Diffusion chamber-type artificial pancreatic islet device

Abstract

To provide a diffusion chamber-type artificial pancreatic islet device.SOLUTION: A diffusion chamber-type artificial pancreatic islet device 1 comprises a ring holder 2 made of polycarbonate, and immunoisolation membranes 3 that are made of polycarbonate and UV-bonded to both upper and lower open end faces of the ring holder 2.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a diffusion chamber-type artificial pancreatic islet device. [Background technology]

[0002] The following artificial organ chamber is known, which has a structure in which pancreatic cells and a cell culture bed that maintains their functions are enclosed in a container made of a silicone rubber ring with a polycarbonate immunoisolation membrane adhered to both the upper and lower open end faces (e.g., Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2003-190259 A Summary of the Invention [Problem to be solved by the invention]

[0004] When a polycarbonate immunoisolation membrane is attached to a silicon ring holder as in conventional artificial organ chambers, industrial adhesives or heat treatment are used to bond the ring holder and immunoisolation membrane, which are different materials. This has led to problems such as peeling of the immunoisolation membrane, damage such as the adhesive being torn, and safety issues such as toxicity of the adhesive. For this reason, technology to solve these problems is required, but no technology for this purpose has been considered so far. [Means for solving the problem]

[0005] The diffusion chamber type artificial islet device according to the present invention is characterized by comprising a polycarbonate ring holder and a polycarbonate immunoisolation membrane UV-bonded to both the upper and lower open end faces of the ring holder. Effect of the Invention

[0006] According to the present invention, both the ring holder and the immunoisolation membrane are made of polycarbonate, and the ring holder and the immunoisolation membrane are UV-bonded together. By UV-bonding the ring holder and the immunoisolation membrane in this way, the adhesive strength can be increased compared to the conventional method of using industrial adhesives or performing heat treatment, and therefore it is possible to prevent the immunoisolation membrane from peeling off or being damaged, such as by breaking the adhesive part. In addition, since no adhesive is used, problems such as the toxicity of the adhesive are eliminated, and safety can be improved. [Brief description of the drawings]

[0007] [Figure 1] FIG. 1 shows the shape of a diffusion chamber-type artificial islet device 1. [Diagram 2] 2A to 2C are diagrams showing the shape of a ring holder 2. [Diagram 3] FIG. 1 shows the internal structure of a diffusion chamber-type artificial islet device 1. [Figure 4] FIG. 1 is a diagram showing an example in which tubes 6 are placed in the pores 4a and 4b of a diffusion chamber-type artificial islet device 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0008] Pancreatic islet transplantation is one of the fundamental therapies that can improve not only the quality of life of diabetic patients, but also their prognosis. However, after transplantation, pancreatic islet cells are destroyed by early rejection, making treatment ineffective. In order to solve this problem, the diffusion chamber type artificial islet device in this embodiment was developed as a xenotransplantable artificial islet device (Bio-artificial endocrine pancreas: Bio-AEP) that does not require immunosuppressants.

[0009] Fig. 1 is a diagram showing the shape of a diffusion chamber type artificial islet device in this embodiment. As shown in Fig. 1, the diffusion chamber type artificial islet device 1 is constructed by adhering a polycarbonate immunoisolation membrane 3 to both the upper and lower open end faces of a polycarbonate ring holder 2. In the diffusion chamber type artificial islet device 1 in this embodiment, the ring holder 2 and the immunoisolation membrane 3 are UV-adhered. The diffusion chamber type artificial islet device 1 is circular in shape to avoid excessive stimulation of tissues near the transplant during transplantation.

[0010] FIG. 2 is a diagram showing the shape of the ring holder 2. In FIG. 2, FIG. 2(A) shows a diagram of the ring holder 2 as viewed from above. FIG. 2(B) shows a diagram of the ring holder 2 as viewed from the vertical side, that is, a diagram showing the side of the ring holder 2 as viewed from the right side of FIG. 2(A), and FIG. 2(C) shows a diagram of the ring holder 2 as viewed from the horizontal side, that is, a diagram showing the side of the ring holder 2 as viewed from the bottom side of FIG. 2(A). The ring holder 2 is configured in a ring shape as shown in FIG. 2(A). An immunoisolation membrane 3 is adhered to both open end faces of the ring holder 2, that is, to both the upper and lower sides. This provides a space, that is, an inner cavity, for enclosing cells and a culture bed inside the diffusion chamber type artificial islet device 1.

[0011] As shown in FIG. 2(C), the side of the ring holder 2 has a fine hole 4 for injecting cells and a culture bed into the space (lumen) provided inside the diffusion chamber type artificial islet device 1. This fine hole 4 is also provided on the side of the ring holder 2 opposite to that shown in FIG. 2(C). Of the two fine holes 4 provided on the side of the ring holder 2, one is used for injecting cells and a culture bed, and the other serves as an air outlet. For example, if two fine holes 4 are provided at symmetrical positions on the side of the ring holder 2, one will function as an injecting hole for cells and a culture bed, and the other will function as an air outlet.

[0012] After injecting the cells and culture bed into the space (lumen) provided inside the diffusion chamber type artificial islet device 1, pins for blocking the holes are inserted into the two pores 4 and fixed with an adhesive that is not toxic to living organisms. This physically closes the two pores 4. When the islet cells are injected into the lumen inside the diffusion chamber type artificial islet device 1, the diffusion chamber type artificial islet device 1 in this embodiment becomes a diffusion chamber type artificial islet that can be transplanted into a patient.

[0013] Fig. 3 is a diagram showing the pores 4 and the inner cavity 5 provided inside the diffusion chamber type artificial islet device 1. In Fig. 3, the inner structure of the diffusion chamber type artificial islet device 1 is indicated by dashed lines. In the example shown in Fig. 3, as indicated by dashed lines, two pores 4a and 4b open at symmetrical positions on the side surface of the ring holder 2 and connect to the inner cavity 5.

[0014] When replacing the cell culture bed with new islet cells, one of the fine holes 4a and 4b provided on the side of the ring holder 2 serves as an inlet for cells, etc., and the other as an outlet for existing cells, etc. For example, after transplanting an artificial islet, when the function of insulin secretion from the transplanted islet cells is reduced, it is necessary to replace the cell culture bed with new islet cells. In this case, as shown in FIG. 4, a tube 6 is connected to the fine holes 4a and 4b, and when new islet cells and the cell culture bed are injected from the tube 6 installed in the fine hole 4a, the existing cells, etc. are discharged from the tube 6 installed in the fine hole 4b. This allows the old and new islet cells, etc. to be replaced using the tubes installed in the fine holes 4a and 4b without the need for a second operation on the diffusion chamber type artificial islet 1 that has been transplanted. In addition, the old and new islet cells, etc. can be easily replaced, reducing the physical and economic burden on the patient. In the example shown in FIG. 4, a plug 7 is provided at the tip of the tube 6 to close the tip of the tube.

[0015] In this embodiment, the ring holder 2 is made of polycarbonate with an outer diameter of 30 mm, an inner diameter of 20 mm, and a thickness of 2 mm, or with an outer diameter of 47 mm, an inner diameter of 30 mm, and a thickness of 2 mm. The diameter of the pores 4 is 0.7 mm. The immunoisolation membrane 3 is made of polycarbonate with a thickness of 10 μm, a pore size of 0.1 μm, and a pore density of 6E8 cm. 2 The outer diameter, inner diameter, and thickness of the ring holder 2, and the thickness, pore size, and pore density of the immunoisolation membrane 3 are not limited to the above, as long as the object of the present invention can be achieved.

[0016] In the diffusion chamber type artificial islet device 1 in this embodiment, the ring holder 2 and the immunoisolation membrane 3 are UV-bonded as described above. This is because in this embodiment, the ring holder 2 and the immunoisolation membrane 3 are both made of polycarbonate, which makes UV bonding possible. Furthermore, when bonding is performed using an adhesive as in the past, there are problems such as the immunoisolation membrane 3 peeling off, the adhesive part being torn off, and safety problems such as toxicity of the adhesive. However, in this embodiment, the adhesive strength can be increased by UV bonding, so that it is possible to prevent the immunoisolation membrane 3 from peeling off, or the adhesive part being torn off, and safety problems such as toxicity of the adhesive. Furthermore, since no adhesive is used, problems such as toxicity of the adhesive can be eliminated, and safety can be improved. Note that the method for UV bonding polycarbonate materials together is a known technique, so a description thereof will be omitted.

[0017] In addition, in the diffusion chamber type artificial islet device 1 of this embodiment, after injecting cells and a culture bed into the space provided inside the diffusion chamber type artificial islet device 1, i.e., the lumen 5, two fine holes 4a and 4b are physically closed by inserting pins to close the holes. In a preliminary study, an attempt was made to close the fine holes 4 using an adhesive that is not toxic to living organisms. However, in this case, if the fine holes 4 were completely dry, the adhesive would harden and it would be possible to completely close the holes, but if they were wet, there was a problem that the adhesion would be incomplete and leakage would occur. For this reason, in this embodiment, a pin suitable for closing the holes is inserted into the fine holes 4 and this pin is fixed using an adhesive that is not toxic to living organisms, thereby solving the above-mentioned problem.

[0018] Next, a method for subcutaneously transplanting the diffusion chamber type artificial islet device 1 will be described. The applicant shifted his / her focus from intraperitoneal transplantation, which is safe and can control rejection reactions, to subcutaneous transplantation, which is less invasive, and decided to subcutaneously transplant the diffusion chamber type artificial islet device 1 in this embodiment as follows. When performing subcutaneous transplantation, there was a problem that the subcutaneous space has fewer blood vessels than the intraperitoneal space, and most of the islet cells after transplantation die due to lack of oxygen and nutrients. To solve this problem, a collagen sponge containing bFGF was placed on both the top and bottom of the diffusion chamber type artificial islet device 1, and it was confirmed that a rich vascular network was formed around the diffusion chamber type artificial islet device 1 that had been subcutaneously transplanted. In this way, in an example in which a bFGF-containing collagen sponge was placed on both the top and bottom surfaces of the diffusion chamber type artificial islet device 1 when the diffusion chamber type artificial islet device 1 of the present embodiment was subcutaneously transplanted, a rich vascular network was formed around the diffusion chamber type artificial islet device 1, the collagen fiber layer around the diffusion chamber type artificial islet device 1 became thinner, and the appearance of new blood vessels was observed. Also, no signs of inflammation were observed around the diffusion chamber type artificial islet device 1.

[0019] According to the present embodiment described above, the following advantageous effects can be obtained. (1) The diffusion chamber type artificial islet device 1 is provided with a polycarbonate ring holder 2 and a polycarbonate immunoisolation membrane 3 UV-bonded to both the upper and lower open end faces of the ring holder 2. In this way, by using polycarbonate as the material for both the ring holder 2 and the immunoisolation membrane 3 and UV-bonding them, the adhesive strength can be increased compared to when they are bonded with an adhesive. Furthermore, the increased adhesive strength between the ring holder 2 and the immunoisolation membrane 3 can eliminate problems that occur when they are bonded with an adhesive, such as peeling of the immunoisolation membrane 3 or damage to the adhesive part. In addition, since no adhesive is used, the problem of toxicity of the adhesive is also eliminated, improving safety.

[0020] (2) The side of the ring holder 2 has an opening 4 for injecting cells and a culture bed into the space provided inside the diffusion chamber type artificial islet device 1, i.e., the inner cavity 5. This allows the user to inject cells and a culture bed into the inner cavity 5 through the opening 4 provided on the side of the ring holder 2.

[0021] (3) After injecting cells and a culture bed into the lumen 5, the pore 4 is closed by inserting a pin and fixing the pin with an adhesive that is not toxic to living organisms. This makes it possible to prevent leakage from the pore 4. In addition, since the pin is fixed with an adhesive that is not toxic to living organisms, safety can be ensured.

[0022] (4) Two fine holes 4 are provided on the side of the ring holder 2, one through which the cells and culture bed are injected, and the other as an air exhaust hole. This allows the air existing inside to be exhausted from the fine hole 4 on the opposite side to the injection side when the cells and culture bed are injected. This means that when cells and the like are injected through the fine holes 4, they can be injected safely without increasing the pressure in the inner cavity 5.

[0023] (5) The pores 4a and 4b are designed to be able to accommodate tubes 6 for replacing the cells injected into the lumen 5 with the culture bed, so that when new islet cells and a cell culture bed are injected from the tube 6 installed in one of the pores, the existing cells, etc. can be discharged from the tube 6 installed in the other pore. This allows the old and new islet cells, etc. to be replaced using the tubes installed in the pores 4a and 4b without the need for a second operation on the diffusion chamber type artificial islet 1 that has been transplanted. In addition, the old and new islet cells, etc. can be easily replaced, reducing the physical and economic burden on the patient.

[0024] It should be noted that the present invention is not limited to the configurations in the above-described embodiments as long as the characteristic functions of the present invention are not impaired. [Explanation of symbols]

[0025] 1. Diffusion Chamber Type Artificial Islet Organizer 2 Ring Holder 3 Immunoisolation membrane 4. Pore 5 lumen 6 Tubes 7 Tube plug

Claims

1. A ring holder made of polycarbonate, and an immunoisolation membrane made of polycarbonate UV-bonded to the upper and lower open end faces of the ring holder, characterized in that it is a Diffusion Chamber type artificial pancreas device.

2. In the Diffusion Chamber type artificial pancreas device according to Claim 1, pores for injecting cells and a culture bed into a lumen provided inside the Diffusion Chamber type artificial pancreas device are opened on the side surface of the ring holder, characterized in that it is a Diffusion Chamber type artificial pancreas device.

3. In the Diffusion Chamber type artificial pancreas device according to Claim 2, the pores are closed by inserting a pin and fixing the pin using an adhesive non-toxic to the living body after cells and a culture bed are injected into the lumen, characterized in that it is a Diffusion Chamber type artificial pancreas device.

4. In the Diffusion Chamber type artificial pancreas device according to Claim 2 or 3, two pores are provided on the side surface of the ring holder, cells and a culture bed are injected into the lumen from one, and the other serves as an air discharge hole, characterized in that it is a Diffusion Chamber type artificial pancreas device.

5. In the Diffusion Chamber type artificial pancreas device according to Claim 4, a tube for replacing the cells and the culture bed injected into the lumen is installed in the pores, characterized in that it is a Diffusion Chamber type artificial pancreas device.

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