JP2011142831A - Porous plate, functional permeable membrane and artificial organ - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a porous plate which can be utilized for barrier membrane and other uses, and to provide a functional permeable membrane and an artificial organ which each utilizes the porous plate. <P>SOLUTION: The porous plate 1 produced by forming a plurality of penetrated holes 2 in a board-like plate is characterized in that the pore diameters of a plurality of the penetrated holes 2 are ϕ1 to ϕ50 μm, and the distance between the central axes of the adjacent penetrated holes 2 is 3 to 300 μm. The porous plate 1 has penetrated holes having the same diameter as those of pores and fluid passages which are formed in a powder-sintered porous material. The density of the penetrated holes is approximately the same density as those of pores and the like of the powder-sintered porous material. Therefore, the porous plate has the same function as that of the powder-sintered porous material, and can more reduce the pressure loss generated on the passage of a fluid than that of the powder-sintered porous material. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a perforated plate, a functional permeable membrane, and an artificial organ.

  The living body has the ability to autonomously recover the tissue lost due to damage and disease, but in order to recover the damage quickly, firstly, the damaged part is covered with a tissue with a high growth rate such as epithelial tissue, and the wound surface is closed. Tend to prioritize. For this reason, it is often the case that a non-original tissue dominates the lost tissue portion, and the form and function before damage cannot be recovered.

  For example, in chronic marginal periodontitis (periodontal disease), if the alveolar bone supporting the teeth is destroyed by an inflammatory reaction and the lost alveolar bone is replaced with granulation tissue or epithelial mucosa, the inflammatory reaction is Once lost, the alveolar bone once lost does not recover. Alveolar bone has the ability to grow and recover, but because its former space is dominated by other tissues, it has no potential to grow and recover by eliminating it. is there.

  In this case, the main principle for maintaining the homeostasis of living tissue, which does not erode other tissues that are already stably present, is to prevent recovery to the original tissue form. By the way, it is a malignant tumor that ignores this principle and erodes other tissues.

  On the other hand, however, it is clear that once a space controlled by another organization is released by some means, the original organization can proceed to that space and re-control. As a means to recover the alveolar bone lost due to periodontal disease, Nyman et al. In 1982 released the space to the alveolar bone side where the alveolar bone was dominated by the space making method using Millipore filter. Successful induction of alveolar bone growth and extension. This method is now widely used in dental practice as a guided tissue regeneration (GTR) method.

  In the current periodontal tissue regeneration induction method, one of the methods for regenerating and recovering periodontal tissue that has been lost due to illness or trauma is a filter that can pass only nutrients and physiologically active substances without passing through cells. GTR is performed to regenerate alveolar bone by performing space making in periodontal tissue using a partition membrane (barrier membrane) for biological tissue regeneration.

  As barrier membranes, polymeric materials with affinity and safety for living organisms have been used as raw materials since the beginning of their development, and many of these products are layered as fibers to satisfy the above conditions. It is a Millipore filter composed of

  In addition to safety and biocompatibility, such a filter-type barrier membrane is required to have a function to prevent the invasion of other cells and tissues while supplying nutrients to the tissue that induces regeneration. The material is limited to biocompatible polymer materials such as PTFE (Teflon) and polylactic acid. For this reason, there is always a problem with the strength of the film itself.

  In order to maintain the space for tissue regeneration in the living body, the filter type barrier membrane must have a physical strength to maintain its shape, and its film thickness is 200 microns or more embedded in the living body when shipped from the factory. After that, it occupies a thickness (Biomend) of about 400 microns due to swelling action.

  The reason why the film thickness is necessary is that the barrier membrane will be crushed if the barrier membrane does not have sufficient strength to maintain the space for the desired regenerated tissue to stretch in the living body, competing with the pressure from surrounding tissues. This is because tissue regeneration cannot be expected. In fact, there are even products that ensure strength by combining a titanium reinforcing frame with the barrier membrane.

  However, when it is embedded in a living body, because of its thickness, even if it has biocompatibility, the volume of the barrier membrane itself gives an obstacle such as compression to surrounding tissues, It may adversely affect certain tissue regeneration. Accordingly, there is a demand for a new material with a smaller thickness that has a function of maintaining the nutrient supply to the tissue intended for regeneration while maintaining the strength for securing the tissue regeneration space for the barrier membrane.

  As such a new material, it has a film strength comparable to that of a biocompatible polymer material having a thickness of 200 microns or more, and can be thinned to a thickness of about 50 microns. Is considered to be used.

  Since biocompatibility is required for the barrier membrane, it is conceivable to apply titanium widely used in the medical field, in particular, pure titanium having high biocompatibility.

  On the other hand, in order to use a metallic barrier membrane as a filter-type barrier membrane, a particularly important filter function is imparted to the metallic barrier membrane within the conditions of the above-mentioned barrier membrane made of a biocompatible polymer material. There is a need to. In order to impart such a filter function to a metallic barrier membrane, it is necessary to apply micron-order fine precision processing to a metallic plate or the like.

  However, at present, pure titanium and titanium alloys are very difficult to process, and micron-order fine precision processing must be further difficult.

  If thermal cutting or thermal drilling with a laser or the like is performed, even if it is pure titanium or a titanium alloy, there is a possibility that precision machining can be performed. Affinity may be impaired and physical properties may be deteriorated. For example, pure titanium has a problem that it is easily combined with oxygen and other elements contained in the surrounding atmosphere and modified by thermal processing. Such a problem may occur even when other metallic materials are processed by a laser or the like.

  Because of the above problems, a barrier membrane having a thin and sufficient strength and a good biocompatibility has not been developed, and such a barrier membrane is required.

In addition to the GTR space making, a wide variety of uses are conceivable for the porous plate that is thin and has sufficient strength and has a large number of micron-order pores, such as the barrier membrane described above. For example, semiconductor manufacturing equipment (flow rate controller), membrane reactor (membrane-based reaction process), microfiltration membrane, electrolysis (electrolytic reaction electrode), bio (cell separation), food (yeast filtration), medical treatment (sanitization filtration), etc. It can be used as a member that allows fluid to pass through.
However, at present, a perforated plate that sufficiently satisfies the above uses has not been developed, and its development is required.

  In view of the above circumstances, an object of the present invention is to provide a porous plate that can be used for barrier membranes and other applications, and a functional permeable membrane and an artificial organ using the porous plate.

The perforated plate of the first invention is a plate in which a plurality of through holes are formed in a plate-like plate, and the diameter of the plurality of through holes is φ1 to φ50 μm, and between the central axes of the adjacent through holes The distance is 3 to 300 μm.
The porous plate of the second invention is characterized in that, in the first invention, the plate thickness of the plate is 2 to 100 μm.
In the first or second invention, the perforated plate according to the third invention is characterized in that a tapered surface is formed at one end of the through hole.
A porous plate of a fourth invention is a plate used as a thin metal permeable membrane for tissue isolation or a barrier membrane in the first, second or third invention, and the material of the plate is a metal having biocompatibility. The hole diameter of the plurality of through holes is φ1 to φ10 μm.
A porous plate of a fifth invention is a plate used as a thin metal permeable membrane for tissue isolation or a barrier membrane in the first, second or third invention, and the material of the plate is a metal having biocompatibility. A plurality of through-holes having a diameter of φ10 μm or more, and a polymer thin film layer having through-holes having a diameter of φ1 to φ10 μm is provided on the surface of the plate. Features.
A functional permeable membrane according to a sixth aspect of the present invention is the porous plate according to any one of the first to fifth aspects of the present invention, which is made of a metal or a metal / polymer composite, and the through hole in the porous plate contains a physiologically active substance and / or a chemical. It is characterized by.
An artificial organ of the seventh invention is characterized by comprising an outer frame formed by the perforated plate according to the first to fifth inventions and a group of artificially cultured organ cells housed in the outer frame. To do.

According to the first invention, the powder sintered porous body has pores and through holes having the same diameter as the fluid passage, and the through hole density is the pores in the powder sintered porous body. Therefore, the pressure loss generated when the fluid passes can be reduced as compared with the powder sintered porous body, while having the same function as the powder sintered porous body.
According to the second invention, the strength of the plate can be increased.
According to the third invention, since the taper is formed, if the pore surface is coated with palladium or the like, the hydrogen is separated and purified with high purity when used as a reactor used for hydrogen steam reforming. can do.
According to the fourth invention, since the material of the plate is a biocompatible metal such as pure titanium or titanium alloy, ceramics, plastics, or polymers, even if it is placed in the living body, it may adversely affect the living body. Absent. Moreover, since the hole diameter of the through-hole formed in the plate is φ1 to φ10 μm, it allows passage of physiologically active substances such as cytokines, nutrients and gas components that control cell growth and differentiation while preventing passage of human cells. Can do. For this reason, it becomes possible to supply nutrients and the like into the space while forming a space in the living body and preventing specific cells from entering the space.
According to the fifth invention, since the material of the plate is a metal, ceramics, plastic, or polymer having biocompatibility such as pure titanium or titanium alloy, it may adversely affect the living body even if it is placed in the living body. Absent. Moreover, since the pore diameter of the through-hole formed in the polymer thin film layer on the plate surface is φ1 to φ10 μm, physiologically active substances such as cytokines, nutrients and gases that control cell proliferation and differentiation while preventing passage of human cells The ingredients can be passed through. For this reason, it becomes possible to supply nutrients and the like into the space while forming a space in the living body and preventing specific cells from entering the space.
According to the sixth invention, since the plate through-hole contains various chemicals such as antibiotics and anticancer agents in addition to physiologically active substances such as tissue growth factors and cytokines, the plate is placed in the living body, and the metal of the plate If the portion is charged, the physiologically active substance or drug in the through-hole can be released into the living body by electrophoresis.
According to the seventh invention, since the organ cell group cultured in the outer frame is accommodated, if the organ cell group is placed in the living body and connected to the vascular system, the cells sealed in the outer frame The life of the group can be maintained, and the physiologically active substance derived from the cell group can be released into the blood, or the waste product in the blood can be removed or purified.

It is a schematic plan view of the porous plate 1 of the present invention. It is a schematic explanatory drawing of the porous plate 1 of this invention. It is a schematic explanatory drawing of the condition which used the perforated plate 1 of this invention for the space making in periodontal tissue regeneration induction method. It is the figure explaining the relationship between the porous plate 1 of this invention, the nutrient 8, and the cell 9 in the condition which used the porous plate 1 of this invention for the space making in a periodontal tissue regeneration induction method. It is the figure which showed an example of the porous plate 10 of this invention installed in a periodontal structure | tissue. It is a schematic explanatory drawing of the surgery which installs the perforated plate 10 of this invention inside a periodontal tissue. It is a schematic explanatory drawing of the surgery which installs the perforated plate 10 of this invention inside a periodontal tissue. It is a schematic explanatory drawing of the surgery which installs the perforated plate 10 of this invention inside a periodontal tissue. It is a schematic explanatory drawing of the surgery which installs the perforated plate 10 of this invention inside a periodontal tissue. It is a microscope picture of the porous plate of this invention. It is a schematic explanatory drawing of the polymer thin film layer provided in the surface of the plate in the porous plate 1 of this invention. It is a schematic perspective view of the processing apparatus 101 which processes the perforated plate 1 of this embodiment. It is a schematic explanatory drawing of the processing apparatus 101 in the condition which processes the perforated plate 1, Comprising: (A) is a front view, (B) is a BB arrow directional view of (A). FIG. 2 is a schematic explanatory diagram of a situation in which a porous plate 1 is processed by a processing apparatus 101. It is a schematic explanatory drawing of the processing apparatus 101 in the condition which processes the punch P, (A) is a front view, (B) is a BB line arrow directional view of (A). FIG. 6 is a schematic explanatory diagram of a situation in which a punch P is processed by the processing apparatus 101. It is a schematic explanatory drawing of the processing apparatus 101 in the condition which processes the dice | dies D, Comprising: (A) is a front view, (B) is a schematic explanatory drawing of a processing condition.

Next, an embodiment of the present invention will be described with reference to the drawings.
The perforated plate 1 of the present invention is a plate in which a large number of micropores are formed in a plate-like plate.
The porous plate 1 of the present invention is a plate that can be used for various applications. For example, regenerative medical materials and medical equipment in medical departments (eg, functional permeable membranes and frames that hold cells of artificial organs), semiconductor manufacturing equipment (flow rate controllers), membrane reactors (membrane-based reaction processes), microfiltration membranes It can be used as a member that allows fluid to pass in electrolysis (electrolytic reaction electrode), bio (cell separation), food (yeast filtration), medicine (sanitization filtration), and the like.

In particular, the perforated plate 1 of the present invention is a tissue partition membrane used for periodontal diseases and surgical operations for augmenting and restoring alveolar bone destroyed or absorbed by loss of teeth for the purpose of periodontal regeneration treatment in dentistry, organs It is suitable for use as a containment shell for derived cultured cells.
For example, in the case of a barrier membrane used for enclosing a space in a living tissue and used for attracting a tissue intended for regeneration during space making in GTR, 1) biocompatibility and It has excellent safety, 2) has the strength to maintain space, 3) has semi-permeability (filter function) that can supply nutrients to the inducing tissue, and 4) other than inducing cells. The function of being able to prevent entry is necessary. The porous plate 1 of the present invention is suitable for such a barrier membrane.

(Description of perforated plate 1)
As shown in FIG. 1, a perforated plate 1 of the present invention has a large number of through holes 2 formed on a plate-like member (hereinafter referred to as a main body).

(Description of the main unit)
The main body is a member formed in a plate shape. The thickness of the main body is not particularly limited as long as it is plate-shaped. However, if it is used for the above-mentioned purposes, the plate thickness is preferably about 2 to 100 μm, and preferably about 2 to 30 μm.
The material of the main body is not particularly limited, and an optimum material for each application can be adopted. For example, in the case of use in living organisms such as regenerative medical materials and medical devices, it is preferable to use biocompatible metals such as pure titanium or titanium alloys, ceramics, plastics, and polymers. With such a material, even if the perforated plate 1 is disposed in the living body, the living body is not adversely affected. In particular, if pure titanium is used, excellent biocompatibility and cell growth promoting ability can be expected. Specifically, it can be used not only as a new periodontal tissue regeneration material in dental clinics but also as a material for regenerative medicine, for example, as a material for artificial organs.

(Description of the through hole 2)
The perforated plate 1 is provided with a plurality of through holes 2. The plurality of through holes 2 may be appropriately formed so as to exhibit a predetermined function in each application, and the diameter and the distance between the central axes of the adjacent through holes 2 (that is, the density at which the through holes 2 are provided) are There is no particular limitation. However, when used in the above-described applications, the hole diameter (diameter) φa is about φ1 to φ50 μm (preferably φ1 to φ30 μm), and the distances D1 and D2 between the central axes of the adjacent through holes 2 are. Is preferably 3 to 300 μm.
With such diameter and density, the through holes 2 have the same diameter as the pores and fluid passages of the powder sintered porous body, and the through hole density is the pores in the powder sintered porous body. The density is about the same. Therefore, the pressure loss generated when the fluid passes can be reduced as compared with the powder sintered porous body while having the same function as the powder sintered porous body.

In particular, when used for regenerative medical materials and medical devices, the through hole 2 preferably has a hole diameter (diameter) φa of about φ1 to φ10 μm.
When the diameter of the through-hole 2 is as described above, it allows passage of physiologically active substances such as cytokines, nutrients and gas components that control cell growth and differentiation while preventing passage of human cells through the through-hole 2. Can do. For this reason, the porous plate 1 makes it possible to supply nutrients and the like into the space while forming a space in the living body and preventing specific cells from entering the space.
When the perforated plate 1 is formed using a biocompatible metal such as pure titanium or titanium alloy as described above, the conventional barrier membrane, for example, a periodontal tissue regeneration barrier, is formed. It can be a periodontal tissue regeneration barrier membrane that is significantly thinner (about 50 μm) than membranes and has the same function, strength, and antibacterial properties.

  Furthermore, a tapered surface may be formed at one end of the through hole 2. In this case, if palladium is coated on the pore surface with plating or the like, there is an advantage that hydrogen can be separated and purified with high purity when used as a reactor used for steam reforming of hydrogen.

(Functional permeable membrane)
Since the porous plate 1 of the present invention as described above has a large number of through holes 2, if the main body is made of metal and a physiologically active substance or chemical is contained in the through holes, the porous plate 1 can function. A permeable membrane.
That is, the perforated plate 1 is placed in the living body in a state where the through-hole 2 of the perforated plate 1 contains physiologically active substances such as tissue growth factors and cytokines as well as various drugs such as antibiotics and anticancer agents. If the main body is charged, it becomes possible to release the physiologically active substance or drug in the through-hole into the living body by electrophoresis.

(Artificial organ)
It is also possible to use the porous plate 1 of the present invention as the basis of an artificial organ.
For example, the porous plate 1 of the present invention is shaped so that a hollow portion can be formed therein, and an artificial organ is formed by accommodating a group of artificially cultured organ cells, or a plurality of porous plates 1 Thus, an artificial organ can be formed by surrounding or sandwiching organ cell groups. That is, an outer frame can be formed by the perforated plate 1 of the present invention, and an artificial organ can be formed by accommodating an artificially cultured organ cell group therein.
Then, if an artificial organ as described above is placed in the living body and the organ cell group is connected to the vascular system, the life of the cell group sealed in the outer frame is maintained, and the cell group is derived from the cell group in the blood. It becomes possible to release physiologically active substances or to remove or purify waste products in blood.

That is, since cells cannot move beyond the porous plate 1, cultured organs or tissue-derived cells can be enclosed in the porous plate 1. Then, by enclosing the encapsulated cultured various organs or tissue-derived cells adjacent to the vascular circulatory system, the encapsulated cells can be functionally linked to the blood circulatory system inside the living body. Then, it is possible to deliver, accept, or exchange biological information transmitting substances such as hormones and cytokines and mediators as well as nutrients for cells, blood, or tissues adjacent to each other via the porous plate 1. Further, since oxygen / carbon dioxide gas can be exchanged, various organs or tissue-derived cells cultured in the porous plate 1 can function as so-called artificial organs or tissues. For example, the cell isolation function of the perforated plate 1 can strictly prevent the stored cells from moving to and out of the vascular circulation system and moving to other tissues in the body. Although it is possible, it is based on iPS cells (Induced pluripotent stem cells) that have been difficult to use directly in the human body because of their high risk of tumorigenesis. It is possible to create a safe internal artificial organ. That is, if organ cells derived from iPS cells are enclosed in a containment vessel sealed in a single layer or multiple layers by a perforated plate 1 and then connected to the body's circulatory system by the above method, iPS cell-derived Even if a tumor occurs in this organ, there is no risk of it flowing into the blood vessels, so safety to the living body is ensured.
Note that if organs or tissues derived from cultured organs are not enclosed in the porous plate 1 and are placed in the living body in a state where a hollow space is formed in the porous plate 1, a new organ or tissue is artificially placed in that space. Can be generated.

(Polymer layer)
If the porous plate 1 is used for a regenerative medical material or a medical device, it is preferable to form a through hole 2 having a diameter φa of about φ1 to φ10 μm in the main body. However, the porous plate 1 may be configured as follows. The same effect can be obtained.
That is, a through-hole 2 having a diameter φa of about φ10 μm or more is formed in the main body of the perforated plate 1 (see FIG. 10), and a polymer thin film layer having through-holes having a hole diameter of φ1 to φ10 μm on the surface of the main body (FIG. 11). Reference) may be provided.
Then, since the through-hole 2 formed in the main body can be made large in diameter, the processing of the main body is facilitated. On the other hand, the filter function that prevents the lost cells from passing through the enlarged through-hole 2 is maintained by the polymer thin film layer. can do.

As such a polymer thin film layer, a honeycomb film made of a biocompatible polymer material such as polycarbonate or prebutadiene can be used. For example, a penetration type honeycomb film made of polybutadiene material manufactured and sold at Fuji Film Co., Ltd. (Nanumagara, Minamiashigara City, Kanagawa Prefecture) has a fine pore size of 10 microns or less in diameter while having a thickness of about 10 microns. The through holes are densely arrayed. If this film is attached to the main body to form a polymer thin film layer, even if the through-hole 2 formed in the main body has a large diameter, the porous plate 1 having a sufficient filter function can be obtained.
In addition, since the biocompatible polymer material as described above can be fused and fixed to the metal plate by heat treatment, if the main body is made of metal, the polymer thin film layer is fixed to the main body. Can be done easily.

  In addition, the honeycomb film can have a uniform pore size in an arbitrary size of 5 to 10 microns, and is satisfactory as a performance to guarantee the filter function. In particular, when a honeycomb film as shown in FIG. 11 is used as a polymer thin film layer, a communication path is secured not only in a direction penetrating the honeycomb film but also between adjacent through holes. Therefore, even if clogging occurs in the through holes 2 or some of the holes in the honeycomb film for some reason, the connection path in the honeycomb film is detoured to prevent the porous plate 1 from being closed. be able to.

  In particular, the polymer thin film layer has abundant cavities inside. Therefore, if the porous plate 1 having a polymer thin film layer is used as a functional permeable membrane, like the porous plate 1 without the polymer thin film layer, in addition to growth factors, hormones, cytokines, etc. in the cavity, sometimes cultured cells Since it can be stored and used in a living body, tissue regeneration can be more actively controlled.

The material encapsulated in the polymer thin film layer can cause a physiologically active effect to promote tissue regeneration by being slowly released into the living body after the porous plate 1 of the present invention is placed in the living body.
If the main body is a metal, the drug or physiologically active substance stored in the polymer thin film layer migrates and is released into the tissue according to the potential difference generated by energizing the main body as an electrode. .
Then, since the release and effect of the drug can be adjusted as needed by adjusting the timing and intensity of energization, it is possible to program a drug release process suitable for each of various processes leading to tissue regeneration. Therefore, it is possible to bring about a more effective tissue regeneration effect.

  In addition, when the polymer thin film layer is provided on the main body, the porous plate 1 has a two-layer structure, but the thickness can still be significantly reduced as compared with the conventional barrier membrane. Therefore, when used as a medical instrument, it is possible to suppress the adverse effect on tissue regeneration caused by the volume of the perforated plate 1.

(Processing method of perforated plate 1)
The method of processing the porous plate 1 of the present invention as described above is not particularly limited. However, if a large number of small holes are formed by a micropiercing technique on a plate-like member having a predetermined thickness, the porous plate of the present invention is formed. A plate 1 can be provided.
When a large number of small holes are formed by such micropiercing technology, the porous plate 1 can be formed by cold working. Then, even if the plate-like member is pure titanium, it is possible to maintain good biocompatibility that is a characteristic of pure titanium.

(Processing equipment 101)
As described above, when the perforated plate 1 of the present invention is processed by the micropiercing technique, if the processing apparatus 101 as described below is used, it is easily denatured by heat, so that it is difficult to be heated by a laser or the like. Even for a metal material, the porous plate 1 of the present invention can be processed with high accuracy while guaranteeing 100% of the desirable property of its original good biocompatibility by using this cold working, for example, titanium.

  As shown in FIGS. 12 and 13, the machining apparatus 101 is provided with a main shaft 102 that can be moved up and down along the vertical direction, and a direction that is perpendicular to the up-and-down direction of the main shaft 102, that is, can move in the horizontal direction. The table 103 is provided. For example, a known machining center or an NC milling machine can be used as the processing apparatus 101. However, any apparatus including the spindle 102 and the table 103 that operate as described above can be used as the processing apparatus 101. It is possible to do.

As shown in FIGS. 12 and 13, a shaft holding portion 102 a is provided at the lower end of the main shaft 102 in the processing apparatus 101. The shaft holding portion 102a can hold one end of the punch P so that its axial direction is parallel to the vertical direction. For example, known chucks, collet chucks, and the like can be mentioned, but not particularly limited.
The main shaft 102 is provided with a shaft-like member rotating mechanism that rotates the punch P held in the shaft holding portion 102a around the central axis for the reason described later.

  On the other hand, as shown in FIG. 13, a die holding portion 103 a for fixing the die D to the table 103 is provided on the table 103. The die holding unit 103a is arranged so as to be positioned vertically below the shaft holding unit 102a when the table 103 is arranged at the reference position (origin). In other words, the die holding unit 103a is arranged on the table 103 so as to be arranged vertically below the shaft holding unit 102a whenever the table 103 is returned to the reference position (origin return).

  On the table 103, a holding table 105 is provided around the die holding unit 103a. The holding table 105 holds the workpiece W (that is, the raw material of the perforated plate 1) to be processed by the punch P and the die D during processing. It arrange | positions so that the to-be-processed member W can be arrange | positioned. The holding table 105 has a function of moving the workpiece W along the upper surface of the table 103.

The processing of the workpiece W by the processing apparatus 101 described above can be performed as follows.
First, with the table 103 returned to the origin, the punch P and the die D are attached to the main shaft 102 and the die holding portion 103a, respectively. At this time, the central axis of the punch P and the central axis of the die hole Dh of the die D are located on the same axis, and this axis coincides with or is parallel to the central axis CL of the main shaft 102 (in other words, the moving direction of the main shaft 102). Both are positioned so as to be (FIG. 13).
Next, the workpiece W is disposed on the holding table 105 of the processing apparatus 101 (FIG. 13). Then, the workpiece W is moved by the holding table 105, and the position where the through hole h is formed in the workpiece W is arranged on the central axis CL.
And if the workpiece W is arrange | positioned in a predetermined position, the main axis | shaft 102 will be raised / lowered. Then, the through hole h can be formed in the workpiece W by the punch P (FIGS. 14A to 14C).

Further, since the workpiece W can be moved along the upper surface of the table 103 by the holding table 105, the positions where the punch P and the die D form the through holes h in the workpiece W while the positions thereof are fixed. Can be changed. In other words, only the workpiece W can be moved to change the position of the central axis of the punch P (the central axis CL of the main shaft 102) and the workpiece W.
For this reason, even if the position where the through hole h is formed in the workpiece W is changed, the relative positions of the punch P and the die D are kept in a state of being positioned before the start of processing. Then, once the relative positions of the punch P and the die D are accurately aligned, even when the punch P having a very thin shaft diameter or the die D having the die hole Dh having a very small hole diameter is used, the workpiece is processed. When a plurality of through holes h are formed in the member W, there is no deviation in the relative positions of the two.
Therefore, even when the through hole h having a very small hole diameter (for example, a diameter of about 1 to 30 μm) is formed, if the workpiece W is moved while raising and lowering the punch P, the workpiece W is penetrated to a different position. Since a plurality of holes h can be formed continuously, a metallic porous plate 1 in which a plurality of through holes 2 are arranged in an orderly manner as shown in FIGS. 1 and 2 can be formed.

  When the through hole h (through hole 2 in FIG. 1) is formed in the porous plate 1 by the punch P, the hole diameter φa of the through hole h is the ratio of the hole diameter φa to the thickness T of the porous plate 1 (T / Φa (hereinafter simply referred to as the aspect ratio) is about 1 to 3. Therefore, when a plurality of through holes h are formed by punch P on a plate having a thickness such that the aspect ratio is not less than the above range, the porous plate 1 may be manufactured as follows.

As shown in FIGS. 14D to 14E, in the plate-like workpiece W used as the material of the perforated plate 1, the upper end of the punch 2 has a diameter higher than the shaft diameter φ2 in advance in the portion where the through hole h1 is formed. A recess DT having a large inner diameter φ5 of the opening is formed. Then, since the thickness T1 of the recess DT is smaller than the thickness T of the workpiece W, the substantial aspect ratio (T1 / φa) of the through hole h1 formed by the punch 2 is 1 to 1. It can be about 3.
Therefore, even if the thickness T of the perforated plate 1 is about 2 to 100 μm, the perforated plate 1 having the through holes h1 of about 1 to 30 μm can be formed.

  In addition, when the porous plate 1 is formed by the above method, a tapered surface is formed at one end of the through hole h1. That is, it is possible to form the porous plate 1 in which a plurality of through holes h1 having a tapered surface are formed. Then, since the pressure loss of the perforated plate 1 is reduced, if the surface of the through hole h1 is coated with palladium or the like, the hydrogen can be obtained with high purity when used as a reactor used for steam reforming of hydrogen. It can be separated and purified.

  Note that the dent DT may be formed by any method and is not particularly limited, and examples thereof include cutting (drilling) processing, etching processing, micro-shot blast processing, and press processing. In addition, when working with materials such as titanium that may cause significant changes in the properties of the material due to thermal denaturation, laser processing can be used only when there is no need to consider the effects of thermal denaturation. It is.

Further, the holding table 105 described above is not particularly limited as long as the workpiece can be moved horizontally with respect to the upper surface of the table 103.
However, when a plurality of through holes having a very small hole diameter as described above are formed at an accurate position, the workpiece W is formed with an accuracy of about 0.1 to 5 μm, such as an XY table with a numerical controller. It is preferable to use one that can be moved horizontally. If such a holding table 105 is used, a semiconductor manufacturing apparatus (flow rate controller), a membrane reactor (membrane-based reaction process), a microfiltration membrane, electrolysis (electrolytic reaction electrode), bio (cell separation) can be processed by a processing apparatus 101. Even a perforated plate 1 used as a member that allows fluid to pass through food (yeast filtration), medical treatment (sanitization filtration), and the like can be produced.

(Explanation of onboard device)
As described above, the processing apparatus 101 can process a workpiece by the punch P having a very thin shaft diameter. However, the punch P having a very thin shaft diameter is compared with the punch P having a large shaft diameter. Therefore, it is very difficult to accurately match the position (center axis) with the center axis CL of the main shaft 102 described above. Therefore, if a punch having a large shaft diameter (original punch) that is relatively easy to align is attached so that its central axis coincides with the central axis CL of the main shaft 102, the punch P is processed into a desired shaft diameter. The position accuracy of the punch P can be increased while facilitating the arrangement of the punch P.
Therefore, if the perforated plate 1 as described above is processed by the processing apparatus 101, the original punch attached to the main shaft 102 of the apparatus 1 is made to have a desired shaft diameter while being attached to the main shaft 102. It is preferable to provide a shaft machining mechanism for machining.
Hereinafter, a shaft machining mechanism provided in the machining apparatus 101 will be described.

(Description of shaft machining mechanism 110)
In FIG. 12, reference numeral 110 denotes a shaft machining mechanism provided in the machining apparatus 101. The shaft machining mechanism 110 is provided on the table 103 of the machining apparatus 101 at a position away from the die holding part 103a and the holding table 105, that is, a position where the machining of the workpiece W by the punch P is not hindered. ing.
Therefore, if the table 103 is moved, the shaft machining mechanism 110 moves the path where the punch P moves up and down (that is, the position of the central axis CL of the main shaft 102, see FIG. 15) and the position away from this path (see FIG. 12). It can be moved between.

  As shown in FIG. 15, the shaft machining mechanism 110 includes a polishing means 111 for machining the side surface of the punch P.

  The polishing means 111 has a pair of grinding wheels 112 and 112 each consisting of a grindstone 112a formed in a substantially cylindrical shape and a shaft 12b to which the grindstone 112a is attached. The base ends of the pair of grinding wheels 112 and 112 are attached to the main shafts of the pair of grinding wheels rotating portions 113 and 113, respectively. In other words, when the pair of grinding wheel rotating portions 113 and 113 are operated, the pair of grinding wheels 112 and 112 rotate about their central axes, respectively.

  The pair of grinding wheel rotating portions 113 and 113 are, for example, spindles, and are attached to the base 15 fixed to the table 103 via the grinding wheel moving portion 114, respectively. The pair of grinding wheel rotating portions 113 and 113 are arranged such that their main axes are located in the same plane IP parallel to the upper surface of the table 103 and the main axes are parallel to each other.

  Further, each grinding wheel moving unit 114 is configured to be able to move in parallel with the upper surface of the table 103 while keeping the main axes of the pair of grinding wheel rotating units 113 and 113 in parallel with each other. For this grinding wheel moving unit 114, for example, a moving mechanism including a linear servo motor arranged in parallel with two axes can be adopted, and if the pair of linear servo motors are moved in synchronization by feedback control, The main shafts of the pair of grinding wheel rotating portions 113 and 113 can be moved in parallel with the upper surface of the table 103 while keeping the main shafts parallel to each other.

The pair of grinding wheel rotating units 113 and 113 and the grinding wheel moving unit 114 are electrically connected to a control unit 116 that controls the operation thereof.
The control unit 116 can control the pair of grinding wheel rotation units 113 and 113 to adjust the rotation direction and the rotation speed of the pair of grinding wheels 112 and 112. For example, the pair of grinding wheels rotating portions 113 and 113 are controlled so that the pair of grinding wheels 112 and 112 rotate in the opposite directions and at the same rotational speed within the plane including the central axis CL. be able to. That is, the pair of grinding wheel rotating portions 113 and 113 can be controlled so that the outer peripheral surfaces facing each other move in the same direction and have the same peripheral speed.
In addition, the control unit 116 can control the pair of grinding wheel moving units 114 and 114 to adjust the moving direction and the moving amount of the pair of grinding wheels 112 and 112. For example, the operation of the pair of grinding wheel moving units 114 and 114 can be controlled so that the intermediate position between the pair of grinding wheels 112 and 112 is always a constant position. For example, in the situation of FIG. 15, it is possible to control so that the position between the pair of grinding wheels 112, 112 is the position of the central axis CL of the main shaft 102.

  The shaft processing mechanism 110 processes the punch P attached to the main shaft 102 as follows.

First, a punch P (original punch) to be machined on the spindle 102 is attached to the shaft machining mechanism 110. At this time, the central axis CL of the main shaft 102 is arranged so as to be coaxial or parallel to the central axis of the punch P to be processed.
When the punch P to be machined is attached to the main shaft 102, the table 103 is moved and the shaft machining mechanism 110 is installed below the main shaft 102. At this time, the control unit 116 operates the grinding wheel moving unit 114 so that the central axis of the punch P coincides with the intermediate position between the pair of grinding wheels 112, 112 (FIG. 15).
The control unit 116 causes the grinding wheel moving unit 114 to move the pair of grinding wheels 112 and 112 so that the space AR between the pair of grinding wheels 112 and 112 is separated by a distance that allows the punch P to be disposed. Arrange (see FIG. 16).

Next, the main shaft 102 is lowered, the punch P is disposed between the pair of grinding wheels 112, 112, and the punch P is rotated around its central axis by the shaft-shaped member rotating mechanism described above. The pair of grinding wheels 112 and 112 are moved toward the punch P by the grinding wheel moving unit 114 while the pair of grinding wheels rotating portions 113 and 113 are operated to rotate the pair of grinding wheels 112 and 112 (FIG. 16 ( A) is moved (in the direction of arrow a) (FIGS. 16A and 16B).
At this time, the control unit 116 has an outer peripheral surface located on the punch P side in the pair of grinding wheels 112, 112, that is, a peripheral surface facing each other in the pair of grinding wheels 112, 112, from the proximal end of the punch P to the distal end. The pair of grinding wheels 112, 112 are rotated so as to move toward the bottom (from top to bottom in FIG. 16).

  Eventually, the grindstone 112a of the pair of grinding wheels 112, 112 comes into contact with the side surface of the punch P from both sides, and the side surface of the punch P is polished by the grindstone 112a (FIG. 16B). At this time, if the main shaft 102 is moved up and down (in the direction of arrow b in FIG. 16B), the punch P can be processed to have the same shaft diameter along the axial direction.

  Then, the pair of grinding wheels 112 and 112 are moved by the grinding wheel moving unit 114 until the distance L between the outer peripheral surfaces of the pair of grinding wheels 112 and 112 becomes the same distance as the desired shaft diameter. Then, since the punch P is rotated around its central axis by the shaft-shaped member rotating mechanism, the punch P is processed into a circular cross section and a desired shaft diameter.

  Here, when the side surface of the punch P is polished by the grindstone 112a of the pair of grinding wheels 112, 112, since the grindstone 112a is pressed against the punch P, the grindstone 112a of the pair of grinding wheels 112, 112 is pressed against the punch P. A force along the radial direction of the punch P is applied. However, the pair of grinding wheels 112 and 112 are located on the same plane IP parallel to each other and perpendicular to the central axis of the punch P (the central axis CL of the main shaft 102), and the pair of grinding wheels rotating portions 113 and 113 Since the grinding wheel moving unit 114 is controlled so that the wheel moves in the opposite direction and by the same amount, a force of the same magnitude and in the opposite direction as the force applied to the punch P from one of the grinding wheels 112a is applied from the other grinding wheel 112a. Join the punch P. Then, the force applied to the punch P from one grindstone 112a can be supported by the other grindstone 112a. Therefore, even if the grindstone 112a of the pair of grinding wheels 112, 112 is pressed against the punch P and polished, the punch P Can be prevented from bending or bending in the radial direction.

  In addition, the pair of grinding wheels 112 and 112 rotate so that the outer peripheral surface located on the punch P side moves from the base end of the punch P toward the tip end. The force to be generated is generated only along the axial direction of the punch P, and is not generated in the radial direction or the circumferential direction of the punch P. Then, since it is possible to prevent the punch P from being bent, distorted, twisted and twisted due to the rotation of the pair of grinding wheels 112, 112, the punch P having a very thin shaft diameter can be processed. The punch P can be processed with high accuracy without being damaged.

In addition, the control unit 116 controls the operation of the pair of grinding wheel moving units 114 and 114 so that the pair of grinding wheel rotating units 113 and 113 moves in the opposite direction and by the same amount. Then, even if the punch P is sandwiched between the pair of grinding wheels 112 and 112, the center axis of the punch P and the intermediate position of the pair of grinding wheels 112 and 112 can always be matched.
Then, even if the punch P is rotated by the shaft-shaped member rotating means, the touching of the punch P does not occur, so that the center axis of the punch P before processing and the center axis of the punch P after processing are prevented from being misaligned. it can.
The cross section of the punch P to be formed is not limited to a circular cross section, and a punch having a polygonal cross section can be formed by processing the punch P at a predetermined angle by the shaft-shaped member rotating means. For example, in the case of processing a punch having a polygonal cross section, if the shaft member rotating means for rotating the punch P has an index mechanism, the punch P can be processed even with a square or pentagonal cross section.

(Description of die processing)
Further, when the shaft machining mechanism 110 as described above is provided, if the die hole Dh of the die D is machined by the punch P, the center axis of the punch P and the die hole Dh of the die D can be easily and reliably established. It is preferable because it can be made to match.

Specifically, as shown in FIG. 17B, a basic hole A having an inner diameter φ1 larger than an axial diameter φ2 of a punch P formed on the die D from the lower surface to the vicinity of the upper surface of the die D, and the foundation A die hole Dh having a reduced diameter portion B reduced in diameter from the hole portion A toward the upper surface of the die D is formed. The diameter-reduced portion B is formed so that the diameter φ3 of the upper end opening is smaller than the shaft diameter φ2 of the punch P.
Then, the punch P is moved to the die D in a state where the center axis of the basic hole portion A of the die hole Dh and the center axis of the punch P coincide with the center axis CL of the main shaft 102. Then, the diameter P 3 of the upper end opening of the reduced diameter portion B is processed to the same size as the shaft diameter φ 2 of the punch P by the punch P. That is, the upper end opening of the die hole Dh is the same as the shaft diameter φ2 of the punch P, and the center axis of the punch P can be made completely coincident.

  When the shaft diameter φ2 of the punch P is thin, the opening diameter of the die hole Dh has to be reduced, so that it is very difficult to match the central axis of the die hole Dh with the central axis CL of the main shaft 102. However, in the case of the above method, if the central axis of the punch P and the central axis CL of the main shaft 102 are accurately positioned, even if the central axis of the die hole Dh is slightly shifted from the central axis CL of the main shaft 102, The central axis of the punch P, the central axis of the upper end opening of the die hole Dh, and the central axis CL of the main shaft 102 can be made to coincide.

In particular, when the punch P is machined to a desired shaft diameter by the shaft machining mechanism 110, the positioning of the punch P is further facilitated, so that the center of the punch P can be accurately and easily performed even by a skilled worker. The axis can coincide with the center axis of the die hole Dh (the center axis of the upper end opening) and the center axis CL of the main shaft 102.
When the shaft diameter φ2 of the punch P is processed by the shaft processing mechanism 110, after processing the die hole Dh in the die D and further processing the punch P by the shaft processing mechanism 110, the upper end opening of the die D and the punch P clearance can be adjusted. Then, since the state when the through hole is formed in the workpiece W by the punch P can be adjusted to an optimum state, the machining accuracy of the through hole of the workpiece W can be improved, which is preferable. is there.

(Description of on-machine measuring device 120)
Further, as shown in FIG. 12, an on-machine measuring device is located on the table 103 of the processing apparatus 101 at a position away from the die holding portion 103a and the holding table 105, that is, a position where the processing by the punch P does not become an obstacle. 120 is provided. The on-machine measuring device 120 is a device that measures the dimensions of the punch P attached to the main shaft 102. Specifically, it is an apparatus that can measure the shaft diameter φ2, the surface roughness of the side surface, the tip outer diameter taper shape portion, and the like of the punch P. The on-machine measuring device 120 can employ, for example, an ultra-fine processing tool measuring device using a pixel measuring method, but is not particularly limited as long as it can measure the shape and the like with nano-order accuracy. .
Since the on-machine measuring device 120 is also provided on the table 103, as with the shaft machining mechanism 110, if the table 103 is moved, the path where the punch P moves up and down (that is, the position of the central axis CL) and It can be moved between positions away from this path.

  Therefore, when the punch P is machined by the shaft machining mechanism 110, the dimension of the punch P can be measured with the punch P attached to the main shaft 102. Therefore, after the inspection is completed, which is necessary when the inspection is performed with the punch P removed. This eliminates the need for attaching the punch P. Then, since the alignment associated with the attachment of the punch P after the inspection is not required, it is possible to quickly return to the processing operation after the inspection of the punch P, and the central axis of the punch P and the central axis of the main shaft 102 It is also possible to prevent the position of CL or the like from shifting.

(Application to periodontal tissue regeneration treatment)
Below, the case where the perforated plate of this invention is used for periodontal tissue regeneration treatment is demonstrated more concretely.

When used for periodontal tissue regeneration therapy, a thin titanium plate 1 (the porous plate of the present invention) that satisfies the conditions as a barrier membrane is placed in a human periodontal tissue as shown in FIG.
In FIG. 3, reference numeral 4 is a gingival tissue of human periodontal tissue, reference numeral 5 is a tooth root, and reference numeral 6 is an alveolar bone that supports the tooth. The thin plate 1 is installed so as to be affixed to the alveolar bone surface layer of the alveolar bone 6, and then a space 7 is formed between the root 1 and the root surface of the root portion 5.

  The space 7 originally was a space that was normally occupied by the alveolar bone, and was connected to the root surface of the root portion 5 to support the teeth. However, due to periodontal disease, the alveolar bone 6 was lost, and the space 7 was occupied by a part of the gingival tissue 4 before the thin plate 1 was installed.

  The thin plate 1 installed in the gingival tissue 4 can exclude the gingival tissue 4 and provide a space 7 between the root portion 5. By maintaining this space 7, it becomes possible for the alveolar bone 6 to extend toward the space 7, and the space 7 is eventually occupied by the alveolar bone 6, and the support of the teeth is restored by coupling with the root surface. That is, the thin plate 1 once occupied a normal space by eliminating the occupied gingival tissue 4 from the space occupied by the surrounding gingival tissue 4 due to the disappearance of the alveolar bone 6 due to periodontal disease. It contributes to periodontal tissue regenerative therapy that re-occupies the alveolar bone and restores its original shape to completely cure periodontal disease.

  In that case, in addition to the function of maintaining the space 7 until the alveolar bone 6 is restored to its original state, the thin plate 1 has a resource for reorganizing the alveolar bone 6 in the space 7 in order to support its organization. Nutrients to become must be supplied from the outside. As a means for that purpose, the thin plate 1 allows the nutrient 8 circulating in the vascular system in the tissue of the gingival tissue 4 to permeate toward the space 7 while eliminating the entry of tissue / cells from the excluded gingival tissue 4. A function is required.

  Therefore, as shown in FIG. 4, although the thin plate 1 can permeate the nutrient 8, it is necessary to prevent the passage of the cells 9 derived from the gingival tissue 4 once removed in order to regenerate the alveolar bone. Therefore, in order to provide the filter action, the through-hole 2 must have a pore diameter of 10 microns or less smaller than the cell size.

A method of providing a living body with a porous metal thin plate satisfying such a filter function of the barrier membrane will be described.
As shown in FIG. 3, periodontal tissue regeneration therapy secures a space for restoring alveolar bone after a porous metal thin plate is placed inside the periodontal tissue by a surgical technique. In the surgical method, the porous metal thin plate is formed in an outer shape that fits the surface shape of the alveolar bone. Specifically, it is formed in a shape like the thin plate 10 of FIG.

  Although the thin plate 10 of FIG. 5 is a rectangle of about 30 × 25 mm, since the cuts 11 are formed at two places, the thin plate 10 has a butterfly wing shape in which the left and right wings communicate with each other at the narrowed portion at the center 12. The two cuts with a width of about 8 mm are provided so that the thin plate 10 fits the shape of the surface of the alveolar bone when the thin plate 10 is applied to the alveolar bone so that the thin plate 10 avoids the root of the tooth. It has been. Further, the outer edge portion 12 of the thin plate 10 is not provided with a through hole in order to use a collar for fixing the thin plate 10.

  A method of actually applying the thin plate 10 to periodontal tissue regeneration treatment is shown in FIGS. FIG. 5 is a schematic diagram of periodontal tissue, in which reference numeral 51 denotes a dentition and reference numeral 52 denotes a gingiva. In the periodontal tissue regeneration treatment, the thin plate 10 is placed inside the periodontal tissue by a surgical technique. Therefore, first, as shown in FIG. 6, 53 incision lines are added to the gingiva, and then 54 parts of the gingiva are formed into a valve shape and peeled and opened.

  FIG. 7 is a schematic view of the inside of the periodontal tissue. Reference numeral 61 denotes an alveolar bone surface, and reference numeral 62 denotes an alveolar bone defect portion lost due to periodontal disease. As shown in FIG. 7, when the 54 parts of gingiva are peeled and opened as a gingival flap, the surface of the alveolar bone 61 under the gingiva is exposed, and at the site affected by periodontal disease, the alveolar bone is destroyed and absorbed A bone defect site like 62 is observed. 62 is often filled with defective tissue such as granulation derived from gingival tissue, and such defective tissue prevents alveolar bone recovery and is curetted and removed at this point.

  FIG. 8 is a schematic view when the thin plate 10 is installed inside the periodontal tissue. As shown in FIG. 3, the thin plate 10 serves as a partition wall to cover the defective portion of the alveolar bone and to reconstruct the alveolar bone therein, so as to surround the defective portion and guide the alveolar bone. Secure.

  Since the thin plate 10 is made of metal, it is plastic and is fixed to the alveolar bone surface by a rough surface generated by drilling. In order to obtain further fixing stability, the outer edge portion 12 is used with a screw pin, a nail or the like. The outer edge portion that is fixed to the alveolar bone surface layer or in contact with the 51 teeth can be fixed by an adhesive or a bonding material used for a dental restorative material and further stabilized.

  FIG. 9 is a schematic view of the 54 gingival flaps that have been incised and peeled after the thin plate 10 is set and fixed inside the periodontal tissue, and then restored. 81 is a suture for restoring 54 and closing the surgical wound. Although the thin plate 10 is completely covered by the gingiva and embedded in the periodontal tissue, the thin plate 10 maintains a space in which the alveolar bone recovers. After installation, the membrane is removed by secondary surgery after 5 to 7 weeks.

  The perforated plate of the present invention is suitable for tissue partition membranes used for periodontal diseases and for surgical operations for augmenting and restoring alveolar bone destroyed or absorbed by loss of teeth for the purpose of periodontal regeneration treatment in dentistry.

1 Perforated plate 2 Through hole

Claims (7)

A plate in which a plurality of through holes are formed in a plate-shaped plate,
The hole diameter of the plurality of through holes is φ1 to φ50 μm,
A perforated plate, wherein the distance between the central axes of the adjacent through holes is 3 to 300 μm. The thickness of the said plate is 2-100 micrometers, The perforated plate of Claim 10 characterized by the above-mentioned. The perforated plate according to claim 1, wherein a tapered surface is formed at one end of the through hole. A plate used as a thin metal permeable membrane or barrier membrane for tissue isolation,
The material of the plate is
A biocompatible metal, ceramic, plastic or polymer,
4. The perforated plate according to claim 1, wherein the plurality of through holes have a diameter of φ1 to φ10 μm. A plate used as a thin metal permeable membrane or barrier membrane for tissue isolation,
The material of the plate is
A biocompatible metal, ceramic, plastic or polymer,
The hole diameter of the plurality of through holes is φ10 μm or more,
4. The perforated plate according to claim 1, wherein a polymer thin film layer having a through hole having a pore diameter of φ1 to φ10 μm is provided on the surface of the plate. A perforated plate according to the first to fifth inventions made of metal or metal-polymer composite,
A functional permeable membrane, wherein a through hole in the porous plate contains a physiologically active substance and / or a chemical. An outer frame formed by the perforated plate according to claim 1;
An artificial organ comprising a group of artificially cultured organ cells housed in the outer frame.

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