Device for transplantation

Abstract

To provide a device for transplantation that can suppress the shortage of supplying oxygen and nutrients to therapeutic cells.SOLUTION: A device for transplantation according to the present disclosure is a device for transplantation that can be transplanted into a living body, which includes: a first chamber section that defines a first storage space that contains therapeutic cells; a second chamber section that defines a second storage space that does not contain the therapeutic cells; and a pump section that circulates a buffer solution through a circulation path that includes the first storage space and the second storage space, the second chamber section including a semipermeable membrane section that moves secretions of the therapeutic cells from the second storage space to the living body, and moves bodily fluids in the living body from the living body to the second storage space.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present disclosure relates to implantable devices. [Background technology]

[0002] Transplant devices used to treat diseases by transplanting therapeutic cells into a living body are known. Patent Document 1 discloses such a transplant device. The transplant device described in Patent Document 1 includes a semipermeable membrane and a cell-fixed substrate wrapped in the semipermeable membrane. The semipermeable membrane in the transplant device described in Patent Document 1 has pores large enough to allow permeation of nutrients and secreted substances from cells fixed to the cell-fixed substrate, but does not allow permeation of external cells such as white blood cells including phagocytes. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2017-196150 A Summary of the Invention [Problem to be solved by the invention]

[0004] According to the transplantation device described in Patent Document 1, while isolating the therapeutic cells from external cells, nutrients outside the device can be supplied to the therapeutic cells, and secretions of the therapeutic cells can be supplied to the living body. However, in the transplantation device described in Patent Document 1, oxygen and nutrients are supplied to the therapeutic cells relatively slowly by diffusion, so that the supply of oxygen and nutrients to the therapeutic cells may be insufficient.

[0005] An object of the present disclosure is to provide a transplant device that can suppress insufficient supply of oxygen and nutrients to therapeutic cells. [Means for solving the problem]

[0006] The implantable device according to the first aspect of the present disclosure comprises: (1) A device for implantation that can be implanted in a living body, comprising: A first chamber portion defining a first storage space for storing therapeutic cells; A second chamber portion defining a second storage space that does not contain the therapeutic cells; a pump unit that circulates a buffer solution through a circulation path including the first storage space and the second storage space, The second chamber portion is a transplant device having a semipermeable membrane portion that moves secretions of the therapeutic cells from the second storage space to the body, and moves bodily fluids within the body from the body to the second storage space.

[0007] The implantable device according to one embodiment of the present disclosure comprises: (2) The first chamber and the second chamber are separate from each other, The transplant device is described in (1) above, wherein the circulation path includes a first flow path connecting one end side of the first chamber portion and one end side of the second chamber portion, and a second flow path connecting the other end side of the first chamber portion and one end side of the second chamber portion.

[0008] The implantable device according to one embodiment of the present disclosure comprises: (3) The implantation device according to (2) above, wherein the length of the first flow path and the length of the second flow path are each 10 mm or more.

[0009] The implantable device according to one embodiment of the present disclosure comprises: (4) The transplant device is described in any one of (1) to (3) above, wherein the first chamber portion is provided with a filter portion that does not allow the therapeutic cells contained in the first storage space to pass through to the upstream and downstream sides of the circulation path.

[0010] The implantable device according to one embodiment of the present disclosure comprises: (5) The implantation device according to any one of (1) to (4) above, further comprising a check valve portion for restricting backflow of the buffer solution in the circulation path.

[0011] The implantable device according to one embodiment of the present disclosure comprises: (6) The transplant device is described in any one of (1) to (5) above, wherein the first chamber portion defines a connecting flow path leading to the first storage space and is provided with a connection portion capable of connecting to an external device.

[0012] The implantable device according to one embodiment of the present disclosure comprises: (7) The transplant device according to any one of (1) to (6) above, wherein the first chamber portion is provided with a carrier portion capable of supporting the therapeutic cells.

[0013] The implantable device according to one embodiment of the present disclosure comprises: (8) The carrier portion of the first chamber portion includes a plurality of hollow fiber membranes arranged in parallel, The transplant device according to (7) above, wherein each of the plurality of hollow fiber membranes defines an internal space between the first storage space and the hollow fiber membrane, through which the buffer solution can move.

[0014] The implantable device according to one embodiment of the present disclosure comprises: (9) the pump unit is a positive displacement pump that defines a third storage space capable of storing the buffer solution, and delivers the buffer solution by alternately increasing and decreasing a volume of the third storage space, A storage section that defines a fourth storage space whose volume varies in response to a change in the volume of the third storage space of the pump section, The implantable device according to any one of (1) to (8) above, wherein the circulation path includes the third storage space and the fourth storage space. Effect of the Invention

[0015] According to the present disclosure, a transplant device capable of suppressing a shortage of oxygen and nutrients to therapeutic cells can be provided. [Brief description of the drawings]

[0016] [Figure 1] FIG. 1 is a system diagram showing the configuration of an implantable device according to one embodiment of the present disclosure. [Diagram 2] FIG. 2 is a diagram showing details of a first chamber section shown in FIG. [Diagram 3] 3 is a diagram showing a modification of the first chamber shown in FIG. 2. FIG. [Figure 4A] FIG. 2 is a diagram showing details of a second chamber section shown in FIG. 1. [Figure 4B] FIG. 4B is a cross-sectional view of FIG. 4A taken along line aa. [Diagram 5] FIG. 4B is a diagram showing a modification of the second chamber shown in FIG. 4A. [Figure 6] FIG. 2 shows a modification of the implantable device shown in FIG. [Figure 7A] FIG. 7 shows a breath-driven pump as an example of the positive displacement pump shown in FIG. [Figure 7B] FIG. 7B is a cross-sectional view of FIG. 7A showing a state in which no compressive force due to the respiratory movement of a living body is applied to the respiratory-driven pump. [Figure 7C] 7B is a cross-sectional view of FIG. 7A, showing a state in which a compressive force due to the respiratory movement of a living body is applied to the respiratory-driven pump. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Hereinafter, an embodiment of an implantable device according to the present disclosure will be illustrated and described with reference to the drawings, in which the same components are designated by the same reference numerals.

[0018] In the present disclosure, a "transplantation device" refers to a device used to transplant therapeutic cells into a patient's body to treat a disease. The use of the transplantation device is not particularly limited. The therapeutic cells to be transplanted by the transplantation device may be appropriately selected depending on the use of the transplantation device. For example, the transplantation device may be used to treat diabetes by transplanting insulin-producing cells as therapeutic cells into a patient's body.

[0019] 1 is a system diagram showing a configuration of an implantation device 1 as one embodiment of the implantation device according to the present disclosure. The implantation device 1 can be implanted into a living body O. The implantation device 1 is implanted, for example, into subcutaneous tissue. However, the implantation site of the implantation device 1 in the living body is not particularly limited.

[0020] As shown in FIG. 1, the transplantation device 1 of this embodiment includes a first chamber section 10, a second chamber section 30, a pump section 40, and a check valve section 50. Therapeutic cells X are accommodated in the first chamber section 10. The transplantation device 1 forms a circulation path 80 through which a buffer solution circulates. Hereinafter, the upstream side of the circulation path 80 may be simply referred to as the "upstream side". Also, the downstream side of the circulation path 80 may be simply referred to as the "downstream side".

[0021] In this embodiment, the buffer acts as a growth environment for the therapeutic cells X. In addition, in this embodiment, the buffer acts as a solvent for circulating the secretion secreted by the therapeutic cells X and the oxygen and nutrients supplied from within the living body O through the circulation path 80. Examples of the buffer include a balanced salt solution (HBSS, PBS, etc.), a culture medium (DMEM, α-MEM, etc.), etc. However, the buffer is not particularly limited.

[0022] The therapeutic cell X produces a secretion for treating a disease of the living body O. Examples of the therapeutic cell X include adhesive cells (adherent cells). Adherent cells are cells that grow by adhering to a carrier or the like in cell culture. The therapeutic cell X includes, for example, somatic stem cells (adult stem cells), or differentiated cells derived from ES cells (embryonic stem cells) or iPS cells (induced pluripotent stem cells). Somatic stem cells include, for example, mesenchymal stem cells, vascular endothelial stem / progenitor cells, and skeletal myoblast cells (myoblast cells). Differentiated cells include, for example, cardiomyocytes, fibroblast cells, pancreatic islet cells, pituitary hormone-producing cells, and the like. In addition, therapeutic cells X may include, for example, cell lines and genetically-modified cells.

[0023] The therapeutic cells X also include floating cells. The floating cells are cells that do not need to adhere to a carrier for cell proliferation. However, floating cells also include cells that can weakly adhere to a carrier.

[0024] However, the therapeutic cells X are not particularly limited. The therapeutic cells X may be a single type of cell or multiple types of cells. The therapeutic cells X may be multiple cells aggregated together or differentiated. The therapeutic cells X may be multiple aggregated cells that function as an organ. The therapeutic cells X may be cells collected from a living body or cultured cells. The therapeutic cells X may be cells collected from a living body that have formed a tissue, organ, or the like.

[0025] <First chamber section 10> FIG. 2 is a diagram showing details of the first chamber section 10 of this embodiment. As shown in FIG. 2, the first chamber section 10 of this embodiment includes filter sections 12a, 12b, an exterior section 14, connection sections 15a, 15b, and a carrier section 16. The exterior section 14 defines a first storage space 10a that stores therapeutic cells X. The first storage space 10a constitutes a part of a circulation path 80. The first storage space 10a is incorporated into the circulation path 80 by an inlet 11a and an outlet 11b. The exterior section 14 does not allow cells and buffer solution to pass through. The exterior section 14 of this embodiment is a cylindrical container made of resin. However, the shape and material of the exterior section 14 are not particularly limited.

[0026] The carrier part 16 can support therapeutic cells X. In cases where the therapeutic cells X are adherent cells, the carrier part 16 acts as a scaffold necessary for the proliferation of the therapeutic cells X. The carrier part 16 of this embodiment is a bead. A plurality of beads as the carrier part 16 of this embodiment are accommodated in the first accommodation space 10a of the first chamber part 10 together with the therapeutic cells X. The beads as the carrier part 16 of this embodiment support the therapeutic cells X. The beads as the carrier part 16 are spherical bodies made of hydrogel. In the present disclosure, hydrogel refers to a polymer having a water-insoluble three-dimensional network structure and its swollen body in water. Examples of hydrogels include collagen, hyaluronan, gelatin, fibronectin, elastin, tenascin, laminin, vitronectin, polypeptides, heparan sulfate, chondroitin, chondroitin sulfate, keratan, keratan sulfate, dermatan sulfate, carrageenan, heparin, chitin, chitosan, alginate, agarose, agar, cellulose, methylcellulose, carboxymethylcellulose, glycogen and derivatives thereof, as well as fibrin, fibrinogen, thrombin, and polyglutamic acid, polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymers, vinyl alcohol polymers, gellan gum, xanthan gum, galactomannan, guar gum, locust bean gum, and tara gum.

[0027] However, the shape of the carrier section 16 is not particularly limited, and may be sheet-like, fibrous, gel-like, or the like. The material for forming the carrier section 16 is not limited to the above-mentioned hydrogel, and may be formed from resins such as polystyrene, polyester, polyethylene terephthalate, polycarbonate, polypropylene, polytetrafluoroethylene, polydimethylsiloxane, or metal. The carrier section 16 may be a porous body. Note that, when the carrier section 16 is not required, for example, when the therapeutic cells X are floating cells, the first chamber section 10 may not be provided with the carrier section 16.

[0028] As shown in Fig. 2, the filter section 12a of this embodiment is provided at the upstream end of the first housing space 10a. The filter section 12b of this embodiment is provided at the downstream end of the first housing space 10a. The buffer solution circulating through the circulation path 80 passes through the inlet 11a and flows into the first housing space 10a via the filter section 12a. The buffer solution circulating through the circulation path 80 flows out of the first housing space 10a via the filter section 12b and flows out to the outside of the first chamber through the outlet 11b.

[0029] The filter unit 12a of this embodiment allows the buffer solution to pass through but does not allow the therapeutic cells X accommodated in the first storage space 10a to pass through to the upstream side of the circulation path 80. Moreover, the filter unit 12b of this embodiment allows the buffer solution to pass through but does not allow the therapeutic cells X accommodated in the first storage space 10a to pass through to the downstream side of the circulation path 80. By providing the first chamber unit 10 with the filter units 12a and 12b, the buffer solution can be circulated through the circulation path 80 while retaining the therapeutic cells X in the first storage space 10a of the first chamber unit 10.

[0030] Examples of the filters constituting the filter units 12a and 12b include membrane filters, porous filters, etc. Examples of the materials forming the filter units 12a and 12b include resins, metals, etc. However, the configuration of the filter units 12a and 12b is not particularly limited.

[0031] External devices can be connected to the connection parts 15a and 15b. The connection part 15a of this embodiment defines a connection flow path leading to the upstream side of the first storage space 10a. The connection part 15b of this embodiment defines a connection flow path leading to the downstream side of the first storage space 10a. The port devices 20a and 20b can be connected to the connection parts 15a and 15b of this embodiment. The port device 20a can supply therapeutic cells X to the first storage space 10a through the connection flow path of the connection part 15a. The port device 20b can extract the therapeutic cells X contained in the first storage space 10a to the outside through the connection flow path of the connection part 15b. In this way, by connecting the port devices 20a and 20b to the connection parts 15a and 15b, the therapeutic cells X contained in the first storage space 10a can be replaced. The port devices 20a and 20b may be, for example, in-vivo port devices that are placed in a living body.

[0032] The configuration of the connection parts 15a, 15b is not limited to the above. For example, each of the connection parts 15a, 15b may define a connection flow path that continues to the upstream side (or downstream side). In addition, although two connection parts 15a, 15b are provided in this embodiment, the number of connection parts may be one. Furthermore, three or more connection parts may be provided. The first chamber section 10 may not have a connection part.

[0033] Fig. 3 is a diagram showing a modified example of the first chamber section 10 shown in Fig. 2. The first chamber section 10 shown in Fig. 3 has the same configuration as the first chamber section 10 shown in Fig. 2, except that it does not include the filter sections 12a and 12b, and the carrier section 16 is composed of a hollow fiber membrane 18. In the modified example shown in Fig. 3, a plurality of hollow fiber membranes 18 as the carrier section 16 are arranged in parallel in the first storage space 10a. Each of the plurality of hollow fiber membranes 18 is a straw-shaped membrane body. The hollow fiber membranes 18 as the carrier section 16 of this embodiment support the therapeutic cells X contained in the first storage space 10a on their outer surface.

[0034] In the modified example shown in FIG. 3, each of the hollow fiber membranes 18 defines an internal space 18a. The internal space 18a of each of the hollow fiber membranes 18 constitutes a part of the circulation path 80. The internal space 18a of each of the hollow fiber membranes 18 is connected to the inlet 11a and the outlet 11b. On the other hand, in the modified example shown in FIG. 3, the first storage space 10a that stores the therapeutic cells X is not connected to the inlet 11a and the outlet 11b. Therefore, in the modified example shown in FIG. 3, the buffer solution that flows into the first chamber 10 from the inlet 11a does not pass through the first storage space 10a, but passes through the internal space 18a of each of the hollow fiber membranes 18, and flows out of the first chamber 10 from the outlet 11b.

[0035] A plurality of minute holes are formed in the peripheral wall of the hollow fiber membrane 18. The diameter of the holes formed in the peripheral wall of the hollow fiber membrane 18 is smaller than the diameter of the therapeutic cells X. Therefore, the therapeutic cells contained in the first storage space 10a cannot pass through the holes formed in the peripheral wall of the hollow fiber membrane 18. In the modified example shown in FIG. 3, the average pore size of the holes formed in the peripheral wall of the hollow fiber membrane 18 is less than 1 μm. However, the average pore size of the holes formed in the peripheral wall of the hollow fiber membrane 18 is not limited to this, and can be appropriately changed in consideration of the strength of the membrane, the permeability of the buffer solution, and the like.

[0036] The first storage space 10a is connected to the internal space 18a only through holes formed in the peripheral walls of the hollow fiber membranes 18. Therefore, the buffer solution can move from the first storage space 10a to the internal space 18a and from the internal space 18a to the first storage space 10a through the holes formed in the peripheral walls of the hollow fiber membranes 18, but the therapeutic cells X cannot pass through the holes in the peripheral walls of the hollow fiber membranes 18 and cannot move from the first storage space 10a to the internal space 18a. As a result, even if the first chamber section 10 does not include the filter sections 12a and 12b, by including the hollow fiber membranes 18 as the carrier section 16 arranged in parallel, the buffer solution can be circulated in the circulation path 80 while the therapeutic cells X are retained in the first storage space 10a of the first chamber section 10.

[0037] In the modified example shown in FIG. 3, when the buffer solution circulates through the circulation path 80, a part of the buffer solution passing through the internal space 18a of each of the hollow fiber membranes 18 moves into the first storage space 10a through the peripheral wall of each of the hollow fiber membranes 18. This allows the oxygen and nutrients contained in the buffer solution circulating through the circulation path 80 to be supplied to the therapeutic cells X contained in the first storage space 10a. Conversely, a part of the buffer solution in the first storage space 10a moves into the internal space 18a of each of the hollow fiber membranes 18 through the peripheral wall of each of the hollow fiber membranes 18. As the buffer solution moves into the internal space 18a, the secretion of the therapeutic cells X contained in the first storage space 10a moves from the first storage space 10a into the internal space 18a of each of the hollow fiber membranes 18. This allows the secretion of the therapeutic cells X to be supplied to the buffer solution circulating through the circulation path 80.

[0038] Examples of the membrane constituting the hollow fiber membrane 18 include an RO membrane, a UF membrane, and an MF membrane. However, the membrane constituting the hollow fiber membrane 18 is not limited to these. In the modified example shown in FIG. 3, the hollow fiber membrane 18 is, for example, constituted by an MF membrane. Examples of the material constituting the hollow fiber membrane 18 include polyethylene, polysulfone, polyvinylidene fluoride, and cellulose acetate. However, the material constituting the hollow fiber membrane 18 is not particularly limited.

[0039] In the modified example shown in FIG. 3, the first chamber section 10 may further include filters 12a and 12b.

[0040] <Second chamber section 30> Fig. 4A is a diagram showing details of the second chamber section 30 of this embodiment. In the transplantation device 1 of this embodiment, the movement of secretions of the therapeutic cells X from within the transplantation device 1 to within the living body O, and the movement of bodily fluids within the living body O from within the living body O to within the transplantation device 1, are performed only via the second chamber section 30. Fig. 4B is a cross-sectional view of aa in Fig. 4A. As shown in Figs. 4A and 4B, the second chamber section 30 of this embodiment includes a membrane section 32 and a support structure 33.

[0041] The membrane portion 32 defines a second storage space 32a that does not store therapeutic cells X. The second storage space 32a constitutes a part of the circulation path 80. The second storage space 32a is incorporated into the circulation path 80 by an inlet 31a and an outlet 31b. The buffer solution circulating through the circulation path 80 flows into the second chamber portion 30 from the inlet 31a, passes through the second storage space 32a, and flows out of the second chamber portion 30 from the outlet 31b.

[0042] As shown in FIG. 4B, the membrane portion 32 of this embodiment includes a semipermeable membrane portion 35 and an impermeable membrane portion 36. The impermeable membrane portion 36 does not allow the buffer solution, cells in the living body O, and oxygen and nutrients contained in the body fluids in the living body O to pass through. Furthermore, the impermeable membrane portion 36 of this embodiment does not allow secretions of the therapeutic cells X to pass through. The impermeable membrane portion 36 of this embodiment is a non-porous membrane made of resin. However, the configuration of the impermeable membrane portion 36 is not limited to this. The membrane portion 32 may not include the impermeable membrane portion 36 and may be configured only by the semipermeable membrane portion 35.

[0043] A plurality of minute holes are formed in the semipermeable membrane portion 35. The diameter of the holes formed in the semipermeable membrane portion 35 is smaller than the diameter of the cells in the living body O. Therefore, the cells in the living body O cannot pass through the holes formed in the semipermeable membrane portion 35. The average pore size of the holes formed in the semipermeable membrane portion 35 in this embodiment is less than 1 μm. However, the average pore size of the holes formed in the semipermeable membrane portion 35 is not limited to this, and can be appropriately changed in consideration of the strength of the membrane, the permeability of the buffer solution, and the like.

[0044] The second storage space 32a is connected to the outside only through the holes formed in the semipermeable membrane part 35, except for the inlets 31a and 31b. Therefore, when the transplantation device 1 is transplanted into a living body O, the cells in the living body O cannot pass through the holes formed in the semipermeable membrane part 35 and cannot enter the second storage space 32a. On the other hand, the body fluid in the living body O can move from the living body O to the second storage space 32a through the holes formed in the semipermeable membrane part 35. Therefore, while preventing the inflow of immune cells such as white blood cells, oxygen and nutrients contained in the body fluid together with the body fluid in the living body O can be taken into the transplantation device 1. In addition, the secretion of the therapeutic cells X stored in the second storage space 32a can move into the living body O (outside the second storage space 32a) together with the buffer solution through the holes formed in the semipermeable membrane part 35. This allows the secretion of the therapeutic cells X to be supplied to the living body O.

[0045] The semipermeable membrane portion 35 of this embodiment contains a resin. Examples of the resin contained in the semipermeable membrane portion 35 include ethylene-vinyl alcohol copolymers, polyamide polymers, polyacrylonitrile polymers, cellulose polymers (such as cellulose acetate), polysulfone polymers, and polycarbonate polymers. However, the resin contained in the semipermeable membrane portion 35 is not particularly limited. The thickness of the semipermeable membrane portion 35 of this embodiment is, for example, 50 μm to 200 μm. However, the thickness of the semipermeable membrane portion 35 is not particularly limited and can be appropriately changed in consideration of the strength of the membrane, the permeability of the buffer solution, the permeability of the secretion of the therapeutic cell X, and the like. In addition, the method of forming the semipermeable membrane portion 35 is not particularly limited.

[0046] As shown in Fig. 4A and Fig. 4B, in this embodiment, the second storage space 32a of the second chamber 30 accommodates the support structure 33. If the support structure 33 is not accommodated in the second storage space 32a, the portions of the membrane 32 facing each other across the second storage space 32a may come close to each other or adhere to each other, causing the second storage space 32a to be partially or entirely narrowed. Then, the second storage space 32a may be partially or entirely narrowed, which may cause the buffer solution to flow less easily through the second storage space 32a. In contrast, the support structure 33 is accommodated in the second storage space 32a, which can prevent the second storage space 32a from being partially or entirely narrowed, and thus can prevent the buffer solution from being less easily able to flow through the second storage space 32a.

[0047] The support structure 33 in this embodiment is a porous body. In this embodiment, the buffer solution that flows into the second storage space 32a from the inlet 31a passes through the porous body serving as the support structure 33 and flows out from the outlet 31b to the outside. The porous body serving as the support structure 33 is, for example, a resin sponge, but is not limited thereto. The material and structure (pore size, porosity, etc.) of the porous body serving as the support structure 33 can be appropriately changed.

[0048] The support structure 33 does not have to be a porous body. The support structure 33 may be, for example, a hard framework structure that divides the buffer solution flow path. The second chamber 30 does not have to include the support structure 33. When the second chamber 30 does not include the support structure 33, the membrane 32 can be formed from a relatively hard material to prevent the second storage space 32a from narrowing partially or entirely, and prevent the buffer solution from becoming difficult to flow through the second storage space 32a.

[0049] Figure 5 is a diagram showing a modified example of the second chamber section 30 shown in Figure 4A. The second chamber section 30 shown in Figure 5 has the same configuration as the second chamber section 30 shown in Figure 4A, except that it does not include a support structure 33 and that the membrane section 32 is composed of multiple hollow fiber membranes 38 arranged in parallel. In the modified example shown in Figure 5, each of the multiple hollow fiber membranes 38 is a straw-shaped membrane body.

[0050] In the modified example shown in FIG. 5, each of the hollow fiber membranes 38 as the membrane portion 32 defines an internal space 38a. In the modified example shown in FIG. 5, the second storage space 32a is constituted by the internal space 38a defined by each of the hollow fiber membranes 38. The internal space 38a defined by each of the hollow fiber membranes 38 defines a part of the circulation path 80. The internal space 38a defined by each of the hollow fiber membranes 38 is incorporated in the circulation path 80 by the inlet 31a and the outlet 31b. The buffer solution circulating in the circulation path 80 flows into the second chamber portion 30 from the inlet 31a, passes through the internal space 38a (second storage space 32a) defined by each of the hollow fiber membranes 38, and flows out of the second chamber portion 30 from the outlet 31b.

[0051] A plurality of minute holes are formed in the peripheral wall of the hollow fiber membrane 38. The diameter of the holes formed in the peripheral wall of the hollow fiber membrane 38 is smaller than the diameter of the cells in the living body O. Therefore, the cells in the living body O cannot pass through the holes formed in the peripheral wall of the hollow fiber membrane 38. More specifically, in the modified example shown in FIG. 5, the average pore size of the holes formed in the peripheral wall of the hollow fiber membrane 38 is less than 1 μm. However, the average pore size of the holes formed in the semipermeable membrane portion 35 is not limited to this, and can be appropriately changed in consideration of the strength of the membrane, the permeability of the buffer solution, and the like.

[0052] The second storage space 32a is connected to the outside only through holes formed in the peripheral wall of the hollow fiber membrane 38, except for the inlets 31a and 31b. With this configuration, the second chamber section 30 according to the modified example shown in FIG. 5 can have the same effect as the second chamber section 30 shown in FIG. 4A. That is, when the transplantation device 1 is transplanted into a living body O, immune cells such as white blood cells in the living body O cannot pass through the peripheral wall of the hollow fiber membrane 38 and cannot enter the second storage space 32a. On the other hand, the body fluid in the living body O can move from the living body O to the second storage space 32a through the holes formed in the peripheral wall of the hollow fiber membrane 38. That is, oxygen and nutrients contained in the body fluid in the living body O can move from the living body O to the second storage space 32a through the holes formed in the peripheral wall of the hollow fiber membrane 38. In addition, the secretion of the therapeutic cells X contained in the second storage space 32a can move into the living body O (outside the second storage space 32a) together with the buffer solution through the holes formed in the peripheral wall of the hollow fiber membrane 38.

[0053] Since the membrane part 32 is composed of a plurality of hollow fiber membranes 38, the surface area of ​​the membrane part 32 can be easily increased compared to the case shown in FIG. 4A. This can promote the movement of the secretion of the therapeutic cells X from the second storage space 32a into the living body O, and the movement of oxygen and nutrients from the living body O to the second storage space 32a. By promoting the movement of the secretion of the therapeutic cells X from the second storage space 32a into the living body O, the therapeutic effect of the transplantation device 1 can be promoted. Furthermore, by promoting the movement of oxygen and nutrients from the living body O to the second storage space 32a, more oxygen and nutrients can be taken into the transplantation device 1, and thus the shortage of supply of oxygen and nutrients to the therapeutic cells X can be suppressed.

[0054] Examples of the membrane constituting the hollow fiber membrane 38 include an RO membrane, a UF membrane, and an MF membrane. However, the membrane constituting the hollow fiber membrane 38 is not limited to these. In the modified example shown in Fig. 5, the hollow fiber membrane 38 is constituted by an MF membrane, as an example. Examples of the material constituting the hollow fiber membrane 38 include polyethylene, polysulfone, polyvinylidene fluoride, and cellulose acetate. However, the material constituting the hollow fiber membrane 38 is not particularly limited.

[0055] In the modification shown in Fig. 5, second chamber section 30 may further include a support structure 33. That is, a structure equivalent to support structure 33 shown in Figs. 4A and 4B may be accommodated in internal space 38a defined by each of multiple hollow fiber membranes 38.

[0056] <Pump section 40> As shown in FIG. 1, the pump section 40 is provided in a circulation path 80. The pump section 40 delivers a buffer solution in a predetermined direction through the circulation path 80. In this embodiment, the buffer solution delivered by the pump section 40 passes through the second chamber section 30 and the first chamber section 10 in this order, and is introduced back into the pump section 40, thereby circulating through the circulation path 80. In the case of FIG. 1, the buffer solution circulates through the circulation path 80 in a counterclockwise direction. However, the implantation device 1 may be configured such that the buffer solution circulates through the circulation path 80 by passing through the first chamber section 10 and the second chamber section 30 in this order, and is introduced back into the pump section 40.

[0057] By circulating the buffer solution in the circulation path 80 by the pump unit 40, the buffer solution in the second storage space 32a of the second chamber 30 can be actively replaced with a buffer solution (the buffer solution that has passed through the first storage space 10a) that contains a large amount of secretions of the therapeutic cells X and has a small amount of oxygen and nutrients. This can promote the movement of the secretions of the therapeutic cells X from the second storage space 32a to the living body O, and the movement of oxygen and nutrients from the living body O to the second storage space 32a. By promoting the movement of the secretions of the therapeutic cells X from the second storage space 32a to the living body O, the therapeutic effect of the transplantation device 1 can be promoted. In addition, by promoting the movement of oxygen and nutrients from the living body O to the second storage space 32a, more oxygen and nutrients can be taken into the transplantation device 1, and thus the shortage of oxygen and nutrients to the therapeutic cells X can be suppressed.

[0058] Furthermore, by circulating the buffer solution in the circulation path 80 by the pump unit 40, the buffer solution in the first storage space 10a of the first chamber 10 can be actively replaced with a buffer solution (the buffer solution that has passed through the second storage space 32a) that contains less secretions from the therapeutic cells X and more oxygen and nutrients. This can promote the supply of oxygen and nutrients to the therapeutic cells X and suppress a shortage of oxygen and nutrients to the therapeutic cells X.

[0059] Examples of the pump constituting the pump unit 40 include a hose pump, a tube pump, a piston pump, a plunger pump, a diaphragm pump, an impeller pump, a rotary pump, a mono pump, and a screw pump. However, the configuration of the pump unit 40 is not particularly limited as long as it can pump the buffer solution. However, considering that the pump unit 40 is implanted into the living body O as a part of the implantation device 1, a pump that is easy to miniaturize (for example, an impeller pump) is preferable. In the present embodiment, as an example, the pump unit 40 is formed of an impeller pump.

[0060] As shown in FIG. 1, a pump control unit 41 is connected to the pump unit 40 of this embodiment. A pump power supply unit 42 is also connected to the pump control unit 41 of this embodiment. The pump control unit 41 controls the flow rate of the buffer solution delivered by the pump unit 40. In this embodiment, as an example, the pump control unit 41 is configured by an inverter. However, as long as the flow rate of the buffer solution delivered by the pump unit 40 can be controlled, the configuration of the pump control unit 41 is not particularly limited. The pump power supply unit 42 of this embodiment supplies power to the pump unit 40 and the pump control unit 41. In this embodiment, as an example, the pump power supply unit 42 is configured by a commercial power source. However, as long as it is possible to supply power to the pump unit 40 and the pump control unit 41, the configuration of the pump power supply unit 42 is not particularly limited.

[0061] In this embodiment, the pump control unit 41 and the pump power supply unit 42 are not implanted into the living body O. That is, in this embodiment, the pump control unit 41 and the pump power supply unit 42 are connected as external devices from outside the living body to the pump unit 40 implanted into the living body O. However, either one or both of the pump control unit 41 and the pump power supply unit 42 may be implanted into the living body O together with the pump unit 40. In addition, the implantation device 1 may be configured to include the pump control unit 41 and the pump power supply unit 42, or may not include them (see FIGS. 7A to 7C).

[0062] 6, when the pump section 40 is a positive displacement pump 45, the implantation device 1 may further include a reservoir section 60. The positive displacement pump 45 defines a third storage space 45a capable of storing a buffer solution, and alternately repeats suction and discharge of the buffer solution by increasing and decreasing the volume of the third storage space 45a to deliver the buffer solution. Examples of the positive displacement pump 45 include a hose pump, a tube pump, a piston pump, a plunger pump, and a diaphragm pump.

[0063] The storage section 60 defines a fourth storage space 60a. The circulation path 80 includes the third storage space 45a of the positive displacement pump 45 and the fourth storage space 60a of the storage section 60. The volume of the fourth storage space 60a of the storage section 60 varies in accordance with the variation in the volume of the third storage space 45a of the positive displacement pump 45. More specifically, the volume of the fourth storage space 60a of the storage section 60 decreases when the volume of the third storage space 45a of the positive displacement pump 45 increases, and increases when the volume of the third storage space 45a of the positive displacement pump 45 decreases.

[0064] When the pump section 40 is a positive displacement pump 45 and the implantation device 1 does not include a storage section 60, the internal pressure of the circulation path 80 may increase or decrease depending on the fluctuation in the volume of the third storage space 45a of the positive displacement pump 45. When the internal pressure of the circulation path 80 increases or decreases, the positive displacement pump 45 as the pump section 40 does not function properly, and the amount of the buffer solution delivered may decrease or the delivery of the buffer solution may not be performed. In contrast, by providing the storage section 60 in the implantation device 1 as in the example shown in FIG. 6, the internal pressure fluctuation of the circulation path 80 caused by the fluctuation in the volume of the third storage space 45a of the positive displacement pump 45 can be suppressed, and the function of the positive displacement pump 45 can be suppressed from being impaired.

[0065] The storage section 60 is, for example, an elastically deformable bag body. However, the configuration of the storage section 60 is not particularly limited.

[0066] The above-mentioned positive-displacement pump 45 may be configured to be driven by the respiratory movement of a living body. FIG. 7A is a diagram showing a respiration-driven pump 90 as an example of the positive-displacement pump 45 driven by the respiratory movement of a living body. FIG. 7B and FIG. 7C are cross-sectional views taken along line bb of FIG. 7A. As shown in FIG. 7A to FIG. 7C, the respiration-driven pump 90 includes a plate member 91, a bag 92, a valve portion 93, and an elastic portion 95. The plate member 91 is two hard plates. The bag 92 is a flexible bag. The bag 92 defines a third storage space 45a capable of storing a buffer solution. The bag 92 is sandwiched between the two plates as the plate member 91. The valve portion 93 is provided at the inlet and outlet of the bag 92, which are connected to the third storage space 45a. The buffer solution that flows in from the inlet of the bag 92 passes through the third storage space 45a and flows out from the outlet of the bag 92. The valve portion 93 regulates the backflow of the buffer solution flowing from the inlet to the outlet of the bag 92. The elastic portion 95 is an elastically deformable rubber member. The elastic portion 95, together with the bag 92, is sandwiched between two plates serving as the plate member 91. Note that the configurations of the plate member 91, the bag 92, the valve portion 93, and the elastic portion 95 are not limited to those described above.

[0067] Next, the mechanism of the respiration-driven pump 90 will be described. The respiration-driven pump 90 is implanted into a living body as a part of the transplantation device 1. When implanted into a living body, a compressive force P is periodically applied to the respiration-driven pump 90 by the respiratory movement of the living body. The compressive force P is a force that presses the two plates as the plate members 91 so that the gap between the two plates as the plate members 91 narrows. When the compressive force P is applied to the respiration-driven pump 90, the bag 92 and the elastic part 95 of the respiration-driven pump 90 are compressed by the two plates as the plate members 91 (see FIG. 7C). When the bag 92 is compressed, the volume of the third storage space 45a decreases. After that, the respiration-driven pump 90 is released from the compressive force P and is in a state where the compressive force P is not applied. In this state, the restoring force of the elastic part 95 acts, and the gap between the two plates as the plate members 91 is pushed wide. By expanding the gap between the two plates serving as the plate member 91, the bag 92 is released from the state in which it is compressed by the two plates serving as the plate member 91, and the volume of the third storage space 45a increases (see FIG. 7B). In this manner, the volume of the third storage space 45a repeatedly increases and decreases, whereby the respiration-driven pump 90 delivers the buffer solution.

[0068] By using the positive displacement pump 45 as the respiration-driven pump 90, the buffer solution can be pumped without the pump control unit 41 and the pump power supply unit .

[0069] The configuration of the respiration-driven pump 90 is not limited to the above. The respiration-driven pump 90 may be configured, for example, such that the bag 92 and the elastic part 95 are integrated together (for example, an elastically deformable bag body).

[0070] <Check valve portion 50> 1, the circulation path 80 of this embodiment is provided with a check valve section 50. The check valve section 50 regulates the backflow of the buffer solution in the circulation path 80. By providing the check valve section 50 in the circulation path 80 and regulating the backflow of the buffer solution in the circulation path 80, it is possible to stabilize the growth environment of the therapeutic cells X contained in the first storage space 10a.

[0071] The check valve section 50 in this embodiment is disposed between the first chamber section 10 and the second chamber section 30 in the circulation path 80. However, the arrangement of the check valve section 50 is not particularly limited. In other words, the check valve section 50 may be disposed at any position in the circulation path 80, for example, between the pump section 40 and the second chamber section 30, or between the pump section 40 and the first chamber section 10. Furthermore, although the implantation device 1 in this embodiment includes only one check valve section 50, it may include two or more check valve sections. The implantation device 1 does not have to include the check valve section 50.

[0072] Examples of the check valve constituting the check valve section 50 include a ball type check valve, a swing type check valve, a lift type check valve, and a disk type check valve. However, the configuration of the check valve section 50 is not particularly limited as long as it can regulate the backflow of the buffer solution in the circulation path 80. In the present embodiment, as an example, the check valve section 50 is constituted by a disk type check valve.

[0073] Next, the connection between the first chamber section 10 and the second chamber section 30 will be described. As shown in FIG. 1, the first chamber section 10 and the second chamber section 30 are separate from each other. A first flow path L1 is connected to one end of each of the first chamber section 10 and the second chamber section 30. A second flow path L2 is connected to the other end of each of the first chamber section 10 and the second chamber section 30. That is, the circulation path 80 of this embodiment includes the first flow path L1 connecting one end of each of the first chamber section 10 and the second chamber section 30, and the second flow path L2 connecting the other end of each of the first chamber section 10 and the second chamber section 30. In this embodiment, a check valve section 50 is provided in the first flow path L1, and a pump section 40 is provided in the second flow path L2.

[0074] The length of each of the first flow path L1 and the second flow path L2 is preferably 10 mm or more, and more preferably 30 mm or more.

[0075] By making the first chamber section 10 and the second chamber section 30 separate, the degree of freedom in designing each of the first chamber section 10 and the second chamber section 30 can be increased compared to when the first chamber section 10 and the second chamber section 30 are integrated. For example, by making the second chamber section 30 flat, the surface area of ​​the semipermeable membrane section 35 can be increased. Furthermore, by making the second chamber section 30 flat, it becomes possible to directly attach the second chamber section 30 to a site to which the secretion of the therapeutic cells X is to be supplied. Furthermore, by making both the first chamber section 10 and the second chamber section 30 flat, the entire transplant device 1 can be made into a shape advantageous for installation in subcutaneous tissue.

[0076] Furthermore, since the first chamber section 10 and the second chamber section 30 are connected via the first flow path L1 and the second flow path L2, the first chamber section 10 and the second chamber section 30 can be set at different installation positions in the living body O. As a result, for example, when there is not enough space near the treatment site (the site to which the secretion of the therapeutic cells X is to be supplied) of the living body O (for example, when the treatment site is in the subcutaneous tissue), only the second chamber section 30 is installed near the treatment site and the first chamber section 10 is installed at another site with enough space, thereby reducing the burden on the living body O caused by using the transplantation device 1.

[0077] In this embodiment, the first flow path L1 and the second flow path L2 are formed by flexible resin tubes. However, the configuration of the members forming the first flow path L1 and the second flow path L2 is not particularly limited and can be changed as appropriate.

[0078] Next, a treatment using the transplantation device 1 of this embodiment will be described. In the following description, the transplantation device 1 is assumed to be transplanted into the living body O of a patient. A buffer solution is circulated in the circulation path 80 by the pump section 40. The first chamber section 10 is assumed to contain therapeutic cells X. The second chamber section 30 is assumed to be disposed near the treatment site and to be in contact with bodily fluids (e.g., interstitial fluid, etc.) in the living body O.

[0079] As the buffer solution circulates through the circulation path 80, the secretions of the therapeutic cells X contained in the circulating fluid flow from the first storage space 10a of the first chamber 10 to the second storage space 32a of the second chamber 30 through the second flow path L2. The secretions of the therapeutic cells X that flow into the second storage space 32a move from the second storage space 32a to the living body O through the semipermeable membrane portion 35. This allows the secretions of the therapeutic cells X to be supplied to the body fluids in the living body O.

[0080] Meanwhile, the body fluid in the living body O moves from inside the living body O to the second housing space 32a through the holes formed in the semipermeable membrane part 35. At this time, immune cells such as white blood cells contained in the body fluid in the living body O cannot pass through the holes formed in the semipermeable membrane part 35 and are left in the living body O. In other words, while preventing the inflow of immune cells such as white blood cells, oxygen and nutrients contained in the body fluid can be taken into the transplantation device 1 together with the body fluid in the living body O.

[0081] The body fluid in the living body O that has moved into the second storage space 32a circulates through the circulation path 80 together with the buffer solution, passes through the first flow path L1, and flows into the first storage space 10a of the first chamber 10. This allows oxygen and nutrients contained in the body fluid in the living body O to be supplied to the therapeutic cells X stored in the first storage space 10a.

[0082] The buffer solution circulating through the circulation path 80 is replaced with bodily fluids within the living body O over time.

[0083] The implantation device according to the present disclosure is not limited to the specific configurations shown in the above-mentioned embodiments and modifications, and various modifications, changes, and combinations are possible without departing from the scope of the claims. For example, in the implantation device 1 of this embodiment, the buffer solution circulating in the circulation path 80 passes through the second chamber section 30 and the first chamber section 10 in this order, and is introduced again into the pump section 40, thereby circulating in the circulation path 80. In contrast, the implantation device 1 may be configured so that the buffer solution circulates in the circulation path 80 by passing through the first chamber section 10 and the second chamber section 30 in this order, and is introduced again into the pump section 40. [Industrial Applicability]

[0084] The present disclosure relates to implantable devices. [Explanation of symbols]

[0085] 1: Implantable devices 10: First chamber section 10a: First containment space 11a: Inlet 11b: Outlet 12a: Filter section 12b: Filter section 14:Exterior part 15a: Connection 15b: Connection 16: Carrier part 18: Hollow fiber membrane 18a:Inner space 20a: Port device 20b: Port device 30: Second chamber section 31a: Inlet 31b: Outlet 32: Membrane part 32a: Second containment space 33: Support structure 35: Semi-permeable membrane part 38: Hollow fiber membrane 38a:Inner space 40: Pump section 41: Pump control unit 42: Pump power supply unit 45: Positive displacement pump 45a: Second Containment Space 50: Check valve section 60: Storage section 80:Circulation path 90: Breathing pump 91: Plate member 92: Bag 93: Valve section 95: Elastic part L1: First flow path L2: Second flow path O: Living organism P: Compressive force X: Therapeutic cells

Claims

1. A device for implantation that can be implanted in a living body, comprising: A first chamber portion defining a first storage space for storing therapeutic cells; A second chamber portion defining a second storage space that does not contain the therapeutic cells; a pump unit that circulates a buffer solution through a circulation path including the first storage space and the second storage space, A transplant device, wherein the second chamber portion is provided with a semipermeable membrane portion that moves secretions of the therapeutic cells from the second storage space to the living body, and moves bodily fluids within the living body from the living body to the second storage space.

2. The first chamber and the second chamber are separate from each other, The implant device of claim 1, wherein the circulation path includes a first flow path connecting one end side of the first chamber portion and the second chamber portion, and a second flow path connecting the other end side of the first chamber portion and the second chamber portion.

3. The implantable device of claim 2 , wherein the first and second flow channels each have a length of 10 mm or more.

4. The transplant device according to claim 1 or 2, wherein the first chamber portion is provided with a filter portion that does not allow the therapeutic cells contained in the first storage space to pass to the upstream and downstream sides of the circulation path.

5. The implantable device according to claim 1 or 2, further comprising a check valve portion that regulates backflow of the buffer solution in the circulation path.

6. The implantation device according to claim 1 or 2, wherein the first chamber defines a connecting flow path communicating with the first storage space and is provided with a connecting portion connectable to an external device.

7. The transplant device according to claim 1 or 2, wherein the first chamber portion comprises a carrier portion capable of supporting the therapeutic cells.

8. The carrier portion of the first chamber portion includes a plurality of hollow fiber membranes arranged in parallel, The implantation device according to claim 7 , wherein each of the plurality of hollow fiber membranes defines an internal space through which the buffer solution can move between the first storage space and the hollow fiber membrane.

9. the pump unit is a positive displacement pump that defines a third storage space capable of storing the buffer solution, and delivers the buffer solution by alternately increasing and decreasing a volume of the third storage space, a storage section defining a fourth storage space whose volume varies in response to a change in the volume of the third storage space of the pump section; The implantable device according to claim 1 or 2, wherein the circulation path includes the third storage space and the fourth storage space.

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