eculizumab (brand name "Soliris (registered trademark)”), omalizumab (brand name "Xolair (registered trademark)”), trastuzumab (brand name "Herceptin (registered trademark)”), per
  • the container of the present invention comprises a containing member capable of containing contents.
  • the container of the present invention may be provided with a member other than the housing member.
  • the syringe can be provided with a sealing member, a gasket, a plunger, etc. as shown in FIG. 1 in addition to an outer cylinder as a housing member.
  • the housing member included in the container of the present invention is formed by molding a molding material containing resin.
  • the zeta potential of the inner wall surface of the housing member at pH 7.0 is less than ⁇ 40.0 mV, and the dispersion term component of the surface free energy is less than 24.5 mJ/m 2 .
  • the housing member provided in the container of the present invention has at least a portion of the inner wall that can come into contact with the content such as protein made of a resin-containing molding material. That is, in the container of the present invention, the resin-containing molding material is positioned on at least a part of the inner wall surface of the housing member, and the resin-containing molding material and the contents such as protein are separated from other members (for example, It is possible to contact directly without passing through a film composed of a material other than a predetermined molding material. In order for the resin-containing molding material and the content such as protein to come into contact with each other, the housing member may be entirely made of the molding material, or may be partially made of the molding material. .
  • the wall forming the internal space of the housing member may have a structure in which a plurality of layers are laminated (multilayer structure), and at least the innermost layer may have a structure composed of a molding material containing resin.
  • the entire inner wall that can be in contact with the contents such as protein is molded containing a resin. It is preferably made of material.
  • the container of the present invention preferably does not have an organic and/or inorganic film or layer on the inner wall surface of the housing member, and does not have a film or layer containing silicon (Si) (i.e., It is more preferable that the inner wall surface of the housing member is not Si-coated.
  • the surface area of the portion having the film or layer is 50% or less of the total surface area of the inner wall surface of the housing member as 100%.
  • the container of the present invention contains It is particularly preferable that the inner wall surface of the member does not have a film or layer made of an organic substance and/or an inorganic substance.
  • the dispersion term components of the zeta potential and the surface free energy at pH 7.0 of the inner wall surface of the container that contacts the content such as protein are less than the above values. Non-specific adsorption of proteins to is reduced.
  • the zeta potential of the inner wall surface of the housing member at pH 7.0 is less than -40.0 mV, so the inner wall surface and the protein having a negative net charge (effective charge) at pH 7.0 Electrostatic repulsion can occur between molecules.
  • the dispersion term component of the surface free energy of the inner wall surface of the housing member is less than 24.5 mJ/m 2 , the content of polar groups on the inner wall surface is low. Therefore, the polar groups in the protein molecules are prevented from interacting with the polar groups on the inner wall surface of the housing member through hydrogen bonding or the like.
  • the molding material used to form the housing member of the container of the present invention contains a resin and optionally antioxidants, light stabilizers and other ingredients.
  • the resin contained in the molding material is not particularly limited, and for example, a thermoplastic resin that is solid under normal temperature and normal pressure can be used.
  • thermoplastic resins that are solid under normal temperature and normal pressure include hydrogenated cyclic olefin ring-opening polymers; copolymers of cyclic olefins and chain olefins; acrylic resins; silicone resins; Polyvinyl chloride; Polyvinylidene chloride; Polyvinyl acetate; Ethylene-vinyl acetate copolymer; Polyvinyl alcohol; Polyacetal; Polyethylene terephthalate; Styrene-acrylonitrile copolymer; acrylonitrile-butadiene-styrene copolymer (ABS resin); styrene-butadiene block copolymer or hydrogenated product thereof; styrene-isoprene block copolymer or hydrogenated product thereof; polyphenylene
  • polystyrene and polycarbonate are preferred, hydrogenated cyclic olefin ring-opening polymers, copolymers of cyclic olefins and chain olefins, polystyrene are more preferred, hydrogenated cyclic olefin ring-opening polymers, cyclic olefins and chain olefins Copolymers are more preferred.
  • "normal temperature” refers to 23°C
  • normal pressure refers to 1 atm (absolute pressure).
  • the resin contained in the molding material preferably contains at least one of a hydrogenated cyclic olefin ring-opening polymer and a copolymer of a cyclic olefin and a chain olefin, and the resin is at least a cyclic olefin ring-opening polymer More preferably, it contains a hydrogenated product.
  • a resin containing at least one of a hydrogenated cyclic olefin ring-opened polymer and a copolymer of a cyclic olefin and a chain olefin it is possible to further reduce non-specific adsorption of proteins to the inner wall surface of the housing member. can.
  • resin may be used individually by 1 type, and may be used in combination of 2 or more types by arbitrary ratios.
  • the hydrogenated cyclic olefin ring-opening polymer is a polymer obtained by further subjecting a cyclic olefin ring-opening polymer obtained by ring-opening polymerization of a cyclic olefin as a monomer to a hydrogenation reaction.
  • the cyclic olefin which is a monomer used for the preparation of the cyclic olefin ring-opening polymer has a cyclic structure formed by carbon atoms and has a polymerizable carbon-carbon double ring structure in the cyclic structure. Compounds with bonds can be used.
  • Specific examples of the cyclic olefin monomer include norbornene-based monomers (monomers containing a norbornene ring) and monocyclic cyclic olefin monomers.
  • the "norbornene ring" contained in the norbornene-based monomer may have one or more carbon atoms interposed between the carbon-carbon single bonds that constitute the ring structure, and these intervening A new ring structure may be formed within the norbornene ring as a result of further single bond formation between the carbon atoms.
  • norbornene-based monomers examples include Bicyclo[2.2.1]hept-2-ene (common name: norbornene) and its derivatives (having a substituent on the ring; the same shall apply hereinafter), 5-ethylidene-bicyclo[2.2.1]hept-2 - bicyclic monomers such as ene (trivial name: ethylidene norbornene) and its derivatives; tricyclic monomers such as tricyclo[4.3.0.1 2,5 ]deca-3,7-diene (common name: dicyclopentadiene) and derivatives thereof; 7,8-benzotricyclo[4.3.0.1 2,5 ]dec-3-ene (common name: methanotetrahydrofluorene, tetracyclo[7.4.0.0 2,7 .1 10,13 ] trideca-2,4,6,11-tetraene) and its derivatives, tetracyclo[4.4.0.1 2,5 .
  • the substituents possessed by the above derivatives include, for example, alkyl groups such as methyl group and ethyl group; alkenyl groups such as vinyl group; alkylidene groups such as ethylidene group and propane-2-ylidene group; aryl group; hydroxy group; acid anhydride group; carboxyl group; alkoxycarbonyl group such as methoxycarbonyl group;
  • Monocyclic cyclic olefin monomers include cyclic monoolefins such as cyclobutene, cyclopentene, methylcyclopentene, cyclohexene, methylcyclohexene, cycloheptene and cyclooctene; cyclohexadiene, methylcyclohexadiene, cyclooctadiene and methylcyclooctadiene; , cyclic diolefins such as phenylcyclooctadiene;
  • the cyclic olefin mentioned above can be used individually by 1 type or in combination of 2 or more types.
  • a block copolymer may be sufficient as a cyclic olefin ring-opening polymer, and a random copolymer may be sufficient as it.
  • norbornene-based monomers are preferred, such as tricyclo[4.3.0.1 2,5 ]deca-3,7-diene and derivatives thereof, tetracyclo[4.4.0 .1 2,5 .
  • the amount of the norbornene-based monomer used for the preparation of the cyclic olefin ring-opening polymer is not particularly limited. It is preferably 80% by mass or more, more preferably 90% by mass or more, and 100% by mass (that is, the cyclic olefin ring-opening polymer contains one or two or more norbornene-based monomers as monomers. It is more preferred that the polymer is obtained using only the polymer).
  • the method of preparing the cyclic olefin ring-opening polymer is not particularly limited, and for example, a known method of ring-opening polymerizing the cyclic olefin as the monomer described above using a metathesis polymerization catalyst can be adopted. Examples of such a method include the method described in JP-A-2016-155327.
  • the weight average molecular weight (Mw) of the cyclic olefin ring-opening polymer obtained as described above is not particularly limited, but is preferably 10,000 or more, more preferably 15,000 or more. It is preferably 100,000 or less, more preferably 50,000 or less. If the weight average molecular weight of the cyclic olefin ring-opening polymer is 10,000 or more, the strength of the container obtained using the resin containing the hydrogenated product of the cyclic olefin ring-opening polymer can be sufficiently ensured.
  • the weight average molecular weight of the cyclic olefin ring-opening polymer is 100,000 or less, the moldability of the resin containing the hydrogenated product of the cyclic olefin ring-opening polymer can be sufficiently ensured.
  • the molecular weight distribution (Mw/Mn) of the cyclic olefin ring-opening polymer is not particularly limited, but is preferably 1 or more and 5 or less, more preferably 1 or more and 4 or less. When the molecular weight distribution of the cyclic olefin ring-opening polymer is within the above range, a container having sufficient mechanical strength can be obtained.
  • the weight average molecular weight (Mw) and number average molecular weight (Mn) of a polymer such as a cyclic olefin ring-opening polymer are determined by gel permeation chromatography (GPC) using cyclohexane as an eluent. It is an isoprene conversion value.
  • a cyclic olefin ring-opening polymer hydrogenate By subjecting the cyclic olefin ring-opening polymer to a hydrogenation reaction, a cyclic olefin ring-opening polymer hydrogenate can be obtained.
  • the method of hydrogenating the cyclic olefin ring-opening polymer is not particularly limited, and for example, a known method of supplying hydrogen into the reaction system in the presence of a hydrogenation catalyst can be adopted. Examples of such a method include the method described in JP-A-2016-155327.
  • the hydrogenation rate (ratio of hydrogenated main chain carbon-carbon double bonds) in the hydrogenation reaction is not particularly limited, but the hydrogenated product of the cyclic olefin ring-opening polymer is molded to produce the housing member. From the viewpoint of suppressing the occurrence of scorching and deterioration due to oxidation, it is preferably 70% or more, more preferably 80% or more, still more preferably 90% or more, and particularly preferably 99% or more.
  • the "hydrogenation rate" in the hydrogenation reaction can be measured using a nuclear magnetic resonance (NMR) method.
  • the weight average molecular weight (Mw) of the hydrogenated cyclic olefin ring-opening polymer obtained after the hydrogenation reaction described above is not particularly limited, but is preferably 10,000 or more, more preferably 15,000 or more. It is preferably 100,000 or less, more preferably 50,000 or less. If the weight average molecular weight of the hydrogenated cyclic olefin ring-opening polymer is 10,000 or more, the strength of the container obtained using the resin containing the hydrogenated cyclic olefin ring-opening polymer can be sufficiently ensured. .
  • the weight average molecular weight of the hydrogenated cyclic olefin ring-opening polymer is 100,000 or less, the moldability of the resin containing the hydrogenated cyclic olefin ring-opening polymer can be sufficiently ensured.
  • the molecular weight distribution (Mw/Mn) of the hydrogenated cyclic olefin ring-opening polymer is not particularly limited, but is preferably 1 or more and 5 or less, more preferably 1 or more and 4 or less. When the molecular weight distribution of the hydrogenated cyclic olefin ring-opening polymer is within the above range, a container having sufficient mechanical strength can be obtained.
  • a copolymer of a cyclic olefin and a chain olefin (hereinafter sometimes simply referred to as a "copolymer”) is a copolymer of a cyclic olefin as a monomer and a chain olefin as a monomer. It is a polymer obtained by
  • Cyclic Olefins As the cyclic olefin that is a monomer used for preparing the copolymer, the same ones as those described above in the section of "hydrogenated product of ring-opening cyclic olefin polymer" can be used.
  • a cyclic olefin can be used individually by 1 type or in combination of 2 or more types. And, among these, bicyclo[2.2.1]hept-2-ene (common name: norbornene) and its derivatives, tetracyclo[4.4.0.1 2,5 . 1 7,10 ]dodeca-3-ene (trivial name: tetracyclododecene) and its derivatives are preferred, and bicyclo[2.2.1]hept-2-ene is more preferred.
  • the linear olefin monomer used for preparing the copolymer has a chain structure formed by carbon atoms and has a polymerizable carbon-carbon double bond in the chain structure.
  • compounds can be used.
  • compounds corresponding to cyclic olefins are not included in chain olefins.
  • chain olefins examples include ⁇ -olefins such as ethylene, propylene, 1-butene, 1-pentene, and 1-hexene; aromatic ring vinyl compounds such as styrene and ⁇ -methylstyrene; 1,4-hexadiene; , 4-methyl-1,4-hexadiene, 5-methyl-1,4-hexadiene, and 1,7-octadiene.
  • the chain olefins can be used singly or in combination of two or more.
  • ⁇ -olefins are preferred as chain olefins, ⁇ -olefins having 1 to 20 carbon atoms are more preferred, and ethylene is even more preferred.
  • a method for preparing the copolymer is not particularly limited, and for example, a known method of addition-polymerizing the above-described cyclic olefins and chain olefins using a polymerization catalyst can be employed. Examples of such a method include the method described in JP-A-2016-155327.
  • the ratio of the amount of the cyclic olefin and the linear olefin used in the preparation of the copolymer is not particularly limited, but the total amount of the cyclic olefin and the linear olefin used in the preparation of the copolymer is 100% by mass.
  • the amount of the cyclic olefin is preferably 30% by mass or more, more preferably 50% by mass or more, still more preferably 70% by mass or more, and 99% by mass or less. It is preferably 97% by mass or less, more preferably 95% by mass or less.
  • the copolymer of cyclic olefin and chain olefin may be a block copolymer or a random copolymer.
  • the weight average molecular weight (Mw) of the copolymer of cyclic olefin and linear olefin is not particularly limited, but is preferably 20,000 or more, more preferably 25,000 or more, and more preferably 100,000. The following are preferable. If the weight average molecular weight of the copolymer is 20,000 or more, the strength of the container obtained using the resin containing the copolymer can be sufficiently ensured. On the other hand, if the weight average molecular weight of the copolymer is 100,000 or less, the moldability of the resin containing the copolymer can be sufficiently ensured.
  • the molecular weight distribution (Mw/Mn) of the copolymer is not particularly limited, but is preferably 1 or more and 5 or less, more preferably 1 or more and 4 or less. When the molecular weight distribution of the copolymer is within the above range, a container having sufficient mechanical strength can be obtained.
  • antioxidants examples include phenol antioxidants, phosphorus antioxidants, sulfur antioxidants, and the like.
  • Phenolic antioxidants include pentaerythritol tetrakis [3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate], 3,5-di-t-butyl-4-hydroxytoluene, dibutylhydroxy Toluene, 2,2'-methylenebis(6-t-butyl-4-methylphenol), 4,4'-butylidenebis(3-t-butyl-3-methylphenol), 4,4'-thiobis(6-t -butyl-3-methylphenol), ⁇ -tocopherol, 2,2,4-trimethyl-6-hydroxy-7-t-butylchroman, tetrakis[methylene-3-(3′,5′-di-t- Butyl-4′-hydroxypheny
  • Phosphorus antioxidants include 6-[3-(3-t-butyl-4-hydroxy-5-methylphenyl)propoxy]-2,4,8,10-tetrakis-t-butyldibenzo[d,f ] [1.3.2] Dioxaphosphepine, distearylpentaerythritol diphosphite, bis(2,4-ditert-butylphenyl) pentaerythritol diphosphite, tris(2,4-ditert-butylphenyl) Phosphite, tetrakis(2,4-ditert-butylphenyl)4,4'-biphenyldiphosphite, trinonylphenylphosphite and the like.
  • sulfur-based antioxidants examples include distearyl thiodipropionate and dilauryl thiodipropionate.
  • phenolic antioxidants are preferred, and pentaerythritol tetrakis[3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate] is more preferred.
  • antioxidant may be used individually by 1 type, and may be used in combination of 2 or more types by arbitrary ratios.
  • the content of the antioxidant in the molding material is preferably 0.001 parts by mass or more per 100 parts by mass of the resin, from the viewpoint of further reducing non-specific adsorption of proteins to the inner wall surface of the housing member. , More preferably 0.005 parts by mass or more, more preferably 0.01 parts by mass or more, preferably 0.9 parts by mass or less, more preferably 0.5 parts by mass or less It is preferably 0.3 parts by mass or less, more preferably 0.1 parts by mass or less.
  • Hindered amine light stabilizers include bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate; bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate; bis(1 ,2,2,6,6-pentamethyl-4-piperidyl)[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]butylmalonate; dibutylamine, 2,4,6 -trichloro-1,3,5-triazine, N,N′-bis(2,2,6,6-tetramethyl-4-piperidyl-1,6-hexamethylenediamine, and N-(2,2,6 ,6-tetramethyl-4-piperidyl)butylamine polycon
  • Benzoate-based light stabilizers include 4-benzoyloxy-2,2,6,6-tetramethylpiperidine and the like. Among these, hindered amine light stabilizers are preferred, and dibutylamine, 2,4,6-trichloro-1,3,5-triazine, N,N'-bis(2,2,6,6-tetramethyl-4 A polycondensate of -piperidyl-1,6-hexamethylenediamine and N-(2,2,6,6-tetramethyl-4-piperidyl)butylamine is more preferred.
  • a light stabilizer may be used individually by 1 type, and may be used in combination of 2 or more types by arbitrary ratios.
  • the content of the light stabilizer in the molding material is preferably 0.01 parts by mass or more per 100 parts by mass of the resin, from the viewpoint of further reducing non-specific adsorption of proteins to the inner wall surface of the housing member.
  • it is more preferably 0.05 parts by mass or more, still more preferably 0.1 parts by mass or more, preferably 0.9 parts by mass or less, and preferably 0.5 parts by mass or less
  • It is more preferably 0.3 parts by mass or less, and particularly preferably 0.2 parts by mass or less.
  • the total content of the antioxidant and light stabilizer in the molding material is 0.001 parts by mass or more per 100 parts by mass of the resin, from the viewpoint of further reducing non-specific adsorption of proteins to the inner wall surface of the housing member. is preferably 0.005 parts by mass or more, more preferably 0.01 parts by mass or more, preferably 1.8 parts by mass or less, and 1.0 parts by mass or less is more preferably 0.6 parts by mass or less, and particularly preferably 0.2 parts by mass or less.
  • the molding material used to form the housing member provided in the container of the present invention can further contain components (other components) other than the above components.
  • the molding material may contain known additives other than the antioxidants and light stabilizers mentioned above.
  • known additives include, for example, ultraviolet absorbers, near-infrared absorbers, plasticizers, antistatic agents, acid scavengers, etc. described in JP-A-2016-155327.
  • other components may be used individually by 1 type, and may be used in combination of 2 or more types by arbitrary ratios.
  • the mixing method for obtaining the molding material containing the resin described above and optionally an antioxidant, a light stabilizer and other components is not particularly limited. , a kneader, a feeder ruder, or the like. After mixing, according to a conventional method, it can be pelletized by extruding into a rod shape and cutting it into an appropriate length with a strand cutter.
  • the zeta potential of the inner wall surface of the housing member at pH 7.0 must be less than -40.0 mV, and the zeta potential of the inner wall surface of the housing member at pH 7.0 is - It is preferably less than 41.0 mV, more preferably less than -42.0 mV, even more preferably less than -43.0 mV, and particularly preferably less than -44.0 mV. If the inner wall surface of the housing member has a zeta potential of ⁇ 40.0 mV or more at pH 7.0, non-specific adsorption of proteins to the inner wall surface of the housing member increases.
  • the lower limit of the zeta potential of the inner wall surface of the housing member at pH 7.0 is not particularly limited, and can be, for example, more than -60.0 mV, or more than -55.0 mV.
  • the zeta potential of the inner wall surface of the housing member at pH 7.0 can be adjusted, for example, by changing the amount (concentration) of the antioxidant and/or light stabilizer described above. In addition, for example, it can be adjusted by changing the molding conditions (back pressure, maximum oxygen concentration, etc.) described in the later-described "Container manufacturing method" section.
  • the dispersion term component of the surface free energy of the inner wall surface of the containing member is required to be less than 24.5 mJ/m 2 , and the dispersion term component of the surface free energy of the inner wall surface of the containing member is required. is preferably less than 23.0 mJ/ m2 , more preferably less than 22.0 mJ/ m2 , even more preferably less than 21.5 mJ/ m2 , and less than 21.0 mJ/ m2 is more preferable, and less than 20.5 mJ/m 2 is particularly preferable.
  • the dispersion term component of the surface free energy of the inner wall surface of the housing member is 24.5 mJ/m 2 or more, non-specific adsorption of proteins to the inner wall surface of the housing member increases.
  • the lower limit of the dispersion term component of the surface free energy of the inner wall surface of the housing member is not particularly limited, and can be, for example, more than 10.0 mJ/m 2 , and more than 15.0 mJ/m 2 . can.
  • the dispersion term component of the surface free energy of the inner wall surface of the housing member can be adjusted, for example, by changing the amount (concentration) of the antioxidant and/or light stabilizer described above. In addition, for example, it can be adjusted by changing the molding conditions (back pressure, maximum oxygen concentration, etc.) described in the later-described "Container manufacturing method" section.
  • the method for producing the container of the present invention is not particularly limited, the container of the present invention can be produced, for example, by molding a molding material containing the above resin and optionally an antioxidant, a light stabilizer and other ingredients. It can be manufactured through a process of obtaining a housing member (molding process).
  • the method for molding the molding material is not particularly limited, and can be appropriately selected from known molding methods according to the desired shape of the housing member.
  • known molding methods include, for example, extrusion molding, injection molding, inflation molding, blow molding, extrusion blow molding, injection blow molding, press molding, vacuum molding, powder slush molding, calendar molding, foam molding, thermoforming. etc.
  • injection molding is preferably used as the molding method.
  • the screw injection molding machine includes, for example, a cylinder, a screw capable of back-and-forth movement inside the cylinder in the longitudinal direction of the cylinder and rotatable in a direction perpendicular to the length direction of the cylinder, and a cylinder provided at the rear part of the cylinder. It is equipped with a hopper that stores the raw material (molding material) to be supplied to and a heater that heats the cylinder. A die corresponding to the desired shape of the housing member is connected to the front end of the cylinder. Preferred molding conditions for injection molding using a screw injection molding machine are described below.
  • the resin is melted by rotating the screw in a cylinder heated by a heater as necessary, and the melted resin moves forward from the tip of the screw due to the rotating motion. It is sent to the front part of the cylinder.
  • pressure (back pressure) is applied in the direction opposite to the retraction direction of the screw (that is, the injection direction).
  • the back pressure when forming the housing member by injection molding is preferably 3 MPa or more, more preferably 5 MPa or more, still more preferably 7 MPa or more, and 12 MPa or less. It is preferably 10 MPa or less, and more preferably 10 MPa or less.
  • the back pressure in injection molding is 3 MPa or more, the amount of air involved when the molding material is melted is reduced, so the generation of polar groups due to oxidative deterioration of the container is suppressed. Therefore, non-specific adsorption of proteins to the inner wall surface of the housing member can be further reduced.
  • the back pressure in injection molding is 12 MPa or less, the rotation of the screw of the injection molding machine is not hindered, so the molding material can be molded in a short time.
  • the maximum oxygen concentration at the raw material (molding material) supply port of the injection molding machine is preferably 7% by volume or less, more preferably 5% by volume or less, It is more preferably 3% by volume or less. If the maximum oxygen concentration is 7% by volume or less, generation of polar groups due to oxidative deterioration of the container is suppressed. Therefore, non-specific adsorption of proteins to the inner wall surface of the housing member can be further reduced. Also, the lower limit of the maximum oxygen concentration is not particularly limited, and can be, for example, 0.05% by volume or more, and can be 0.1% by volume or more.
  • the "maximum oxygen concentration" at the raw material supply port of the injection molding machine can be measured using the method described in the examples of the present specification. Also, the maximum oxygen concentration can be adjusted, for example, by changing the feed rate of the inert gas (such as nitrogen gas) introduced into the injection molding machine. Specifically, the maximum oxygen concentration can be lowered by increasing the supply rate of the inert gas.
  • the inert gas such as nitrogen gas
  • injection molding cylinder temperature, mold temperature, injection speed, injection pressure, screw rotation speed, etc.
  • other conditions in injection molding cylinder temperature, mold temperature, injection speed, injection pressure, screw rotation speed, etc.
  • the container of the present invention may optionally be manufactured through processes (other processes) other than the molding process described above.
  • Other processes include, for example, a process of pre-drying the molding material prior to the molding process (pre-drying process), and a process of assembling the container by combining the housing member obtained in the molding process with other members (assembling process ).
  • ⁇ Zeta potential at pH 7.0> Using a zeta potential measuring instrument (manufactured by Anton Paar Co., Ltd., model number "SurPASS3”), the zeta potential of the inner wall surfaces of the syringe outer cylinders produced in Examples and Comparative Examples was determined.
  • a 1.0 mM KCl solution was prepared as an electrolytic solution.
  • the 1.0 mM KCl solution prepared above was injected into the cell.
  • a pH electrode and conductivity meter were then set up.
  • the zeta potential of the syringe barrel at pH 7.0 was measured by titrating to pH 7.0 with HCl and KOH solutions.
  • ⁇ Dispersion term component of surface free energy The surface free energy of the inner wall surface of the syringe outer cylinders produced in Examples and Comparative Examples was measured using a contact angle meter (manufactured by Kyowa Interface Science Co., Ltd., product name "Drop Master 300").
  • the molded syringe outer cylinder was cut with a nipper to cut out the solution contact surface, 2 ⁇ L of pure water was applied, the droplet image was taken 30 seconds later, and the pure water contact angle was obtained by the curve fitting method. Further, 2 ⁇ L of formamide was dropped on the solution contact surface, and the contact angle of formamide was obtained by photographing the droplet image after 30 seconds.
  • fibronectin solution (product number F0895, manufactured by Sigma-Aldrich LLC, 1 mg/ml solution) was diluted 10-fold with phosphate buffered saline (PBS, pH 7.4, manufactured by TOHO Co., Ltd., product number 09-2051-100). , 100 ⁇ g/ml fibronectin solutions were prepared.
  • An isoprene rubber cap was attached to the tip of the syringe barrel prepared in Examples and Comparative Examples, and the barrel was filled with 1.0 mL of the 100 ⁇ g/ml fibronectin solution prepared above. Then, a plunger fitted with a butyl rubber gasket was inserted from the rear end side of the outer cylinder and sealed to obtain a syringe filled with the fibronectin solution. After the obtained syringe was stored at 4° C. for 3 days, 1.0 mL of fibronectin solution was recovered. After collecting the fibronectin solution, the syringe barrel was washed three times with 1.5 mL of phosphate buffer.
  • the syringe outer cylinder was filled with 1 mL of 3% sodium dodecyl sulfate (SDS) solution and subjected to ultrasonic treatment at room temperature for 20 minutes to recover the fibronectin adsorbed on the syringe outer cylinder.
  • SDS sodium dodecyl sulfate
  • the recovered fibronectin solution was analyzed by ultra high performance liquid chromatography (UPLC). Fibronectin was adjusted to 5 ⁇ g/mL with a 3% SDS solution, serially diluted two-fold, and a calibration curve was drawn from each peak area.
  • the concentration was calculated from the peak area obtained by measuring the recovered fibronectin solution, and converted into the amount of fibronectin adsorbed per 1 m 2 of the inner wall surface of the syringe outer cylinder.
  • a smaller amount of fibronectin adsorption means less non-specific adsorption of protein to the inner wall surface of the housing member.
  • Example 1 ⁇ Production of housing member (syringe outer cylinder)> ⁇ Preparation of hydrogenated cyclic olefin ring-opening polymer (hydride A)>>> Under a nitrogen atmosphere, 0.82 parts of 1-dodecene, 0.15 parts of dibutyl ether, and 0.30 parts of triisobutylaluminum were added to 500 parts of dehydrated cyclohexane, mixed in a reactor at room temperature, and then the mixture was kept at 45°C.
  • tricyclo[4.3.0.1 2,5 ]deca-3,7-diene (common name: dicyclopentadiene, hereinafter abbreviated as “DCP”) 68 parts, and 8-methyl-tetracyclo[4 .4.0.1 2,5 . 1 7,10 ]dodeca-3-ene (hereinafter abbreviated as “TCD”) 74 parts and tetracyclo[7.4.0.0 2,7 . 1 10,13 ]trideca-2,4,6,11-tetraene (hereinafter abbreviated as “MTF”) and 80 parts of tungsten hexachloride (0.7% toluene solution) were added in parallel for 2 hours.
  • DCP dicyclopentadiene
  • TCD 8-methyl-tetracyclo[4 .4.0.1 2,5 . 1 7,10 ]dodeca-3-ene
  • TCD 8-methyl-tetracyclo[4 .4.0.1 2,5 . 1 7,10 ]dode
  • This pelletized hydrogenated cyclic olefin ring-opening polymer (hydride A) has an Mw of 31,000, a molecular weight distribution (Mw/Mn) of 2.5, a hydrogenation rate of 99.6%, and a Tg of 135. °C.
  • antioxidant X pentaerythritol tetrakis [3-(3,5-di-t-butyl-4-hydroxyphenyl) propionate] as an antioxidant
  • Example 2 A syringe outer cylinder was produced in the same manner as in Example 1, except that the back pressure during injection molding was changed from 8 MPa to 5 MPa when molding the syringe outer cylinder, and various evaluations were performed. Table 1 shows the results.
  • Example 3 A syringe outer cylinder was produced in the same manner as in Example 1, except that the back pressure during injection molding was changed from 8 MPa to 10 MPa when molding the syringe outer cylinder, and various evaluations were performed. Table 1 shows the results.
  • Example 4 A syringe outer cylinder was produced in the same manner as in Example 1, except that the nitrogen supply rate was changed from 7 L/min to 5.5 L/min when molding the syringe outer cylinder, and various evaluations were performed. Table 1 shows the results.
  • Example 5 When preparing resin pellets containing hydride A, a syringe outer cylinder was prepared in the same manner as in Example 1, except that the amount of antioxidant X added was changed from 0.012 parts to 0.1 parts, and various evaluations were performed. did Table 1 shows the results.
  • Example 7 When producing resin pellets containing hydride A, except that the amount of light stabilizer Y added was changed from 0.1 parts to 0.2 parts, a syringe barrel was produced in the same manner as in Example 6, and various evaluations were performed. did Table 1 shows the results.
  • Example 8 ⁇ Production of housing member (syringe outer cylinder)> ⁇ Preparation of Copolymer (Copolymer B) of Cyclic Olefin and Chain Olefin>> Norbornene (120 kg) was added to a reaction vessel charged with 258 liters of cyclohexane at room temperature under a nitrogen stream, and the mixture was stirred for 5 minutes. Further, triisobutylaluminum was added so that the concentration in the system was 1.0 ml/liter. Subsequently, while stirring, ethylene was circulated under normal pressure to create an ethylene atmosphere in the system.
  • the internal temperature of the autoclave was kept at 70° C., and the internal pressure was increased to 6 kg/cm 2 in gauge pressure with ethylene. After stirring for 10 minutes, 0.4 liter of a pre-prepared toluene solution containing isopropylidene(cyclopentadienyl)(indenyl)zirconium dichloride and methylalumoxane was added into the system to copolymerize ethylene and norbornene. The reaction was started.
  • the catalyst concentration was 0.018 mmol/liter for isopropylidene(cyclopentadienyl)(indenyl)zirconium dichloride and 8.0 mmol/liter for methylalumoxane with respect to the entire system.
  • ethylene was continuously fed into the system to keep the temperature at 75° C. and the internal pressure at 6 kg/cm 2 in gauge pressure. After 60 minutes, the copolymerization reaction was stopped by adding isopropyl alcohol.
  • the polymer solution was taken out and then brought into contact with an aqueous solution of 5 liters of concentrated hydrochloric acid to 1 m 3 of water with strong stirring at a ratio of 1:1 to transfer the catalyst residue to the aqueous phase.
  • the aqueous phase was separated and removed, and the mixture was washed with water twice to purify and separate the polymerization liquid phase.
  • the purified and separated polymer liquid phase is brought into contact with 3 times the amount of isopropyl alcohol under strong stirring to precipitate the copolymer, and then the solid portion (copolymer) is collected by filtration, and isopropyl alcohol is sufficient. washed.
  • this solid portion was put into isopropyl alcohol so as to be 40 kg/m 3 and then subjected to an extraction operation at 70° C. for 3 hours. After the extraction treatment, the solid portion was collected by filtration and dried at 150° C. and 350 mmHg for 10 hours under a stream of nitrogen to obtain an ethylene/norbornene copolymer (copolymer B). Then, the copolymer B was pelletized in the same manner as the hydride A of Example 1. The pelletized copolymer B had a weight average molecular weight (Mw) of 95,000, a molecular weight distribution (Mw/Mn) of 2.4, and a Tg of 138°C.
  • Mw weight average molecular weight
  • Mw/Mn molecular weight distribution
  • ⁇ Molding>> A syringe outer cylinder was molded in the same manner as in Example 1, except that the resin pellets containing the copolymer B obtained as described above were used, and the injection molding conditions were changed as follows. made an evaluation. Table 1 shows the results.
  • Cylinder temperature 300°C Mold temperature: 105°C Injection speed: 50 mm/sec Cooling time: 30 sec Injection pressure (holding pressure): 85 MPa Screw rotation speed: 50 rpm Back pressure: 9MPa Supply rate of inert gas (nitrogen): 7 L/min
  • Example 9 In the production of resin pellets containing copolymer B, a syringe outer cylinder was produced in the same manner as in Example 8, except that 0.1 part of light stabilizer Y was used instead of 0.02 part of antioxidant X. made an evaluation. Table 1 shows the results.
  • Example 10 The same as in Example 1, except that polystyrene (Toyo Styrol GP G200C, manufactured by Toyo Styrene Co., Ltd.) was used in place of hydride A when producing the syringe barrel, and the injection molding conditions were changed as follows. Then, a syringe outer cylinder was produced and various evaluations were performed. Table 1 shows the results. Cylinder temperature: 280°C Mold temperature: 85°C Injection speed: 50 mm/sec Cooling time: 30 sec Injection pressure (holding pressure): 70 MPa Screw rotation speed: 50 rpm Back pressure: 8MPa Supply rate of inert gas (nitrogen): 7 L/min
  • Example 11 A syringe barrel was produced in the same manner as in Example 10, except that 0.1 part of antioxidant X was added in producing the syringe barrel, and various evaluations were performed. Table 1 shows the results.
  • Example 3 A syringe outer cylinder was produced in the same manner as in Example 1, except that the back pressure during injection molding was changed from 8 MPa to 2.5 MPa when molding the syringe outer cylinder, and various evaluations were performed. Table 2 shows the results.
  • Example 4 A syringe outer cylinder was produced in the same manner as in Example 1, except that the nitrogen supply rate was changed from 7 L/min to 3 L/min when molding the syringe outer cylinder, and various evaluations were performed. Table 2 shows the results.
  • Example 7 A syringe outer cylinder was produced in the same manner as in Example 8, except that the back pressure during injection molding was changed from 9 MPa to 2.5 MPa when molding the syringe outer cylinder, and various evaluations were performed. Table 2 shows the results.
  • Example 8 A syringe outer cylinder was produced in the same manner as in Example 8, except that the nitrogen supply rate was changed from 7 L/min to 3 L/min when molding the syringe outer cylinder, and various evaluations were performed. Table 2 shows the results.
  • Hydride A represents a cyclic olefin ring-opening polymer hydrogenate (DCP/TCD/MTF ring-opening copolymer hydrogenate)
  • Copolymer B represents a copolymer of a cyclic olefin and a chain olefin (ethylene-norbornene copolymer)
  • PS indicates polystyrene
  • Antioxidant X denotes pentaerythritol tetrakis [3-(3,5-di-t-butyl-4-hydroxyphenyl) propionate]
  • Light stabilizer Y is dibutylamine, 2,4,6-trichloro-1,3,5-triazine, N,N'-bis(2,2,6,6-tetramethyl-4-piperidyl-1 ,6-hexamethylenediamine and N-(2,2,6,6-tetramethyl-4-piperidy

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