Medical multilayer container and method for manufacturing the same

Abstract

The present invention relates to a transparent medical multilayer container which is steam sterilizable and a method for its manufacture. The medical multilayer container comprises at least two layers. One layer consists of a first co-polyamide which comprises at least one co-polyamide formed mainly from isophthalic acid (I), hexamethylene diamine (HMD) and meta-xylylene diamine (MXD). The other layer consists of a second co-polyamide which comprises at least one amorphous co-polyamide having a glass transition temperature higher than 165°C. According to one aspect of the invention, it is allowed to provide a plastic-based medical multilayer container having excellent gas barrier properties, water vapor barrier properties, mechanical properties and transparency, which has a sterilizability sufficient to be suitable for heat sterilization at least at 134°C.

Description

Technical Field

[0001] This invention relates to medical multilayer containers and their manufacturing methods, particularly to plastic-based medical multilayer containers and their manufacturing methods that possess excellent gas barrier properties, water vapor barrier properties, mechanical properties, transparency, and sterilizability. Background Technology

[0002] Due to its sterilizability, transparency, and good gas barrier properties, glass is often used to make items for medical purposes.

[0003] These items can be sterilized in boiling water (approximately 100°C) or at elevated temperatures in a saturated steam atmosphere (steam sterilization) or a dry gas atmosphere (hot air sterilization). Steam sterilization is the method used in hospitals and practice, at least because hot air sterilization carries a number of safety risks compared to steam sterilization: in dry heat conditions, heat transfer to the product occurs relatively slowly, and the formation of cold islands can affect sterilization success; therefore, validation of the hot air sterilization method is not possible.

[0004] Glass containers, in the form of ampoules, vials, and pre-filled syringes, have been used to store chemicals in a sealed manner. However, these glass containers have drawbacks: they produce fine glassy particles called "flakes" and are prone to breakage upon impact, such as from drops. Another disadvantage of glass containers is their weight due to the relatively high density of glass.

[0005] In comparison, plastics are lighter than glass, and some plastics even excel in impact resistance, heat resistance, and transparency depending on their material composition. Therefore, plastic containers have been investigated as alternatives to glass containers. For example, cyclic olefin polymers (hereinafter sometimes referred to as "COP") have been widely used as a substitute for glass materials in the field of medical containers due to their high impact resistance, heat resistance, and transparency.

[0006] However, known extruders and molded parts are unsuitable for producing transparent multilayer containers for medical use that are steam sterilizable and should withstand more than 5 cycles of steam sterilization without damage, because under the conditions of steam sterilization cycles, plastic-based transparent multilayer containers for medical use produced from known extruders and molded parts will suffer deformation and / or show cracks.

[0007] Furthermore, unlike single-layer structures, multi-layer structures present additional challenges, as different materials will not behave in exactly the same way due to their varying coefficients of thermal expansion. This can lead to negative consequences, such as stresses exerted by the layers on each other and the resulting mechanical damage or shape changes.

[0008] Furthermore, many polymer containers are inferior to glass containers in terms of gas barrier performance, which is particularly desirable for improvement. In particular, it is desirable in the art to provide a plastic container with improved gas barrier performance, especially a multilayer plastic container having a gas barrier layer as an inner layer. Summary of the Invention

[0009] In view of the above-mentioned problems in the prior art, one aspect of the present invention aims to provide a plastic-based medical multilayer container with excellent gas barrier properties, water vapor barrier properties, mechanical properties and transparency, which has sterilizability sufficient to be suitable for heat sterilization at at least 134°C.

[0010] The inventors have extensively studied sterilizable plastic materials, particularly those exhibiting excellent performance in areas such as gas barrier properties, water vapor barrier properties, mechanical properties, and transparency after heat sterilization. They discovered that by using two specific copolyamide resin layers, excellent gas barrier properties, water vapor barrier properties, mechanical properties, and transparency can be achieved even after heat sterilization. Preferably, the medical multilayer container does not contain polymers other than polyamide. This polyamide layer structure has the additional advantage of easy recyclability.

[0011] According to one aspect of the invention, the inventors have discovered that transparent plastics sterilized using hot steam, if in direct contact with steam, should have a glass transition temperature (Tg) of at least 165°C, such that they do not suffer any mechanical or visual quality loss or shape change during hot steam sterilization, preferably at 134°C. Transparent plastics sterilized using hot steam, without direct contact with steam (inner layer), should have a glass transition temperature (Tg) of at least 140°C, such that they do not suffer any mechanical or visual quality loss or shape change during hot steam sterilization, preferably at 134°C. According to one aspect of the invention, preferably, instead of a sterilization time of 3 minutes, the duration of hot steam sterilization at 134°C is increased to 7 minutes to obtain a safety factor of at least 2. Furthermore, according to one aspect of the invention, the products are capable of withstanding at least 5 hot steam sterilization cycles, preferably at least 10 hot steam sterilization cycles, without suffering mechanical and / or visual changes or deviations in their dimensions, and possess excellent gas barrier properties (measured using O2-TR and CO2-TR, where TR represents transmittance).

[0012] According to one aspect of the present invention, a multilayer medical container is provided, comprising an inner layer containing copolyamide A and an outer layer containing copolyamide B, wherein the monomer of the copolyamide A comprises or is composed of the following:

[0013] 10 mol% to 40 mol% m-phenylenedimethyldiamine;

[0014] 10 mol% to 40 mol% 1,6-hexanediamine;

[0015] 46 mol% to 54 mol% phthalic acid, wherein the phthalic acid is composed of isophthalic acid and optionally terephthalic acid, wherein the content of terephthalic acid in the phthalic acid is 0 mol% to 50 mol%;

[0016] The copolyamide B comprises or consists of the following: an amorphous copolyamide with a glass transition temperature above 165°C, preferably in the range of 170°C to 220°C, and particularly preferably in the range of 180°C to 210°C.

[0017] According to one aspect of the present invention, a method for manufacturing a multilayer medical container is provided, comprising forming the multilayer medical container according to the present invention by injection blow molding.

[0018] According to one aspect of the invention, through the conceived structure / composition / method, the invention allows for the provision of plastic-based multilayer medical containers with excellent sterilizability and excellent gas barrier properties, water vapor barrier properties, mechanical properties, and transparency even after undergoing multiple thermal steam sterilization cycles. Detailed Implementation

[0019] This disclosure will be described in more detail below to aid in understanding it.

[0020] The terms or words used in this disclosure should not be construed as limited to their general or dictionary meanings, but should be interpreted based on their meanings and concepts corresponding to the technical aspects of the content of this disclosure, on the basis of the principle that the inventors are allowed to define terms appropriately for the best explanation.

[0021] The terms or words used in this disclosure are for the purpose of describing exemplary embodiments of the disclosure, but these terms, words or embodiments are not intended to be limiting.

[0022] As used herein, the terms “comprising” and “including” mean that other components are not excluded. Within the framework of this invention, the term “composed of” should be understood as the preferred embodiment of the terms “comprising” or “including”. If a group is defined as “comprising” or “including” at least a certain number of components, this should also be understood as disclosing a group preferably “composed” of those components.

[0023] As used in this disclosure, the terms “containing… as a principal ingredient” or “comprising… as a principal ingredient” mean, for example, at least 50% by weight (e.g., 60% by weight, 70% by weight, 80% by weight, 90% by weight or more, or even about 100% by weight) of the specified ingredient.

[0024] The terms “about” and “substantially” as used in this disclosure are used in the sense of being equal to or nearly equal to when taking into account the manufacturing and material tolerances inherent in the stated circumstances, and are intended to prevent unethical infringers from unfairly exploiting the precise or absolute values ​​stated in this disclosure in order to aid in the understanding of the disclosure.

[0025] Unless otherwise stated, the proportions and contents (%) described in this disclosure are based on moles (amount of substance), i.e., molar ratios and molar contents (mol%).

[0026] The following definitions are also specifically used in this disclosure.

[0027] Symbols and abbreviations for polyamides and their monomers:

[0028] In the context of this invention, the term "polyamide" (abbreviated PA) is understood as a general term; it includes homopolymers and copolymers. The selected symbols and abbreviations for polyamides and their monomers correspond to those set forth in ISO standard 16396-1 (2015, (D)). The abbreviations used herein are used hereinafter as synonyms for the IUPAC names of the monomers. Specifically, the following abbreviations are used for monomers in this application: BAC represents bis(aminomethyl)cyclohexane (including, for example, 1,3-BAC or 1,4-BAC); 1,3-BAC represents 1,3-bis(aminomethyl)cyclohexane (also known as 1,3-cyclohexanedimethylamine, CAS No. 2579-20-6); 1,4-BAC represents 1,4-bis(aminomethyl)cyclohexane (also known as 1,4-cyclohexanedimethylamine, CAS No. 2549-93-1); IPD represents... Epiisophorone diamine (also known as 3-(aminomethyl)-3,5,5-trimethylcyclohexaneamine, 1-amino-3-aminomethyl-3,5,5-trimethylcyclohexane, or 5-amino-1,3,3-trimethylcyclohexanemethaneamine, CAS No. 2855-13-2); MXD represents 1,1'-(1,3-phenylene)di(methylamine) (also known as m-phenylenedimethyldiamine, CAS No. 1477-55-0); MACM represents bis(4-amino-3-methylcyclohexyl). Methane (also known as 3,3'-dimethyl-4,4'-diaminodicyclohexylmethane, CAS No. 6864-37-5); PACM represents bis(4-aminocyclohexyl)methane (also known as 4,4'-diamino-dicyclohexylmethane, CAS No. 1761-71-3); HMD represents 1,6-hexanediamine (also known as hexamethylenediamine, hexamethylenediamine, CAS No. 124-09-4); TPS or T represents terephthalic acid (CAS No. 100-21-0). ); IPS or I represent isophthalic acid (CAS No. 121-95-5), 6 represents 1,6-adipic acid (also known as adipic acid, CAS No. 124-04-9), L12 represents lactam-12 (also known as laurolactam, CAS No. 947-04-6), A12 represents 1,12-dodecanoic acid (also known as dodecanoic acid, CAS No. 693-23-2), and 11 represents 11-aminoundecanoic acid (CAS No. 2432-99-7). When lactams are mentioned, this patent application also includes the use of the corresponding amino acids, and vice versa.

[0029] Accordingly, the polyamide used in this disclosure:

[0030] For example, PA HMDI represents a polyamide formed by polymerizing monomers HMD (1,6-hexanediamine) and I (isophthalic acid) in a molar ratio of approximately 1:1;

[0031] For example, PA MXDI represents a polyamide formed by polymerizing monomers MXD (m-phenylenedimethyldiamine) and I (isophthalic acid) in a molar ratio of approximately 1:1;

[0032] For example, PA HMDI / MXDI represents a copolyamide formed by polymerization of monomers HMD (1,6-hexanediamine), MXD (m-phenylenediamine), and I (isophthalic acid), including units (HMDI) formed by polymerization of monomers HMD (1,6-hexanediamine) and I (isophthalic acid) in a molar ratio of about 1:1 and units (MXDI) formed by polymerization of monomers MXD (m-phenylenediamine) and I (isophthalic acid) in a molar ratio of about 1:1.

[0033] For example, PA MXD6 represents a polyamide formed by polymerizing monomers MXD (m-phenylenedimethyldiamine) and 6 (1,6-adipic acid) in a molar ratio of approximately 1:1;

[0034] For example, PA MXD6 / MXDI represents a copolyamide formed by polymerization of monomers MXD (m-phenylenedimethyldiamine), 6 (1,6-adipic acid), and I (isophthalic acid), including units (MXD6) formed by polymerization of monomers MXD (m-phenylenedimethyldiamine) and 6 (1,6-adipic acid) in a molar ratio of about 1:1 and units (MXDI) formed by polymerization of monomers MXD (m-phenylenedimethyldiamine) and I (isophthalic acid) in a molar ratio of about 1:1.

[0035] For example, PA MACMI represents a polyamide formed by polymerizing monomers MACM (bis(4-amino-3-methylcyclohexyl)methane) and I (isophthalic acid) in a molar ratio of approximately 1:1;

[0036] For example, PA MACMT represents a polyamide formed by polymerizing monomers MACM (bis(4-amino-3-methylcyclohexyl)methane) and T (terephthalic acid) in a molar ratio of approximately 1:1;

[0037] For example, PA MACMA12 represents a polyamide formed by polymerizing monomers MACM (bis(4-amino-3-methylcyclohexyl)methane) and A12 (1,12-dodecanoic acid) in a molar ratio of approximately 1:1.

[0038] For example, PA L12 represents a polyamide formed by polymerization (e.g., ring-opening polymerization) of monomer L12 (lactam 12);

[0039] For example, PA MACMI / MACMT / L12 represents a copolyamide formed by polymerization of monomers MACM (bis(4-amino-3-methylcyclohexyl)methane), I (isophthalic acid), T (terephthalic acid), and lactam 12. This includes units (MACMI) formed by polymerization of monomers MACM (bis(4-amino-3-methylcyclohexyl)methane) and I (isophthalic acid) in a molar ratio of approximately 1:1, units (MACMI) formed by polymerization of monomers MACM (bis(4-amino-3-methylcyclohexyl)methane) and T (terephthalic acid) in a molar ratio of approximately 1:1, and units (L12) formed by ring-opening polymerization of monomer L12 (lactam 12).

[0040] And so on.

[0041] If the copolyamide contains only diacid and diamine, the diacid and diamine react in a stoichiometric ratio of 1:1. In actual production, the total molar ratio of all diamines is 46 mol% to 54 mol% of the copolyamide composition, and the total molar ratio of all diacids is 46 mol% to 54 mol% of the copolyamide composition.

[0042] In addition, the copolyamide may contain a chain regulator, which, together with the diamine and diacid, makes up 100 mol of the copolyamide composition.

[0043] In this disclosure, the inner layer is defined as a layer surrounded by the outer layers. When the open multilayer container according to this disclosure is sterilized, the sterilization medium is in direct contact only with the outer layers. When the container is cut open, the inner layers between the outer layers become visible in the container wall. In other words, the multilayer container has a container wall consisting of at least three layers, wherein two outer layers are made of the same or different materials, and the inner layers between them are made of a material different from the outer layers. Additional layers may exist between the outer layers. Preferably, the container wall has a three-layer structure in which the inner layers are surrounded by the outer layers.

[0044] In this disclosure, the term "transparent" means a transmittance of at least 70% (e.g., 75 wt%, 80 wt%, 85 wt%, 90 wt%, 95 wt%, 98 wt%, or higher). In some embodiments, "transparent" means that when provided in the form of a plate (e.g., a circular plate) with a thickness of 2 mm, its transmittance is at least 70%. In some embodiments, the transmittance is measured in the range of 200 nm to 800 nm on a UV / VIS spectrometer from PerkinElmer. In some embodiments, the transmittance value is for a wavelength of 560 nm. Preferably, the transmittance is at least 70% when measured in a square plate with a thickness of 500 µm, more preferably 800 µm, and dimensions of 100 mm × 100 mm.

[0045] In this disclosure, the term "transparent polyamide" refers to (co)polyamide and / or (co)polyamide molding compound having a light transmittance of at least 70% when provided in the form of a sheet (e.g., a disc) with a thickness of 2 mm.

[0046] In this disclosure, in addition to amorphous polyamides, "transparent polyamides" also include those polyamides that are no longer completely amorphous but remain transparent due to their microcrystalline structure invisible to the naked eye. Amorphous or microcrystalline polyamides primarily comprise alicyclic diamines, aromatic dicarboxylic acids, and / or alicyclic dicarboxylic acids. Alicyclic diamines are, for example, MACM (e.g., Laromin from BASF), PACM (e.g., Dicycan from BASF), and cyclohexyldiamine. Aromatic dicarboxylic acids are, for example, isophthalic acid, terephthalic acid, and naphthalenedicarboxylic acid.

[0047] Transmittance Measurement: In some technical solutions, 70 mm × 2 mm circular plates are produced in polished molds on Arburg injection molding machines, with barrel temperatures between 240°C and 340°C and mold temperatures between 20°C and 140°C. Transmittance is typically measured on these 70 mm × 2 mm circular plates in the range of 200 nm to 800 nm using a Perkin-Elmer UV / VIS spectrometer. The transmittance value is specified for a wavelength of 560 nm in each case.

[0048] The yellow index is an important quality dimension for transparent, colorless parts. Any yellowing in copolyamide molding compounds can be compensated for by adding blue pigment before or during further processing.

[0049] In this disclosure, the term "transparent medical multilayer container" can refer to a container comprising an inner layer containing copolyamide A as the main component and an outer layer containing a cyclic olefin copolymer B as the main component, having a light transmittance of at least 70% through the container walls. To measure the light transmittance, the container walls are cut to dimensions suitable for measurement. In some embodiments, the transparent medical multilayer container for sterilization, light transmittance measurement, and permeability measurement (O2-TR, CO2-TR, WVTR) is produced on an injection blow molding machine from Nissei ASB Machine Ltd., at a barrel temperature of 280°C for copolyamide A, a barrel temperature of 300°C for cyclic olefin copolymer B, and a blow molding temperature of 150°C. In some embodiments, the light transmittance can be measured in the range of 200 nm to 800 nm using a 100 mm × 100 mm square plate on a UV / VIS spectrometer from PerkinElmer. The transmittance value is specified for a wavelength of 560 nm in each case. Preferably, the transmittance of the container wall on a square plate with a thickness of 500 µm, more preferably 800 µm and a size of 100 mm × 100 mm, is at least 70%.

[0050] According to one aspect of the present invention, a multilayer medical container is provided, comprising an inner layer containing copolyamide A and an outer layer containing copolyamide B, wherein the monomer of the copolyamide A comprises or is composed of the following:

[0051] 10 mol% to 40 mol% m-phenylenedimethyldiamine (MXD);

[0052] 10 mol% to 40 mol% 1,6-hexanediamine (HMD);

[0053] 46 mol% to 54 mol% phthalic acid, wherein the phthalic acid is composed of isophthalic acid (IPS) and optionally terephthalic acid (T), wherein the content of terephthalic acid (T) in the phthalic acid is 0 mol% to 50 mol%;

[0054] According to one aspect of the invention, the amount of m-phenylenedimethyldiamine in the monomer of the copolyamide A can be any value between 10 mol% and 40 mol%, for example: 15 mol%, 20 mol%, 25 mol%, 30 mol%, 35 mol%.

[0055] According to one aspect of the invention, the amount of 1,6-hexanediamine in the monomer of the copolyamide A can be any value between 10 mol% and 40 mol%, for example: 15 mol%, 20 mol%, 25 mol%, 30 mol%, 35 mol%.

[0056] According to one aspect of the invention, the amount of phthalic acid in the monomer of the copolyamide A can be any value between 46 mol% and 54 mol%, for example: 47 mol%, 48 mol%, 49 mol%, 50 mol%, 51 mol%, 52 mol%, 53 mol%.

[0057] According to one aspect of the invention, the amount of terephthalic acid (T) in the phthalic acid can be any value between 0 mol% and 50 mol%, for example: 5 mol%, 10 mol%, 20 mol%, 30 mol%, 40 mol%. In particular, the amount of terephthalic acid (T) in the phthalic acid can be 0 mol%, but cannot exceed 50 mol%.

[0058] According to one aspect of the invention, the copolyamide B comprises or consists of an amorphous copolyamide with a glass transition temperature above 165°C, preferably in the range of 170°C to 220°C, and particularly preferably in the range of 180°C to 210°C (especially, for example, 185°C, 190°C, 195°C, 200°C, 205°C).

[0059] According to one aspect of the invention, the inner layer contains at least 50 wt% (e.g., 60 wt%, 70 wt%, 80 wt%, 90 wt% or more, or even about 100 wt%) of copolyamide A. According to one aspect of the invention, the outer layer contains at least 50 wt% (e.g., 60 wt%, 70 wt%, 80 wt%, 90 wt% or more, or even about 100 wt%) of copolyamide B.

[0060] In a preferred embodiment, copolyamide A comprises or consists of a copolyamide with a glass transition temperature above 140°C, preferably in the range of 140°C to 220°C, and particularly preferably in the range of 145°C to 200°C.

[0061] In another preferred embodiment, copolyamide A comprises or is composed of the following:

[0062] 15 mol% to 35 mol% m-phenylenedimethyldiamine (MXD);

[0063] 15 mol% to 35 mol% 1,6-hexanediamine (HMD);

[0064] 46 mol% to 54 mol% phthalic acid, wherein the phthalic acid is composed of isophthalic acid (IPS) and optionally terephthalic acid (T), wherein the content of terephthalic acid (T) in the phthalic acid is 0 mol% to 50 mol.

[0065] In a preferred embodiment, copolyamide B comprises or is composed of the following:

[0066] 35 mol% to 42 mol% bis(4-amino-3-methylcyclohexyl)methane (MACM), bis(4-aminocyclohexyl)methane (PACM) and / or bis(aminomethyl)cyclohexane (BAC, e.g., 1,3-BAC or 1,4-BAC);

[0067] 35 mol% to 42 mol% aromatic dicarboxylic acid, wherein the aromatic dicarboxylic acid is composed of isophthalic acid, optionally terephthalic acid, and optionally naphthalenedicarboxylic acid, wherein the total content of terephthalic acid and naphthalenedicarboxylic acid in the phthalic acid is 0%-50%;

[0068] 17 mol% to 26 mol% lactam 12 or 11-aminoundecanoic acid.

[0069] In another preferred embodiment, copolyamide B is selected from PA MACMI / 12, PA PACMI / L12, PAMACMI / MACMT / L12, PA MACMI / PACMI / L12, PA PACMI / PACMT / L12, PA MACMI / 11, PA PACMI / 11, PA MACMI / MACMT / 11, PA MACMI / PACMI / 11, PA PACMI / PACMT / 11, PA BACI / L12 and / or PABACI / BACT / L12.

[0070] According to one aspect of the invention, the O2 permeability (O2-TR) determined according to DIN 53380-3:1998 is less than or equal to 10 cm⁻¹. 3 / (m 2 (·Tian·Ba), preferably less than or equal to 8 cm 3 / (m 2 (·Tian·Ba), less than or equal to 7 cm 3 / (m 2 (·Tian·Ba), less than or equal to 6 cm 3 / (m 2 (·Tian·Ba), less than or equal to 5 cm 3 / (m 2 (·Tian·Ba), less than or equal to 4cm 3 / (m 2 (·Tian·Ba), less than or equal to 3 cm 3 / (m 2 (·Tian·Ba), less than or equal to 2 cm 3 / (m 2 (·tian·ba), less than or equal to 1 cm 3 / (m 2 (·Tian·Ba). In one exemplary embodiment, a transparent medical multilayer container comprises a 100 µm thick membrane having a 50-micron inner layer and two 25-micron outer layers, the outer layers being coated on both sides of the inner layer, and the O2 permeability (O2-TR) of the membrane, as determined according to DIN 53380-3:1998, is less than or equal to 10 cm⁻¹. 3 / (m 2 (·Tian·Ba), preferably less than or equal to 8 cm 3 / (m 2 (·Tian·Ba), less than or equal to 7 cm 3 / (m 2 (·Tian·Ba), less than or equal to 6cm 3 / (m 2 (·Tian·Ba), less than or equal to 5 cm 3 / (m 2 (·Tian·Ba), less than or equal to 4 cm 3 / (m 2 (·Tian·Ba), less than or equal to 3 cm 3 / (m 2 (·Tian·Ba), less than or equal to 2 cm 3 / (m 2 (·tian·ba), less than or equal to 1 cm 3 / (m 2 ·Tian·Ba).

[0071] According to one aspect of the invention, the CO2 permeability (CO2-TR) determined according to DIN 53380-4:2006 is less than or equal to 25 cm³. 3 / (m 2 (·Tian·Ba), preferably less than or equal to 20 cm 3 / (m 2 (·Tian·Ba), less than or equal to 18 cm 3 / (m 2 (·Tian·Ba), less than or equal to 15 cm 3 / (m 2 (·Tian·Ba), less than or equal to 13 cm 3 / (m 2 (·Tian·Ba), less than or equal to 10 cm 3 / (m 2(·Tian·Ba). In one exemplary embodiment, the transparent medical multilayer container comprises a 100 µm thick membrane having a 50-micron inner layer and two 25-micron outer layers, the outer layers being coated on both sides of the inner layer, and having a CO2 permeability (CO2-TR) less than or equal to 25 cm² as determined according to DIN 53380-4:2006. 3 / (m 2 (·Tian·Ba), preferably less than or equal to 20 cm 3 / (m 2 (·Tian·Ba), less than or equal to 18 cm 3 / (m 2 (·Tian·Ba), less than or equal to 15 cm 3 / (m 2 (·Tian·Ba), less than or equal to 13 cm 3 / (m 2 (·Tian·Ba), less than or equal to 10 cm 3 / (m 2 ·Tian·Ba).

[0072] According to one aspect of the invention, the water vapor transmission rate, as determined according to DIN 53122-1:2001, is less than or equal to 8 g / (m²). 2 • day), preferably less than or equal to 7 g / (m 2 • day), less than or equal to 6 g / (m 2 • day), less than or equal to 5 g / (m 2 • day), less than or equal to 4 g / (m 2 • day), less than or equal to 3 g / (m 2 • day), less than or equal to 2 g / (m 2 • day), less than or equal to 1 g / (m 2 • Days). In one exemplary embodiment, a transparent medical multilayer container comprises a 100 µm thick membrane having a 50-micron inner layer and two 25-micron outer layers, the outer layers being coated on both sides of the inner layer, and the water vapor transmission rate of the membrane, as determined according to DIN 53122-1:2001, is less than or equal to 8 g / (m²). 2 • day), preferably less than or equal to 7 g / (m 2 • day), less than or equal to 6 g / (m 2 • day), less than or equal to 5 g / (m 2 • day), less than or equal to 4 g / (m 2 • day), less than or equal to 3 g / (m 2 • day), less than or equal to 2 g / (m 2 • day), less than or equal to 1 g / (m 2·sky).

[0073] The copolyamide according to the invention can be produced in any suitable manner known in the art. For example, it can be produced as a molding compound in a known stirred pressure autoclave having a receiving vessel and a reaction vessel.

[0074] As an exemplary, not restrictive, example:

[0075] Deionized water is placed in a receiving vessel, and monomers and additives are added. The mixture is then inertized multiple times using nitrogen. While stirring, the mixture is heated to 180°C to 230°C under the generated pressure to obtain a homogeneous solution. This solution is pumped through a sieve into a reaction vessel at a pressure of up to 30 bar and heated thereto to the desired reaction temperature of 270°C to 310°C. The batch is maintained at the reaction temperature during the pressure phase for 2 to 4 hours. In the subsequent relaxation phase, the pressure is reduced to atmospheric pressure over 1 to 2 hours, allowing the temperature to drop easily.

[0076] In the subsequent degassing stage, the batch is held at atmospheric pressure at a temperature of 270°C to 340°C for 0.5 to 1 hour.

[0077] The polymer melt is discharged in strands, cooled in a water bath at 15°C to 80°C, and then granulated. The granules are dried under nitrogen at 80°C to 120°C for 12 hours until the water content is less than 0.06% by weight.

[0078] According to one aspect of the invention, the relative viscosity of the copolyamide according to the invention used in the polyamide molding compound according to the invention can be adjusted by chemical and / or methodological measures, as known to those skilled in the art. The use of a chain control agent can be a chemical measure, wherein the relative viscosity decreases if the amount of the chain control agent increases. Suitable chain control agents are monocarboxylic acids, such as benzoic acid, acetic acid, propionic acid, or monoamines, such as stearylamine. Dicarboxylic acids or diamines, or chain control agents having amine or carboxylic acid groups, are known, containing HALS-type or tert-butylphenol-type stabilizer groups, such as triacetone diamine or di-triacetone diamine derivatives of isophthalic acid. Chain control agents having stabilizer groups result in improved light / UV and / or thermal stability of the copolyamide. Preferred chain control agents for the copolyamide according to the invention are benzoic acid, acetic acid, or triacetone diamine. They are used at concentrations of 20 to 100 mol per ton of final product, preferably 30 to 80 mol per ton of final product, and even more preferably 40 to 50 mol per ton of final product.

[0079] Methods and technical measures include, for example, changing the duration of the pressure phase, the duration of the degassing phase, the shutdown torque, or the temperature profile.

[0080] According to one aspect of the invention, a suitable catalyst for accelerating the polycondensation reaction can be a phosphorus-containing acid, such as H3PO2, H3PO3, H3PO4, their salts, or organic derivatives, which has the additional benefit of reducing discoloration during processing. The catalyst can be added in the range of 0.01 to 0.5% by weight, preferably 0.03 to 0.1% by weight, of the copolymer.

[0081] According to one aspect of the invention, a suitable defoamer for preventing foaming during degassing can be a silicone or a silicone derivative, such as an aqueous emulsion (e.g., 10% emulsion) containing a silicone or a silicone derivative, and can be used in an amount of 0.01 to 1.0% by weight of the copolymer, preferably 0.1 to 0.9% by weight or 0.5% by weight.

[0082] Preferred applications of the invention relate to the production of heat-steam-sterilizable molded parts and extrusions for medical use, such as containers, tubes, bottles, beakers, measuring cups, and boxes. Preferably, the transparent multilayer medical containers are ampoules, vials, vacuum blood collection tubes, or pre-filled syringes.

[0083] Preferably, the thickness of the inner layer accounts for 2% to 50% of the total thickness of the medical multilayer container, for example, 5%, 8%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%.

[0084] In one embodiment, the transparent medical multilayer container comprises all layers containing polyamide as the main component, or is made solely of a polyamide composition without other polymers.

[0085] In a preferred embodiment, the transparent medical multilayer container comprises only an inner layer and an outer layer.

[0086] In a preferred embodiment, the transparent medical multilayer container is an injection blow molded product.

[0087] According to one aspect of the present invention, measurements are performed on the following test specimens according to the following criteria:

[0088] The relative viscosity (RV) was determined according to ISO standard 307:2007 in a 0.5% m-cresol solution at 20°C.

[0089] The glass transition temperature was determined using differential scanning calorimetry (DSC) at a heating rate of 10 °C / min according to ISO standards 11357-1:2016 and 11357-2:2013.

[0090] Permeability measurements (O2-TR, CO2-TR, WVTR) were carried out on membranes with a diameter of 100 mm, which had a 50-μm inner layer coated with a 25-μm outer layer on both sides. Thus, the entire membrane was 100 μm thick.

[0091] The O2 permeability (O2-TR) was determined on 100-μm thick membranes using an oxygen permeation analyzer, Systech 8001, in accordance with DIN 53380-3:1998. The lower the measured value, the better the O2 barrier performance. The measured values are specified in [cm 3 / (m 2 ·day·bar)].

[0092] The CO2 permeability (CO2-TR) was determined on 100-μm thick membranes using a CO2 permeation analyzer, Permatram C4 / 41, in accordance with DIN 53380-4:2006. The lower the measured value, the better the CO2 barrier performance. The measured values are specified in [cm 3 / (m 2 ·day·bar)].

[0093] The water vapor permeability (WVTR) was determined on 100-μm thick membranes in accordance with DIN 53122-1:2001 (gravimetric method). The lower the measured value, the better the vapor barrier performance. The measured values are specified in [g / (m 2 ·day)].

[0094] Examples

[0095] In an exemplary embodiment of the present invention, the test sterilization method employed (134 °C / 7 minutes) was carried out as follows: 1.

[0097] Thermal steam sterilization equipment

[0098] A 2549 E pressure autoclave with a chamber volume of 26 l from Tuttnauer was used. A rack with a perforated plate for receiving four layers of samples was located inside the circular pressure chamber oriented horizontally. 2.

[0100] Standard test bodies and pretreatment

[0101] The multi-layer test bodies for sterilization were placed on the rack as injection-molded objects without pretreatment and without contacting each other. Then the autoclave was closed and tightened. The amount of test bodies required was determined according to the planned removal time. 3.

[0103] Thermal steam sterilization was carried out

[0104] The autoclave was heated to 134°C, and the previously dispensed water (approximately 350 ml) was vaporized within it. This process was continued for 20 to 30 minutes at a steam pressure of 2 bar. After 5 x 7 minutes (corresponding to 5 sequential counting cycles), the autoclave was cooled to room temperature. The next five-zone group was then started. Three test samples were removed each time according to the planned removal time. 4.

[0106] Analysis of heat steam sterilization performance based on cycle number

[0107] The thermal steam sterilization performance was measured on a 45 mm long multilayer container with an outer diameter of 24 mm and a thickness of 800 micrometers. The container wall has an inner layer of 200 micrometers coated on both sides with an outer layer of 300 micrometers. Therefore, the entire membrane is 800 micrometers thick.

[0108] Steam sterilization is provided if no cracks or identifiable discoloration are observed to the naked eye, and at least 70% light transmittance (as defined in this invention). Cracks are primarily observed at the bends in the bottom of the container or at the transition from the sidewall to the container opening.

[0109] The monomer materials used in the embodiments are shown in Table 1 below.

[0110] Table 1

[0111] monomer Commercial products Manufacturer MXD MXDA Jiangsu Xinhe Agricultural Chemical Co., Ltd. (CN) HMD Hexamethylenediamine (Hexamethylenediamine) BASF (DE) 6 adipic acid Brunttiger (DE) MACM Laromin C260 BASF (DE) PACM Dicycan BASF (DE) I (IPS) Purified isophthalic acid (PIA) BP Amoco (GB) T(TPS) Amoco TA-33 BP Amoco (GB) L12 (lactam 12) laurolactam Emans (CH)

[0112] The following explains the production of the copolyamide molding compound according to the present invention based on the composition used in PA5:

[0113] 42 kg of deionized water was provided in the delivery vessel of a 300 L autoclave, and a mixture consisting of 17.0 kg of IPS and 17.0 kg of TPS was stirred in. With the stirrer off, 48.2 kg of MACM, 28.8 kg of lactam 12, and 0.54 kg of benzoic acid were added.

[0114] After inertizing the mixture 10 times, heat it to 230°C, and then start the stirrer after it reaches 180°C. Pump the homogenized solution through a sieve into the reaction vessel at 230°C.

[0115] The batch is heated to 295°C with stirring and maintained at a pressure of 20 bar for 4 hours. It is then released to atmospheric pressure over 1.5 hours and subsequently degassed for 40 minutes.

[0116] The polymer melt is discharged, cooled in a water bath (65°C), and granulated. The granules are then dried at 100°C under nitrogen for 24 hours until the water content is less than 0.06% by weight.

[0117] Following the above method, polyamides and copolyamides PA1 to PA8 having the compositions shown in Table 2 below were produced and are listed in Table 2 together with other materials used in the production of transparent medical multilayer containers.

[0118] Table 2

[0119] abbreviation Material PA1 HMDI / MXDI 57 / 43, Tg 150℃ (A) PA2 MXDI / 6I 66 / 34, Tg 177℃ (A) PA3 MXD6, Tg 85℃, RV 2.65 PA4 MXD6 / MXDI 94 / 6, Tg 88℃, RV 2.68 PA5 MACMI / MACMT / L12 38 / 38 / 24, Tg 194℃, RV 1.49 PA6 MACMI / L12 76 / 24, Tg 188℃, RV 1.49 (B) PA7 MACMI / PACMI / L12 38 / 44 / 18, Tg 200℃, RV 1.51 (B) PA8 MACMA12, Tg 155℃, RV 1.73 PP Polypropylene, Tm 163℃ COC Cyclic olefin copolymer (49 Mol% cyclic olefin content), Tg 140℃ PC Polycarbonate, Tg 130℃

[0120] Transparent medical multilayer containers of the examples and comparative examples were produced according to the composition and structure specified in Tables 3 and 4. The only difference between the examples and comparative examples is the material of the inner and outer layers. The transparent medical multilayer containers produced in the examples and comparative examples were tested according to the methods described above, and the results are shown in Tables 3 and 4.

[0121] Table 3

[0122] Example 1 2 3 4 Inner layer PA1 PA1 PA2 PA2 outer layer PA5 PA6 PA6 PA7 <![CDATA[O2-TR[cm 3 / (m 2 ·Tian·Ba)]]]> 6 6 5 4 <![CDATA[CO2-TR[cm 3 / (m 2 ·Tian·Ba)]]]> 17 16 14 14 <![CDATA[WVTR[g / (m 2 ·day)]]]> 5 6 6 6 Visually acceptable sterilization cycle 10 5 5 50

[0123] Table 4

[0124] Comparative example 1 2 3 4 5 6 Inner layer PA1 PA3 PA4 PA1 PA1 PA1 outer layer PA8 PA5 PA6 COC PC PP <![CDATA[O2-TR[cm 3 / (m 2 ·Tian·Ba)]]]> 7 12 13 24 29 25 <![CDATA[CO2-TR[cm 3 / (m 2 ·Tian·Ba)]]]> 18 35 38 39 46 40 <![CDATA[WVTR[g / (m 2 ·day)]]]> 7 10 11 1 13 2 Visually acceptable sterilization cycle 0 0 0 0 0 0

[0125] Comparative Examples 1 and 5 show that the standard test specimens made of transparent polymers involving materials PA8 or PC could not be sterilized at 134°C for 7 minutes. The standard test specimens were severely deformed and unusable after 5 sterilization cycles.

[0126] Compared with Comparative Example 1, the standard test specimen according to the present invention, made of materials PA5, PA6 or PA7 with high Tg and having a higher lactam 12 content than Comparative Example 1, meets the requirements.

[0127] The standard test specimens made of materials PA1 or PA2 with high Tg according to the present invention also meet the requirements.

[0128] Materials PA3 and PA4 in Comparative Examples 2 and 3 each have low Tg and cannot withstand thermal steam sterilization cycles.

[0129] Unlike all other embodiments and comparative examples, such as Comparative Example 6, a transparent medical multilayer container was not produced using polypropylene.

[0130] Comparative Examples 2 to 6 show that the permeation data for O2 and CO2 are consistently poor.

[0131] As in Examples 1 to 4, only by combining an internal gas barrier layer composed of suitable monomers with an external resistant protective layer can excellent gas barrier properties be achieved in conjunction with the good sterilization properties of the multilayer structure.

Claims

1. A multi-layer medical container, characterized in that, It includes an inner layer containing copolyamide A and an outer layer containing copolyamide B, wherein the monomer of copolyamide A comprises or is composed of the following: 10 mol% to 40 mol% m-phenylenedimethyldiamine; 10 mol% to 40 mol% 1,6-hexanediamine; 46 mol% to 54 mol% phthalic acid, wherein the phthalic acid is composed of isophthalic acid and optionally terephthalic acid, wherein the terephthalic acid content in the phthalic acid is 0 mol% to 50 mol%; and The copolyamide B comprises or consists of the following: an amorphous copolyamide with a glass transition temperature higher than 165°C, and the monomers of the copolyamide B comprise or consist of the following: 35 mol% to 42 mol% bis(4-amino-3-methylcyclohexyl)methane, bis(4-aminocyclohexyl)methane and / or bis(aminomethyl)cyclohexane; 35 mol% to 42 mol% aromatic dicarboxylic acid, wherein the aromatic dicarboxylic acid is composed of isophthalic acid, optionally terephthalic acid, and optionally naphthalenedicarboxylic acid, wherein the total content of terephthalic acid and naphthalenedicarboxylic acid in the phthalic acid is 0%-50%; 17 mol% to 26 mol% lactam 12 or 11-aminoundecanoic acid.

2. The medical multi-layer container according to claim 1, characterized in that, The relative viscosity of the copolyamide B molding compound is higher than 1.

30.

3. The medical multi-layer container according to claim 1, characterized in that, The copolyamide A comprises or is composed of the following: a copolyamide with a glass transition temperature higher than 140°C.

4. The medical multi-layer container according to claim 1, characterized in that, The monomer of the copolyamide A comprises or is composed of the following: 15 mol% to 35 mol% m-phenylenedimethyldiamine; 15 mol% to 35 mol% 1,6-hexanediamine; The phthalic acid is 46 mol% to 54 mol%.

5. The medical multi-layer container according to claim 1, characterized in that, The copolyamide B comprises or is composed of the following: a copolyamide selected from PA MACMI / 12, PA PACMI / 12, PA MACMI / MACMT / 12, PA MACMI / PACMI / 12, PAPACMI / PACMT / 12, PA MACMI / 11, PA PACMI / 11, PA MACMI / MACMT / 11, PA MACMI / PACMI / 11, PAPACMI / PACMT / 11, PA BACI / 12 and / or PA BACI / BACT / 12.

6. The medical multi-layer container according to claim 1, characterized in that, All layers are made of polyamide composition.

7. The medical multi-layer container according to claim 1, characterized in that, It consists of only an inner layer and an outer layer.

8. The medical multi-layer container according to claim 1, characterized in that, The thickness of the inner layer accounts for 2% to 50% of the total thickness of the medical multilayer container.

9. The medical multi-layer container according to claim 1, characterized in that, The light transmittance is at least 70%.

10. The medical multi-layer container according to any one of claims 1 to 9, characterized in that, Ampoules, vials, vacuum blood collection tubes, or pre-filled syringes are available.

11. The medical multi-layer container according to any one of claims 1 to 9, characterized in that, It is an injection blow molded product.

12. A method for manufacturing a multi-layered medical container, characterized in that, This includes forming the medical multilayer container according to any one of claims 1 to 11 by injection blow molding.