Porous membrane, biocapsule, and implant device

Abstract

To precisely control a hole array of a microporous membrane.SOLUTION: A microporous membrane (1) is composed of a material mainly containing a resin, where a through hole (2) having a hole diameter (φ) of less than 30 μm is arranged with a fixed hole pitch distance (P) in at least one region so that an opening ratio (R) is 20% or less. A biocapsule and an implant device use the microporous membrane (1). A method for producing a microporous membrane performs plasma etching on a membrane (10) coated with a mask plate (20) from the mask plate (20) side (surface side), and obtains a microporous membrane.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a porous membrane having a novel pore structure, and a biocapsule and an implant using the porous membrane. [Background technology]

[0002] As described in Patent Documents 1 and 2, implant devices capable of delivering specific physiologically active substances to a living body from a container placed inside the body have been proposed as medical devices used in biochemical treatment. These implant devices include a container for storing the specific physiologically active substance, which is made of a porous membrane. The physiologically active substance to be administered to the living body is released from the container through the pores in the porous membrane. The container containing the specific physiologically active substance that constitutes such an implant device is referred to herein as a "biocapsule." A "biocapsule" selectively allows specific sizes of physiologically active substance particles to pass through. To release a specific physiologically active substance from a biocapsule, the pore size of the porous membrane constituting the biocapsule must be larger than the particle size of the physiologically active substance. However, if particles undesirable for the physiologically active substance (ineffective particles) are present outside the biocapsule or if particles that should not be delivered to the living body (ineffective particles) are present inside the biocapsule, the pore size of the porous membrane constituting the biocapsule must be smaller than the size of the ineffective particles to prevent the intrusion and release of the ineffective particles.

[0003] Expanded polytetrafluoroethylene porous membranes are generally preferred as biocapsule materials. As described in Patent Documents 3 and 4, expanded polytetrafluoroethylene porous membranes have a mesh or ladder structure, with pores of varying sizes and shapes. In the manufacturing process for such porous membranes, it is technically difficult to control the pore size of the porous membrane to a uniform, minute size. Therefore, as long as expanded polytetrafluoroethylene porous membranes are used, the function and ability of biocapsules to selectively release physiologically active substances with specific particle sizes in vivo is limited.

[0004] Meanwhile, precision filters for capturing various physiologically active substances are already known. Patent Document 5 describes a filter for physiologically active substances, which has pores of precisely controlled size and shape manufactured by electroforming. The porous filter described in Patent Document 5 does not come into direct contact with the living body, but is a component of an analytical instrument used outside the body. Therefore, the porous filter described in Patent Document 5 is a rigid structure made of nickel alone or a nickel-palladium alloy, and does not require the biocompatibility required for medical implant devices. Such filters are unsuitable for biocapsules that are placed in the body for relatively long periods of time. Furthermore, electroforming cannot be applied to resin materials.

[0005] Patent Document 6 describes the production of a highly permeable porous membrane with through-holes having an average diameter of 30 μm or more and less than 100 μm by forming a pattern on the surface of a sheet of non-degradable biocompatible material and then performing a dry etching process from the backside. However, this method has proven technically difficult to precisely arrange smaller through-holes, for example, through-holes with an average diameter of less than 10 μm, in the membrane. For this reason, the porous membrane described in Patent Document 6 is not effective for biocapsules that can block the passage of specific particles. Therefore, the present inventors have completed a novel microporous membrane with extremely minute through-holes regularly opened, which is useful for biochemical and medical devices such as biocapsules, unlike porous membranes made by conventional stretching or dry etching methods (Patent Document 7).However, from a practical standpoint, the strength of this microporous membrane was insufficient. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Special Publication No. 2020-500580 [Patent Document 2] Special Publication No. 2012-508584 [Patent Document 3] Special Publication No. 7-500122 [Patent Document 4] Special Publication No. 3-11259 [Patent Document 5] Japanese Patent Publication No. 2020-112452 [Patent Document 6] Patent Publication No. 2021-164532 [Patent Document 7] Patent Application No. 2023-022897 Summary of the Invention [Problem to be solved by the invention]

[0007] Thus, there is still room for improvement in porous membranes useful as materials for biocapsules and in their manufacturing methods. Therefore, the present inventors sought to develop a microporous membrane that has regularly opening micropores of uniform size and shape and that also has excellent strength. [Means for solving the problem]

[0008] The present inventors have completely redesigned the arrangement of through-holes in a microporous membrane with extremely small through-holes regularly opened, which is useful for biochemical and medical devices such as biocapsules.

[0009] (Invention 1) A microporous membrane (1) made of a material mainly composed of resin, in which through holes (2) having a pore diameter (φ) of less than 30 μm are arranged in at least one region at a constant hole pitch distance (P) so that the opening ratio (R) is 20% or less. (Invention 2) The microporous membrane (1) of Invention 1, wherein the material is a biocompatible material conforming to JIS T 0993-1:2020 (ISO 10993-1:2018). (Invention 3) The microporous membrane (1) of Invention 1, wherein the pore diameter (φ) is smaller than the size of mammalian immune cells. (Invention 4) The microporous membrane (1) of invention 1, wherein the pore diameter (φ) is less than 20 μm. (Invention 5) The microporous membrane (1) of Invention 1, wherein the through holes (2) are arranged in a staggered pattern at 60 degrees. (Invention 6) A biocapsule (3) comprising the microporous membrane (1) according to any one of claims 1 to 5. (Invention 7) An implant device (4) comprising a biocapsule (3) according to claim 6. [Effects of the Invention]

[0010] The microporous membrane and biocapsules comprising the membrane of the present invention allow efficient passage of physiologically active substance molecules such as insulin but do not allow passage of mammalian immune cells. An implant device comprising the biocapsule of the present invention can administer physiologically active substances to a living body in a treated subject's body without being attacked by the body's immune cells. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a schematic diagram for understanding the microporous membrane of the present invention. [Figure 2] FIG. 1 is a schematic diagram for understanding the microporous membrane of the present invention. [Figure 3] FIG. 1 is a schematic diagram for understanding the microporous membrane of the present invention. [Figure 4] 1 is a photograph of an example of a microporous membrane of the present invention. [Figure 5] 1 is a photograph of an example of a microporous membrane of the present invention. [Figure 6] 1 is a schematic diagram for understanding the biocapsule and implant device of the present invention. [Figure 7] 1 is a schematic diagram for understanding the biocapsule and implant device of the present invention. [Figure 8] FIG. 1 is a schematic diagram for understanding the method for producing a microporous membrane of the present invention. [Figure 9] FIG. 1 is a schematic diagram for understanding the method for producing a microporous membrane of the present invention. [Figure 10] FIG. 1 is a schematic diagram for understanding the method for producing a microporous membrane of the present invention. [Figure 11] FIG. 1 is a schematic diagram for understanding the method for producing a microporous membrane of the present invention. [Figure 12] FIG. 1 is a schematic diagram for understanding the method for producing a microporous membrane of the present invention. [Figure 13] FIG. 1 is a schematic diagram for understanding the method for producing a microporous membrane of the present invention.

[0012] In the drawings, details are exaggerated or omitted. The dotted lines and arrows shown in the drawings are auxiliary lines and do not exist in the product of the present invention. The features of the product of the present invention are not limited to the shapes, structures, and positional relationships shown in Figures 1 to 12. DETAILED DESCRIPTION OF THE INVENTION

[0013] [Microporous membrane (1)] The microporous membrane (1) of the present invention is made of a material primarily composed of a resin. There are no limitations on the resin, so long as it can be formed into a membrane and can be perforated by plasma irradiation. Therefore, in addition to general-purpose resins, resins known as (super) engineering plastics are also acceptable. Specifically, any of acrylic resins, polyolefin resins, polystyrene resins, polyvinyl chloride resins, polyester resins, polyamide resins, polycarbonate resins, fluorine-containing resins, polyacetal resins, and polyphenylene ether resins are acceptable. Engineering plastics and super engineering plastics such as polyacetal (POM), polyamide (PA), polycarbonate (PC), modified polyphenylene ether (m-PPE), polybutylene terephthalate (PBT), glass fiber reinforced polyethylene terephthalate (GF-PET), ultra-high molecular weight polyethylene (UHPE), syndiotactic polystyrene (SPS), amorphous polyarylate (PAR), polysulfone (PSF), polyethersulfone (PES), polyphenylene sulfide (PPS), polyetheretherketone (PEEK), polyimide (PI), polyetherimide (PEI), fluororesins such as tetrafluoroethylene (co)polymer (PTFE), and film-forming grades of liquid crystal polymer (LCP) can also be used. These resins may be mixed with other resins or additives as long as they do not interfere with the perforation described below.

[0014] When the microporous membrane (1) is used as a material for biocapsules, the material must be a biocompatible material conforming to JIS T 0993-1:2020 (ISO 10993-1:2018). To accommodate sterilization of biocapsules or implant devices containing biocapsules, the microporous membrane (1) is preferably made of a material primarily composed of a resin with excellent heat resistance and radiation resistance. Among these, tetrafluoroethylene (co)polymer (PTFE) and polyether ether ketone (PEEK) are suitable materials for the microporous membrane (1).

[0015] The thickness of the microporous membrane (1) is not particularly limited. The thickness of the microporous membrane (1) for biocapsules is generally from 1 μm to 2 mm, preferably from 3 μm to 200 μm, and more preferably from 5 μm to 50 μm.

[0016] In at least one region of the microporous membrane of the present invention, through-holes having a pore diameter (φ) of less than 30 μm are arranged at a certain hole pitch distance (P) so that the aperture ratio (R) is 20% or less. For example, relatively large particles such as mammalian immune cells have difficulty passing through through-holes having a pore diameter (φ) of less than 30 μm. In terms of the balance between permeability and strength, the pore diameter (φ) of the microporous membrane of the present invention is preferably 1 μm or more and 25 μm or less, and more preferably 3 μm or more and less than 20 μm.

[0017] The opening shape of the through hole (2) is not particularly limited and may be either circular or polygonal. The hole diameter (φ) means the average inside length of the opening of the through hole (2). Preferably, the opening shape of the through hole (2) is circular. Here, "circular" includes not only a perfect circle but also an approximately circular shape that can be called circular based on the circularity or average hole diameter.

[0018] Figures 1, 2, and 3 show schematic diagrams of the microporous membrane of the present invention. Figure 1 shows a portion of the surface of the microporous membrane (1) of the present invention. Numerous circular through-holes (2) are arranged in the region shown in Figure 1. Figures 2 and 3 show cross sections of the microporous membrane (1) in the thickness direction.

[0019] The diameter (φ) of the through-holes (2) is controlled to a constant length of less than 30 μm, preferably 1 μm or more and 25 μm or less, more preferably 3 μm or more and less than 20 μm.

[0020] By controlling the pore diameter (φ) in this manner, various physiologically active substances (5) having particle sizes smaller than the pore diameter (φ), such as human insulin molecules with a molecular weight of 5803, pass through the through-holes (2).

[0021] On the other hand, by controlling the pore size (φ) within the above-mentioned range, the microporous membrane (1) can prevent the passage of various mammalian, particularly human, immune cells (6). For example, human immune cells (white blood cells) include lymphocytes with a diameter ranging from 6 μm to 15 μm, neutrophils with a diameter ranging from 12 μm to 15 μm, basophils with a diameter ranging from 10 μm to 15 μm, eosinophils with a diameter ranging from 13 μm to 17 μm, monocytes with a diameter ranging from 20 μm to 30 μm, and macrophages with a diameter ranging from 20 μm to 50 μm.

[0022] When a biocapsule is produced by storing cells that produce various physiologically active substances (5) in a capsule made of a microporous membrane (1) with a pore size (φ) controlled within the above-mentioned range, the physiologically active substances (5) are produced in the biocapsule without immune cells (6) invading the biocapsule and attacking the producing cells, and the produced physiologically active substances (5) can pass through the through-holes (2) and move out of the biocapsule.

[0023] At least a portion of the microporous membrane (1) of the present invention consists of a region in which through holes (2) are regularly arranged. FIG. 1 schematically shows a portion of such a region. In the microporous membrane (1) of the present invention, the through holes (2) are circular and arranged at a constant hole pitch distance (P) so that the aperture ratio (R) in the region is 20% or less, preferably 15% or less. By setting the aperture ratio (R) to 20% or less, the strength of the microporous membrane (1) is improved. In the present invention, an aperture pattern that combines an appropriate hole pitch distance (P) with the above-mentioned hole diameter (φ) is selected to design the aperture ratio (R) to 20% or less, preferably 15% or less. By appropriately selecting the pore diameter (φ), pore pitch (P), and aperture ratio (R), a microporous membrane for biocapsules having an excellent balance between selective permeability and strength can be obtained. For example, the microporous membrane of the present invention can be used to efficiently release a physiologically active substance (3) from the biocapsule while preventing the entry of immune cells (6) into the biocapsule.

[0024] The arrangement of the through holes (2) in the microporous membrane (1) of the present invention is not limited as long as it has a regularity that realizes the opening ratio (R) in the above region at the above hole pitch distance (P).

[0025] The through holes (2) in the microporous membrane (1) of the present invention are typically arranged in a 60-degree staggered pattern. A "60-degree staggered pattern" is a common circular hole arrangement in wire mesh and filters. In this arrangement, the centers of the circular through holes (2) (uniform circular holes) are at the vertices of an equilateral triangle. Figures 4 and 5 show photographs of a microporous membrane (1) in which the through holes (2) are arranged in a 60-degree staggered pattern. In the microporous membrane (1) shown in Figures 4 and 5, the through holes (2) with a pore diameter (φ) of 5 μm are arranged at a pore pitch distance (P) of 15.1 μm, and the aperture ratio (R) is 10%. Such a microporous membrane of the present invention can be used as a variety of separation membranes. The material to be separated can be appropriately selected based on the pore diameter (φ).

[0026] [Biocapsules (3), Implant Devices (4)] The microporous membrane (1) of the present invention can be used, for example, as a material for biocapsules (3). The shape of the biocapsules (3) is not limited as long as they can be placed in a living body and can release the encapsulated specific physiologically active substance. For example, the microporous membrane (1) can be molded into a bag, tube, or box shape and used as the biocapsule (3). In addition to the molded body of the microporous membrane (1), the biocapsule (3) may have a member for supporting or holding the molded body. The volume and dimensions of the biocapsule (3) are determined appropriately to suit the biological site where it is to be placed.

[0027] The implant device 4 of the present invention includes a biocapsule 3. The implant device 4 generally includes accessories such as a catheter or the like for moving and positioning the biocapsule 3 inside a living body, and a culture medium circulation tube or the like for controlling a physiologically active substance in the biocapsule 3.

[0028] FIG. 6 shows a schematic representation of a portion of an implant device (4) of the present invention. The implant device (4) comprises a biocapsule (3) and a tube (41) as an accessory member. The biocapsule (3) is placed in a living body. FIG. 7 shows a schematic cross section of the biocapsule (3) shown in FIG. 6 taken along the dotted line. FIG. 7 also shows a schematic representation of the biocapsule (3) being filled with a solution containing a physiologically active substance (5). Cells that produce the physiologically active substance (5) are omitted from FIG. 7. After the biocapsule (3) is placed in a living body, the physiologically active substance (5) migrates out of the biocapsule (3) through the through-holes (2) in the microporous membrane (1).

[0029] [Manufacturing method (1)] The microporous membrane (1) of the present invention can be produced by the following method (1), which is an application of the "Method for producing a microporous membrane (100)" disclosed in Japanese Patent Application No. 2023-022897.

[0030] The microporous membrane (1) of the present invention can be produced by a method (1) comprising the steps of: step 1: adhering a mask plate (20) having a plurality of through holes (21) arranged therein to one side of a membrane (10) made of a material mainly composed of resin to obtain a laminate (30) of the membrane (10) and the mask plate (20); step 2: irradiating the laminate (30) obtained in step 1 with plasma from the front side of the mask plate (20) to perforate the membrane (10); and step 3: separating the mask plate (20) from the laminate (30) that has been subjected to step 2 to obtain a microporous membrane (1) made of the material mainly composed of resin and having a plurality of through holes (2) formed in at least one region of its surface.

[0031] In short, method (1) is a method for producing a microporous membrane (1) by plasma etching a membrane (10) covered with a mask plate (20) from the mask plate (20) side (front side). In this technique, through-holes (2) are formed in the membrane (10) located at the openings of the mask plate (20), so that, theoretically, the through-hole (21) pattern in the mask plate (20) is reproduced as the through-hole pattern in the microporous membrane (1). By precisely designing the arrangement of the through-holes (21), it is possible to produce a microporous membrane (1) with precisely arranged through-holes.

[0032] In method (1), for example, the membrane (10) is introduced into a drum-type plasma irradiation device or a flat-plate plasma irradiation device, and the plasma is irradiated onto the surface of the membrane (10) in the device. When using a drum-type plasma irradiation device, the plasma irradiation voltage is generally 1.0 kV to 4.0 kV, preferably 1.5 kV to 3.5 kV, and more preferably 1.5 kV to 3.0 kV. Plasma treatment can also be performed using other methods, such as a flat-plate plasma irradiation device, under conditions that provide equivalent plasma irradiation intensity.

[0033] The mask plate (20) used in step 1 is made of a material that is resistant to deformation and damage caused by plasma irradiation. A metal filter made of electroformed metal can be used as this mask plate (20). Nickel or a nickel-palladium alloy is preferred as the electroformed metal material. The thickness of the mask plate (20) is generally 4 μm to 50 μm, preferably 5 μm to 20 μm. In actual step 1, the membrane (10) and the mask plate (20) are pressed together with a jig to obtain a laminate (30). For example, by stacking and fixing a stainless steel cover, nickel mask plate (20), membrane (10), stainless steel plate, neodymium magnet plate, and stainless steel plate in this order, the nickel mask plate (20) and the membrane (10) can be tightly and securely attached without any gaps.

[0034] The opening shape of the through holes (21) is not particularly limited and may be either circular or polygonal. The hole diameter (φ) refers to the average internal length of the opening of the through holes (2). Preferably, the opening shape of the through holes (2) is circular. Here, "circular" includes not only a perfect circle but also an approximately circular shape that can be called circular based on the circularity or average hole diameter. In step 1 of method (1), the through holes in the mask plate (20) and their hole pitch distance are not limited as long as they do not interfere with steps 2 and 3 described below.

[0035] FIG. 8 shows a photograph of an example of a mask plate (20). This mask plate (20) has round through-holes (21) arranged in a 60-degree staggered pattern. The through-holes (21) have a hole diameter (φM) of 5.5 μm and a hole pitch distance (P) of 15.1 μm. The mask plate (20) used in step 1 is not limited to the mask plate (20) shown in FIG. 8. In step 1, a mask plate (21) with irregularly arranged through-holes (21) can also be used. FIG. 9 schematically shows a laminate (30) formed by laminating the mask plate (20) and the film (10) in step 1.

[0036] In step 2, the jig-fixed laminate (30) is actually carried into a plasma irradiation device, and plasma is irradiated from the open surface side of the mask plate (20). A vacuum ion method is generally used for plasma irradiation. The plasma irradiation conditions are appropriately adjusted depending on the thickness of the film (10), the shape and thickness of the mask plate (20), etc. If the stainless steel cover, nickel mask plate (20), film (10), stainless steel plate, neodymium magnet plate, and stainless steel plate are stacked and fixed in this order in step 1, then in step 2, only the laminated portion of the stainless steel cover, nickel mask plate (20), film (10), and stainless steel plate is carried into the plasma irradiation device.

[0037] FIG. 10 shows a schematic diagram of the state at the start of step 2. The dotted line shows a schematic diagram of the plasma irradiation. FIG. 11 shows a schematic diagram of the etching of the film (10) progressing as the plasma irradiation continues. Recesses (11) can be seen in the film (10). FIG. 12 shows a schematic diagram of the laminate (30) after step 2 has been completed. The recesses (11) in the film (10) have been transformed into through-holes (12).

[0038] In step 3, the jig fixing the laminate 30 is actually released, and the mask plate 20 is removed from the laminate 30. The membrane 10 with through holes 12 formed therein is recovered as a microporous membrane 1. FIG. 13 schematically shows the obtained microporous membrane 1. In the example of the microporous membrane 1 shown in FIG. 13, through holes 2 are opened and arranged with a hole diameter (φ) and a hole pitch distance (P) according to the hole diameter (φM) and hole pitch distance (P) of the through holes 21 in the mask plate 20.

[0039] [Manufacturing method (2)] The microporous membrane (1) of the present invention can also be produced by the following method (2), which is an application of the "method for producing a microporous membrane (1)" disclosed in Japanese Patent Application No. 2023-022897. That is, the microporous membrane (1) of the present invention can be produced by using method (2), which is a special embodiment of the above-mentioned method (1).

[0040] The manufacturing method (2) includes the following steps: step 1': attaching a mask plate (20) having through holes (21) with a constant hole diameter (φM) arranged at a constant hole pitch distance (P) to one side of a membrane (10) made of a material mainly composed of resin to obtain a laminate (30) of the membrane (10) and the mask plate (20); step 2': irradiating the laminate (30) obtained in step 1' with plasma from the front side of the mask plate (20) to perforate the membrane (10); and step 3': separating the mask plate (20) from the laminate (30) that has been subjected to step 2' to obtain a microporous membrane (1) made of a material mainly composed of resin, in at least one region of which through holes (2) with a hole diameter (φ) of less than 30 μm are arranged at a constant hole pitch distance (P) so that the opening ratio (R) is 20% or less.

[0041] The plasma irradiation method is as described in the manufacturing method of the microporous membrane 100. The plasma irradiation conditions can be selected depending on the thickness and material of the membrane 10.

[0042] In the method for producing a microporous membrane (1) of the present invention, a pore diameter (φ) close to the pore diameter (φM) of the through-holes (21) in the mask plate (20) is formed in the microporous membrane (1) in at least one region of the microporous membrane (1), and the pore pitch distance (P) of the through-holes (21) in the mask plate (20) is reproduced as the pore pitch distance (P) of the through-holes (2) in the microporous membrane (1). The pore diameter (φM) means the average inside dimension of the openings of the through-holes (2).

[0043] In the method for producing a microporous membrane (1) of the present invention, the opening shape and arrangement of the through holes (21) are suitable for the through holes (2) in the final microporous membrane (1). Therefore, in the method for producing a microporous membrane (1) of the present invention, the opening shape of the through holes (21) is circular. Here, "circular" includes not only a perfect circle but also an approximate circle that can be called a circle based on the circularity or average pore diameter. The arrangement of the through holes (21) has a regularity that achieves the above-mentioned hole pitch distance (P) and the above-mentioned opening ratio (R) in the final microporous membrane (1), and is typically a 60-degree staggered pattern.

[0044] The material and thickness of the mask plate (20) used in step 1' are the same as those described for step 1. The opening pattern of the mask plate (20) used in step 1' is designed according to the opening pattern of the target microporous membrane (1). The actual procedures for steps 2' and 3' are the same as those described for steps 2 and 3. Figures 8 to 13 also correspond to steps 1', 2', and 3'.

[0045] [effect] The microporous membrane (1) of the present invention is made of a resin-based material, preferably a biocompatible material conforming to JIS T 0993-1:2020 (ISO 10993-1:2018), more preferably a polytetrafluoroethylene or a polyether ether ketone, and is therefore useful as a material for medical devices.

[0046] In at least one region of the microporous membrane (1) of the present invention, circular through-holes (2) with a pore diameter (φ) of less than 30 μm are arranged at a constant hole pitch distance (P), typically in a 60-degree staggered pattern, with an opening ratio (R) of 20% or less. The microporous membrane (1) blocks large particles equivalent to or larger than human immune cells and allows small particles of various physiologically active substances, such as insulin particles, to pass through with high efficiency. Moreover, the microporous membrane (1) has appropriate strength. Therefore, the microporous membrane (1) is highly practical as a material for implant devices and biochemical analysis filters that must block or allow the passage of specific biologically relevant substances. The microporous membrane (1) of the present invention is useful, for example, as an implanted biocapsule for administering insulin. [Example]

[0047] [Example 1] The following steps 1, 2, and 3 were carried out in this order.

[0048] (Step 1) A mask plate was prepared which was made of nickel alone by electroforming and had a thickness of 5 μm and through holes with a diameter of 5.5 μm arranged at a 60-degree staggered pattern with a hole pitch of 15.1 μm.

[0049] Separately, a 6 μm thick PEEK film (Shin-Etsu Sepla Film (registered trademark), low crystallinity type, manufactured by Shin-Etsu Polymer Co., Ltd.) was prepared. The PEEK film is a biocompatible material that complies with JIS T 0993-1:2020 (ISO 10993-1:2018).

[0050] Next, the mask plate and the PEEK film were fixed and pressed with a jig to be tightly attached within the mold.

[0051] (Step 2) The laminate consisting of the mask plate and the PEEK film was carried into a plasma irradiation device together with the mold, and plasma was irradiated from the front side of the mask plate under the conditions of voltage: 3 kV, treatment time: 20 minutes, gas used: oxygen, and gas pressure: 25 Pa.

[0052] (Step 3) The laminate consisting of the mask plate and the PEEK film was cooled while still in the mold, and then the mold was dismantled to remove the PEEK film. Microscopic observation of the PEEK film confirmed that through-holes with a pore diameter of 5 μm were arranged in a 60-degree staggered pattern with a hole pitch of 15.1 μm. The aperture ratio was 10%. Thus, a PEEK microporous membrane corresponding to the present invention was completed.

[0053] [Example 2] The mask plate used in Example 1 was changed to a mask plate of the same material and thickness but with a different hole diameter and hole pitch distance, and the same steps as in Example 1 were carried out to produce a PEEK microporous membrane corresponding to the present invention, which had a thickness of 6 μm, a hole diameter of 17.5 μm, a hole pitch distance of 52.7 μm, and holes with an opening rate of 10% arranged in a 60-degree staggered pattern.

[0054] [Example 3] The mask plate used in Example 1 was changed to a mask plate of the same material and thickness but with a different hole diameter and hole pitch distance, and the same steps as in Example 1 were carried out to produce a PEEK microporous membrane corresponding to the present invention, with a thickness of 6 μm, a hole diameter of 5 μm, a hole pitch distance of 10.6 μm, and holes with an opening rate of 20% arranged in a 60-degree staggered pattern.

[0055] [Comparative Example 1] A comparative PEEK microporous membrane having a thickness of 6 μm, a pore diameter of 5 μm, a pore pitch of 9 μm, an aperture ratio of 30%, and pores arranged at a 60° staggered pattern was produced by carrying out the same process as in Example 1 using a mask plate having the same material and thickness as the mask plate used in Example 1 but a different pore diameter and pore pitch.

[0056] Comparative Example 2 A comparative PEEK microporous membrane having a thickness of 6 μm, a pore diameter of 65 μm, a pore pitch of 195.7 μm, an aperture ratio of 10%, and pores arranged at a 60-degree staggered pattern was produced by carrying out the same process as in Example 1 using a mask plate having the same material and thickness as the mask plate used in Example 1 but a different pore diameter and pore pitch.

[0057] [Evaluation of tensile strength] Tensile tests were conducted under the following conditions on the microporous membranes obtained in Examples 1, 2, and 3 and Comparative Examples 1 and 2. Table 1 shows the average value of the maximum tensile stress (MPa) measured for three samples cut out from the film of each example, as the tensile strength (MPa).

[0058] Testing machine: Test conditions: Universal testing machine Autograph AGX plus 100kN (Shimadzu Corporation) Grip movement speed: 5mm / min Initial shape of film test piece: Width 30 mm, length (distance between grips) 22 mm Test room temperature: 23℃ Test room humidity: 50%

[0059] [Table 1]

[0060] From these results, the PEEK microporous membrane of the present invention is expected to be a permselective film that combines biocompatibility, strength, and permeability. [Industrial Applicability]

[0061] The present invention provides a permselective film that combines biocompatibility, strength, and permeability. The microporous membrane of the present invention is useful as a biochemical and medical material. The microporous membrane of the present invention can be used, for example, in the treatment of diabetes. The present invention contributes to the medical device market and welfare. [Explanation of symbols]

[0062] 1. Microporous membrane 2 through holes 3 Biocapsules 4 Implant devices 5 Physiologically active substances 6 Immune cells 10 membrane 11 Recess 12 Through holes 20 Mask board 30 laminate 41 Accessory parts (tubes)

Claims

1. The microporous membrane (1) is made of a material mainly composed of resin, and in at least one region, through holes (2) having a pore diameter (φ) of less than 30 μm are arranged at a constant hole pitch distance (P) so that the opening ratio (R) is 20% or less.

2. The microporous membrane (1) according to claim 1, wherein the material is a biocompatible material in accordance with JIS T 0993-1:2020 (ISO 10993-1:2018).

3. The microporous membrane (1) according to claim 1, wherein the pore diameter (φ) is less than the size of mammalian immune cells.

4. The microporous membrane (1) according to claim 1, wherein the pore diameter (φ) is less than 20 μm.

5. The microporous membrane (1) according to claim 1, wherein the through holes (2) are staggered at 60 degrees.

6. A biocapsule (3) comprising a microporous membrane (1) according to any one of claims 1 to 5.

7. An implant device (4) comprising a biocapsule (3) according to claim 6.

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