Amphiphilic intermediate layer for a polymeric container

Abstract

The pharmaceutical container made of COP or COC imparts high resistance to the oxidation of drugs. 【Solution means】The layered polymer material includes a first layer containing a first cyclic olefin polymer or a first cyclic olefin copolymer, a third layer containing a second cyclic olefin polymer or a second cyclic olefin copolymer, and a Hansen solubility parameter distance from oxygen gas is 8 MPa 1 / 2 or more, and at the same time has a hydrophilic component, and a Hansen solubility parameter distance from COC or COP is 8 MPa 1 / 2 or less, and includes a second layer containing an amphiphilic polymer having a hydrophobic component. The second layer is in contact with the first layer and the third layer and can be between the first layer and the third layer. The layered polymer material can be used to form the body of a vial or syringe. Also described are a method for manufacturing the layered polymer material, a kit including the layered polymer material, or a container having a body composed of the layered polymer material.

Description

Technical Field

[0001] (Cross - reference to related applications) This application claims the priority of U.S. Provisional Patent Application No. 63 / 330,200, filed on April 22, 2022, the disclosure of which is incorporated herein by reference.

[0002] The present disclosure relates to a laminated polymer material having at least a three - layer structure for use in a pharmaceutical container, wherein the first and third (outer) layers are cyclic olefin polymer (COP) or cyclic olefin copolymer (COC), and the second layer (intermediate layer) sandwiched between the first layer and the third layer has a hydrophilic component with a Hansen solubility parameter distance from oxygen gas of 8 MPa 1 / 2 or more, and at the same time has a hydrophobic component with a Hansen solubility parameter distance from COC or COP of 8 MPa 1 / 2 or less, and is composed of an amphiphilic polymer.

Background Art

[0003] COP - or COC - based pharmaceutical containers have better fracture resistance and pH stability than glass containers and have fewer particle detachment problems. As such, they are increasingly being used in pharmaceutical packaging. However, they also suffer from high oxygen gas permeability and can deteriorate oxygen - sensitive drugs during long - term storage. This deterioration problem can also lead to an overall drug shortage problem when the storage life of parenteral drugs is unexpectedly shortened.

[0004] To overcome the problems associated with such pharmaceutical containers, hydrophilic polymers having high oxygen barrier properties, such as ethylene-vinyl alcohol (EVOH), have been co-injection molded onto the outer surface of COP / COC containers. However, the adhesion between the hydrophilic polymer and the hydrophobic COP / COC surface is insufficient, allowing oxygen to penetrate through the gaps between the incompatible layered structures. Therefore, conventional attempts to modify COC / COP containers by directly molding a hydrophilic oxygen barrier layer onto the hydrophobic COP / COP container have failed due to poor adhesion between the layers.

[0005] Therefore, there is a need for improved COP or COC-based pharmaceutical containers that provide improved resistance to oxidation of the drug (i.e., degradation of the drug stored in the container by oxygen entering the container through the walls of the container).

Summary of the Invention

[0006] A layered polymer material is described that includes at least two outer layers formed from COP or COC, with an intermediate layer composed of an amphiphilic polymer sandwiched therebetween. The amphiphilic polymer used in the intermediate layer has a hydrophilic component with a Hansen solubility parameter distance from oxygen gas of 8 MPa 1 / 2 or more, and at the same time has a hydrophobic component with a Hansen solubility parameter distance from COC or COP of 8 MPa 1 / 2 or less. The layered polymer material preferably has three layers, but additional layers may be added to at least two outer layers on each side of the outer layers that are not in contact with the intermediate layer.

[0007] Thus, in one embodiment, the layered polymer material includes a first layer composed of a first cyclic olefin polymer or a first cyclic olefin copolymer, a third layer composed of a second cyclic olefin polymer or a second cyclic olefin copolymer, and a second layer that contacts and is between the first layer and the third layer. The second layer has a Hansen solubility parameter distance from oxygen gas of 8 MPa 1 / 2It has the hydrophilic component as described above, and at the same time, it is composed of an amphiphilic polymer having a hydrophobic component with a Hansen solubility parameter distance from COC or COP of 8 MPa 1 / 2 or less. In a specific embodiment, the first layer and the third layer surround the second layer.

[0008] The second (intermediate) layer can be modified to include an ultraviolet light absorbing material having an aromatic ring and / or an antioxidant. In a specific embodiment, the amphiphilic polymer has a Hansen solubility parameter distance of 17 MPa or more from oxygen gas 1 / 2 for the hydrophilic component. In other embodiments, the amphiphilic polymer has a Hansen solubility parameter distance of 4 MPa or less from the first layer and the third layer 1 / 2 for the hydrophilic component.

[0009] A variety of different amphiphilic polymers can be used. In one embodiment, the amphiphilic polymer has the following chemical formula.

[0010] [Chemical formula] In a specific embodiment, R 1 and R 2 are alkylene groups. In some embodiments, the amphiphilic polymer is poly(ethylene carbonate) or propylene carbonate. In other embodiments, the amphiphilic polymer is poly(ethylene-co-acrylic acid) or poly(ethylene-co-methylacrylic acid).

[0011] Injecting a first layer composed of a first cyclic olefin polymer or a first cyclic olefin copolymer, injecting a third layer composed of a second cyclic olefin polymer or a second cyclic olefin copolymer, and injecting a second layer composed of an amphiphilic polymer between the first layer and the third layer such that the second layer contacts between the first layer and the third layer are also described, a method for producing a layered polymer material. In some embodiments, the polymer has already been polymerized and the method is carried out under conditions where the polymer is liquid. In particular, the polymer may be supplied as pellets that are melted just prior to direct injection.

[0012] The layered polymer material can be used, for example, to constitute the body of a container such as a vial or a syringe. In certain embodiments, the container can be sealed. The layered polymer material can also be sterilized, or a container (e.g., a vial or a syringe) having a body composed of the layered polymer material can be provided as part of a kit. A pharmaceutical composition can also be filled into a container having a body composed of the layered polymer material (e.g., a vial or a syringe).

Brief Description of the Drawings

[0013] The summary and the following detailed description will be better understood when read in conjunction with the accompanying drawings. For purposes of illustration, exemplary embodiments are shown in the drawings. However, the embodiments are not limited to the specific methods and compositions disclosed, and the drawings are not necessarily drawn to scale. The drawings are as follows.

Figure 1

Figure 2A

Figure 2B

Figure 3C

Mode for Carrying Out the Invention

[0014] In the following detailed description of exemplary embodiments, reference is made to the accompanying drawings that form a part hereof. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and other embodiments may be utilized and logical, structural, mechanical, electrical, and / or chemical changes may be made without departing from the spirit or scope of the invention. To avoid details that are not necessary to enable those skilled in the art to practice the embodiments described herein, the description may omit specific information known to those skilled in the art.

[0015] Using the Hansen solubility parameter principle, an amphiphilic polymer that behaves as a good oxygen barrier and strongly adheres to the hydrophobic COP / COC surface can be selected for use in COP / COC containers. Specifically, using the Hansen solubility parameter principle, the amphiphilic polymer-based intermediate layer between the two COP / COC layers is designed to form a three-layer structure having good adhesion between the three individual layers, and the intermediate layer (intermediate layer) in these structures behaves as a bifunctional bonding layer and an oxygen barrier.

[0016] Accordingly, a three-layered polymeric material is described in which an intermediate layer composed of an amphiphilic polymer is sandwiched between COP / COC layers. The intermediate layer has certain characteristics, namely, a Hansen solubility parameter distance from oxygen gas of 8 MPa 1 / 2 or more, and at the same time has a hydrophobic component with a Hansen solubility parameter distance from COC or COP of 8 MPa 1 / 2 or less.

[0017] Compared to a composition containing only COP / COC layers, the three-layered polymeric material has reduced gas permeability, which enables it to be suitable for longer storage of oxygen-sensitive therapeutic agents (e.g., drugs).

[0018] Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the technical field to which this invention belongs. In the description and claims of this invention, the following terms are used.

[0019] As used herein, the articles "a" and "an" are used to refer to one or more than one (i.e., at least one) of the grammatical objects of the article. By way of example, "an element" means one element or a plurality of elements.

[0020] As used herein, when referring to measurable values (e.g., amounts, durations, etc.), the term "about" means including variations of ±20% or ±10% from a specific value, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1%, such variations being appropriate for carrying out the disclosed methods.

[0021] As used herein, the terms "comprising," "including," "containing," "comprised," and "characterized by" are interchangeable, inclusive, open-ended, and do not exclude additional unrecited elements or method steps. In particular, any recitation herein of the term "comprising" in the description of the components of a composition or the elements of a device is understood to encompass compositions and methods consisting essentially of and consisting of the recited components or elements.

[0022] As used herein, the term "consisting of" excludes any element, step, or component not recited in the claim.

[0023] As used herein, the term "therapeutic compound" includes any compound or biological agent (e.g., antibody, nucleotide, antibody fragment, peptide) for therapy.

[0024] Ranges: Throughout this disclosure, various aspects of the invention can be presented in range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, a recitation of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, a recitation of a range such as 1-6 should be considered to specifically disclose sub-ranges such as 1-3, 1-4, 1-5, 2-4, 2-6, 3-6, and individual numbers within that range, such as 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the width of the range.

[0025] Layered polymer material The present disclosure provides a layered polymeric material having at least three layers, with an intermediate layer sandwiched between and in contact with the outer layers. In some embodiments, the layered polymeric material has only three layers. In other embodiments, the layered polymeric material has additional layers. In some embodiments, the intermediate layer is configured to adhere to the COC / COP outer layers.

[0026] In certain embodiments, the outer layer of the layered polymeric material is formed from a cyclic olefin polymer and / or a cyclic olefin copolymer, and the middle layer is formed from an amphiphilic polymer. Without being bound by theory, it is believed that the amphiphilic polymer improves the adhesion of the layers so that gaps are not formed between the polymer layers that would allow oxygen to leak into the container. In some embodiments, the amphiphilic polymer has the characteristics described in Example 2 below.

[0027] The layered polymeric material can be used to construct the body of a parenteral drug container, such as a vial, cartridge, or syringe, etc. In one embodiment, the first layer is an outer layer of the layered polymeric material and the third layer is an inner layer of the layered polymeric material, e.g., that contacts a liquid or solid (e.g., a parenteral drug) stored within the layered polymeric material.

[0028] Thus, one embodiment of the present disclosure provides a cyclic olefin polymer comprising a first layer made of a first cyclic olefin polymer or a first cyclic olefin copolymer, a third layer made of a second cyclic olefin polymer or a second cyclic olefin copolymer, and a cyclic olefin copolymer, the third layer being heated to 8 MPa from oxygen gas. 1 / 2 It has a hydrophilic component with a Hansen solubility parameter distance of 8MPa or more, and at the same time, 1 / 2 A layered polymeric material comprising a first layer and a second layer in contact with and between the first layer and the second layer, the first layer being composed of an amphiphilic polymer having a hydrophobic component having a Hansen solubility parameter distance of:

[0029] In one embodiment, the first layer is composed of a first cyclic olefin polymer. In another embodiment, the first layer is composed of a first cyclic olefin copolymer. In another embodiment, the third layer is composed of a second cyclic olefin polymer different from the first cyclic olefin polymer. In still another embodiment, the third layer is composed of a second cyclic olefin copolymer different from the first cyclic olefin copolymer.

[0030] The cyclic olefin polymers and cyclic olefin copolymers in the first layer and / or the second layer can be independently selected, for example, such that the first layer is composed of a cyclic olefin polymer and the second layer is composed of a cyclic olefin copolymer. Different types of polymers can be used for each layer even when the first layer and the second layer are composed of polymers of the same category (i.e., cyclic olefin polymers or cyclic olefin copolymers). In a particular embodiment, the first layer is composed of a first cyclic olefin polymer, the second layer is composed of a second cyclic olefin polymer, and the first cyclic olefin polymer and the second cyclic olefin polymer are the same. In another embodiment, the first layer is composed of a first cyclic olefin copolymer, the second layer is composed of a second cyclic olefin copolymer, and the first cyclic olefin copolymer and the second cyclic olefin copolymer are the same.

[0031] In the layered polymer material of the present disclosure, the first layer and the third layer surround the second layer, particularly when viewed in a cross-sectional perspective view. The first layer and the third layer are in contact with the second layer such that there is no gap between the layers.

[0032] The second layer or the intermediate layer of the polymer material is composed of an amphiphilic polymer. In some embodiments, the hydrophobic component of the amphiphilic polymer has a δ close to 0 p and / or a δ h having. In other embodiments, the amphiphilic polymer has a solubility parameter of 17 MPa from oxygen gas 1 / 2Have the Hansen solubility parameter distance as described above. In certain embodiments, the amphiphilic polymer is 4 MPa from the first and third layers 1 / 2 Have the following Hansen solubility parameter distance.

[0033] In some embodiments, the amphiphilic polymer in the second layer has a higher δ p value or a higher δ d value (δ d > 18). In other embodiments, the amphiphilic polymer includes a nonpolar polymer.

[0034] In one embodiment, the amphiphilic polymer is a poly(ethylene carbonate) having a set of Hansen solubility parameters of δ d , δ p , δ h = 14.3, 16.5, 4.9. This polymer has an HSP distance of 17.2 MPa from oxygen and, without being bound by theory, is thought to be able to act as a good oxygen barrier. 1 / 2 In certain embodiments, the amphiphilic polymer is poly(ethylene carbonate) and the first layer is a first cyclic olefin polymer. In another embodiment, the amphiphilic polymer is poly(ethylene carbonate), the first layer is a first cyclic olefin polymer, and the second layer is a second cyclic olefin polymer, which is the same as the first cyclic olefin polymer.

[0035] A variety of amphiphilic polymers can be used. For example, the amphiphilic polymer may include polyethylene or a derivative thereof, such as poly(ethylene carbonate) or a derivative thereof. The amphiphilic polymer can include a poly(alkylene carbonate) having the structure of formula I.

[0036] Wherein R

[0037] [Chemical formula] Here, R 1 and R 2It may be an alkylene group. The nonpolar hydrophobic alkylene group can have a closer HSP distance to COP / COC, and thus can be used to attach the modified poly(ethylene carbonate) onto the COP / COC material (they typically have a lower δ closer to 0 like polyethylene). p , δ h values). It is different from EVOH or other hydrophilic oxygen barriers that have a long HSP distance to COP / COC and thus poor adhesion to COP / COC.

[0038] Without being bound by theory, the R 1 and R 2 alkylene groups are considered to introduce hydrophobicity into the hydrophilic poly(ethylene carbonate). In certain embodiments of the present disclosure, commercially available poly(ethylene carbonate) polymers are used as amphiphilic polymers. (C 3 H 4 O 3 ) n The commercial grade QPAC® 25 poly(ethylene carbonate) having the chemical formula of, and QPAC® 40 (propylene carbonate) having the chemical formula of (C 4 H 6 O 3 ) n are examples of suitable amphiphilic polymers that act as a bonding layer between two COP / COC layers and as an oxygen barrier.

[0039] Other commercially available amphiphilic polymers having two components that meet the HSP requirements listed in the analysis shown in Example 2 can also be used. Examples of such suitable amphiphilic polymers are poly(ethylene - co - acrylic acid) or poly(ethylene - co - methylacrylic acid).

[0040]

Chemical formula

[0041] Thus, in some embodiments of the layered polymer material, the amphiphilic polymer has the following chemical formula.

[0042] [Chemical formula]

[0043] In certain embodiments, R 1 and R 2 are alkylene groups. In another embodiment, the amphiphilic polymer is poly(ethylene carbonate), poly(propylene carbonate), or a combination thereof. Alternatively, in some embodiments, the amphiphilic polymer is poly(ethylene-co-acrylic acid), poly(ethylene-co-methylacrylic acid), or a combination thereof.

[0044] Without being bound by theory, it is believed that the new layered polymer material can block UV in a wider wavelength range and thus better protect the drug stored within the components (e.g., containers, etc.) under daylight. A UV absorber having an aromatic ring can be intentionally added to the intermediate layer to block more UV.

[0045] [Chemical formula]

[0046] Thus, in certain embodiments of the present disclosure, the second layer is modified to contain an ultraviolet light absorbing material. Examples of suitable ultraviolet light absorbing materials include, but are not limited to, hydroxybenzophenone, hydroxyphenylbenzotriazole, benzophenone, benzotriazole, hydroxyphenyltriazine, oxanilide, camphor, cinnamate, and other triazines. In one embodiment, the second layer further comprises an ultraviolet light absorbing material having an aromatic ring.

[0047] Additional modifications to the second layer can be carried out. In certain embodiments, the second layer comprises a mixture of an amphiphilic polymer and an antioxidant such as butylated hydroxytoluene or Irganox® 1010, Irganox® 1076, and Irganox® 1098. Without being bound by theory, the antioxidant is thought to remove oxygen as it passes through the intermediate layer.

[0048] Vials, syringes, and kits The present disclosure also provides containers such as vials and syringes composed of a layered polymer material, and kits containing such vials and syringes. Examples of the layered polymer materials of the present disclosure are shown in FIGS. 2A - 2C. As shown in FIGS. 2A and 2B, a vial or syringe having a body composed of a polymer material can be sealed. The present disclosure also encompasses bags composed of a layered polymer material.

[0049] Thus, one embodiment of the present disclosure relates to a vial comprising a body made of a layered polymer material. The vial can be sealed and / or sterilized. In certain embodiments, the vial is packaged with a pharmaceutical composition. The pharmaceutical composition contains a therapeutic compound and a pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical composition is ready for administration.

[0050] Yet another embodiment of the present disclosure relates to a syringe comprising a body made of a layered polymeric material. The syringe can be sealed and / or sterilized. In certain embodiments, the syringe is packaged with a pharmaceutical composition. In other embodiments, the pharmaceutical composition is ready for administration.

[0051] Another embodiment of the present disclosure is a kit comprising a vial and / or a syringe, and optionally instructions for use. The kit can be sterilized.

[0052] Method for producing a layered polymeric material Yet another aspect of the present disclosure relates to a method for producing the layered polymeric material described herein. In one embodiment, the method comprises producing the layered polymeric material by direct injection molding.

[0053] The process of forming this three-layer structure is a stepwise injection molding that includes co-molding as extruded from a die. During stepwise injection molding, no surface treatment is required. In certain embodiments, the polymeric resin as pellets is used directly in each step of the injection molding.

[0054] A method of generating a structure by injection molding includes providing a mold configured to provide a desired shape of a layered polymer material after direct injection molding. In certain embodiments, the mold is configured to contain a removable spacer configured for a third layer. As a result of the presence of the space, a cavity is formed for each of the first and second layers. In that embodiment, the method includes providing a cyclic olefin polymer (COP) and / or a cyclic olefin copolymer (COC) in liquid form, such that the COP and / or COC can be injected (i.e., introduced) into the cavities formed for each of the first and second layers under conditions that allow the polymer to be melted. Once the first and second layers are formed, the spacer is removed and an amphiphilic polymer is injected (i.e., introduced) between the first and second layers under conditions that allow the polymer to be melted and enable the formation of the third layer, thereby generating a layered polymer material. Accordingly, the method includes removal of the spacer after formation of the first and second layers, provision of the amphiphilic polymer, and injection (i.e., introduction) between the first and second layers under conditions that allow the polymer to be melted, and formation of the third layer, thereby generating a layered polymer material. In certain embodiments, the method includes providing pellets of the polymer to be melted. The method may also include cooling the mold and / or the polymer after injection of the first, second, and / or third layers. In certain embodiments, the method includes forming a container (e.g., a vial or syringe) having a body composed of the layered polymer material.

[0055] In certain embodiments, the method includes sterilizing a layered polymer material. In other embodiments, the method includes filling a container (e.g., a vial or syringe) composed of the layered polymer material with a pharmaceutical composition. The pharmaceutical composition contains a therapeutic compound and a pharmaceutically acceptable carrier. In certain embodiments, a container having a body composed of the layered polymer material containing the pharmaceutical composition is packaged to produce a kit that may include instructions for use. The kit can also be sterilized. Thus, the method includes sterilizing the kit.

[0056] Yet another embodiment of the present disclosure relates to a method of producing the above-described layered polymer material. The method includes injection molding a first layer composed of a first cyclic olefin polymer or a first cyclic olefin copolymer, injection molding a third layer composed of a second cyclic olefin polymer or a second cyclic olefin copolymer, and injection molding a second layer composed of an amphiphilic polymer between the first layer and the third layer such that the second layer contacts the first layer and the third layer.

[0057] In some embodiments, the injection molding of the first layer, the second layer, and the third layer is carried out under conditions where the first cyclic olefin polymer or the first cyclic olefin copolymer, the second cyclic olefin polymer or the second cyclic olefin copolymer, and the amphiphilic polymer are in a liquid (melt) state. The first cyclic olefin polymer or the first cyclic olefin copolymer can be injection molded simultaneously with, before, or after the second cyclic olefin polymer or the second cyclic olefin copolymer. In certain embodiments of the method, the polymers are provided as pellets. In one embodiment, the method also includes providing pellets of the first cyclic olefin polymer, the first cyclic olefin copolymer, the second cyclic olefin polymer, the second cyclic olefin copolymer, and / or the amphiphilic polymer. In some embodiments, the method also includes melting the pellets. In other embodiments, the method includes cooling the mold and / or the polymer after injection of the first layer, the second layer, and / or the third layer. In further embodiments, the method includes sterilizing the layered polymer material.

[0058] Instead of pellets, in certain embodiments, it is also contemplated that the injection molding of the first layer, the second layer, and the third layer is carried out under conditions that allow the polymerization of the first cyclic olefin polymer or the first cyclic olefin copolymer, the second cyclic olefin polymer or the second cyclic olefin copolymer, and the amphiphilic polymer.

[0059] Without further elaboration, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. Accordingly, the following examples are illustrative of the preferred embodiments of the present invention and should in no way be construed as limiting the remainder of the disclosure.

Examples

[0060] The present invention will be described with reference to the following examples. These examples are provided for illustrative purposes only and the present invention should in no way be construed as being limited to these examples, but rather should be construed as encompassing any and all variations that become apparent as a result of the teachings provided herein.

[0061] Example 1 - Composition According to the Present Disclosure Figure 1 shows a cross-sectional view of a three-layer injection-molded container having outer layers 1 and 3 and an intervening second layer (intermediate layer). Each of the outer layers 1 and 3 is a COP or COC layer. Layer 2 (intermediate layer) is an amphiphilic polymer having a hydrophilic component with a Hansen solubility parameter distance from oxygen gas of 8 MPa 1 / 2 or more, and at the same time having a hydrophobic component with a Hansen solubility parameter distance from COC or COP of 8 MPa 1 / 2 or less. The structure of Figure 1 may be produced by direct injection molding.

[0062] Example 2 - Determination of Appropriate Amphiphilic Layer Properties As described above, Figure 1 shows an example of a three-layer container of the present disclosure. The process for forming this three-layer structure is stepwise injection molding. During stepwise injection molding, no surface treatment is required. As shown in Figure 1, there are a total of three layers in the injection-molded container.

[0063] The chemical structure of the intermediate layer polymer needs to be selected according to the guidelines of the Hansen solubility parameter theory. Oxygen gas has a set of Hansen solubility parameters (HSP) of δ d , δ p , δ h = 14.7, 0, 0. In order to increase the barrier properties of the selected polymer against oxygen, it is necessary to reduce the solubility of oxygen in this polymer. Permeability = Diffusion rate × Solubility

[0064] In order to reduce the solubility of oxygen in this selected polymer, it is necessary to maximize the HSP distance between the selected polymer and oxygen. Most non-polar polymers such as polyethylene (PE), for example, have δp , δ h has δ = 0.0 and thus is not a good barrier to oxygen. Instead, it is preferable to use a polymer having a higher δ p and δ h as an oxygen barrier. Thus, a polymer having δ d , δ p , δ h = 14.3, 16.5, 4.9 Hansen solubility parameter set was selected for poly(ethylene carbonate). This polymer has an HSP distance of 17.2 MPa from oxygen and can thus act as a good oxygen barrier. 1 / 2

[0065] In addition, in order to function as an effective oxygen barrier in the three-layer structure shown in FIG. 1, the amphiphilic polymer should also have a component having a set of Hansen solubility parameters (HSP) close to that of COC / COP. The smaller the HSP distance, the better the adhesion. According to the literature, COC has a set of HSPs of (18.0, 3.0, 2.0). Thus, a non-polar polymer such as PE having an HSP of (δ d , δ p , δ h = 16.9, 0.8, 2.8) has an HSP distance close to that of COC and should be regarded as a suitable non-polar component of the amphiphilic polymer that can be injection molded into the intermediate layer of the three-layer structure shown in FIG. 1.

[0066] Although the present disclosure has been described in conjunction with its preferred specific embodiments, it should be understood that the foregoing description and the following examples are intended to illustrate and not to limit the scope of the present disclosure. It will be understood by those skilled in the art that various changes can be made without departing from the scope of the present disclosure and equivalents can be substituted, and further, other aspects, advantages, and modifications will be apparent to those skilled in the art to which the present disclosure pertains.

Claims

1. A layered polymer material comprising: a first layer composed of a first cyclic olefin polymer or a first cyclic olefin copolymer; a third layer composed of a second cyclic olefin polymer or a second cyclic olefin copolymer; a first layer and a third layer in contact with each other and disposed between them, the first layer and the third layer being spaced apart from each other by a Hansen solubility parameter distance of 8 MPa from oxygen gas; 1 / 2 At the same time, the distance of the Hansen solubility parameter from COC or COP is 8 MPa or less. 1 / 2 and a second layer comprised of an amphiphilic polymer having a hydrophobic component that is:

2. The layered polymer material according to claim 1, wherein the first layer is composed of a first cyclic olefin polymer.

3. The layered polymer material according to claim 1, wherein the first layer is composed of a first cyclic olefin copolymer.

4. The layered polymer material according to any one of claims 1 to 3, wherein the third layer is composed of a second cyclic olefin polymer.

5. The layered polymer material according to any one of claims 1 to 3, wherein the third layer is composed of a second cyclic olefin copolymer.

6. The layered polymer material according to claim 1, wherein the first layer is composed of a first cyclic olefin polymer, the second layer is composed of a second cyclic olefin polymer, and the first cyclic olefin polymer and the second cyclic olefin polymer are the same.

7. The layered polymer material according to claim 1, wherein the first layer is composed of a first cyclic olefin copolymer, the second layer is composed of a second cyclic olefin copolymer, and the first cyclic olefin copolymer and the second cyclic olefin copolymer are the same.

8. The layered polymer material according to any one of claims 1 to 7, wherein the first layer and the third layer surround the second layer.

9. The layered polymer material according to any one of claims 1 to 8, wherein the second layer further comprises an ultraviolet light absorbing material having an aromatic ring.

10. The amphiphilic polymer has a δ of 0 h The layered polymer material according to any one of claims 1 to 9, which has

11. The amphiphilic polymer has a Hansen solubility parameter distance of 17 MPa or more from oxygen gas 1 / 2 The layered polymer material according to any one of claims 1 to 10, which has a Hansen solubility parameter distance of 17 MPa or more from oxygen gas.

12. The layered polymer material according to any one of claims 1 to 11, wherein the amphiphilic polymer has the following chemical formula. 【Chemical 1】

13. R 1 and R 2 The layered polymer material according to claim 12, wherein R and R are alkylene groups.

14. The layered polymer material according to claim 12, wherein the amphiphilic polymer is poly(ethylene carbonate) or propylene carbonate.

15. The layered polymer material according to any one of claims 1 to 9, wherein the amphiphilic polymer is poly(ethylene-co-acrylic acid) or poly(ethylene-co-methylacrylic acid).

16. The amphiphilic polymer has a Hansen solubility parameter distance of 4 MPa or less from the first layer and the third layer. 1 / 2 The layered polymer material according to any one of claims 1 to 11, having the following Hansen solubility parameter distance.

17. The amphiphilic polymer is poly(ethylene carbonate), and the first layer is a first cyclic olefin polymer. The layered polymer material according to claim 1.

18. The second layer is a second cyclic olefin polymer, which is the same as the first cyclic olefin polymer. The layered polymer material according to claim 17.

19. The second layer further contains an antioxidant. The layered polymer material according to any one of claims 1 to 18.

20. The layered polymer material is formed by direct injection molding. The layered polymer material according to any one of claims 1 to 19.

21. A vial containing a body made of the layered polymer material according to any one of claims 1 to 20.

22. The vial is packaged with a pharmaceutical composition. The vial according to claim 21.

23. The pharmaceutical composition is ready for administration. The vial according to claim 22.

24. A kit containing the vial according to any one of claims 21 to 23 and an instruction manual.

25. A syringe containing a body made of the layered polymer material according to any one of claims 1 to 20.

26. The syringe is packaged with a pharmaceutical composition. The syringe according to claim 25.

27. The pharmaceutical composition is ready for administration. The syringe according to claim 25.

28. A kit containing the syringe according to any one of claims 25 to 27.

29. A container formed from the layered polymer material according to any one of claims 1 to 20.

30. The container is packaged with a pharmaceutical composition. The container according to claim 29.

31. A kit containing the container according to claim 29 or 30 and an instruction manual.

32. The kit is sterilized. The kit according to claim 31.

33. A method for producing a layered polymer material according to any one of claims 1 to 19, comprising: injection molding the first layer composed of a first cyclic olefin polymer or a first cyclic olefin copolymer; injection molding the third layer composed of a second cyclic olefin polymer or a second cyclic olefin copolymer; and injection molding the second layer composed of the amphiphilic polymer between the first layer and the third layer so as to be in contact between the first layer and the third layer.

34. The method according to claim 33, wherein the injection molding of the first layer, the second layer, and the third layer is carried out under the condition that the first cyclic olefin polymer or the first cyclic olefin copolymer, the second cyclic olefin polymer or the second cyclic olefin copolymer, and the amphiphilic polymer are in a liquid state.

35. The method according to claim 33 or 34, further comprising providing pellets of a first cyclic olefin polymer, a first cyclic olefin copolymer, a second cyclic olefin polymer, a second cyclic olefin copolymer, and / or an amphiphilic polymer.

36. The method according to claim 35, further comprising melting the pellets.

37. The method according to any one of claims 33 to 36, wherein the first cyclic olefin polymer or the first cyclic olefin copolymer is injection molded simultaneously with, before, or after the second cyclic olefin polymer or the second cyclic olefin copolymer.

38. The method according to any one of claims 33 to 36, comprising simultaneously forming the first layer, the second layer, and the third layer.

39. The method according to any one of claims 33 to 36, wherein the first layer, the second layer, and the third layer are formed individually, the first layer is adhered to the second layer, and the second layer is adhered to the third layer.

40. The method according to claim 39, wherein the layers are adhered using heat or an adhesive.

41. The method according to any one of claims 33 to 39, further comprising sterilizing the layered polymer material.

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