JP7451818B1 - Diffusion Chamber type artificial islet device - Google Patents
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- JP7451818B1 JP7451818B1 JP2023192562A JP2023192562A JP7451818B1 JP 7451818 B1 JP7451818 B1 JP 7451818B1 JP 2023192562 A JP2023192562 A JP 2023192562A JP 2023192562 A JP2023192562 A JP 2023192562A JP 7451818 B1 JP7451818 B1 JP 7451818B1
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- 238000009792 diffusion process Methods 0.000 title claims abstract description 48
- 210000004153 islets of langerhan Anatomy 0.000 claims abstract description 52
- 239000012528 membrane Substances 0.000 claims abstract description 26
- 229920000515 polycarbonate Polymers 0.000 claims abstract description 19
- 239000004417 polycarbonate Substances 0.000 claims abstract description 19
- 210000000056 organ Anatomy 0.000 claims abstract description 9
- 239000011148 porous material Substances 0.000 claims description 41
- 239000000853 adhesive Substances 0.000 claims description 28
- 230000001070 adhesive effect Effects 0.000 claims description 28
- 231100000331 toxic Toxicity 0.000 claims description 5
- 230000002588 toxic effect Effects 0.000 claims description 5
- 238000010586 diagram Methods 0.000 abstract description 8
- 238000004113 cell culture Methods 0.000 description 6
- 238000002054 transplantation Methods 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 102100024392 Insulin gene enhancer protein ISL-1 Human genes 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000000515 collagen sponge Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 108010090448 insulin gene enhancer binding protein Isl-1 Proteins 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
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- 229920001296 polysiloxane Polymers 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
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Abstract
【課題】Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器を提供すること。【解決手段】Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１は、ポリカーボネート製のリングホルダー２と、リングホルダー２の上下両開口端面にＵＶ接着されたポリカーボネート製の免疫隔離膜３とを備える。【選択図】図１An object of the present invention is to provide a diffusion chamber type artificial pancreatic islet organ. SOLUTION: A diffusion chamber type artificial pancreatic islet device 1 includes a ring holder 2 made of polycarbonate, and an immunoisolation membrane 3 made of polycarbonate UV-bonded to both upper and lower open end surfaces of the ring holder 2. [Selection diagram] Figure 1
Description
本発明は、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器に関する。 The present invention relates to a diffusion chamber type artificial pancreatic islet device.
次のような人工臓器用チャンバーが知られている。この人工臓器用チャンバーでは、シリコーンゴムリングの上下両開口端面にポリカーボネート製の免疫隔離膜を接着してなる容器の中に膵細胞とその機能を維持する細胞培養床を封入する構造になっている（例えば、特許文献１）。 The following chambers for artificial organs are known. This artificial organ chamber has a structure in which pancreatic cells and a cell culture bed that maintains their functions are enclosed in a container made by adhering polycarbonate immunoisolation membranes to the upper and lower open end surfaces of a silicone rubber ring. (For example, Patent Document 1).
従来の人工臓器用チャンバーのように、シリコン製のリングホルダーにポリカーボネート製の免疫隔離膜を接着した場合には、異種素材であるリングホルダーと免疫隔離膜を接着させるために工業用接着剤を用いたり加熱処理を行った。それ故、免疫隔離膜が剥離したり、接着部が敗れるなど破損したり、接着剤による毒性などの安全性に問題があるといった課題があった。このため、このような課題を解決するための技術が求められているが、従来はこのための技術について何ら検討されていなかった。 When a polycarbonate immunoisolation membrane is bonded to a silicone ring holder, as in conventional artificial organ chambers, industrial adhesives are used to bond the ring holder and the immunoisolation membrane, which are dissimilar materials. or heat treatment. Therefore, there have been problems with safety, such as peeling of the immunoisolation membrane, damage such as failure of the adhesive part, and toxicity due to the adhesive. Therefore, there is a need for a technology to solve these problems, but no technology has been studied in the past.
本発明によるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器は、ポリカーボネート製のリングホルダーと、リングホルダーの上下両開口端面にＵＶ接着されたポリカーボネート製の免疫隔離膜とを備えることを特徴とする。 The diffusion chamber type artificial pancreatic islet device according to the present invention is characterized by comprising a ring holder made of polycarbonate and an immunoisolation membrane made of polycarbonate UV bonded to both upper and lower open end surfaces of the ring holder.
本発明によれば、リングホルダーと免疫隔離膜をどちらもポリカーボネート製にして、リングホルダーと免疫隔離膜をＵＶ接着するようにした。このようにリングホルダーと免疫隔離膜をＵＶ接着することによって、従来のように工業用接着剤を用いたり加熱処理を行う場合と比較して接着力を上げることができるため、免疫隔離膜が剥離したり、接着部が敗れるなど破損したりすることを防ぐことができる。また、接着剤を用いないため接着剤の毒性などの問題も解消して安全性を向上させることができる。 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. By UV bonding the ring holder and the immunoisolation membrane in this way, it is possible to increase the adhesive strength compared to the conventional methods of using industrial adhesives or heat treatment, so the immunoisolation membrane can be peeled off. This can prevent damage such as damage to the bonded parts. Furthermore, since no adhesive is used, problems such as the toxicity of adhesives can be resolved and safety can be improved.
膵島移植は糖尿病患者の生活の質だけでなく、生命予後も改善し得る根本療法の一つである。しかしながら、移植後の膵島細胞は早期拒絶反応に依って破壊され、治療が効果的に得られなかった。本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ（ディフュージョンチャンバー）型人工膵島器は、このような問題を解消するために、免疫抑制剤を必要としない異種移植可能な人工膵島Ｄｅｖｉｃｅ（Ｂｉｏ－ａｒｔｉｆｉｃｉａｌ ｅｎｄｏｃｒｉｎｅ ｐａｎｃｒｅａｓ ： Ｂｉｏ－ＡＥＰ)として開発された。 Pancreatic islet transplantation is one of the fundamental treatments that can improve not only the quality of life of diabetic patients but also their life prognosis. However, post-transplant pancreatic islet cells were destroyed due to early rejection, making it impossible to obtain effective treatment. In order to solve such problems, the diffusion chamber type artificial pancreatic islet device in this embodiment is a xenotransplantable artificial pancreatic islet device (Bio-artificial endocrine pancreas) that does not require immunosuppressants. Developed as AEP).
図１は、本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器の形状を示す図である。図１に示すように、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１は、ポリカーボネート製のリングホルダー２の上下両開口端面に、ポリカーボネート製の免疫隔離膜３を接着して構成される。本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１では、リングホルダー２と免疫隔離膜３はＵＶ接着される。なお、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の形状を円形としたのは、移植の際に移植近辺の組織に必要以上に刺激を与えないためである。 FIG. 1 is a diagram showing the shape of a diffusion chamber type artificial pancreatic islet organ in this embodiment. As shown in FIG. 1, the diffusion chamber type artificial pancreatic islet device 1 is constructed by adhering polycarbonate immunoisolation membranes 3 to both upper and lower open end surfaces of a polycarbonate ring holder 2. In the diffusion chamber type artificial pancreatic islet device 1 in this embodiment, the ring holder 2 and the immunoisolation membrane 3 are bonded by UV. The reason why the Diffusion Chamber type artificial pancreatic islet device 1 is circular is to avoid unnecessarily stimulating the tissue near the transplant during transplantation.
図２は、リングホルダー２の形状を示した図である。図２において、図２（Ａ）はリングホルダー２を上面から見た図を示している。また、図２（Ｂ）はリングホルダー２を縦側面から見た図、すなわちリングホルダー２を図２（Ａ）の右側から見た場合の側面を示す図であり、図２（Ｃ）はリングホルダー２を横側面から見た図、すなわちリングホルダー２を図２（Ａ）の下側から見た場合の側面を示す図である。リングホルダー２は、図２（Ａ）に示すようにリング状に構成されている。該リングホルダー２の両開口端面、すなわち上下両面に免疫隔離膜３が接着される。これによって、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部には細胞と培養床を封入するための空間、すなわち内腔が設けられる。 FIG. 2 is a diagram showing the shape of the ring holder 2. As shown in FIG. In FIG. 2, FIG. 2(A) shows a top view of the ring holder 2. Moreover, FIG. 2(B) is a view showing the ring holder 2 from the vertical side, that is, a side view when the ring holder 2 is viewed from the right side of FIG. 2(A), and FIG. FIG. 2 is a side view of the holder 2 viewed from the side, that is, a side view of the ring holder 2 viewed from below in FIG. 2(A). The ring holder 2 is configured in a ring shape as shown in FIG. 2(A). Immune isolation membranes 3 are adhered to both open end surfaces of the ring holder 2, that is, to the upper and lower surfaces. As a result, a space, ie, a lumen, for enclosing cells and a culture bed is provided inside the diffusion chamber type artificial pancreatic islet device 1.
また、図２（Ｃ）に示すように、リングホルダー２の側面には、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部に設けられた空間（内腔）に細胞と培養床を注入するための細孔４が開口している。この細孔４は、リングホルダー２の図２（Ｃ）とは反対側の側面にも設けられる。リングホルダー２の側面に設けられた２つの細孔４は、一方から細胞と培養床が注入され、他方は空気の排出孔となる。例えば、リングホルダー２の側面の対称位置に２つの細孔４を設ければ、一方が細胞と培養床の注入孔として機能し、他方は空気の排出孔として機能する。 In addition, as shown in FIG. 2(C), the side surface of the ring holder 2 has pores for injecting cells and a culture bed into the space (lumen) provided inside the diffusion chamber type artificial pancreatic islet device 1. 4 is open. This pore 4 is also provided on the side surface of the ring holder 2 opposite to that shown in FIG. 2(C). One of the two pores 4 provided on the side of the ring holder 2 allows cells and a culture bed to be injected therein, and the other serves as an air outlet hole. For example, if two pores 4 are provided at symmetrical positions on the side surface of the ring holder 2, one will function as an injection hole for cells and a culture bed, and the other will function as an air discharge hole.
Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部に設けられた空間（内腔）に細胞と培養床を注入した後は、２つの細孔４に孔を塞ぐためのピンを挿入し、このピンを生体に毒性のない接着剤を用いて固定する。これによって２つの細孔４は物理的に閉鎖される。なお、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１内の内腔に膵島細胞が注入されると、本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１は、患者に移植可能なＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島となる。 After injecting cells and a culture bed into the space (lumen) provided inside the Diffusion Chamber type artificial islet device 1, pins are inserted into the two pores 4 to close the holes, and the pins are inserted into the living body. Secure using non-toxic adhesive. This physically closes the two pores 4. Note that when pancreatic islet cells are injected into the inner cavity of the Diffusion Chamber type artificial pancreatic islet device 1, the Diffusion Chamber type artificial pancreatic islet device 1 in this embodiment becomes a Diffusion Chamber type artificial pancreatic islet that can be transplanted into a patient.
図３は、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部に設けられた細孔４と内腔５を示した図である。なお、図３では、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部構造を破線で示している。図３に示す例では、破線で示すように、２つの細孔４ａ及び４ｂは、リングホルダー２の側面の対称位置に開口しており、内腔５に接続している。 FIG. 3 is a diagram showing the pores 4 and lumen 5 provided inside the diffusion chamber type artificial pancreatic islet device 1. As shown in FIG. In addition, in FIG. 3, the internal structure of the Diffusion Chamber type artificial pancreatic islet device 1 is shown by a broken line. In the example shown in FIG. 3, the two pores 4a and 4b open at symmetrical positions on the side surface of the ring holder 2 and are connected to the inner cavity 5, as shown by broken lines.
なお、リングホルダー２の側面に設けられた細孔４ａ及び４ｂは、新たな膵島細胞と細胞培養床を入れ替える際には、一方の細孔は細胞等の注入口となり、他方の細孔は既存細胞等の流出口となる。例えば、人工膵島を移植した後に、移植膵島細胞からのインスリン分泌の機能低下を来したときには新たな膵島細胞と細胞培養床を入れ替える必要がある。このときは、図４に示すように、細孔４ａと細孔４ｂにチューブ６を接続し、細孔４ａに設置したチューブ６から新たな膵島細胞と細胞培養床を注入すると、細孔４ｂに設置したチューブ６から既存細胞等が排出される。これによって、一旦移植したＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島１を、再手術することなく、細孔４ａ及び細孔４ｂに設置したチューブを用いて新旧膵島細胞等の入れ替えを行うことができる。また、新旧膵島細胞等の入れ替えを容易に行うことができ、患者への肉体的負担や経済的負担を軽減することができる。なお、図４に示す例では、チューブ６の先端には、チューブの先端を塞ぐための栓７が設けられている。 Note that when replacing the cell culture bed with new pancreatic islet cells, one of the pores 4a and 4b provided on the side of the ring holder 2 serves as an inlet for cells, etc., and the other pore serves as an inlet for the existing cell culture bed. Serves as an outlet for cells, etc. For example, after transplanting an artificial pancreatic islet, if insulin secretion from the transplanted islet cells decreases, it is necessary to replace the cell culture bed with new pancreatic islet cells. At this time, as shown in FIG. 4, a tube 6 is connected to the pore 4a and the pore 4b, and new islet cells and a cell culture bed are injected from the tube 6 installed in the pore 4a. Existing cells and the like are discharged from the installed tube 6. Thereby, old and new pancreatic islet cells, etc. can be exchanged using the tubes installed in the pores 4a and 4b of the Diffusion Chamber-type artificial pancreatic islet 1 that has been transplanted, without undergoing re-surgery. Furthermore, old and new pancreatic islet cells, etc. can be easily replaced, and the physical and economic burden on the patient can be reduced. In the example shown in FIG. 4, a plug 7 is provided at the distal end of the tube 6 to close the distal end of the tube.
本実施の形態では、リングホルダー２は、例えば、外径３０ｍｍ、内径２０ｍｍ、厚さ２ｍｍのポリカーボネート製、または外径４７ｍｍ、内径３０ｍｍ、厚さ２ｍｍのポリカーボネート製とする。そして、細孔４の径は０．７ｍｍとする。また、免疫隔離膜３は、厚さ（Ｔｈｉｃｋｎｅｓｓ）１０μｍのポリカーボネート製とし、微細孔の大きさ（ｐｏｒｅ ｓｉｚｅ）は０．１μｍ、微細孔密度（ｐｏｒｅ ｄｅｎｓｉｔｙ）は６Ｅ８ｃｍ２とする。なお、リングホルダー２の外径、内径、厚さと、免疫隔離膜３のＴｈｉｃｋｎｅｓｓ、ｐｏｒｅ ｓｉｚｅ、ｐｏｒｅ ｄｅｎｓｉｔｙは、本発明の目的を達成することができるものであれば、上記の内容に限定されない。 In this embodiment, the ring holder 2 is made of polycarbonate and has an outer diameter of 30 mm, an inner diameter of 20 mm, and a thickness of 2 mm, or a polycarbonate member that has an outer diameter of 47 mm, an inner diameter of 30 mm, and a thickness of 2 mm. The diameter of the pore 4 is set to 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 . Note that 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-mentioned values as long as they can achieve the object of the present invention.
本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１では、上述したようにリングホルダー２と免疫隔離膜３はＵＶ接着されるようにした。これは、本実施の形態では、リングホルダー２と免疫隔離膜３の素材をどちらもポリカーボネート製としたことによって、ＵＶ接着が可能になった。また、従来のように接着剤を用いて接着する場合、免疫隔離膜３が剥離したり、接着部が敗れるなど破損したり、接着剤による毒性などの安全性に問題があるといった課題があったが、本実施の形態では、ＵＶ接着によって接着力を上げることができるため、免疫隔離膜３が剥離したり、接着部が敗れるなど破損したりすることを防ぐことができる。また、接着剤を用いないため接着剤の毒性などの問題も解消して安全性を向上させることができる。なお、ポリカーボネート素材同士をＵＶ接着するための方法は、公知の技術のため説明を省略する。 In the diffusion chamber type artificial pancreatic islet device 1 in this embodiment, the ring holder 2 and the immunoisolation membrane 3 are bonded together by UV as described above. In this embodiment, the ring holder 2 and the immunoisolation membrane 3 are both made of polycarbonate, making UV adhesion possible. In addition, when bonding using adhesive as in the past, there were problems such as the immunoisolation membrane 3 peeling off, damage such as the adhesive part breaking, and safety problems such as toxicity due to the adhesive. However, in this embodiment, since the adhesive force can be increased by UV adhesion, it is possible to prevent the immunoisolation membrane 3 from peeling off or from being damaged, such as the adhesive portion breaking. Furthermore, since no adhesive is used, problems such as the toxicity of adhesives can be resolved and safety can be improved. Note that the method for UV bonding polycarbonate materials to each other is a well-known technique, and therefore a description thereof will be omitted.
また、本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１では、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部に設けられた空間、すなわち内腔５に細胞と培養床を注入した後は、２つの細孔４ａおよび４ｂには、孔を塞ぐためのピンを挿入して物理的に閉鎖するようにした。事前の検討では、生体に毒性のない接着剤を用いて細孔４を塞ぐ事を試みた。しかしながら、この場合は、細孔４が完全に乾いていれば接着剤が固まり孔を完全に塞ぐことは可能であったが、濡れていると接着が不完全となり漏れが生じるという問題があった。このため、本実施の形態では、孔を塞ぐのに適したピンを細孔４に挿入し、このピンを生体に毒性のない接着剤を用いて固定するようにして、上記のような問題を解消した。 In addition, in the Diffusion Chamber type artificial islet device 1 according to the present embodiment, after cells and culture bed are injected into the space provided inside the Diffusion Chamber type artificial islet device 1, that is, into the lumen 5, two pores are formed. Pins were inserted into holes 4a and 4b to physically close them. In preliminary studies, an attempt was made to close the pores 4 using an adhesive that is not toxic to living organisms. However, in this case, if the pores 4 were completely dry, the adhesive would solidify and completely close the pores, but if the pores were wet, the adhesive would be incomplete and leakage would occur. . Therefore, in this embodiment, a pin suitable for closing the hole is inserted into the pore 4, and this pin is fixed using an adhesive that is not toxic to living organisms, thereby solving the above problem. It was resolved.
次に、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１を皮下移植するための方法について説明する。出願人は、移植部位を安全かつ拒絶反応を制御しうる腹腔内移植から低襲撃性の皮下移植に着眼点を移した結果、本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１を以下のように皮下移植することにした。皮下移植を行う場合、皮下は腹腔内と比較して血管に乏しく、移植後の膵島細胞は酸素と栄養不足により大半が死滅するという問題があった。この問題を解消するために、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の上下両面にｂＦＧＦ含有コラーゲン・スポンジを設置したところ、皮下移植したＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の周辺に豊富な血管網が作成されるのを確認することができた。このように、本実施の形態におけるＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１を皮下移植する際に、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の上下両面にｂＦＧＦ含有コラーゲン・スポンジを設置した例では、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の周辺に豊富な血管網が作成され、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１周辺の膠原繊維層が薄くなり、新生血管の出現が認められた。また、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の周辺に炎症所見が認められなかった。 Next, a method for subcutaneously transplanting the Diffusion Chamber type artificial pancreatic islet device 1 will be described. As a result of the applicant's focus on transplantation from intraperitoneal transplantation, which is safe and can control rejection reactions, to subcutaneous transplantation, which is less aggressive, the applicant developed the Diffusion Chamber type artificial islet device 1 in the present embodiment as follows. I decided to have it transplanted subcutaneously. When subcutaneous transplantation is performed, there is a problem in that subcutaneous cells have fewer blood vessels than intraperitoneal cells, and most of the transplanted pancreatic islet cells die due to lack of oxygen and nutrients. In order to solve this problem, bFGF-containing collagen sponges were placed on both the upper and lower surfaces of the Diffusion Chamber type artificial islet device 1, and a rich vascular network was created around the subcutaneously implanted Diffusion Chamber type artificial islet device 1. I was able to confirm that. As described above, when subcutaneously transplanting the Diffusion Chamber type artificial islet device 1 in this embodiment, in the example in which bFGF-containing collagen sponges are placed on both the upper and lower surfaces of the Diffusion Chamber type artificial islet device 1, the Diffusion Chamber type artificial pancreatic islet device A rich vascular network was created around the organ 1, the collagen fiber layer around the Diffusion Chamber type artificial pancreatic islet organ 1 became thinner, and the appearance of new blood vessels was observed. Further, no inflammation was observed around the Diffusion Chamber type artificial pancreatic islet organ 1.
以上説明した本実施の形態によれば、以下のような作用効果を得ることができる。
（１）Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１は、ポリカーボネート製のリングホルダー２と、リングホルダー２の上下両開口端面にＵＶ接着されたポリカーボネート製の免疫隔離膜３とを備えるようにした。このように、リングホルダー２と免疫隔離膜３の素材をどちらもポリカーボネート製にしてＵＶ接着することによって、接着剤で接着した場合よりも接着力を上げることができる。さらに、リングホルダー２と免疫隔離膜３の接着力が上がったことによって、接着剤で接着した場合に生じる免疫隔離膜３が剥離したり、接着部が敗れるなど破損したりする問題を解消することができる。また、接着剤を用いないため、接着剤の毒性の問題も解消して安全性を向上させることができる。
According to this embodiment described above, the following effects can be obtained.
(1) The Diffusion Chamber type artificial pancreatic islet device 1 is equipped with a ring holder 2 made of polycarbonate and an immunoisolation membrane 3 made of polycarbonate that is UV-adhered to both the upper and lower opening end surfaces of the ring holder 2. In this way, by making both the ring holder 2 and the immunoisolation membrane 3 made of polycarbonate and bonding them with UV light, the adhesive strength can be increased compared to the case where they are bonded with an adhesive. Furthermore, by increasing the adhesive strength between the ring holder 2 and the immunoisolation membrane 3, problems such as the immunoisolation membrane 3 peeling off or damage such as the bonded portion breaking, which occur when the ring holder 2 and the immunoisolation membrane 3 are bonded with adhesive, can be solved. I can do it. Furthermore, since no adhesive is used, the problem of adhesive toxicity can be resolved and safety can be improved.
（２）リングホルダー２の側面には、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器１の内部に設けられた空間、すなわち内腔５に細胞と培養床を注入するための細孔４が開口している。これによって、使用者は、リングホルダー２の側面に設けられた細孔４から内腔５に細胞と培養床を注入することができる。 (2) A pore 4 is opened on the side surface of the ring holder 2 for injecting cells and a culture bed into a space provided inside the Diffusion Chamber type artificial pancreatic islet device 1, that is, a lumen 5. This allows the user to inject cells and a culture bed into the lumen 5 through the pore 4 provided on the side surface of the ring holder 2.
（３）細孔４は、内腔５に細胞と培養床を注入した後に、ピンを挿入して該ピンを生体に毒性のない接着剤を用いて固定することによって閉鎖するようにした。これによって、細孔４からの漏れを防ぐことができる。また、ピンは生体に毒性のない接着剤を用いて固定するようにしたため、安全性も確保することができる。 (3) After injecting cells and a culture bed into the lumen 5, the pore 4 was closed by inserting a pin and fixing the pin using an adhesive that is not toxic to living organisms. Thereby, leakage from the pores 4 can be prevented. Furthermore, since the pins are fixed using an adhesive that is not toxic to living organisms, safety can also be ensured.
（４）細孔４は、リングホルダー２の側面に２つ設けられ、、一方から細胞と培養床が注入され、他方は空気の排出孔となるようにした。これによって、細胞と培養床を注入する際に、注入側とは反対側の細孔４から内部の既存空気を排出することができる。このことは、細孔４から細胞等を注入する際に、内腔５の圧を上げることなく安全に注入することが可能となる。 (4) Two pores 4 were provided on the side surface of the ring holder 2, and cells and culture bed were injected from one side, and the other hole was used as an air discharge hole. Thereby, when injecting cells and a culture bed, existing air inside can be exhausted from the pores 4 on the opposite side to the injection side. This makes it possible to safely inject cells and the like through the pores 4 without increasing the pressure in the lumen 5.
（５）細孔４ａと細孔４ｂには内腔５に注入された細胞と培養床の入れ替えを行うためのチューブ６を設置できるようにしたため、一方の細孔に設置したチューブ６から新たな膵島細胞と細胞培養床を注入すると、他方の細孔に設置したチューブ６から既存細胞等を排出することができる。これによって、一旦移植したＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島１を、再手術することなく、細孔４ａ及び細孔４ｂに設置したチューブを用いて新旧膵島細胞等の入れ替えを行うことができる。また、新旧膵島細胞等の入れ替えを容易に行うことができ、患者への肉体的負担や経済的負担を軽減することができる。 (5) A tube 6 can be installed in the pores 4a and 4b for exchanging the cells injected into the lumen 5 and the culture bed. Once pancreatic islet cells and cell culture bed are injected, existing cells etc. can be discharged from the tube 6 installed in the other pore. Thereby, old and new pancreatic islet cells, etc. can be exchanged using the tubes installed in the pores 4a and 4b of the Diffusion Chamber-type artificial pancreatic islet 1 that has been transplanted, without undergoing re-surgery. Furthermore, old and new pancreatic islet cells, etc. can be easily replaced, and the physical and economic burden on the patient can be reduced.
なお、本発明の特徴的な機能を損なわない限り、本発明は、上述した実施の形態における構成に何ら限定されない。 Note that the present invention is not limited to the configurations of the above-described embodiments as long as the characteristic functions of the present invention are not impaired.
１ Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器
２ リングホルダー
３ 免疫隔離膜
４ 細孔
５ 内腔
６ チューブ
７ チューブの栓
1 Diffusion Chamber type artificial islet device 2 Ring holder 3 Immunoisolation membrane 4 Pore 5 Lumen 6 Tube 7 Tube stopper
Claims (5)
前記リングホルダーの上下両開口端面にＵＶ接着されたポリカーボネート製の免疫隔離膜とを備えることを特徴とするＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器。 polycarbonate ring holder,
A diffusion chamber type artificial pancreatic islet device, characterized in that the ring holder is provided with an immunoisolation membrane made of polycarbonate that is UV-adhered to both upper and lower opening end surfaces.
前記リングホルダーの側面には、Ｄｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器の内部に設けられた内腔に細胞と培養床を注入するための細孔が開口していることを特徴とするＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器。 The Diffusion Chamber type artificial islet device according to claim 1,
Diffusion Chamber type artificial pancreatic islet device, characterized in that a side surface of the ring holder is opened with a pore for injecting cells and a culture bed into a lumen provided inside the Diffusion Chamber type artificial pancreatic islet device. .
前記細孔は、前記内腔に細胞と培養床が注入された後に、ピンを挿入して該ピンを生体に毒性のない接着剤を用いて固定することによって閉鎖されることを特徴とするＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器。 The Diffusion Chamber type artificial pancreatic islet device according to claim 2,
Diffusion, wherein the pore is closed by inserting a pin and fixing the pin using an adhesive that is not toxic to living organisms after cells and a culture bed are injected into the lumen. Chamber type artificial pancreatic islet organ.
前記細孔は、前記リングホルダーの側面に２つ設けられ、一方から細胞と培養床が前記内腔に注入され、他方は空気の排出孔となることを特徴とするＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器。 The Diffusion Chamber type artificial pancreatic islet device according to claim 2 or 3,
A diffusion chamber type artificial pancreatic islet device, characterized in that two pores are provided on the side surface of the ring holder, cells and culture bed are injected into the lumen from one, and the other serves as an air discharge hole.
前記細孔には前記内腔に注入された細胞と培養床の入れ替えを行うためのチューブが設置されることを特徴とするＤｉｆｆｕｓｉｏｎ Ｃｈａｍｂｅｒ型人工膵島器。
The Diffusion Chamber type artificial pancreatic islet device according to claim 4,
A diffusion chamber type artificial pancreatic islet device, wherein a tube for exchanging cells injected into the lumen and a culture bed is installed in the pore.
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