JP2022055089A - Medical device capable of storing plural implant pieces - Google Patents

Abstract

To provide a medical device capable of easily delivering a plurality of implant pieces to a target site.SOLUTION: A medical device for delivering an implant piece to a target site includes a delivery mechanism capable of storing two or more supports 3a to 3d longitudinally on which implant pieces S1 to S4 are placed, and delivering the supports 3a to 3d continuously in order from a tip end side. The plurality of implant pieces S1 to S4 can be continuously delivered to the target site in a series of operations, so that an operation is simple, and a risk of damaging the implant pieces can be reduced. The total time for implanting is also reduced, so that a burden on a target subjected to the implanting can be reduced.SELECTED DRAWING: Figure 1

Description

The present invention relates to a medical device capable of storing a plurality of implant pieces.

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. In addition, Non-Patent Document 3 describes that a skeletal myoblast sheet can be used for the treatment of gastric perforation model animals.

Regarding the method of 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 for delivering and administering the sheet-shaped cell culture to the target site. Various instruments have been proposed.
For example, the sheet-like material affixing device described in Patent Document 1 includes a support for supporting the sheet-like material and a striatum locked to the support, and the sheet-like material is gradually peeled off. By doing so, it is possible to efficiently attach the sheet to the target portion while maintaining the shape of the sheet-like object.
In the transplantation device described in Patent Document 2, the medical sheet can be transferred to a desired position by adsorbing the medical sheet to the holding surface by suction of a syringe, and the head of the device is for medical use. By being shared for both adsorption of the sheet and discharge of the fibrin solution, the medical sheet can be attached and the fibrin solution can be sprayed on the medical sheet in the same position by the same instrument.
The cell culture transfer device described in Patent Document 3 desires a sheet-shaped cell culture by adsorbing the sheet-shaped cell culture to the holding portion of the device by utilizing the ability of the absorber to absorb water. Can be transferred to the position of.

International Publication No. 2020/138261 Japanese Unexamined Patent Publication No. 2010-82026 Japanese Unexamined Patent Publication No. 2012-10630

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, the present inventor often administers in multiple divided doses in order to apply cell cultures such as sheet-like cell cultures and grafts in clinical application, and at that time, one graft at a time. Repeated delivery to the target site of application has faced the problem that the work becomes complicated and there is a risk of damage to the graft. Therefore, an object of the present invention is to solve such a problem and to provide a medical device capable of easily delivering a plurality of implants to a target site.

The present inventor uses a medical device including a delivery mechanism capable of storing a plurality of grafts and continuously delivering them in order from the tip side while conducting intensive research to solve the above problems. As a result, it was found that the graft can be easily and continuously delivered to the target site, and further research was continued based on such findings, and as a result, the present invention was completed.

That is, the present invention relates to the following.
[1] A medical device for delivering a graft to a target site.
A delivery mechanism capable of vertically storing two or more supports for placing a graft and continuously delivering the supports in order from the distal end side is included.
The medical device.
[2] The medical device according to [1], wherein the delivery mechanism is configured to engage detachably with the support.
[3] The medical device according to [1] or [2], wherein the delivery mechanism is configured so that the support can be slid toward the tip side.
[4] The medical device according to any one of [1] to [3], wherein the implant is placed on at least the surface of the support facing the tip end side of the medical device.
[5] The medical device according to any one of [1] to [4], wherein the support has a plurality of holes.

[6] A method for delivering a graft to a target site, and the following:
The graft can be continuously delivered to the target site, including a delivery mechanism capable of vertically storing two or more supports for placing the graft and delivering the support in order from the distal end side. Steps to provide medical equipment for delivery to,
A step of placing a graft on a support and bringing the tip of the medical device closer to the target site,
The step of delivering the support to the target site in order from the most distal support,
The method described above.
[7] The delivery mechanism is configured to be detachably engaged with the support, and delivery to the target site is performed by disengaging the delivery mechanism and the support and opening the support. The method according to [6], which is performed.
[8] The method according to [6] or [7], wherein the delivery mechanism is configured so that the support can be slid toward the tip side, further comprising a step of sliding the support toward the tip side.
[9] Delivery to the target site is performed by inserting a medical device including a support on which a graft is placed into a tubular body inserted transperitoneally into a body cavity [6] to [ 8] The method according to any one of.
[10] The method according to any one of [6] to [9] for transperitoneally inserting a graft into a body cavity and attaching it to a target site.

According to the present invention, a plurality of implant pieces can be continuously delivered to a target site by a series of actions. As a result, delivering one graft to the target site using a conventional device is easier to operate than repeating the required number of times, and the risk of damaging the graft is reduced. In addition, the total time required to deliver the required number of grafts to the target site is also reduced, so that the burden on the subject when transplanting the grafts to the target site can be reduced.

FIG. 1 is a perspective view of a medical device according to the first embodiment of the present invention. FIG. 2 is a conceptual diagram of a medical device according to the first embodiment of the present invention.

Hereinafter, the present invention will be described in detail.
The present invention includes, on one side, a delivery mechanism capable of vertically storing two or more supports for placing a graft and continuously delivering the supports in order from the distal end side. It relates to a medical device for delivering a graft to a target site.

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 without such a scaffold. 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" means a plate-like body having a flat surface capable of supporting the implant piece while maintaining its shape. The size of the support is not particularly limited as long as the implant can be placed on the plane thereof, but is, for example, in the range of 1 to 5 cm in diameter, preferably in the range of 2 to 3 cm in diameter. 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 implant may be placed on only one side of the support, or may be placed on both sides of the support.

In the present invention, the "delivery mechanism" means that two or more supports can be vertically stored in the mechanism with the graft placed on the support, and the support on which the graft is placed can be stored from the tip side thereof. In order, it refers to a mechanism for continuously delivering. In the present invention, the proximal end side refers to the operator side of the medical device, and the distal end side refers to the target site side to which the graft is delivered.
In one aspect, the delivery mechanism is configured to engage detachably with the retracted support, thereby accommodating the supports vertically side by side. By disengaging the support near the target site and releasing it from the delivery mechanism, the implant placed on the support can be delivered to the target site. In the present invention, the term "vertically stored" means that the support or the support on which the implant is placed is lined up one by one from the distal end side to the proximal end side of the delivery mechanism. The retracted support may be oriented in any direction, but it is preferable that the surface on which the support implant is placed is aligned with the opening of the delivery mechanism. It is more preferable that the surface on which the graft of the support is placed faces the tip side and is arranged horizontally.

In one embodiment, the delivery mechanism comprises one or more elongated bodies. In such an embodiment, the elongated bodies are arranged in parallel from the proximal end side to the distal end side, and the support is engaged with at least one elongated body and is stored in the vertical direction. Further, in such an embodiment, the vertical direction means a direction along a long axis of a long body. In this case, the support on which the graft is placed can be arranged so as to have an angle with respect to the long axis of the elongated body. Here, the angle of the support with respect to the long body can be, for example, 45 ° to 135 °. Further, the two or more supports are engaged with the elongated body at intervals so that the supports do not come into contact with each other. It is preferable that 3 or more elongated bodies are included in order for the engaged support to be stable in the medical device. In another aspect, the delivery mechanism may be tubular. In such an embodiment, for example, the delivery mechanism may have one or more grooves extending from the proximal end side to the distal end side inside the tubular shape, in which the delivery mechanism and the support may be engaged.

In one aspect, the support of the present invention has a plurality of holes. 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 graft support surface of the support so that the graft detachment position 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 a luminal tissue that has damage on at least one side of the luminal wall, the graft can be implanted on the opposite side corresponding to the site of the damage to promote tissue healing. 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.

In another aspect, the implant comprises a delivery mechanism capable of vertically accommodating two or more supports on which the implant is placed and delivering the support in order from the distal end side. A step of providing a medical device for continuously delivering to a target site, a step of placing a graft on a support and bringing the tip side of the medical device closer to the target site, a support on the most tip side. The present invention relates to a method for delivering a graft to a target site, comprising the step of delivering the support to the target site in order from.
In one aspect of the method described in the invention, delivery to the site of interest is performed by disengagement of the delivery mechanism and the support. In one aspect of the method described in the present invention, the method for delivering the implant to the site of interest may further include the step of sliding the support towards the tip. In such an embodiment, the step of sliding the support to the distal end side disengages the support on which one implant is placed, disengages the support from the delivery mechanism, and then places the next implant. The support may be arranged so as to be located on the most distal side of the delivery mechanism.

<First Embodiment>
Hereinafter, the medical device 1 according to a preferred embodiment of the present invention will be described. FIG. 1 is a perspective view of the medical device 1 according to the first embodiment of the present invention. FIG. 2 is a conceptual diagram of the medical device 1 according to the first embodiment of the present invention. In addition, in each figure in this disclosure, the size of each member is emphasized as appropriate for easy explanation, and each member in the figure does not show an actual size.
As shown in FIGS. 1 and 2, the medical device 1 includes a delivery mechanism 2 and a support 3. The delivery mechanism 2 includes one or more elongated bodies 4, which are detachably engaged with the support 3 in which the graft S is placed. Engagement is performed by the elongated body 4 having a groove and the end portion of the support 3 being fitted into the groove. In this case, the engagement can be disengaged by shifting either the support 3 or the elongated body 4. For example, when two or more elongated bodies 4 are included, one of them is configured to be removable from the support 3, and by removing the elongated body 4, the delivery mechanism 2 and the support 3 are included. Can be disengaged.

When using the medical device 1 of the present invention, first, the support 3 on which the graft S is placed is engaged with the delivery mechanism 2. That is, the support 3 is arranged so that the end portion of the support 3 fits into the groove existing in the long body 4 of the delivery mechanism 2. When the support 3a is placed in the groove on the most distal end side of the elongated body 4, the support 3b is then placed in the next groove. The support 3 is engaged with the delivery mechanism 2 by the number of the number of grafts S required for transplantation to the target site. Subsequently, the tip end side of the medical device 1 is brought close to the target site. In the vicinity of the target site, the elongated body 4 or the support 3a is moved and displaced from the groove to disengage the engagement, and the support 3a is released from the delivery mechanism 2. Here, the opened support 3a may be delivered to the target site by forceps or the like (not shown) prepared separately.
In one embodiment, the elongated body 4 is configured to be removable in multiple stages in front of each groove, and the elongated body 4 is removed after the support 3a is opened and then before the support 3b is released. The tip end side may be removed in front of the support 3b. The removal of the tip end side of the long body 4 may be performed by folding the tip end side of the long body 4 in front of the groove. When the delivery mechanism 2 is moved to the distal end side in the medical device 1 by the amount of the folding of the elongated body 4, the support 3b is located at the most distal end side of the delivery mechanism 2, and the support 3b is more targeted. It can be brought close to the site. By repeating in this way, the supports 3b, 3c, 3d and, by extension, the grafts S2, S3, S4 placed on those supports can be continuously delivered to the target site.

In one embodiment, the medical device 1 according to the present invention is inserted through a tubular body 5 and used. For example, by using a port that is transperitoneally inserted into the body cavity used in endoscopic surgery as the tubular body 5, the tip side of the medical device 1 is pushed out from the port and brought close to the target site. It can be appropriately delivered to the target site from there without damaging the graft S.
In one embodiment, the support 3 may be configured to have a plurality of holes (not shown). In such an embodiment, when the graft S is peeled from the support 3, the fluid is discharged from a part of a plurality of holes to peel the graft S from the support 3 and to the target site of the graft S. Can also be fixed more reliably. The supply of the fluid to the support 3 may be performed by connecting a device other than the medical device 1 to the support 3 released from the medical device 1.

In one aspect, in the medical device 1 according to the present invention, the support 3 is configured to be slidable on the elongated body 4. For example, the support 3 may be configured to provide a cylindrical engaging portion (not shown) at the end, and the elongated body 4 may be slidably inserted through the engaging portion. It is preferable that the engaging portion is provided with a locking mechanism that can be fixed at an appropriate position on the long body 4.
In such an embodiment, when the medical device 1 is used, the support 3 is arranged in the delivery mechanism 2 by the number of the number of grafts S required for transplantation to the target site in the same manner as described above, and the medical device 1 is used. Bring the tip side of 1 closer to the target site. Next, the distal end side of the medical device 1 is brought into contact with the target site, and the implant piece S1 placed on the support 3a on the most distal end side is pressed against the target site to deliver the medical device 1 to the target site. After delivering the implant S1, the support 3a may be disengaged from the delivery mechanism 2 to open the support 3a. After opening the support 3a, the support 3b on the most distal side of the medical device 1 is then slid toward the distal end side of the delivery mechanism 2, and similarly, the graft S2 on the support 3b is used as the target site. It can be delivered by pressing. By repeating these steps, the graft S can be continuously delivered to the target site one after another.
Delivery of the implant S to the site of interest may be by the release of fluid from the plurality of pores of the support 3. The fluid was released from the medical device 1 only to the most distal support 3 (when the support 3a was the most distal, the support 3a, then the support 3b to the most distal side). In some cases, the support 3b) may be provided with a mechanism capable of discharging the fluid.

The medical device 1 of the present invention can be used sequentially by, for example, the following steps.
(1) The implant piece S is placed on the support 3, and the tip end side of the medical device 1 is brought close to the target site.
(2) The support 3 is delivered to the target site in order from the support 3a on the most distal end side.
Further, the delivery to the target site may be performed by disengaging the delivery mechanism 2 and the support 3 and releasing the support 3 from the delivery mechanism 2. At this time, the delivery of the graft S to the target site may be due to the release of the fluid from the plurality of pores of the support 3.
The sequential delivery to the target site may be performed by sliding the support 3 one after another toward the tip end side of the delivery mechanism 2. In this case, the graft S may be delivered to the target site by bringing the tip end side of the medical device 1 into contact with the target site and pressing the graft piece S against the target site. Further, the support 3 that has finished delivering the graft S may be disengaged and released on the distal end side of the delivery mechanism 2.

As described above, according to the medical device 1 according to the first embodiment of the present invention, a plurality of implant pieces can be continuously delivered to a target site by a series of operations. As a result, delivering one graft to the target site using a conventional device is easier to operate than repeating the required number of times, and the risk of damaging the graft is reduced. In addition, the total time required to deliver the required number of grafts to the target site is also reduced, so that the burden on the subject when transplanting the grafts to the target site can be reduced.
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 Medical device 2 Delivery unit 3, 3a, 3b, 3c, 3d Support 4 Long body 5 Cylindrical body S, S1, S2, S3, S4 Graft

Claims (10)

A medical device for delivering a graft to a target site.
A delivery mechanism capable of vertically storing two or more supports for placing a graft and continuously delivering the supports in order from the distal end side is included.
The medical device. The medical device of claim 1, wherein the delivery mechanism is configured to engage detachably with the support. The medical device of claim 1 or 2, wherein the delivery mechanism is configured to be slidable towards the tip of the support. The medical device according to any one of claims 1 to 3, wherein the implant can be placed on the support at least on the surface facing the tip end side of the medical device. The medical device according to any one of claims 1 to 4, wherein the support has a plurality of holes. A method for delivering a graft to a target site, such as:
The graft can be continuously delivered to the target site, including a delivery mechanism capable of vertically storing two or more supports for placing the graft and delivering the support in order from the distal end side. Steps to provide medical equipment for delivery to,
A step of placing a graft on a support and bringing the tip of the medical device closer to the target site,
The step of delivering the support to the target site in order from the most distal support,
The method described above. The delivery mechanism is configured to engage detachably with the support, and delivery to the destination site is performed by disengaging the delivery mechanism from the support and releasing the support. The method according to claim 6. The method of claim 6 or 7, wherein the delivery mechanism is configured to be slidable towards the tip, further comprising a step of sliding the support towards the tip. One of claims 6-8, wherein delivery to the target site is performed by inserting a medical device including a support on which a graft is placed into a tubular body inserted transperitoneally into a body cavity. The method described in paragraph 1. The method according to any one of claims 6 to 9, wherein the implant is transperitoneally inserted into a body cavity and attached to a target site.

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