JP2022055086A - Medical device including deformation mechanism for transferring implant piece and transferring method of implant piece - Google Patents

Abstract

To provide means capable of efficiently and quickly peeling off an implant piece from a device without causing a damage or wrinkle.SOLUTION: A device 1 includes a support 2 on which an implant piece S can be placed. The support 2 includes a deformation portion 4 on a side in which the implant piece S is placed. The deformation portion 4 is arranged at a tip end side of the support 2. A tip end side of the deformation portion 4 can be arranged so as to be inward from the tip end portion of the support 2. The deformation portion 4 can be deformed in a direction perpendicular to a support surface of the support 2 to lift up a tip end side of the implant piece S placed on the support 2 in a direction perpendicular to the support surface. A placement surface of the deformation portion 4 can be designed to have a certain angle with respect to another placement surface of the support 2 after deformation.SELECTED DRAWING: Figure 1

Description

The present invention relates to a medical device provided with a deformation mechanism for transferring the graft to a target site and a method for transporting the graft using the medical device.

In recent years, attempts have been made to transplant various cells for repairing damaged tissues and the like. For example, use of fetal cardiomyocytes, skeletal myoblasts, mesenchymal stem cells, cardiac stem cells, ES cells, iPS cells, etc. for repairing myocardial tissue damaged by ischemic heart disease such as angina and myocardial infarction. Has been attempted (Non-Patent Document 1).

As a part of such an attempt, a cell structure formed by using a scaffold and a sheet-shaped cell culture in which cells are formed in a sheet shape have been developed (Non-Patent Document 2).
For therapeutic application of sheet-shaped cell culture, use of cultured epidermal sheet for skin damage caused by burns, use of corneal epithelial sheet-shaped cell culture for corneal damage, oral mucosal sheet for endoscopic resection of esophageal cancer The use of cell culture is under study, and some of them are in the stage of clinical application.
Non-Patent Document 3 describes that skeletal myoblast sheets can be used for healing pancreatic fistulas and gastric perforations in model animals. In recent years, endoscopic submucosal dissection (ESD) has attracted attention as a method for minimally invasive excision of early-stage tumors. This involves injecting a local injection into the submucosal layer of the lesion, artificially causing edema, and then excising the raised submucosal lesion together with the submucosal layer. However, it has been reported that ESD in the duodenum causes complications such as perforation with a probability of about 30% due to the operability of the endoscope and the thinness of the intestinal wall.

Regarding the surgical method for administering the sheet-shaped cell culture to the target site, endoscopic surgery is widely used as a minimally invasive surgical method for the human body, and the sheet-shaped cell culture is delivered to the target site and administered. Various instruments have been proposed.
For example, in the transport administration device described in Patent Document 1, the seat support member is made into a tubular shape and stored in an outer cylinder to reduce the degree of invasion to the human body, and the sheet-shaped therapeutic substance up to the transplant site. Can be carried.

The sheet attaching device described in Patent Document 2 peels off a rod-shaped member arranged along the surface of the sheet support portion by moving it along the surface of the sheet support portion, and releases the sheet-like substance to a target site. Can be affixed to.
The transporting administration tool described in Patent Document 3 is a sheet desorption device capable of applying a negative pressure for adsorbing and holding a sheet-shaped therapeutic substance to a sheet support portion and a positive pressure for separating the sheet-shaped therapeutic substance from the sheet support portion. By means, the sheet can be administered.
In the transport device described in Patent Document 4, the sheet-shaped therapeutic substance can be attached by ejecting a fluid from a plurality of ventilation holes provided on the surface of the head holding the sheet-shaped therapeutic substance.

Japanese Unexamined Patent Publication No. 2009-511 Japanese Unexamined Patent Publication No. 2016-187601 Japanese Unexamined Patent Publication No. 2008-173333 International Publication No. 2014/062922

Haraguchi et al., Stem Cells Transl Med. 2012 Feb; 1 (2): 136-41 Sawa et al., Surg Today. 2012 Jan; 42 (2): 181-4 Tanaka et al., Surg Today. 2017 Jan; 47 (1): 114-121

Under these circumstances, it is difficult for the present inventors to remove the graft from the device without causing damage or wrinkles in developing a means for efficiently transporting the graft to the target site. Faced with problems such as. Therefore, an object of the present invention is to solve such a problem and to realize a medical device having a simple structure and rational.

The present inventors have focused on the fact that the graft can be appropriately peeled off by deforming the support on which the graft is placed, while conducting intensive research to solve the above problems. Then, he found that the graft can be efficiently transferred to the target site by using a medical device including a support having a deformed portion on which the graft can be placed, and as a result of further research, the result of further research. The present invention has been completed.

That is, the present invention relates to the following.
[1] A medical device for transferring a graft to a target site, including a support having a deformed portion on which the graft can be placed, and a deformed portion of the support on which the graft is placed. The device configured to allow the implant to be transferred to a destination site by deforming and lifting at least a portion of the implant from the support.
[2] The device according to [1], wherein the deformed portion is provided on the tip end side of the support.
[3] The device according to [1] or [2], wherein the tip of the deformed portion is arranged inside the tip of the support.
[4] The device according to any one of [1] to [3], wherein the support has a plurality of holes.
[5] The device according to any one of [1] to [4], wherein the support has a plurality of deformed portions.

[6] A method for transferring a graft to a target site, the step of providing a medical device including a support having a deformed portion on which the graft can be placed, a step of providing the graft to the support. The method comprising a step of placing the implant, a step of deforming a deformed portion of the support on which the implant is placed, and a step of lifting at least a portion of the implant from the support and transferring it to a target site.
[7] The method according to [6], wherein the step of placing the graft comprises extending the tip of the graft from the tip of the deformed portion and placing the graft.
[8] Delivery of the support to the target site is performed by inserting a support in which the graft is placed in a tubular body inserted transperitoneally into the body cavity, [6] or [7]. The method described in.
[9] The method according to any one of [6] to [8] for transperitoneally inserting a graft into a body cavity and attaching it to a target site.

According to the present invention, the graft can be easily detached from the support and transferred to the target site. In addition, the graft can be fixed to the target site while maintaining the shape of the graft without causing damage or wrinkles. In addition, the tip of the graft can be held without contacting anything. Then, the surface shape of the support can be freely deformed according to the shape of the target portion.

FIG. 1 is a conceptual diagram of one aspect of the device of the present invention. FIG. 2 is a conceptual diagram of an aspect in which a graft is transferred to a target site using the device of the present invention.

In the present invention, the "graft" means a structure for transplanting into a living body, and particularly means a structure for transplantation containing living cells as a constituent component. Preferably, the graft is a structure for transplantation that does not contain a living cell and a structure other than a substance derived from the living cell (for example, scaffold, etc.). Examples of the transplant piece of the present invention include, but are not limited to, sheet-like cell cultures, spheroids, cell aggregates and the like, preferably sheet-like cell cultures or spheroids, and more preferably sheet-like cells. It is a culture.

In the present invention, the "sheet-like cell culture" refers to cells connected to each other to form a sheet. The cells may be linked to each other directly (including those via cell elements such as adhesion molecules) and / or via intervening substances. The intervening substance is not particularly limited as long as it is a substance capable of at least physically (mechanically) connecting cells to each other, and examples thereof include an extracellular matrix. The mediators are preferably derived from cells, particularly those derived from the cells that make up the cell culture. The cells are at least physically (mechanically) linked, but may be more functionally, for example, chemically or electrically linked. The sheet-like cell culture may be composed of one cell layer (single layer) or two or more cell layers (laminated (multilayer) body, for example, two layers, three layers, etc. It may be 4 layers, 5 layers, 6 layers, etc.). Further, the sheet-shaped cell culture may have a three-dimensional structure having a thickness exceeding the thickness of one cell without showing a clear layered structure of the cells. For example, in a vertical cross section of a sheet-like cell culture, cells may be present in a non-uniformly (for example, mosaic-like) arrangement without being uniformly aligned in the horizontal direction.

Sheet cell cultures are preferably free of scaffolds (supports). Scaffolds may be used in the art to attach cells to and / or inside the surface and maintain the physical integrity of sheet cell cultures, eg, polyvinylidene difluoride. Although membranes made of PVDF) and the like are known, the sheet-shaped cell culture of the present invention can maintain its physical integrity even in the absence of such scaffolds. In addition, the sheet-shaped cell culture of the present invention preferably comprises only cell-derived substances constituting the sheet-shaped cell culture, and does not contain any other substances.

The cells constituting the sheet-shaped cell culture are not particularly limited as long as they can form the sheet-shaped cell culture, and include, for example, adherent cells (adherent cells). Adhesive cells include, for example, adherent somatic cells (eg, myocardial cells, fibroblasts, epithelial cells, endothelial cells, hepatocytes, pancreatic cells, renal cells, adrenal cells, root membrane cells, gingival cells, bone membrane cells, skin. Cells, synovial cells, cartilage cells, etc.) and stem cells (eg, myoblasts, tissue stem cells such as heart stem cells, embryonic stem cells, pluripotent stem cells such as iPS (induced pluripotent stem) cells, mesenchymal stem cells, etc.) And so on. Somatic cells may be stem cells, particularly those differentiated from iPS cells (iPS cell-derived adherent cells). Non-limiting examples of cells constituting the sheet-like cell culture include, for example, myoblasts (eg, skeletal myoblasts, etc.), mesenchymal stem cells (eg, bone marrow, adipose tissue, peripheral blood, skin, hair roots, etc.). Muscle tissue, endometrial membrane, placenta, umbilical cord blood, etc.), myocardial cells, fibroblasts, heart stem cells, embryonic stem cells, iPS cells, synovial cells, chondrocytes, epithelial cells (eg, oral mucosal epithelial cells) , Retinal pigment epithelial cells, nasal mucosal epithelial cells, etc.), endothelial cells (eg, vascular endothelial cells, etc.), hepatocytes (eg, hepatic parenchymal cells, etc.), pancreatic cells (eg, pancreatic islet cells, etc.), renal cells, adrenal cells , Root membrane cells, gingival cells, bone membrane cells, skin cells and the like. Non-limiting examples of iPS cell-derived adherent cells include iPS cell-derived myocardial cells, fibroblasts, epithelial cells, endothelial cells, hepatocytes, pancreatic cells, renal cells, adrenal cells, root membrane cells, gingival cells, and bone membrane cells. , Skin cells, synovial cells, cartilage cells and the like.

In the present invention, the "support" refers to a structure having a surface capable of supporting the implant piece while maintaining its shape. The support is provided with a deformed portion, and by deforming the deformed portion, the implant piece placed on the support can be peeled off. The deformed portion is provided on the tip end side of the support, deforms in the direction perpendicular to the support surface of the support, and the tip portion of the implant placed on the support is oriented in the direction perpendicular to the support surface. Can be lifted. The deforming portion (deformation mechanism) can be realized by using, for example, an expanding balloon-type mechanism, a rotating hinge-type mechanism, a hydraulic mechanism that moves up and down, and the like.
In one embodiment, the support has flexibility and moderate flexibility, can be curved while supporting the graft, and can be stored along the inside of the tubular body or the like, and is exposed from the tubular body. Then, it can be expanded in a plane due to its resilience. The material of the support is not particularly limited, and various known materials can be used alone or in combination of two or more. Examples of such materials include metals, soft vinyl chloride resins, polyurethane resins, silicone rubbers, natural rubbers, synthetic rubbers, styrene-ethylene-butylene-styrene copolymers (SEBS), and styrene-ethylene-propylene-styrene. Polymer (SEPS), ethylene vinyl acetate copolymer (EVA), polyamide resin and polyamide elastomer such as nylon, polyester resin and polyester elastomer such as polyethylene terephthalate (PET), olefin resin such as polyethylene, fluororubber, fluororesin Etc., and one or more of these can be used in combination.

In the present invention, the "plurality of holes" means two or more through holes provided in the support, and the fluid is sent from the surface opposite to the surface supporting the implant of the support, and the fluid is passed through the holes. By discharging, the graft can be peeled off from the support surface and attached. It suffices if the hole can discharge the fluid, and at least one hole may be provided in the support.

The plurality of holes are preferably arranged discretely on the surface of the support that supports the implant so that the detachment position and the holding position of the implant can be adjusted. For example, by providing at least one of the plurality of holes in the vicinity of the edge of the support, the graft can be configured so that the graft can be peeled off from the vicinity of the edge. The arrangement of the plurality of holes can be a matrix arrangement of rows × columns such as 2 × 2 to 40 × 40, 5 × 5 to 20 × 20, and the distance between the holes is, for example, 0.05 mm or more. It can be 10 mm, 0.5 mm to 2 mm, and the diameter of the hole can be, for example, 0.05 mm to 10 mm, 0.3 to 0.6 mm, but is not limited to these, and any person skilled in the art can use it. For example, it can be freely selected according to the size of the implant, the degree of adhesion between the implant and the support, and the like. By making the structure of the support a mesh structure, it is also possible to achieve a matrix arrangement of a plurality of holes.

In the present invention, "fluid" is a general term for gas and liquid that can be extruded and exfoliated without damaging the implant. The liquid is composed of at least one kind of component, and the component thereof is not particularly limited, and is composed of, for example, a liquid such as water, an aqueous solution, a non-aqueous solution, a suspension, and a milky lotion. The components constituting the liquid are not particularly limited as long as they have little effect on the implant. When the graft is a membrane made of biogenic material, the components that make up the liquid are biocompatible, that is, they cause unwanted effects such as inflammatory, immune, and toxic reactions on living tissues and cells. It is preferable that there is no such effect, or at least the effect is small.

In the present invention, the "target site" means a portion to which the graft is applied (attached). Examples of the target site include, in a luminal organ, a site where an injury (wound) is present, and the opposite side of the luminal wall corresponding to the site where the injury is present. "Luminous organ" means an organ having a lumen contained in a body cavity, that is, an organ having a tubular or sac-like structure, for example, gastrointestinal system, circulatory system, urinary tract system, respiratory system, etc. Examples include female reproductive organs. It is typically an organ of the gastrointestinal system. Further, the "luminal wall" means an organ wall constituting a tube or a bag of a luminal organ. The lumen wall has an inner portion facing the lumen and an outer portion forming the outer surface of the organ, and "one side of the lumen wall" means either inside or outside the lumen wall. The outside to the inside or the inside to the outside is called the "opposite side". Further, the area located on the opposite side of the lumen wall with respect to a certain area on one side is referred to as "corresponding opposite side".
In some embodiments, in luminal tissue with damage on at least one side of the luminal wall, transplantation of a sheet-like cell culture on the opposite side corresponding to the site of the damage may promote tissue healing. can. In particular, even injuries formed by treatments such as ESD are effective, so that it is possible to prevent complications after these treatments and improve the prognosis.

Hereinafter, the apparatus according to the preferred embodiment of the present invention will be described in detail with reference to the drawings.
As shown in FIGS. 1 and 2, the device 1 according to the first embodiment of the present invention includes a support 2 on which the graft S can be placed. The support 2 is provided with a deformed portion 4 on the side on which the implant piece S is placed, and the deformed portion 4 is arranged on the distal end side of the support 2. In one embodiment, the tip portion of the deformed portion 4 may be arranged so as to be inside the tip portion of the support 2 (FIG. 1A). The deforming portion 4 may be deformed in a direction perpendicular to the support surface of the support 2 (FIG. 1B), and the tip end side of the graft S mounted on the support 2 may be lifted in a direction perpendicular to the support surface. can. The mounting surface of the deformed portion 4 can be designed to have a certain angle with respect to the other mounting surface of the support 2 after the deformation.

In one embodiment, the support 2 (and the deformed portion 4) is a plate-shaped body having flexibility and appropriate flexibility, is curved while supporting the implant piece S, and is inserted into the tubular body 5 or the like ( Can be stored). A part of the contour of the support 2 (for example, the tip portion) is molded so as to have a convex shape (for example, a circular shape), and the top portion of the convex shape portion is pressed against the opening of the tubular body 5. By doing so, it can be curved (rolled) so that the support 2 can be easily pushed into the tubular body 5 or the like. When the support 2 (and the deformed portion 4) is rolled, the deformed portion 4 is placed in a compact state before the deformation, that is, the mounting surface of the deformed portion 4 is horizontal to the other mounting surfaces of the support 2. By keeping it, it is possible to easily push it into the tubular body 5 or the like.

In one aspect, the support 2 can also be configured to expand in a planar manner due to its resilience when extruded (or pulled out) from the tubular body 5. For example, by using a port that is transperitoneally inserted into the body cavity used in endoscopic surgery as the tubular body 5, when the support 2 is pushed out from the port and brought close to the target site A. , Can also be configured to automatically unfold in a plane. The support 2 that supports the graft S is rolled so that the graft S is on the inside, and the peripheral portion thereof is gripped by a forceps 6 or the like, and the support 2 is inserted from outside the body into the opening of the tubular body 5. It is also possible to appropriately transfer the graft S to the target site A without damaging it.

As shown in FIG. 2, when the device 1 of the present invention is used, the graft S is placed on the support 2 across the deformed portion 4. That is, the distal end side of the graft S is placed on the deformed portion 4 of the support 2, and the other portion of the graft S is placed on the other portion of the support 2. Then, the support 2 that supports the graft S is positioned close to the target site A, and the deformed portion 4 is deformed so that the tip end side of the graft S can be lifted from the support 2. Then, after lifting the tip of the graft S and pressing it against the target site A to fix (paste) it, the support 2 is moved (for example, lateral slide) to pull the graft S while pulling the graft S. The other portion can be peeled off from the support 2. That is, by peeling the graft piece S while pulling it, the graft piece S can be fixed to the target site A in a stretched state, so that the graft piece S is less likely to wrinkle.

Further, when the graft S is placed, the tip of the graft S is extended from the tip of the deformed portion 4 and placed, so that at least the tip of the graft S is supported anywhere (supported) after the deformation. It is also possible to maintain the peeled state without contacting the body 2 or the deformed portion 4. As a result, the extended tip of the graft S is grasped and pulled by another forceps (not shown) or the like, fixed (attached) to the target site A, and the support 2 is moved to move the graft S. It is also possible to peel off the other part of the graft S from the support 2 while pulling. When the support 2 has a plurality of holes 3 (not shown), the separation of the implant S from the support 2 as described above is performed by discharging the fluid from some of the holes of the plurality of holes 3. It can be done more reliably.

When the transplant piece S is transplanted to a target site A such as an organ by using the device 1 of the present invention, the support 2 supporting the transplant piece S is delivered directly into the abdominal cavity (inside the body cavity), or , The transplant piece S can be delivered transperitoneally into the body cavity via a hollow port (cylindrical body 5) penetrated into the abdominal wall used in endoscopic surgery or the like. When the graft S is delivered transperitoneally, the graft S and the support 2 are inserted into a hollow port (cylindrical body 5) and delivered into the body cavity. At this time, by rolling the support 2 as described above, the implant piece S can be delivered after further preventing the possibility of damage.

The movement of the support 2 in the port can be performed by grasping the support 2 with forceps 6 or the like and moving the forceps 6 back and forth. Then, by extending the support 2 from the tip of the hollow port, the support 2 can be positioned with respect to the target portion A. Positioning of the support 2 to the target site A may be performed using another forceps (not shown) inserted into the abdominal cavity. After positioning the support 2, the deformed portion 4 is deformed to peel off the implant piece S, and the implant piece S is attached (implanted) to the target site A. To attach the graft S to the target site A, either bring the support 2 (deformed portion 4) into contact with the target site A, or use another forceps (not shown) for the peeled portion of the graft S. It can be realized by grasping with and contacting the target portion A.

The device 1 may include at least a support 2 having a deformed portion 4 on which the graft S can be placed. The deformed portion 4 can also be used as a pressing portion for pressing a target site (affected portion) such as an organ to stop bleeding by deforming the deformed portion 4. Further, as described above, the device 1 may further include forceps 6, another forceps (not shown), a tubular body 5, and the like. The support 2 (deformed portion 4) may have a plurality of holes 3. After fixing the graft S to the target site A, the support 2 can also be recovered using a laparoscopic surgical excision bag (INZII®, etc.).

In the present embodiment, the deformed portion 4 has been described as being arranged on the tip end side of the support 2, but the deformed portion 4 may be freely arranged on the proximal end side, the center, the right side, the left side, etc. of the support 2. good. That is, it is preferable that the shape of the support surface of the support 2 is deformable according to the surface shape of the target portion A and the like. For example, when the deformed portion 4 is provided on the proximal end side of the support 2, the proximal end portion of the graft S can be fixed to the target portion A and then peeled off by sliding the support 2 toward the distal end. .. Similarly, when the deformed portion 4 is provided on the right side and the left side of the support 2, it is slid to the right and left.

Further, for example, when the deformed portion 4 is provided in the center of the support 2, the central portion of the graft S can be lifted to form a convex shape, and the deformed portion 4 can be appropriately attached to the concave target portion A or the like. In this way, the deformed portion 4 is located on the tip end side, the base end side, the center, the right side, the left side, etc. of the support 2 so that the shape of the support surface of the support 2 can be deformed according to the surface shape of the target portion A. A plurality of them may be provided and each may be deformed separately. Therefore, the support 2 of the present invention also includes the support 2 provided with the plurality of deformed portions 4. For the portion of the implant piece S that cannot be peeled off even if the deformed portion 4 is deformed, another deformed portion 4 corresponding to such a portion may be deformed, or fluid may be discharged from a plurality of holes 3 to be peeled off. You may.

The device 1 of the present invention can be used in sequence by, for example, the following steps.
(1) The support 2 on which the graft S is placed is brought close to the target site A.
(2) The deformed portion 4 is deformed and a part of the transplant piece S is lifted from the support 2.
(3) A part of the lifted graft S is fixed to the target site A.
(4) The support 2 is moved to peel off the other portion and fixed to the target portion A.
At least a part of the graft S is pressed against the target site A to be firmly fixed, and by using it as an anchor, the other part can be easily peeled off.

The support 2 on which the graft S is placed may be brought close to the target site A in a spatially separated state. At this time, the support 2 can be floated in the air so as not to come into contact with the target portion A. Thereby, even after the graft S is peeled off from the support 2, the state in which the graft S does not come into contact with the target site A can be maintained until the graft S is attached to the target site A. The detachment of the graft S and the attachment to the target site A may occur separately or at the same time.

Further, after the implant piece S is attached, a step of injecting a fluid from the attached implant piece S may be added. As a result, the graft S can be more reliably adhered to the target site A. Also at this time, the graft S can be adhered to the target site A in a state where the support 2 does not come into contact with the target site A. Further, by injecting a gel and / or a polymer as a fluid, a reinforcing layer for reinforcing the sheet-like material may be formed.

As described above, according to the device 1 according to the first embodiment of the present invention, the graft can be easily peeled off from the support and transferred to the target site. In addition, the graft can be fixed to the target site while maintaining the shape of the graft without causing damage or wrinkles. In addition, the tip of the graft can be held without contacting anything. Then, the surface shape of the support can be freely deformed according to the shape of the target portion.
Although the present invention has been described in the illustrated embodiment, the present invention is not limited thereto. In the present invention, each configuration can be replaced with any configuration capable of exhibiting the same function, or any configuration can be added.

1 Equipment 2 Support 3 Multiple holes 4 Deformation part 5 Cylindrical body 6 Forceps S Graft A Target site

Claims (9)

A medical device for transferring a graft to a target site, including a support having a deformed portion on which the graft can be placed, and deforming the deformed portion of the support on which the graft is placed. The device configured to allow the implant to be transferred to a destination site by lifting at least a portion of the implant from the support. The device according to claim 1, wherein the deformed portion is provided on the tip end side of the support. The device according to claim 1 or 2, wherein the tip of the deformed portion is arranged inside the tip of the support. The device according to any one of claims 1 to 3, wherein the support has a plurality of holes. The device according to any one of claims 1 to 4, wherein the support has a plurality of deformed portions. A method for transferring a graft to a target site,
A step of providing a medical device, including a support with a variant on which the implant can be placed,
Steps to place the graft on the support,
The method comprising the step of deforming the deformed portion of the support on which the implant is placed, and the step of lifting at least a part of the implant from the support and transferring it to a target site. The method of claim 6, wherein the mounting step comprises placing the tip of the implant extending from the tip of the deformed portion. The method according to claim 6 or 7, wherein delivery of the support to the target site is performed by inserting a support in which a graft is placed in a tubular body inserted transperitoneally into a body cavity. The method according to any one of claims 6 to 8, wherein the implant is transperitoneally inserted into a body cavity and attached to a target site.

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