JP6015344B2 - Biopharmaceutical storage method - Google Patents

Description

  The present invention relates to a biopharmaceutical storage method for storing a biopharmaceutical in a medical multilayer container having oxygen barrier performance and oxygen absorption performance.

  Conventionally, glass ampoules, vials, prefilled syringes, and the like have been used as medical packaging containers for filling and storing chemical solutions in a sealed state. However, glass containers are used to store sodium ion etc. in the liquid in the container during storage in a state filled with chemicals, to generate fine substances called flakes, or to use colored light-shielding glass containers. When used, there are problems such that the coloring metal is mixed into the contents and is easily broken. In addition, there is a problem that the chemical deteriorates due to oxygen remaining inside the container after filling. Furthermore, since the specific gravity is large, there is a problem that the medical packaging container becomes heavy, and development of an alternative material has been expected.

  Plastics are lighter than glass. For example, polycarbonate, polypropylene, cycloolefin polymers, etc. are being investigated as plastic substitutes for glass. However, oxygen barrier properties and water vapor barrier properties do not meet the requirements and can be replaced. The current situation is not progressing.

  In recent years, new drug registrations for biopharmaceuticals are rapidly increasing, and the ratio of biopharmaceuticals to approved drugs is increasing. These drugs are particularly required to be stored in containers with a guaranteed oxygen barrier performance. Unlike glass and metal containers, plastic has a property of permeating oxygen and has a problem in the storage stability of chemicals. In order to impart gas barrier properties to such plastic containers, multilayer containers having a gas barrier layer as an intermediate layer have been proposed.

  Patent Document 1 discloses a prefilled syringe in which an innermost layer and an outermost layer of a barrel are made of a polyolefin-based resin, a resin having an excellent oxygen barrier property is used for an intermediate layer, and an oxygen barrier property is improved.

  In addition, as a gas barrier layer, a polyamide obtained from metaxylylenediamine and adipic acid (hereinafter sometimes referred to as nylon MXD6), an ethylene-vinyl alcohol copolymer, polyacrylonitrile, polyvinylidene chloride, aluminum A method of laminating a gas barrier layer such as foil, carbon coat, and inorganic oxide vapor deposition as a constituent material has been carried out, but residual oxygen in the headspace gas existing above the contents after filling in the molded body is removed. It is impossible to do.

  In recent years, a small amount of transition metal compound is added to and mixed with nylon MXD6 to give an oxygen absorption function, and this is used as an oxygen barrier material that constitutes containers and packaging materials. In addition, by absorbing oxygen remaining in the inside of the container, a method for improving the storage stability of the contents more than a container using a conventional oxygen-barrier thermoplastic resin is being put into practical use (see Patent Document 2).

  On the other hand, in order to remove oxygen in a container, it is conventionally known to use an oxygen absorbent or an oxygen-absorbing resin. For example, an oxygen-absorbing resin composition comprising a resin and a transition metal catalyst and having oxygen scavenging properties is known. For example, a resin composition comprising a polyamide, particularly a xylylene group-containing polyamide and a transition metal catalyst, is known as an oxidizable organic component, and further a resin composition having an oxygen scavenging function and oxygen obtained by molding the resin composition There are also examples of absorbents, packaging materials, and multilayer laminated films for packaging (see Patent Document 3).

  Further, as an oxygen-absorbing resin composition that does not require moisture for oxygen absorption, an oxygen-absorbing resin composition comprising a resin having a carbon-carbon unsaturated bond and a transition metal catalyst is known (see Patent Document 4).

  Furthermore, as a composition for collecting oxygen, a composition comprising a polymer containing a substituted cyclohexene functional group or a low molecular weight substance bonded with the cyclohexene ring and a transition metal is known (see Patent Document 5).

JP 2004-229750 A Japanese Patent Laid-Open No. 2-500846 JP 2001-252560 A Japanese Patent Laid-Open No. 05-115776 Special table 2003-521552 gazette

  However, in the prefilled syringe of Patent Document 1, the oxygen barrier property is insufficient to completely block oxygen, and the residual oxygen in the gas in the headspace existing above the contents of the container is removed. There was a problem that was impossible.

  Moreover, since the resin composition of patent document 2 and 3 expresses an oxygen absorption function by containing a transition metal catalyst and oxidizing a xylylene group-containing polyamide resin, strength reduction due to oxidative degradation of the resin occurs. There is a problem that the strength of the packaging container itself is lowered. Furthermore, this resin composition has a problem that oxygen absorption performance is still insufficient, and the object to be preserved exhibits only an effect of high moisture.

  Furthermore, the oxygen-absorbing resin composition of Patent Document 4 generates a low molecular weight organic compound that becomes an odor component by breaking a polymer chain accompanying oxidation of the resin, and when the content is a chemical solution, the organic compound is There is a problem of moving to contents.

  On the other hand, the composition of Patent Document 5 requires the use of a special material containing a cyclohexene functional group, and there is a problem that this material generates a low molecular weight compound relatively easily.

  The present invention has been made in view of the above problems, and an object of the present invention is to provide a method capable of suppressing deterioration of biopharmaceuticals and lowering of drug efficacy and storing them for a long period of time without mixing impurities.

  As a result of studying a method for preserving biopharmaceuticals, the present inventors have obtained the above problem by storing biopharmaceuticals in an oxygen-absorbing medical multilayer molded container using a polyester compound having a tetralin ring and a transition metal catalyst. The present invention has been completed.

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍは０〜３、ｎは０〜７の整数を表し、テトラリン環のベンジル位に少なくとも１つ以上の水素原子が結合している。Ｘは芳香族炭化水素基、飽和または不飽和の脂環式炭化水素基、直鎖状または分岐状の飽和または不飽和の脂肪族炭化水素基及び複素環基からなる群から選ばれる少なくとも１つの基を含有する２価の基を表す。）
からなる群より選択される少なくとも１つのテトラリン環を有する構成単位を含有する、
バイオ医薬の保存方法。
＜２＞ 前記遷移金属触媒が、マンガン、鉄、コバルト、ニッケルおよび銅からなる群より選択される少なくとも１種以上の遷移金属を含むものである、上記＜１＞記載のバイオ医薬の保存方法。
＜３＞ 前記遷移金属触媒が、前記ポリエステル化合物１００質量部に対し、遷移金属量として０．００１〜１０質量部含まれる、上記＜１＞または＜２＞に記載のバイオ医薬の保存方法。
＜４＞ 前記一般式（１）で表される構成単位が、下記式（５）〜（７）からなる群より選択される少なくとも１つである、上記＜１＞〜＜３＞のいずれかに記載のバイオ医薬の保存方法。

That is, the present invention provides the following <1> to <4>.
<1> An oxygen absorption layer (layer A) made of an oxygen-absorbing resin composition containing a polyester compound and a transition metal catalyst, and a resin layer (layer B) containing a thermoplastic resin are added to the layer A. A biopharmaceutical storage method for storing in an oxygen-absorbing medical multilayer molded container containing at least three layers laminated on both sides,
The polyester compound is represented by the following general formulas (1) to (4).

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group At least one selected from the above, which may further have a substituent, m represents an integer of 0 to 3, n represents an integer of 0 to 7, and at least one hydrogen atom at the benzyl position of the tetralin ring. X is an aromatic hydrocarbon group, a saturated or unsaturated alicyclic hydrocarbon group, a linear or branched saturated or unsaturated aliphatic hydrocarbon group, and a heterocyclic ring. It represents a divalent group containing at least one group selected from the group consisting of.)
Containing a structural unit having at least one tetralin ring selected from the group consisting of:
Biopharmaceutical storage method.
<2> The method for preserving a biopharmaceutical according to the above <1>, wherein the transition metal catalyst contains at least one transition metal selected from the group consisting of manganese, iron, cobalt, nickel and copper.
<3> The biopharmaceutical storage method according to <1> or <2> above, wherein the transition metal catalyst is contained in an amount of 0.001 to 10 parts by mass as a transition metal amount with respect to 100 parts by mass of the polyester compound.
<4> Any of the above <1> to <3>, wherein the structural unit represented by the general formula (1) is at least one selected from the group consisting of the following formulas (5) to (7): The biopharmaceutical storage method as described in 1.

  According to the present invention, biopharmaceuticals can be stored under a low oxygen concentration, so that deterioration of biopharmaceuticals and reduction of drug efficacy can be suppressed. Moreover, in the medical multilayer container used in the present invention, generation of low-molecular organic substances after oxygen absorption is suppressed, so that it is possible to prevent impurities from being mixed into the contents. In addition, the medical multilayer container used in the present invention is capable of preserving biopharmaceuticals for a long period of time because the deterioration of the polyester compound due to oxidation is extremely small even after oxygen absorption and the strength of the container is maintained even in long-term use.

  Embodiments of the present invention will be described below. In addition, the following embodiment is an illustration for demonstrating this invention, and this invention is not limited only to the embodiment.

  The oxygen-absorbing medical multilayer molded container of the present embodiment has at least three layers each having an oxygen-absorbing layer (layer A) and laminated with a resin layer (layer B) containing a thermoplastic resin on both sides of the layer A. Containing. The layer structure in the oxygen-absorbing medical multilayer molded container of the present embodiment may have a B / A / B structure, and any other layer can be provided. Further, the number and type of the layer A are not particularly limited as long as the layer A is one or more layers and the layer B is two or more layers. For example, a five-layer configuration of B1 / B2 / A / B2 / B1 composed of one layer A and two layers 4 layers B of layers B1 and B2 may be used. Furthermore, in the oxygen-absorbing medical multilayer molded container of the present embodiment, an arbitrary layer such as an adhesive layer (layer AD) may be included between the layer A and the layer B as necessary, for example, B1 / A seven-layer configuration of B2 / AD / A / AD / B2 / B1 may be used.

[Oxygen absorbing layer (layer A)]
The oxygen absorption layer (layer A) of this embodiment comprises a polyester compound and a transition metal catalyst containing a structural unit having at least one tetralin ring selected from the group consisting of the above general formulas (1) to (4). It consists of an oxygen-absorbing resin composition.

  The content of the polyester compound in the layer A is preferably 50% by mass or more, more preferably 70% by mass or more, and particularly preferably 90% by mass or more. In the case of the said range, compared with the case where it is less than 50 mass%, oxygen absorption performance can be improved more.

[Polyester compound]
The polyester compound of this embodiment contains the structural unit which has at least 1 type of tetralin ring selected from the group which consists of said general formula (1)-(4).

  In the general formulas (1) to (4) and (8) to (15) of the present application, examples of the monovalent substituent represented by R include a halogen atom (for example, a chlorine atom, a bromine atom, an iodine atom), and an alkyl group. (Preferably a linear, branched or cyclic alkyl group having 1 to 15 carbon atoms, more preferably 1 to 6 carbon atoms such as methyl group, ethyl group, n-propyl group, isopropyl group, t- A butyl group, an n-octyl group, a 2-ethylhexyl group, a cyclopropyl group, a cyclopentyl group), an alkenyl group (preferably having 2 to 10 carbon atoms, more preferably 2 to 6 linear, branched or branched) Cyclic alkenyl groups such as vinyl and allyl groups, alkynyl groups (preferably alkynyl groups having 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms such as ethynyl groups and propargyl groups), Group (preferably an aryl group having 6 to 16 carbon atoms, more preferably an aryl group having 6 to 10 carbon atoms, such as a phenyl group or a naphthyl group), a heterocyclic group (preferably having a carbon number of 1 to 12, more preferably A monovalent group obtained by removing one hydrogen atom from a 5-membered or 6-membered aromatic or non-aromatic heterocyclic compound having 2 to 6 carbon atoms, such as a 1-pyrazolyl group, 1 -Imidazolyl group, 2-furyl group), cyano group, hydroxy group, carboxyl group, ester group, amide group, nitro group, alkoxy group (preferably having 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms). A linear, branched or cyclic alkoxy group such as a methoxy group or an ethoxy group, an aryloxy group (preferably an aryloxy group having 6 to 12 carbon atoms, more preferably 6 to 8 carbon atoms, eg A phenoxy group), an acyl group (including a formyl group, preferably an alkylcarbonyl group having 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, preferably 7 to 12 carbon atoms, more preferably carbon. An arylcarbonyl group having 7 to 9 carbon atoms, for example, an acetyl group, a pivaloyl group, a benzoyl group), an amino group (preferably having 1 to 10 carbon atoms, more preferably an alkylamino group having 1 to 6 carbon atoms, preferably An anilino group having 6 to 12 carbon atoms, more preferably 6 to 8 carbon atoms, preferably a heterocyclic amino group having 1 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, such as an amino group, methyl Amino group, anilino group), mercapto group, alkylthio group (preferably an alkylthio group having 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, such as methylthio group, ethyl Luthio group), an arylthio group (preferably an arylthio group having 6 to 12 carbon atoms, more preferably an arylthio group having 6 to 8 carbon atoms, such as a phenylthio group), a heterocyclic thio group (preferably having 2 to 10 carbon atoms, and more). Preferably a heterocyclic thio group having 1 to 6 carbon atoms, such as a 2-benzothiazolylthio group, an imide group (preferably an imide group having 2 to 10 carbon atoms, more preferably 4 to 8 carbon atoms, Examples thereof include N-succinimide group and N-phthalimide group), but are not particularly limited thereto.

  In addition, when said monovalent substituent R has a hydrogen atom, the hydrogen atom is a substituent T (Here, the substituent T is synonymous with what was demonstrated by said monovalent substituent R.). ) May be further substituted. Specific examples thereof include, for example, an alkyl group substituted with a hydroxy group (for example, hydroxyethyl group), an alkyl group substituted with an alkoxy group (for example, methoxyethyl group), and an alkyl group substituted with an aryl group (for example, Benzyl group), alkyl groups substituted with primary or secondary amino groups (eg aminoethyl group), aryl groups substituted with alkyl groups (eg p-tolyl group), substituted with alkyl groups Aryloxy groups (for example, 2-methylphenoxy group) and the like, but are not particularly limited thereto. When the monovalent substituent R has a monovalent substituent T, the carbon number described above does not include the carbon number of the substituent T. For example, a benzyl group is regarded as a C 1 alkyl group substituted with a phenyl group, and is not regarded as a C 7 alkyl group substituted with a phenyl group. When the monovalent substituent R has a substituent T, there may be a plurality of the substituents T.

  X is at least one selected from the group consisting of an aromatic hydrocarbon group, a saturated or unsaturated alicyclic hydrocarbon group, a linear or branched saturated or unsaturated aliphatic hydrocarbon group, and a heterocyclic group. Represents a divalent group containing one group. The aromatic hydrocarbon group, saturated or unsaturated alicyclic hydrocarbon group, linear or branched saturated or unsaturated aliphatic hydrocarbon group and heterocyclic group may be substituted or unsubstituted. . X may contain a hetero atom, and may contain an ether group, sulfide group, carbonyl group, hydroxy group, amino group, sulfoxide group, sulfone group, and the like. Here, as the aromatic hydrocarbon group, for example, o-phenylene group, m-phenylene group, p-phenylene group, methylphenylene group, o-xylylene group, m-xylylene group, p-xylylene group, naphthylene group, Anthracenylene group, phenanthrylene group, biphenylene group, fluoronylene group and the like can be mentioned, but not limited thereto. Examples of the alicyclic hydrocarbon group include a cycloalkylene group such as a cyclopentylene group, a cyclohexylene group, a methylcyclohexylene group, a cycloheptylene group, and a cyclooctylene group, and a cycloalkenylene group such as a cyclohexenylene group. Although it is mentioned, it is not specifically limited to these. Examples of the aliphatic hydrocarbon group include methylene group, ethylene group, trimethylene group, propylene group, isopropylidene group, tetramethylene group, isobutylidene group, sec-butylidene group, pentamethylene group, hexamethylene group, heptamethylene group, Linear or branched alkylene groups such as octamethylene group, nonamethylene group, decamethylene group, vinylene group, propenylene group, 1-butenylene group, 2-butenylene group, 1,3-butadienylene group, 1-pentenylene group Alkenylene groups such as 2-pentenylene group, 1-hexenylene group, 2-hexenylene group, 3-hexenylene group and the like, but are not particularly limited thereto. These may further have a substituent, and specific examples thereof include, for example, halogen, alkoxy group, hydroxy group, carboxyl group, carboalkoxy group, amino group, acyl group, thio group (for example, alkylthio group, Phenylthio group, tolylthio group, pyridylthio group, etc.), amino group (for example, unsubstituted amino group, methylamino group, dimethylamino group, phenylamino group, etc.), cyano group, nitro group and the like, but not limited thereto .

  The polyester compound containing the structural unit represented by the general formula (1) can be obtained by polycondensation of a dicarboxylic acid having a tetralin ring or a derivative (I) thereof and a diol or a derivative (II) thereof.

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍは０〜３、ｎは０〜７の整数を表し、テトラリン環のベンジル位に少なくとも１つ以上の水素原子が結合している。Ｙは水素原子又はアルキル基を表す。） The dicarboxylic acid having a tetralin ring or its derivative (I) used in the present embodiment is represented by the following general formula (8). These can be used alone or in combination of two or more.

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group At least one selected from the above, which may further have a substituent, m represents an integer of 0 to 3, n represents an integer of 0 to 7, and at least one hydrogen atom at the benzyl position of the tetralin ring. Atoms are bonded. Y represents a hydrogen atom or an alkyl group.)

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍはそれぞれ独立して０〜３の整数を表す。Ｙは水素原子又はアルキル基を表す。） The compound represented by the general formula (8) can be obtained by reacting a dicarboxylic acid having a naphthalene ring represented by the following general formula (9) or a derivative thereof with hydrogen.

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group These are at least one selected, and may further have a substituent, each m independently represents an integer of 0 to 3, and Y represents a hydrogen atom or an alkyl group.)

  Examples of the diol or derivative (II) used in the present embodiment include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, 1,3-propanediol, 2-methyl- 1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1 , 9-nonanediol, neopentyl glycol, 1,4-cyclohexanedimethanol, 2-phenylpropanediol, 2- (4-hydroxyphenyl) ethyl alcohol, α, α-dihydroxy-1,3-diisopropylbenzene, α, α Dihydroxy-1,4-diisopropylbenzene, o- xylene glycol, m- xylene glycol, p- xylene glycol, hydroquinone, 4,4-dihydroxyphenyl, naphthalene diol or derivatives thereof,. These can be used alone or in combination of two or more.

  The polyester compound containing the structural unit represented by the general formula (2) is obtained by polycondensation of a diol having a tetralin ring or a derivative (III) thereof and a dicarboxylic acid or a derivative (IV) thereof. It is done.

（式中、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍは０〜３、ｎは０〜７の整数を表し、テトラリン環のベンジル位に少なくとも１つ以上の水素原子が結合している。） A diol having a tetralin ring or a derivative (III) thereof used in the present embodiment is represented by the following general formula (10). These can be used alone or in combination of two or more.

(In the formula, each independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, hydroxy group, Selected from the group consisting of a group, carboxyl group, ester group, amide group, nitro group, alkoxy group, aryloxy group, acyl group, amino group, mercapto group, alkylthio group, arylthio group, heterocyclic thio group and imide group At least one kind, which may further have a substituent, m represents an integer of 0 to 3, n represents an integer of 0 to 7, and at least one hydrogen atom is bonded to the benzyl position of the tetralin ring. doing.)

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍはそれぞれ独立して０〜３の整数を表す。） The compound represented by the general formula (10) can be obtained by reacting a diol having a naphthalene ring represented by the following general formula (11) or a derivative thereof with hydrogen.

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group These are at least one selected, and may further have a substituent, each m independently represents an integer of 0 to 3.)

  Examples of the dicarboxylic acid or derivative (IV) used in the present embodiment include oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, undecanedioic acid, dodecanedioic acid. Benzenedicarboxylic acid such as 3,3-dimethylpentanedioic acid, phthalic acid, isophthalic acid and terephthalic acid, naphthalenedicarboxylic acid such as 2,6-naphthalenedicarboxylic acid, anthracene dicarboxylic acid, phenylmalonic acid, phenylenediacetic acid, pheny Examples include dibutyric acid, 4,4-diphenyl ether dicarboxylic acid, p-phenylene dicarboxylic acid, and derivatives thereof. These can be used alone or in combination of two or more.

  The polyester compound containing the structural unit represented by the general formula (3) or (4) can be obtained by polycondensation of a hydroxycarboxylic acid having a tetralin ring or a derivative (V) thereof.

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍは０〜３、ｎは０〜７の整数を表し、テトラリン環のベンジル位に少なくとも１つ以上の水素原子が結合している。Ｙは水素原子又はアルキル基を表す。） The hydroxycarboxylic acid having a tetralin ring or its derivative (V) used in the present embodiment is represented by the following general formula (12) or (13). These can be used alone or in combination of two or more.

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group At least one selected from the above, which may further have a substituent, m represents an integer of 0 to 3, n represents an integer of 0 to 7, and at least one hydrogen atom at the benzyl position of the tetralin ring. Atoms are bonded. Y represents a hydrogen atom or an alkyl group.)

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍはそれぞれ独立して０〜３の整数を表す。Ｘは芳香族炭化水素基、飽和または不飽和の脂環式炭化水素基、直鎖状または分岐状の飽和または不飽和の脂肪族炭化水素基及び複素環基からなる群から選ばれる少なくとも１つの基を含有する２価の基を表す。）

（式中、Ｒは、それぞれ独立して、水素原子または一価の置換基を示し、一価の置換基は、ハロゲン原子、アルキル基、アルケニル基、アルキニル基、アリール基、複素環基、シアノ基、ヒドロキシ基、カルボキシル基、エステル基、アミド基、ニトロ基、アルコキシ基、アリールオキシ基、アシル基、アミノ基、メルカプト基、アルキルチオ基、アリールチオ基、複素環チオ基及びイミド基からなる群より選択される少なくとも１種であり、これらはさらに置換基を有していてもよい。ｍはそれぞれ独立して０〜３の整数を表す。Ｘは芳香族炭化水素基、飽和または不飽和の脂環式炭化水素基、直鎖状または分岐状の飽和または不飽和の脂肪族炭化水素基及び複素環基からなる群から選ばれる少なくとも１つの基を含有する２価の基を表す。） The polyester compound containing the structural unit represented by the general formula (1) or (2) is obtained by hydrogenation reaction of the polyester compound containing the structural unit represented by the following general formula (14) or (15). You can also

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group At least one selected from the above, which may further have a substituent, each m independently represents an integer of 0 to 3. X is an aromatic hydrocarbon group, a saturated or unsaturated fat. Represents a divalent group containing at least one group selected from the group consisting of a cyclic hydrocarbon group, a linear or branched saturated or unsaturated aliphatic hydrocarbon group and a heterocyclic group. )

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group At least one selected from the above, which may further have a substituent, each m independently represents an integer of 0 to 3. X is an aromatic hydrocarbon group, a saturated or unsaturated fat. Represents a divalent group containing at least one group selected from the group consisting of a cyclic hydrocarbon group, a linear or branched saturated or unsaturated aliphatic hydrocarbon group and a heterocyclic group. )

  In the polyester compound of the present embodiment, a constitutional unit having no tetralin ring may be incorporated as a copolymer component to the extent that it does not affect the performance. Specifically, the compounds shown in the diol or its derivative (II) and the dicarboxylic acid or its derivative (IV) can be used as a copolymerization component.

Preferred specific examples of the polyester compound containing the structural unit represented by the general formula (1) include the above formulas (5) to (7) and the following formulas (16) to (18). It is not limited to.

  There is no restriction | limiting in particular in the method of manufacturing the polyester compound used for this embodiment, All the manufacturing methods of conventionally well-known polyester can be applied. Examples thereof include a melt polymerization method such as a transesterification method and a direct esterification method, or a solution polymerization method. Among the above-described methods for producing a polyester compound, a transesterification method is preferably used from the viewpoint of easy availability of raw materials.

  Various known catalysts such as transesterification catalysts, esterification catalysts, polycondensation catalysts, etc., etherification inhibitors, heat stabilizers, light stabilizers, polymerization regulators, etc., used in the production of polyester compounds Any of these can be used, and these are appropriately selected according to the reaction rate, the color tone of the polyester compound, safety, thermal stability, weather resistance, self-elution, and the like. For example, the above-mentioned various catalysts include zinc, lead, cerium, cadmium, manganese, cobalt, lithium, sodium, potassium, calcium, nickel, magnesium, vanadium, aluminum, titanium, antimony, tin, and other metal compounds (for example, fatty acid salts , Carbonates, phosphates, hydroxides, chlorides, oxides, alkoxides), magnesium metal, and the like. These can be used alone or in combination.

  All of the above-mentioned polyester compounds have hydrogen at the benzylic position of the tetralin ring, and when used in combination with the above-described transition metal catalyst, the hydrogen at the benzylic position is extracted, thereby exhibiting excellent oxygen absorption capacity. .

  In addition, the oxygen-absorbing resin composition of the present embodiment is one in which the generation of low molecular weight compounds after oxygen absorption is suppressed. Although the reason is not clear, for example, the following oxidation reaction mechanism is assumed. That is, in the polyester compound, first, hydrogen at the benzylic position of the tetralin ring is extracted to generate a radical, and then the benzylic carbon is oxidized by the reaction between the radical and oxygen to generate a hydroxy group or a ketone group. Conceivable. Therefore, in the oxygen-absorbing resin composition of the present embodiment, the molecular chain is not broken by the oxidation reaction as in the above-described conventional technique, and the structure of the polyester compound is maintained, so that a low molecular weight compound is generated after oxygen absorption. As a result, it is presumed that the low molecular weight compound is prevented from being mixed into the contents after oxygen absorption.

  The intrinsic viscosity of the polyester compound of the present embodiment (measured value at 25 ° C. using a mixed solvent of phenol and 1,1,2,2-tetrachloroethane in a mass ratio of 6: 4) is not particularly limited. From the viewpoint of moldability, 0.1 to 2.0 dL / g is preferable, and 0.5 to 1.5 dL / g is more preferable.

  The transition metal catalyst used in the oxygen-absorbing resin composition of the present embodiment can be appropriately selected from known ones as long as it can function as a catalyst for the oxidation reaction of the polyester compound, There is no particular limitation.

  Specific examples of the transition metal catalyst include, for example, organic acid salts, halides, phosphates, phosphites, hypophosphites, nitrates, sulfates, oxides and hydroxides of transition metals. Here, examples of the transition metal contained in the transition metal catalyst include, but are not limited to, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, ruthenium, and rhodium. Among these, manganese, iron, cobalt, nickel, and copper are preferable. Examples of organic acids include acetic acid, propionic acid, octanoic acid, lauric acid, stearic acid, acetylacetone, dimethyldithiocarbamic acid, palmitic acid, 2-ethylhexanoic acid, neodecanoic acid, linoleic acid, toluic acid, oleic acid, Although capric acid and naphthenic acid are mentioned, it is not limited to these. The transition metal catalyst is preferably a combination of these transition metals and an organic acid, the transition metal is manganese, iron, cobalt, nickel or copper, and the organic acid is acetic acid, stearic acid, 2-ethylhexanoic acid, olein. A combination that is an acid or naphthenic acid is more preferred. In addition, a transition metal catalyst can be used individually by 1 type or in combination of 2 or more types.

  The compounding quantity of a transition metal catalyst can be suitably set according to the kind and desired performance of the said polyester compound and transition metal catalyst to be used, and is not specifically limited. From the viewpoint of the oxygen absorption amount of the oxygen-absorbing resin composition, the blending amount of the transition metal catalyst is preferably 0.001 to 10 parts by mass as the transition metal amount, more preferably 100 parts by mass of the polyester compound. Is 0.002 to 2 parts by mass, more preferably 0.005 to 1 part by mass.

  The polyester compound and the transition metal catalyst can be mixed by a known method, but can be used as an oxygen-absorbing resin composition having good dispersibility, preferably by kneading with an extruder. Further, in the oxygen-absorbing resin composition, additives such as a desiccant, a pigment, a dye, an antioxidant, a slip agent, an antistatic agent, a stabilizer, etc., calcium carbonate, A filler such as clay, mica, and silica, a deodorant, and the like may be added, but various materials can be mixed without being limited to the above-described ones.

  Note that the oxygen-absorbing resin composition of the present embodiment may further contain a radical generator or a photoinitiator as necessary in order to promote the oxygen absorption reaction. Specific examples of the radical generator include various N-hydroxyimide compounds such as N-hydroxysuccinimide, N-hydroxymaleimide, N, N′-dihydroxycyclohexanetetracarboxylic acid diimide, N-hydroxyphthalimide, N-hydroxytetrachlorophthalimide, N-hydroxytetrabromophthalimide, N-hydroxyhexahydrophthalimide, 3-sulfonyl-N-hydroxyphthalimide, 3-methoxycarbonyl-N-hydroxyphthalimide, 3-methyl-N-hydroxyphthalimide, 3 -Hydroxy-N-hydroxyphthalimide, 4-nitro-N-hydroxyphthalimide, 4-chloro-N-hydroxyphthalimide, 4-methoxy-N-hydroxyphthalimide, 4-dimethylamino -N-hydroxyphthalimide, 4-carboxy-N-hydroxyhexahydrophthalimide, 4-methyl-N-hydroxyhexahydrophthalimide, N-hydroxyhetic acid imide, N-hydroxyhymic acid imide, N-hydroxytrimellitic acid imide , N, N-dihydroxypyromellitic acid diimide and the like, but are not particularly limited thereto. Specific examples of the photoinitiator include, but are not limited to, benzophenone and its derivatives, thiazine dyes, metal porphyrin derivatives, anthraquinone derivatives, and the like. In addition, these radical generators and photoinitiators can be used individually by 1 type or in combination of 2 or more types.

  In addition, the oxygen-absorbing resin composition of the present embodiment can be kneaded with another thermoplastic resin and an extruder as long as the purpose of the present embodiment is not impaired. Examples of the thermoplastic resin used for kneading include low density polyethylene, medium density polyethylene, high density polyethylene, linear low density polyethylene, linear ultra low density polyethylene, polypropylene, poly-1-butene, and poly-4-methyl. -1-pentene, polyolefins such as random or block copolymers of α-olefins such as ethylene, propylene, 1-butene, 4-methyl-1-pentene, maleic anhydride grafted polyethylene, maleic anhydride grafted polypropylene, etc. Acid-modified polyolefin, ethylene-vinyl acetate copolymer, ethylene-vinyl alcohol copolymer, ethylene-vinyl chloride copolymer, ethylene- (meth) acrylic acid copolymer and its ionic cross-linked product (ionomer), ethylene- Methyl methacrylate copolymer, etc. Styrene resins such as ethylene-vinyl compound copolymers, polystyrene, acrylonitrile-styrene copolymers, α-methylstyrene-styrene copolymers, polyvinyl compounds such as polymethyl acrylate and polymethyl methacrylate, nylon 6, nylon 66, nylon 610, nylon 12, polyamide such as polymetaxylylene adipamide (MXD6), polyethylene terephthalate (PET), polybutylene terephthalate (PBT), polytrimethylene terephthalate (PTT), polyethylene naphthalate (PEN), glycol Modified polyethylene terephthalate (PETG), polyethylene succinate (PES), polybutylene succinate (PBS), polylactic acid, polyglycolic acid, polycaprolactone, polyhydroxyalkano Polyester over preparative like, polycarbonate, polyether, or mixtures thereof, such as polyethylene oxide.

  The thickness of the oxygen absorbing layer (layer A) is preferably from 1 to 1000 μm, more preferably from 50 to 1000 μm, from the viewpoint of having oxygen absorbing performance and ensuring various physical properties required for the medical multilayer molded container. It is 900 micrometers, More preferably, it is 100-800 micrometers.

[Resin layer containing thermoplastic resin (layer B)]
The resin layer (layer B) containing the thermoplastic resin of the present embodiment is a layer containing a thermoplastic resin. The content of the thermoplastic resin in the layer B is not particularly limited, but the content of the thermoplastic resin relative to the total amount of the layer B is preferably 70 to 100% by mass, more preferably 80 to 100% by mass, and 90 to 90%. 100% by mass is particularly preferred.

  The oxygen-absorbing medical multilayer molded container of the present embodiment may have a plurality of layers B, and the configurations of the plurality of layers B may be the same as or different from each other. The thickness of the layer B can be appropriately determined according to the use, and is preferably 50 to 10,000 μm, more preferably 100 to 7000 μm, and more preferably 100 to 7000 μm, from the viewpoint of securing various physical properties required for the medical multilayer molded container. Preferably it is 300-5000 micrometers.

  Arbitrary thermoplastic resins can be used for the thermoplastic resin of this embodiment, and it is not specifically limited. Examples thereof include polyolefins, polyesters, polyamides, ethylene-vinyl alcohol copolymers, plant-derived resins, and chlorinated resins. In the present embodiment, the thermoplastic resin preferably includes at least one selected from the group consisting of these resins. Moreover, in the said thermoplastic resin, it is preferable that content of thermoplastic resins other than the said polyester compound of this invention is 50-100 mass%, 70-100 mass% is more preferable, 90-100 mass% Is particularly preferred.

[Polyolefin]
Specific examples of polyolefin include polyethylene (low density polyethylene, medium density polyethylene, high density polyethylene, linear (linear) low density polyethylene), polypropylene, polybutene-1, poly-4-methylpentene-1, and ethylene. Copolymers with α-olefin, propylene and α-olefin copolymers, ethylene-α, β-unsaturated carboxylic acid copolymers, ethylene-α, β-unsaturated carboxylic acid ester copolymers, etc. Preferred are cycloolefins ring-opening polymers such as norbornene or tetracyclododecene or derivatives thereof and hydrogenated products thereof, cycloolefins such as norbornene or tetracyclododecene or derivatives thereof, and ethylene or propylene. And cyclopentyl residues in the molecular chain Conversion cyclopentyl residue is a resin which is a copolymer that is inserted. Here, the cycloolefin includes monocyclic and polycyclic ones. Preference is given to thermoplastic norbornene resins or thermoplastic tetracyclododecene resins. Examples of thermoplastic norbornene resins include ring-opening polymers of norbornene monomers, hydrogenated products thereof, addition polymers of norbornene monomers, addition polymers of norbornene monomers and olefins, and the like. It is done. Thermoplastic tetracyclododecene resins include ring-opening polymers of tetracyclododecene monomers, hydrogenated products thereof, addition polymers of tetracyclododecene monomers, tetracyclododecene monomers. And addition polymers of monomers and olefins. Thermoplastic norbornene resins are described in, for example, JP-A-3-14882, JP-A-3-122137, JP-A-4-63807, and the like.

  Particularly preferred are copolymers of norbornene and olefins such as ethylene as raw materials, cycloolefin copolymer (COC) which is a copolymer of tetracyclododecene and olefins such as ethylene as raw materials, and norbornene. A cycloolefin polymer (COP) which is a polymer obtained by ring polymerization and hydrogenation is also preferable. Such COC and COP are described in, for example, JP-A-5-300939 or JP-A-5-317411.

  COC is commercially available, for example, as Mitsui Chemicals, Inc. (Appel (registered trademark)), and COP is, for example, manufactured by Nippon Zeon Co., Ltd., Zeonex (registered trademark) or Zeonore (registered trademark), or manufactured by Daikyo Seiko Co., Ltd. , Commercially available as Daikyo Resin CZ®.

  COC and COP show chemical properties such as heat resistance and light resistance, and chemical resistance as a polyolefin resin, and physical properties such as mechanical properties, melting, flow properties, and dimensional accuracy are as non-crystalline resins. It is the most preferred material because of its characteristics

[polyester]
The polyester described here is a polyester that can be used as a thermoplastic resin, and is not a polyester compound of the present embodiment. In the present embodiment, the polyester is composed of one or more selected from polycarboxylic acids containing dicarboxylic acids and ester-forming derivatives thereof, and one or more selected from polyhydric alcohols containing glycol. Or those composed of hydroxycarboxylic acids and their ester-forming derivatives, or those composed of cyclic esters. The ethylene terephthalate-based thermoplastic polyester is composed of an ethylene terephthalate unit in the majority of ester repeating units, generally 70 mol% or more, and has a glass transition point (Tg) of 50 to 90 ° C. and a melting point (Tm) of 200 to 275. Those in the range of ° C. are preferred. Polyethylene terephthalate is particularly excellent as an ethylene terephthalate thermoplastic polyester in terms of pressure resistance, heat resistance, heat pressure resistance, etc. In addition to ethylene terephthalate units, dibasic acids such as isophthalic acid and naphthalenedicarboxylic acid and diols such as propylene glycol Copolyesters containing a small amount of ester units consisting of can also be used.

  Examples of dicarboxylic acids include oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, decanedicarboxylic acid, dodecanedicarboxylic acid, tetradecanedicarboxylic acid, hexadecanedicarboxylic acid, 3- Exemplified as cyclobutanedicarboxylic acid, 1,3-cyclopentanedicarboxylic acid, 1,2-cyclohexanedicarboxylic acid, 1,3-cyclohexanedicarboxylic acid, 1,4-cyclohexanedicarboxylic acid, 2,5-norbornanedicarboxylic acid, dimer acid, etc. Saturated aliphatic dicarboxylic acids or ester-forming derivatives thereof, unsaturated aliphatic dicarboxylic acids exemplified by fumaric acid, maleic acid, itaconic acid or the like, or ester-forming derivatives thereof, orthophthalic acid, isophthalic acid, terephthalic acid 1,3-na Taleenedicarboxylic acid, 1,4-naphthalenedicarboxylic acid, 1,5-naphthalenedicarboxylic acid, 2,6-naphthalenedicarboxylic acid, 2,7-naphthalenedicarboxylic acid, 4,4′-biphenyldicarboxylic acid, 4,4′- Aromatic dicarboxylic acids exemplified by biphenylsulfone dicarboxylic acid, 4,4′-biphenyl ether dicarboxylic acid, 1,2-bis (phenoxy) ethane-p, p′-dicarboxylic acid, anthracene dicarboxylic acid, etc. or ester formation thereof Metal, exemplified by 5-sodium sulfoisophthalic acid, 2-sodium sulfoterephthalic acid, 5-lithium sulfoisophthalic acid, 2-lithium sulfoterephthalic acid, 5-potassium sulfoisophthalic acid, 2-potassium sulfoterephthalic acid, etc. Sulfonate group-containing aromatic dicarboxylic acid or Such lower alkyl esters thereof derivative.

  Among the above dicarboxylic acids, the use of terephthalic acid, isophthalic acid, and naphthalenedicarboxylic acid is particularly preferable in terms of the physical properties of the resulting polyester, and other dicarboxylic acids may be copolymerized as necessary. .

  As polyvalent carboxylic acids other than these dicarboxylic acids, ethanetricarboxylic acid, propanetricarboxylic acid, butanetetracarboxylic acid, pyromellitic acid, trimellitic acid, trimesic acid, 3,4,3 ′, 4′-biphenyltetracarboxylic acid, And ester-forming derivatives thereof.

  As glycols, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, diethylene glycol, triethylene glycol, 1,2-butylene glycol, 1,3-butylene glycol, 2,3-butylene glycol, 1,4 -Butylene glycol, 1,5-pentanediol, neopentyl glycol, 1,6-hexanediol, 1,2-cyclohexanediol, 1,3-cyclohexanediol, 1,4-cyclohexanediol, 1,2-cyclohexanedimethanol 1,3-cyclohexanedimethanol, 1,4-cyclohexanedimethanol, 1,4-cyclohexanediethanol, 1,10-decamethylene glycol, 1,12-dodecanediol, polyethylene glycol, polytrimethyl Aliphatic glycols exemplified by tylene glycol and polytetramethylene glycol, hydroquinone, 4,4′-dihydroxybisphenol, 1,4-bis (β-hydroxyethoxy) benzene, 1,4-bis (β- Hydroxyethoxyphenyl) sulfone, bis (p-hydroxyphenyl) ether, bis (p-hydroxyphenyl) sulfone, bis (p-hydroxyphenyl) methane, 1,2-bis (p-hydroxyphenyl) ethane, bisphenol A, bisphenol Examples thereof include aromatic glycols exemplified by C, 2,5-naphthalenediol, glycols obtained by adding ethylene oxide to these glycols, and the like.

  Among the above glycols, it is particularly preferable to use ethylene glycol, 1,3-propylene glycol, 1,4-butylene glycol, and 1,4-cyclohexanedimethanol as the main component. Examples of polyhydric alcohols other than these glycols include trimethylolmethane, trimethylolethane, trimethylolpropane, pentaerythritol, glycerol, hexanetriol, and the like. Examples of hydroxycarboxylic acids include lactic acid, citric acid, malic acid, tartaric acid, hydroxyacetic acid, 3-hydroxybutyric acid, p-hydroxybenzoic acid, p- (2-hydroxyethoxy) benzoic acid, 4-hydroxycyclohexanecarboxylic acid, or these And ester-forming derivatives thereof.

  Examples of the cyclic ester include ε-caprolactone, β-propiolactone, β-methyl-β-propiolactone, δ-valerolactone, glycolide, and lactide.

  Examples of ester-forming derivatives of polyvalent carboxylic acids and hydroxycarboxylic acids include these alkyl esters, acid chlorides, acid anhydrides and the like.

  The polyester used in this embodiment is preferably a polyester in which the main acid component is terephthalic acid or an ester-forming derivative thereof or naphthalenedicarboxylic acid or an ester-forming derivative thereof, and the main glycol component is alkylene glycol.

  The polyester in which the main acid component is terephthalic acid or an ester-forming derivative thereof is preferably a polyester containing 70 mol% or more of terephthalic acid or an ester-forming derivative thereof in total with respect to the total acid component. A polyester containing 80 mol% or more is preferable, and a polyester containing 90 mol% or more is more preferable. Similarly, the polyester in which the main acid component is naphthalenedicarboxylic acid or an ester-forming derivative thereof is also preferably a polyester containing 70 mol% or more of naphthalenedicarboxylic acid or an ester-forming derivative thereof, more preferably 80 Polyesters containing at least mol%, more preferably polyesters containing at least 90 mol%.

  Examples of the naphthalenedicarboxylic acid or ester-forming derivative thereof used in the present embodiment include 1,3-naphthalenedicarboxylic acid, 1,4-naphthalenedicarboxylic acid, 1,5-naphthalenedicarboxylic acid, and the like exemplified in the above dicarboxylic acids. 1,6-naphthalenedicarboxylic acid, 2,7-naphthalenedicarboxylic acid, or ester-forming derivatives thereof are preferred.

  The polyester whose main glycol component is an alkylene glycol is preferably a polyester containing 70 mol% or more of the total amount of alkylene glycol with respect to all glycol components, more preferably a polyester containing 80 mol% or more, More preferably, it is a polyester containing 90 mol% or more. The alkylene glycol here may contain a substituent or an alicyclic structure in the molecular chain.

  The copolymer components other than the terephthalic acid / ethylene glycol are isophthalic acid, 2,6-naphthalenedicarboxylic acid, diethylene glycol, neopentyl glycol, 1,4-cyclohexanedimethanol, 1,2-propanediol, 1,3-propane. It is preferably at least one selected from the group consisting of diol and 2-methyl-1,3-propanediol in order to achieve both transparency and moldability, particularly isophthalic acid, diethylene glycol, neopentyl glycol, More preferably, it is at least one selected from the group consisting of 1,4-cyclohexanedimethanol.

  A preferred example of the polyester used in this embodiment is a polyester in which the main repeating unit is composed of ethylene terephthalate, more preferably a linear polyester containing 70 mol% or more of ethylene terephthalate units, and still more preferably an ethylene terephthalate unit. Is a linear polyester containing 80 mol% or more, and particularly preferred is a linear polyester containing 90 mol% or more of ethylene terephthalate units.

  Another preferred example of the polyester used in this embodiment is a polyester in which the main repeating unit is composed of ethylene-2,6-naphthalate, and more preferably 70 mol% or more of ethylene-2,6-naphthalate unit. A linear polyester containing 80 mol% or more of ethylene-2,6-naphthalate units, particularly preferably a linear polyester containing 90 mol% or more of ethylene-2,6-naphthalate units. Polyester.

  Other preferred examples of the polyester used in this embodiment include linear polyesters containing 70 mol% or more of propylene terephthalate units, linear polyesters containing 70 mol% or more of propylene naphthalate units, and 1,4-cyclohexanedimethylene. A linear polyester containing 70 mol% or more of terephthalate units, a linear polyester containing 70 mol% or more of butylene naphthalate units, or a linear polyester containing 70 mol% or more of butylene terephthalate units.

  In particular, the composition of the whole polyester is a combination of terephthalic acid / isophthalic acid // ethylene glycol, terephthalic acid // ethylene glycol / 1,4-cyclohexanedimethanol, and terephthalic acid // ethylene glycol / neopentyl glycol. This is preferable in order to satisfy both the moldability and the moldability. Needless to say, a small amount (5 mol% or less) of diethylene glycol produced by dimerization of ethylene glycol may be included in the esterification (transesterification) reaction or polycondensation reaction.

  Other preferred examples of the polyester used in this embodiment include polyglycolic acid obtained by polycondensation of glycolic acid or methyl glycolate or ring-opening polycondensation of glycolide. This polyglycolic acid may be copolymerized with other components such as lactide.

[polyamide]
The polyamide used in the present embodiment is a polyamide having a unit derived from a lactam or an aminocarboxylic acid as a main constituent unit, or an aliphatic having a unit derived from an aliphatic diamine and an aliphatic dicarboxylic acid as a main constituent unit. Polyamide, Partially aromatic polyamide whose main constituent unit is a unit derived from aliphatic diamine and aromatic dicarboxylic acid, Partially aromatic whose main constituent unit is a unit derived from aromatic diamine and aliphatic dicarboxylic acid Examples thereof include polyamide, and a monomer unit other than the main structural unit may be copolymerized as necessary.

  Examples of the lactam or aminocarboxylic acid include lactams such as ε-caprolactam and laurolactam, aminocarboxylic acids such as aminocaproic acid and aminoundecanoic acid, and aromatic aminocarboxylic acids such as para-aminomethylbenzoic acid. .

  As the aliphatic diamine, an aliphatic diamine having 2 to 12 carbon atoms or a functional derivative thereof can be used. Furthermore, an alicyclic diamine may be used. The aliphatic diamine may be a linear aliphatic diamine or a branched chain aliphatic diamine. Specific examples of such linear aliphatic diamines include ethylenediamine, 1-methylethylenediamine, 1,3-propylenediamine, tetramethylenediamine, pentamethylenediamine, hexamethylenediamine, heptamethylenediamine, octamethylenediamine, Examples include aliphatic diamines such as nonamethylenediamine, decamethylenediamine, undecamethylenediamine, and dodecamethylenediamine. Specific examples of the alicyclic diamine include cyclohexanediamine, 1,3-bis (aminomethyl) cyclohexane, 1,4-bis (aminomethyl) cyclohexane, and the like.

  Moreover, as said aliphatic dicarboxylic acid, linear aliphatic dicarboxylic acid and alicyclic dicarboxylic acid are preferable, and also linear aliphatic dicarboxylic acid which has a C4-C12 alkylene group is especially preferable. Examples of such linear aliphatic dicarboxylic acids include adipic acid, sebacic acid, malonic acid, succinic acid, glutaric acid, pimelic acid, suberic acid, azelaic acid, undecanoic acid, undecadioic acid, dodecanedioic acid, dimer Examples thereof include acids and functional derivatives thereof. Examples of the alicyclic dicarboxylic acid include alicyclic dicarboxylic acids such as 1,4-cyclohexanedicarboxylic acid, hexahydroterephthalic acid, and hexahydroisophthalic acid.

  Examples of the aromatic diamine include metaxylylenediamine, paraxylylenediamine, para-bis (2-aminoethyl) benzene, and the like.

  Examples of the aromatic dicarboxylic acid include terephthalic acid, isophthalic acid, phthalic acid, 2,6-naphthalenedicarboxylic acid, diphenyl-4,4′-dicarboxylic acid, diphenoxyethanedicarboxylic acid, and functional derivatives thereof. It is done.

  Specific polyamides include polyamide 4, polyamide 6, polyamide 10, polyamide 11, polyamide 12, polyamide 4, 6, polyamide 6, 6, polyamide 6, 10, polyamide 6T, polyamide 9T, polyamide 6IT, polymetaxylylene azide. Pamide (Polyamide MXD6), Isophthalic acid copolymer polymetaxylylene adipamide (Polyamide MXD6I), Polymetaxylylene sebamide (Polyamide MXD10), Polymetaxylylene decanamide (Polyamide MXD12), Poly 1,3-bis Examples include aminocyclohexane adipamide (polyamide BAC6) and polyparaxylylene sebacamide (polyamide PXD10). More preferable polyamides include polyamide 6, polyamide MXD6, and polyamide MXD6I.

  Further, as a copolymerization component of the polyamide, a polyether having at least one terminal amino group or a terminal carboxyl group and a number average molecular weight of 2000 to 20000, or an organic carboxylate of the polyether having the terminal amino group, or An amino salt of a polyether having a terminal carboxyl group can also be used. Specific examples include bis (aminopropyl) poly (ethylene oxide) (polyethylene glycol having a number average molecular weight of 2000 to 20000).

  The partially aromatic polyamide may contain a structural unit derived from a polybasic carboxylic acid having 3 or more bases such as trimellitic acid and pyromellitic acid within a substantially linear range.

[Ethylene-vinyl alcohol copolymer]
Although it does not specifically limit as an ethylene vinyl alcohol copolymer used by this embodiment, Preferably it is 15-60 mol%, More preferably, it is 20-55 mol%, More preferably, it is 29-44 mol%. The saponification degree of the vinyl acetate component is preferably 90 mol% or more, more preferably 95 mol% or more.
Further, the ethylene vinyl alcohol copolymer has a smaller amount of α-olefin such as propylene, isobutene, α-octene, α-dodecene, α-octadecene, unsaturated carboxylic acid, etc., as long as the effect of the present embodiment is not adversely affected. A comonomer such as an acid or a salt thereof, a partial alkyl ester, a complete alkyl ester, a nitrile, an amide, an anhydride, an unsaturated sulfonic acid or a salt thereof may be contained.

[Plant-derived resin]
The plant-derived resin used in the present embodiment is not particularly limited as long as it is a resin containing a plant-derived material as a raw material. Specific examples include aliphatic polyester-based biodegradable resins. Examples of the aliphatic polyester-based biodegradable resin include poly (α-hydroxy acids) such as polyglycolic acid (PGA) and polylactic acid (PLA); polybutylene succinate (PBS), polyethylene succinate (PES), and the like. And polyalkylene alkanoates.

[Chlorine resin]
The chlorine-based resin used in the present embodiment may be a resin containing chlorine as a structural unit, and a known resin can be used. Specific examples include polyvinyl chloride, polyvinylidene chloride, and copolymers of these with vinyl acetate, maleic acid derivatives, higher alkyl vinyl ethers, and the like.

  In addition to the oxygen absorbing layer (layer A) and the resin layer containing the thermoplastic resin (layer B), the oxygen-absorbing medical multilayer molded container of the present embodiment has an optional layer depending on the desired performance and the like. May be included. Examples of such an arbitrary layer include an adhesive layer.

  In the oxygen-absorbing medical multilayer molded container of the present embodiment, when a practical interlayer adhesive strength cannot be obtained between two adjacent layers, an adhesive layer (layer AD) is provided between the two layers. It is preferable to provide it. The adhesive layer preferably contains a thermoplastic resin having adhesiveness. As the thermoplastic resin having adhesiveness, for example, an acid modification in which a polyolefin resin such as polyethylene or polypropylene is modified with an unsaturated carboxylic acid such as acrylic acid, methacrylic acid, maleic acid, maleic anhydride, fumaric acid, itaconic acid, etc. Examples thereof include polyester-based thermoplastic elastomers mainly composed of a polyolefin resin and a polyester-based block copolymer. As the adhesive layer, it is preferable to use a modified resin of the same type as the thermoplastic resin used as the layer B from the viewpoint of adhesiveness. The thickness of the adhesive layer is preferably 2 to 100 μm, more preferably 5 to 90 μm, and still more preferably 10 to 80 μm, from the viewpoint of ensuring molding processability while exhibiting practical adhesive strength.

The manufacturing method and layer structure of the oxygen-absorbing medical multilayer molded container of the present embodiment are not particularly limited, and can be manufactured by a normal injection molding method. For example, using a molding machine equipped with two or more injection machines and an injection mold, the material constituting the layer A and the material constituting the layer B are passed from the respective injection cylinders through the mold hot runner into the cavity. The medical multilayer molded container corresponding to the shape of the injection mold can be manufactured. First, the material constituting the layer B is injected from the injection cylinder, then the material constituting the layer A is injected from another injection cylinder simultaneously with the resin constituting the layer B, and then the resin constituting the layer B By injecting a necessary amount of the solution to fill the cavity, a medical multilayer molded container having a three-layer structure B / A / B can be manufactured.
In addition, first, the material constituting the layer B is injected, then the material constituting the layer A is injected alone, and finally the material constituting the layer B is injected by a necessary amount to fill the mold cavity. A medical multilayer molded container having a five-layer structure B / A / B / A / B can be manufactured.
First, the material constituting the layer B1 is injected from the injection cylinder, then the material constituting the layer B2 is injected from another injection cylinder simultaneously with the resin constituting the layer B1, and then the resin constituting the layer A Is injected at the same time as the resin constituting the layer B1 and the layer B2, and then the necessary amount of the resin constituting the layer B1 is injected to fill the cavity, thereby medical treatment of the five-layer structure B1 / B2 / A / B2 / B1 Multi-layer molded containers can be manufactured.
Further, although not an injection molding method, a multilayer molded body may be obtained by a compression molding method. For example, a molded article can be obtained by providing an oxygen-absorbing resin agent in a thermoplastic resin melt, supplying the molten mass to a male mold, compressing the molten mass with a female mold, and cooling and solidifying the compression molded article.
In order to give heat resistance to the mouth and neck of the obtained molded body, the mouth and neck may be crystallized by heat treatment at this stage. The degree of crystallinity is preferably 30 to 50%, more preferably 35 to 45%. In addition, you may implement crystallization, after giving the secondary process mentioned later.
Moreover, you may shape | mold into a desired container shape by shaping | molding means, such as extrusion molding and compression molding (sheet molding, blow molding).
Although the shape of this container is not specifically limited, For example, a vial, an ampule, a prefilled syringe, and a vacuum blood collection tube are mentioned.

[Vial]
The configuration of the vial of this embodiment is not different from that of a general vial, and includes a bottle, a rubber stopper, and a cap. The bottle is filled with a chemical solution, sealed with a rubber stopper, and a cap is wound around the top. The bottle portion is an oxygen-absorbing medical multilayer molded container used in this embodiment, wherein at least one of the intermediate layers is an oxygen-absorbing layer (layer A) made of an oxygen-absorbing resin composition, The outermost layer is a resin layer (layer B) containing a thermoplastic resin.

The method for molding the bottle portion of the vial of this embodiment is manufactured by injection blow molding or extrusion blow molding. As an example, an injection blow molding method is shown below.
For example, using a molding machine equipped with two or more injection machines and an injection mold, the material constituting the layer A and the material constituting the layer B are passed from the respective injection cylinders through the mold hot runner into the cavity. The multilayer molded body corresponding to the shape of the injection mold can be manufactured. First, the material constituting the layer B is injected from the injection cylinder, then the material constituting the layer A is injected from another injection cylinder simultaneously with the resin constituting the layer B, and then the resin constituting the layer B By injection of the required amount to fill the cavity, a three-layer structure B / A / B shaped body can be produced.
In addition, first, the material constituting the layer B is injected, then the material constituting the layer A is injected alone, and finally the material constituting the layer B is injected by a necessary amount to fill the mold cavity. A multilayer molded body having a five-layer structure B / A / B / A / B can be produced.
First, the material constituting the layer B1 is injected from the injection cylinder, then the material constituting the layer B2 is injected from another injection cylinder simultaneously with the resin constituting the layer B1, and then the resin constituting the layer A Is injected at the same time as the resin constituting the layers B1 and B2, and then the required quantity of the resin constituting the layer B1 is injected to fill the cavity, thereby providing a multi-layer injection of B1 / B2 / A / B2 / B1. A molded body can be produced.
In injection blow molding, the multilayer molded body obtained by the above method is fitted in the final shape mold (blow mold) while maintaining a certain degree of heating, blown in air, inflated and brought into close contact with the mold, and cooled and solidified. By making it, it can shape | mold in a bottle shape.

〔ampoule〕
The configuration of the ampule according to the present embodiment is a small container having a narrow neck without changing from a general ampule. After filling with chemicals, it is used by sealing the tip of the neck. The above-mentioned ampule is an oxygen-absorbing medical multilayer molded container used in the present invention, wherein at least one of the intermediate layers is an oxygen-absorbing layer (layer A) made of an oxygen-absorbing resin composition, and the innermost layer and the outermost layer are It is a resin layer (layer B) containing a thermoplastic resin. The ampoule molding method of this embodiment is manufactured by injection blow molding or extrusion blow molding.

[Prefilled syringe]
The configuration of the prefilled syringe according to the present embodiment is not different from that of a general prefilled syringe. At least a barrel for filling a chemical, a joint for joining a syringe needle to one end of the barrel, and a chemical at the time of use are extruded. It consists of a plunger for the purpose. The barrel is an oxygen-absorbing medical multilayer molded container used in the present invention, wherein at least one of the intermediate layers is an oxygen-absorbing layer (layer A) made of an oxygen-absorbing resin composition, and the innermost layer and the outermost layer are It is a resin layer (layer B) containing a thermoplastic resin.

  The molding method of the prefilled syringe of the present invention is manufactured by an injection molding method. The barrel that becomes the multilayer molded body first injects a certain amount of the resin constituting the layer B into the cavity, then injects a certain amount of the resin constituting the layer A, and again injects a certain amount of the resin constituting the layer B. Manufactured by. The barrel and the joint may be molded as an integral part, or separately molded products may be joined. The tip of the joint must be sealed, but the method may be to heat the resin at the tip of the joint to a molten state, sandwich it with pliers or the like, and fuse it.

  The thickness of the container may be about 0.5 to 20 mm depending on the purpose of use and size. Moreover, even if thickness is uniform, what changed thickness may be sufficient. Further, another gas barrier film or a light shielding film may be formed on the surface (not treated) for the purpose of long-term storage stability. As such a film and a method for forming the film, a method described in JP-A-2004-323058 can be employed.

[Vacuum blood collection tube]
The configuration of the vacuum blood collection tube of this embodiment is not different from that of a general vacuum blood collection tube, and is composed of a tubular body and a plug body. The tubular body is an oxygen-absorbing medical multilayer molded container used in this embodiment, wherein at least one of the intermediate layers is an oxygen-absorbing layer (layer A) made of an oxygen-absorbing resin composition, and the innermost layer and the innermost layer. The outer layer is a resin layer (layer B) containing a thermoplastic resin.

  The vacuum blood collection tube forming method of the present embodiment is manufactured by an injection molding method. The tubular body that is a multilayer molded body first injects a certain amount of the resin constituting the layer B into the cavity, then injects a certain amount of the resin that constitutes the layer A, and again injects a certain amount of the resin that constitutes the layer B. It is manufactured by.

[Biopharmaceutical]
The biopharmaceutical filled in the oxygen-absorbing medical multilayer molded container of the present embodiment is not particularly limited, but from the viewpoint of the effect of the present embodiment, protein pharmaceuticals, nucleic acid pharmaceuticals and the like can be mentioned. Narnal antibody, various vaccines, interferon, insulin, growth hormone, erythropoietin, colony stimulating factor, TPA, interleukin, blood coagulation factor VIII, blood coagulation factor IX, natriuretic hormone, somatomedin, glucagon, serum albumin, calcitonin, growth Examples include hormone releasing factors, digestive enzyme agents, inflammatory enzyme agents, antibiotics, antisense nucleic acids, antigene nucleic acids, decoy nucleic acids, aptamers, siRNA, and microRNA. When these biopharmaceuticals are filled in a medical multilayer container, it is possible to suppress deterioration due to oxidation and a decrease in medicinal efficacy.

  In addition, before and after filling these objects to be stored, the medical multilayer container and the objects to be stored can be sterilized in a form suitable for the objects to be stored. Sterilization methods include hot water treatment at 100 ° C. or lower, pressurized hot water treatment at 100 ° C. or higher, heat sterilization such as high temperature heat treatment at 121 ° C. or higher, electromagnetic wave sterilization of ultraviolet rays, microwaves, gamma rays, ethylene oxide, etc. Gas treatment, and chemical sterilization such as hydrogen peroxide and hypochlorous acid.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto. Unless otherwise specified, NMR measurements were performed at room temperature. In the examples, vials are used as examples. However, as shown in the present specification, the required characteristics for ampoules and prefilled syringes are the same as those for vials, and therefore the scope of the present invention is limited by these examples. Is not to be done.

[Monomer synthesis example]
An autoclave having an internal volume of 18 L was charged with 2.20 kg of dimethyl naphthalene-2,6-dicarboxylate, 11.0 kg of 2-propanol, and 350 g (50 wt% water-containing product) of 5% palladium supported on activated carbon. Next, after the air in the autoclave was replaced with nitrogen, and further nitrogen was replaced with hydrogen, hydrogen was supplied until the pressure in the autoclave reached 0.8 MPa. Next, the agitator was started, the rotation speed was adjusted to 500 rpm, the internal temperature was raised to 100 ° C. over 30 minutes, and hydrogen was further supplied to make the pressure 1 MPa. Thereafter, the supply of hydrogen was continued to maintain 1 MPa in accordance with the pressure drop due to the progress of the reaction. Since the pressure drop disappeared after 7 hours, the autoclave was cooled, unreacted residual hydrogen was released, and then the reaction solution was taken out from the autoclave. The reaction solution was filtered to remove the catalyst, and then 2-propanol was evaporated from the separated filtrate with an evaporator. To the obtained crude product, 4.40 kg of 2-propanol was added and purified by recrystallization to obtain dimethyl tetralin-2,6-dicarboxylate in a yield of 80%. The NMR analysis results are as follows. 1H-NMR (400 MHz CDCl ₃ ) δ7.76-7.96 (2H m), 7.15 (1H d), 3.89 (3H s), 3.70 (3H s), 2.70-3.09 (5H m), 1.80-1.95 (1H m ).

[Polymer production example]
(Production Example 1)
In a polyester resin production apparatus equipped with a fractionator, total condenser, cold trap, stirrer, heating device, and nitrogen introduction pipe, 543 g of dimethyl tetralin-2,6-dicarboxylate as a monomer synthesis example , 1,4-butanediol (315 g) and tetrabutyl titanate (0.171 g) were charged, and the temperature was raised to 230 ° C. in a nitrogen atmosphere to conduct a transesterification reaction. After setting the reaction conversion rate of the dicarboxylic acid component to 85% or more, 0.171 g of tetrabutyl titanate is added, the temperature is increased and the pressure is gradually reduced, polycondensation is performed at 245 ° C. and 133 Pa or less, and the polyester compound (1) Got.

As a result of measuring the weight average molecular weight and number average molecular weight of the obtained polyester compound (1) by GPC (gel permeation chromatography), the weight average molecular weight in terms of polystyrene was 8.7 × 10 ⁴ , and the number average molecular weight was It was 3.1 × 10 ⁴ . As a result of measuring the glass transition temperature and the melting point by DSC, the glass transition temperature was 36 ° C. and the melting point was 145 ° C.

(Production Example 2)
A polyester compound (2) was synthesized in the same manner as in Production Example 1 except that 1,4-butanediol of Production Example 1 was changed to ethylene glycol and its weight was changed to 217 g. The weight average molecular weight in terms of polystyrene of the polyester compound (2) was 8.5 × 10 ⁴ , the number average molecular weight was 3.0 × 10 ⁴ , the glass transition temperature was 67 ° C., and the melting point was not recognized because it was amorphous.

(Production Example 3)
A polyester compound (3) was synthesized in the same manner as in Production Example 1 except that 1,4-butanediol in Production Example 1 was changed to 1,6-hexanediol and its weight was changed to 413 g. The weight average molecular weight of the polyester compound (3) was 8.9 × 10 ⁴ , the number average molecular weight was 3.3 × 10 ⁴ , the glass transition temperature was 16 ° C., and the melting point was 137 ° C.

(Production Example 4)
A polyester compound (4) was synthesized in the same manner as in Production Example 1 except that 315 g of 1,4-butanediol in Production Example 1 was changed to 258 g of 1,4-butanediol and 44 g of ethylene glycol. The weight average molecular weight of the polyester compound (4) was 1.1 × 10 ⁵ , the number average molecular weight was 4.1 × 10 ⁴ , the glass transition temperature was 39 ° C., and the melting point was 135 ° C.

[Manufacture of vials]

  Under the following conditions, the material constituting the layer B is injected from the injection cylinder, then the material constituting the layer A is injected from another injection cylinder at the same time as the resin constituting the layer B, and then the layer A is constituted. After injection of the required amount of resin to fill the cavity in the injection mold, an injection molded body having a three-layer structure of B / A / B is obtained, and then the injection molded body is cooled to a predetermined temperature, and a blow mold The vial (bottle part) was manufactured by performing blow molding after shifting to. The total mass of the vial was 24 g, and the mass of layer A was 30% by mass of the total mass of the vial. As the resin constituting the layer B, a cycloolefin copolymer (manufactured by Ticona GmbH, trade name: TOPAS6013) was used.

(Vial shape)
The total length was 89 mm, the outer diameter was 40 mmφ, and the wall thickness was 1.8 mm. For the manufacture of the vial, an injection blow integrated molding machine (manufactured by UNILOY, model: IBS 85, 4 pieces) was used.
(Vial molding conditions)
Injection cylinder temperature for layer A: 260 ° C
Injection cylinder temperature for layer B: 280 ° C
Resin channel temperature in injection mold: 280 ° C
Blow temperature: 150 ° C
Blow mold cooling water temperature: 15 ° C

[Performance evaluation of vials]
The oxygen permeability of the vials obtained in Examples and Comparative Examples, appearance after molding, drop test, dissolution test, and biopharmaceutical storage test were measured and evaluated by the following methods.

(1) Vials oxygen permeability (OTR)
The oxygen permeability on the 30th day from the start of measurement was measured in an atmosphere of 23 ° C., 50% relative humidity outside the molded body, and 100% relative humidity inside. For the measurement, an oxygen permeability measuring device (manufactured by MOCON, trade name: OX-TRAN 2-21 ML) was used. The lower the measured value, the better the oxygen barrier property. The lower limit of detection of the measurement is oxygen permeability 5 × 10 ⁻⁵ mL / (0.21 atm · day · package).

(2) Appearance after molding The presence or absence of whitening of the vial after molding was visually observed.

(3) Drop test After the vial was stored at 40 ° C. and 90% RH for 1 month, it was filled with 50 mL of pure water and sealed with a rubber stopper and an aluminum cap. The container appearance was examined when the container was dropped from a height of 2 m.

(4) Dissolution test After storing the vial at 40 ° C. and 90% RH for 1 month, a container filled with 50 mL of pure water and sealed with a rubber stopper and an aluminum cap was placed under 40 ° C. and 60% RH. After storing for months, the total amount of carbon (hereinafter referred to as TOC) in pure water was measured.
(TOC measurement)
Equipment: Shimadzu Corporation TOC-V _CPH
Combustion furnace temperature: 720 ° C
Gas and flow rate: High purity air, TOC meter section 150mL / min
Injection volume: 150 μL
Detection limit: 1 μg / mL

(5) Biopharmaceutical preservation test (binding ratio measurement method)
Using an isothermal titration calorimeter, a 5 μM antigen solution (FGF1-Mouse manufactured by Biologic Industries Ltd.) was filled on the cell side, and the binding ratio was measured at 25 ° C. while 10 μL of the antibody solution was dropped into the cell.
(Preservation test)
The vial was filled with 1 cc of ANTI FGF1, Monoclonal Antibody (mAb1) manufactured by Wako Pure Chemical Industries, Ltd. adjusted to 50 μM, and stored for 180 days under 8 ° C. and 50% RH conditions. As a solvent, Invitrogen phosphate buffer (PBS pH 7.4) was used. The binding ratio of the antibody solution before storage test and after storage for 180 days was measured by the above method, and the antibody activity retention before and after storage was determined by the following formula.
Antibody activity retention rate (%)
= (Binding ratio of antibody solution after storage for 180 days / Binding ratio of antibody solution before storage) × 100

Example 1
Polyester compound (1) is 100 parts by weight of cobalt stearate (II) dry blended so that the amount of cobalt is 0.02 parts by weight, and 15 kg / h in a twin screw extruder having two screws with a diameter of 37 mm. The above materials were supplied at a speed, melt kneaded under the condition of a cylinder temperature of 220 ° C., a strand was extruded from the extruder head, cooled, and pelletized to obtain an oxygen-absorbing resin composition. Using the oxygen-absorbing resin composition as the resin constituting the layer A, a vial was produced and performance evaluation was performed. The results are shown in Table 1.

(Examples 2 to 4)
A vial was produced in the same manner as in Example 1 except that the polyester compound (1) was changed to the polyester compound shown in Table 1, and performance evaluation was performed. The results are shown in Table 1.

(Example 5)
A vial was produced in the same manner as in Example 1 except that 100 parts by mass of the polyester compound (1) was changed to a resin composition obtained by blending 90 parts by mass of the polyester compound (1) and 10 parts by mass of the polyester compound (2). Evaluation was performed. The results are shown in Table 1.

(Comparative Example 1)
A single-layer vial having the same shape as in Example 1 was produced using a cycloolefin copolymer (Ticona GmbH, TOPAS 6013) manufactured by Ticona GmbH, and performance evaluation was performed. The results are shown in Table 1.

(Comparative Example 2)
The polyester compound (1) is changed to nylon MXD6 (S7007 manufactured by Mitsubishi Gas Chemical Co., Ltd.), the amount of cobalt stearate (II) used is 0.04 parts by mass as the amount of cobalt, and the cylinder temperature is 280 ° C. A vial was produced in the same manner as in Example 1, and the performance was evaluated. The results are shown in Table 1.

  When biopharmaceuticals are stored in the containers obtained in Examples 1 to 5, good strength is maintained even after long-term storage, the amount of elution from the containers to the contents is low, and a decrease in medicinal efficacy after storage is suppressed. I know that.

Claims (4)

The biopharmaceutical is laminated on both sides of the layer A with an oxygen-absorbing layer (layer A) comprising an oxygen-absorbing resin composition containing a polyester compound and a transition metal catalyst and a resin layer (layer B) containing a thermoplastic resin. A biopharmaceutical storage method for storing in an oxygen-absorbing medical multilayer molded container containing at least three layers,
The polyester compound is represented by the following general formulas (1) to (4).

(In the formula, each R independently represents a hydrogen atom or a monovalent substituent, and the monovalent substituent is a halogen atom, alkyl group, alkenyl group, alkynyl group, aryl group, heterocyclic group, cyano group, A group consisting of a group, a hydroxy group, a carboxyl group, an ester group, an amide group, a nitro group, an alkoxy group, an aryloxy group, an acyl group, an amino group, a mercapto group, an alkylthio group, an arylthio group, a heterocyclic thio group, and an imide group At least one selected from the above, which may further have a substituent, m represents an integer of 0 to 3, n represents an integer of 0 to 7, and at least one hydrogen atom at the benzyl position of the tetralin ring. X is an aromatic hydrocarbon group, a saturated or unsaturated alicyclic hydrocarbon group, a linear or branched saturated or unsaturated aliphatic hydrocarbon group, and a heterocyclic ring. It represents a divalent group containing at least one group selected from the group consisting of.)
Containing a structural unit having at least one tetralin ring selected from the group consisting of:
Biopharmaceutical storage method.   The biopharmaceutical storage method according to claim 1, wherein the transition metal catalyst contains at least one transition metal selected from the group consisting of manganese, iron, cobalt, nickel and copper.   The biopharmaceutical storage method according to claim 1 or 2, wherein the transition metal catalyst is contained in an amount of 0.001 to 10 parts by mass as a transition metal amount with respect to 100 parts by mass of the polyester compound. The biopharmaceutical according to any one of claims 1 to 3, wherein the structural unit represented by the general formula (1) is at least one selected from the group consisting of the following formulas (5) to (7). Preservation method.