JP2021049071A - Fistula treatment device - Google Patents

Abstract

To provide a fistula treatment device for carrying to a predetermined position and supplying a cellular structure to close a fistula such as a bronchial stump fistula.SOLUTION: A fistula treatment device 1 includes an exterior part 2 having a substantially columnar through-hole, a bottomless cylindrical body 3 inserted and fitted in a through-hole 21 of the exterior part 2, and an extruding member 4 capable of freely sliding the inside of the cylindrical body 3 in an axial direction. The cylindrical body 3 has one end side protruding to the outside of the exterior part 2, and is capable of holding a solidified cellular structure 5 inside the other end side. When the extruding member 4 held in the cylindrical body 3 is extruded from the one end side toward the other end side, the cellular structure 5 held inside the other end side is pushed outside and can be detached from the cylindrical body 3.SELECTED DRAWING: Figure 1

Description

The present invention relates to a treatment device for a fistula. More specifically, it relates to a therapeutic instrument that can be used to treat a fistula such as a bronchial stump fistula.

Bronchial stump fistulas are a serious complication after pulmonary resection with a frequency of 0.5% after lobectomy and 4.5-20% after total lobectomy, with a mortality rate of 16-70%. Are known.

Treatment methods for bronchial stump fistula are roughly divided into surgical treatment and bronchoscopic treatment. However, surgical treatment is highly invasive, and if inflammation is widespread, more invasive two-stage surgery, including fenestration drainage, is required and requires long-term treatment. On the other hand, bronchoscopic treatments are relatively less burdensome to patients than surgical treatments and do not require general anesthesia, so various treatments have been reported.

For example, as one of the bronchoscopic treatment methods, a method of temporarily placing a silicone filler called EWS (Endobronchial Watanabe Spigot) on the bronchial stump to promote fistula closure has been proposed (Non-Patent Documents). 1).

Further, as another method, for example, a method of isolating autologous adipose stem cells and injecting them into the bronchial stump under a bronchoscope to promote fistula closure has been proposed (Non-Patent Documents 2 and 3).

Bronchial studies JJSB 23 (6): 510-515, 2001 Thorax 2008; 63: 374-376 Cytotherapy, 2016; 18: 36-40 Sayako Morikawa et al. Ther Adv Respir Dis 2016, Vol. 10 (6): 518-524

However, the method of Non-Patent Document 1 has problems such as low closure rate and occurrence of complications. Specifically, the fistula closure rate by EWS is said to be 83%, but this includes cases in which some kind of therapeutic intervention such as pleurodesis was performed before EWS was performed, and the actual EWS alone. The success rate in Japan is estimated to be about 33%. Although it is considered to be a relatively minimally invasive local treatment that does not require general anesthesia, serious complications such as myocardial infarction, arrhythmia, and obstructive pneumonia have also been reported (Non-Patent Document 4). In addition, EWS itself is a non-biomaterial, and mechanical stimuli due to its low biocompatibility may cause the above complications. On the other hand, since the methods of Non-Patent Documents 2 and 3 are in the form of injecting a liquid, there is a possibility of leakage into the thoracic cavity from the target bronchial stump. As described above, the treatment results of all the methods are not good, and the development of a new treatment method for effectively treating the bronchial stump fistula has been desired.

In such a situation, the present inventors have conducted diligent research, and if the cell structure solidified by fusing spheroids can be supplied to the bronchial stump, the closure of the fistula is promoted and the bronchial stump is promoted. I got a new idea that the fistula could be treated effectively.

However, in this case, since the cell structure cannot be directly held by a bronchoscope or the like, it is considered necessary to develop a new device for reliably transporting and supplying the cell structure to a predetermined position. ..

The present invention has been made in view of the above circumstances, and provides a fistula treatment device for transporting and supplying a cell structure for closing a fistula such as a bronchial stump fistula to a predetermined position. That is the issue.

In order to solve the above problems, the fistula treatment device of the present invention is a fistula treatment device for transporting and supplying a cell structure for closing a fistula to a predetermined position.
An exterior part with a substantially columnar through hole and
A bottomless cylindrical cylinder inserted into the through hole of the exterior portion, and
An extruded member that can slide inside the cylinder in the axial direction,
With
The cylindrical body has one end side protruding to the outside of the exterior portion and can hold a solidified cell structure inside the other end side.
When the extrusion member is slid from the one end side of the cylinder toward the other end side, the cell structure held inside the other end side is pushed out and can be detached from the cylinder. It is characterized by being.

In this fistula treatment instrument, the cylindrical body includes a first cylindrical portion and a second cylindrical portion having a diameter larger than that of the first cylindrical portion.
The first cylindrical portion is provided with a protruding portion projecting to the outside of the exterior portion at one end, and the other end is connected to the second cylindrical portion.
It is preferable that the second cylindrical portion is inserted into the through hole and can hold the cell structure inside.

In this fistula treatment instrument, the extrusion member is
A substantially cylindrical body portion inserted into the first cylindrical portion and the second cylindrical portion, and a substantially cylindrical main body portion.
A substantially disk-shaped flange portion provided at one end of the main body portion and exposed to the outside of the first cylindrical portion, and a substantially disk-shaped flange portion.
A substantially disk-shaped extruded portion provided at the other end of the main body portion and located inside the second cylindrical portion, and
With
The outer diameters of the flange portion and the extruded portion are preferably larger than the inner diameter of the first cylindrical portion.

In this fistula treatment instrument, it is preferable that the extruded member includes a handle portion protruding from the vicinity of the center of the flange portion.

The assembly kit of the present invention is an assembly kit for the treatment instrument for a fistula.
An exterior part with a substantially columnar through hole and
A bottomless cylindrical cylinder inserted into the through hole of the exterior portion, and
An extruded member that can slide inside the cylinder in the axial direction,
It is characterized by having.

The treatment device for a fistula of the present invention can reliably carry and supply a cell structure for closing a fistula to a predetermined position, and can effectively treat various diseases associated with a fistula.

It is an internal perspective perspective view which illustrates one Embodiment of the treatment instrument for a fistula of this invention. FIG. 1 is a cross-sectional view taken along the line AA'in FIG. It is a perspective view which showed the exterior part in the treatment instrument for a fistula shown in FIG. It is a perspective view which showed the cylindrical body in the treatment instrument for a fistula shown in FIG. It is a schematic diagram which exemplifies the outline of the assembly process of the fistula treatment instrument shown in FIG. 1 and the process of holding a cell structure. It is a schematic diagram which illustrated the state which carried the fistula treatment instrument of this invention into the fistula of a bronchial stump fistula using the forceps of a bronchoscope. It is a schematic diagram which exemplifies the form which detaches the cell structure from the carried fistula treatment instrument and supplies it to a fistula. It is a schematic diagram which illustrated the state which pulled out the forceps from the carried fistula treatment instrument.

The fistula treatment device of the present invention is a fistula treatment device for transporting and supplying a cell structure for closing a fistula to a predetermined position.

The fistula treatment device of the present invention can be suitably used for closing a fistula generated in various organs such as digestive organs, respiratory organs, and circulatory organs. Specifically, bronchial stump fistula, gastrointestinal cutaneous fistula (inflammatory bowel disease such as Crohn's disease and ulcerative colitis, fistula due to delayed postoperative gastrointestinal suture failure, postoperative biliary fistula, postoperative pancreatic fluid) It can be suitably used for fistula, etc.), hemorrhagic fistula, bladder-vaginal fistula, rectal-vaginal fistula, tracheo-esophageal fistula, etc. It may also be applicable to bronchoscopic lung volume loss therapy (BLVR) for emphysema.

An embodiment of the fistula treatment instrument of the present invention will be described with reference to the drawings. FIG. 1 is an internal perspective perspective view illustrating an embodiment of the fistula treatment instrument of the present invention. FIG. 2 is a cross-sectional view taken along the line AA'in FIG. FIG. 3 is a perspective view showing an exterior portion of the fistula treatment instrument shown in FIG. 4 (A) and 4 (B) are perspective views showing a cylindrical body in the fistula treatment instrument shown in FIG.

The fistula treatment instrument 1 includes an exterior portion 2, a cylindrical body 3, and an extrusion member 4.

The exterior portion 2 has a substantially columnar through hole 21. In this embodiment, the exterior portion 2 has a substantially cylindrical shape having an upper surface portion 23 and a bottom surface portion 24, and the outer diameter decreases from the upper surface portion 23 side to the bottom surface portion 24 side. Further, the through hole 21 penetrates up and down near the center of the upper surface portion 23 and the bottom surface portion 24.

The size of the exterior portion 2 can be appropriately designed, and for example, the outer diameter is 5 mm to 10 mm, and the length (the length from the top surface portion to the bottom surface portion) is in the range of 8 mm to 12 mm. Can be done.

The material of the exterior portion 2 is not particularly limited, but is preferably made of a resin such as silicon. When the exterior portion 2 is made of a resin such as silicon, it is easy to handle and it is possible to suppress adverse effects on the patient in the treatment of the fistula.

The cylindrical body 3 has a cylindrical shape (substantially bottomless cylindrical shape) having no bottom portion, and is inserted into the through hole 21 of the exterior portion 2. Further, in the cylindrical body 3, one end 3A side (upper end side) protrudes to the outside of the exterior portion 2, and the solidified cell structure 5 can be held inside the other end 3B side (lower end side). .. The material of the cylindrical body 3 is not particularly limited and can be appropriately designed, and examples thereof include metals such as stainless steel, titanium alloys, and cobalt alloys.

More specifically, in this embodiment, in the cylindrical body 3, the first cylindrical portion 31 and the second cylindrical portion 32 having a diameter larger than that of the first cylindrical portion 31 are vertically connected to each other.

At one end of the first cylindrical portion 31, a protruding portion 31a projecting to the outside of the exterior portion 2 is formed. Further, the other end of the first cylindrical portion 31 is connected to the second cylindrical portion 32, and the outer periphery between the first cylindrical portion 31 and the second cylindrical portion 32 extends outward in the circumferential direction. An expanding step 33 is formed. Further, the space inside the first cylindrical portion 31 and the space inside the second cylindrical portion 32 communicate with each other.

The second cylindrical portion 32 is entirely inserted into the through hole 21, and the cell structure 5 can be held inside from the open end portion 32a. The inner diameter and outer diameter of the second cylindrical portion 32 are designed to be larger than the inner diameter and outer diameter of the first cylindrical portion 31. Further, the length of the second cylindrical portion 32 is designed to be longer than the length of the first cylindrical portion 31.

The dimensions of the first cylindrical portion 31 and the second cylindrical portion 32 are not particularly limited and can be appropriately designed. For example, the inner diameter of the first cylindrical portion 31 is 2 mm to 6 mm, and the outer diameter is 3 mm to 7 mm. The range can be exemplified. Further, the inner diameter of the second cylindrical portion 32 may be in the range of 3 mm to 7 mm, and the outer diameter may be in the range of 4 mm to 8 mm.

In this embodiment, the extrusion member 4 includes a main body portion 41, a flange portion 42, and an extrusion portion 43.

The main body portion 41 has a vertically long substantially cylindrical shape, and is inserted into the inside of the first cylindrical portion 31 and the second cylindrical portion 32. The main body 41 is designed so that the outer diameter is substantially equal to the inner diameter of the first cylindrical portion 31, and is in contact with the inner peripheral surface of the first cylindrical portion 31. The main body 41 can slide in the axial direction (longitudinal direction) in a state of being in contact with the first cylindrical portion 31, whereby the extrusion member 4 slides in the cylindrical body 3 in the axial direction.

The flange portion 42 is provided at one end (upper end) of the main body portion 41 and is exposed to the outside (upper side) of the first cylindrical portion 31. The flange portion 42 has a substantially disk shape having an outer diameter larger than the inner diameter of the first cylindrical portion 31. In this embodiment, the outer diameter of the flange portion 42 is designed to be substantially equal to the outer diameter of the first cylindrical portion 31. Further, a handle portion 44 protruding from the vicinity of the center is provided on the upper surface of the flange portion 42. The handle 44 is designed to have a shape and size that can be gripped by, for example, forceps of a bronchoscope.

The extruded portion 43 is provided at the other end (lower end) of the main body portion 41 and is located inside the second cylindrical portion 32. The extruded portion 43 has a substantially disk shape having an outer diameter larger than the inner diameter of the first cylindrical portion 31. In this embodiment, the outer diameter of the extruded portion 43 is designed to be one size smaller than the inner diameter of the second cylindrical portion and substantially equal to the outer diameter of the first cylindrical portion 31. The extruded portion 43 can be formed integrally with the main body portion 41 or can be formed as a separate body.

The material of the extruded member 4 is not particularly limited and can be appropriately designed, and examples thereof include metals such as stainless steel, titanium alloys, and cobalt alloys.

Next, the outline of the assembling step of the fistula treatment instrument and the holding step of the cell structure of the present invention will be described. FIG. 5 is a schematic view illustrating the outline of the process of assembling the treatment instrument for fistula shown in FIG. 1 and the process of retaining the cell structure.

As illustrated in FIGS. 5A and 5B, the cell structure 5 is held inside the second cylindrical portion 32 by inserting the cell structure 5 into the open end portion 32a of the second cylindrical portion 32. .. Then, as illustrated in FIG. 5C, the fistula treatment instrument 1 can be obtained by inserting the cylindrical body 3 holding the cell structure 5 from one of the through holes 21 of the exterior portion 2. Due to the elasticity of the exterior portion 2, the through hole 21 of the exterior portion 2 and the periphery of the cylindrical body 3 can be brought into close contact with each other, and the cylindrical body 3 can be stably fixed.

As described above, in the fistula treatment instrument 1 of the present invention, each member can be appropriately assembled by the user. Therefore, as described above, the assembly kit for the fistula treatment instrument 1 of the present invention has an exterior portion 2 having a substantially cylindrical through hole 21 and a bottomless cylinder inserted into the through hole 21 of the exterior portion 2. A cylindrical body 3 having a shape and an extrusion member 4 that is slidable in the axial direction inside the cylindrical body 3 can be included.

Next, a cell structure that can be held and used in the fistula treatment instrument of the present invention will be described.

The cell structure 5 is solidified by fusing spheroids containing mesenchymal stem cells. Mesenchymal Stem Cells (MSCs) are pluripotent cells that can differentiate into various types of cells and have self-renewal ability. Mesenchymal stem cells can be obtained from test animals (for example, experimental animals such as mice, rabbits, rats, guinea pigs, dogs, pigs, goats, and cows) or human bone marrow by the Dexter method, magnetic bead method, cell sorting method, etc. It can be collected by the known method of. Furthermore, it is also possible to collect mesenchymal stem cells from skin, subcutaneous fat, muscle tissue and the like.

Examples of mesenchymal stem cells include human bone marrow-derived mesenchymal stem cells, human umbilical cord matrix-derived mesenchymal stem cells, and human adipose tissue-derived mesenchymal stem cells. In addition, mesenchymal stem cells are preferably autologous cells of patients who require treatment for bronchial stump fistula.

"Spheroid" refers to a spherical cell aggregate in which cells are aggregated and aggregated.

The spheroid can include various cells other than mesenchymal stem cells, and the type and the like are not particularly limited. Specifically, as the cells constituting the spheroid, for example, one or more types of cells such as fibroblasts, vascular endothelial cells, chondrocytes, and iPS cells can be exemplified, but fibroblasts can be used. It preferably contains cells or vascular endothelial cells. In this case, the proportion of mesenchymal stem cells contained in the spheroid is more preferably 50% or more. In addition, the various cells constituting the spheroid are preferably autologous cells of the patient who needs treatment of the fistula.

The method for producing the spheroid is not particularly limited, and a conventionally known method can be adopted. For example, when cells are cultured on a Teflon®-processed plate, the cells seek a scaffold and adhere to each other to form cell aggregates or spheroids. Furthermore, when the spheroids adhere to each other and fuse with each other, the spheroids have a larger shape. In addition, for example, when cells are sown and cultured on a non-adhesive plate, the cells spontaneously aggregate to form spheroids. The culture time until spheroids are formed is approximately 6 to 48 hours, preferably 24-48 hours.

The method for producing spheroids is not limited to the above-mentioned method, and is a swirling culture method in which the cell suspension is placed in a swirling solution, a method in which the cell suspension is placed in a test tube and precipitated by a centrifuge, or Many methods are known, such as the alginate bead method. Among them, a method of placing a cell suspension in a water-repellent or non-adhesive multi-well can be preferably exemplified in that a large amount of homogeneous spheroids can be treated and recovered.

The cell structure 5 is a structure solidified by adhering a plurality of spheroids including mesenchymal stem cells to each other. The cell structure 5 can be obtained, for example, by recovering the contacted and fused spheroids by the procedure described above. The cell structure 5 is excellent in strength and stability because it contains mesenchymal stem cells. Further, here, "solidified" means that it has a certain shape rather than a liquid, but it is in a semi-solidified state having both liquid and solid attributes (semi-fluid). The form of can also be included.

In the production of the cell structure 5, it is preferable to use a known 3D bioprinting technique. 3D bioprinting is a method of creating cell patterns in a limited space using 3D printer technology. As the "biological" ink "(bio-ink)", the above-mentioned mesenchymal stem cells or the like or a gel containing the above-mentioned mesenchymal stem cells or the like can be used to produce a cell structure 5 having a desired shape fused with spheroids. .. Further, in order to obtain such a cell structure 5, for example, the description of Patent 4517415 can be referred to.

Further, a commercially available 3D bioprinter can be used for producing the cell structure 5, and for example, Regenova manufactured by Cyfuse Co., Ltd. can be exemplified. By using these 3D bioprinters, spheroids can be fused to obtain spatially arranged cell structures 5 of arbitrary shape.

The shape of the cell structure 5 is not particularly limited, but for example, a spherical shape, a substantially columnar shape, or the like can be preferably exemplified. In addition, the size of the cell structure 5 and the like can be appropriately designed.

Further, the cell structure 5 containing two or more types of cells can be obtained by fusing spheroids formed from different types of cells. Among them, from the viewpoint of its strength and stability, the cell structure 5 can include fibroblasts or vascular endothelial cells in addition to mesenchymal stem cells.

Next, an embodiment of the method of using the fistula treatment instrument of the present invention will be described by taking the treatment of bronchial stump fistula as an example. FIG. 6 is a schematic view illustrating a state in which the fistula treatment instrument of the present invention is carried into the fistula of a bronchial stump fistula using forceps of a bronchoscope. FIG. 7 is a schematic view illustrating a form in which the cell structure is detached from the carried fistula treatment instrument and supplied to the fistula. FIG. 8 is a schematic view illustrating a state in which forceps are pulled out from the carried fistula treatment instrument.

As illustrated in FIG. 6, the forceps 61 of the bronchoscope 6 can be used to grip the handle 44 of the extruded member 4 of the fistula treatment instrument 1. Since the handle portion 44 projects upward from the vicinity of the center of the flange portion 42, it can be easily grasped by using the forceps 61 of the bronchoscope 6 and can be reliably transported to the bronchial stump fistula S to be treated. can do. Further, in the extruded member 4, since the outer diameters of the flange portion 42 and the extruded portion 43 are larger than the inner diameter of the first cylindrical portion 31, the extruded member 4 does not fall out of the first cylindrical portion 31. Therefore, even when the handle 44 is gripped by the forceps 61 of the bronchoscope 6 and the fistula treatment instrument 1 is operated and transported, it can be stably performed.

As illustrated in FIG. 7 (A), after grasping the handle 44 with forceps 61 of the bronchoscope 6 and carrying the fistula treatment instrument 1 of the present invention to the bronchial stump fistula S to be treated, FIG. 7 As illustrated in (B), the extrusion member 4 can be pushed into the cylindrical body 3 (first cylindrical portion 31 and second cylindrical portion 32). As a result, the extruded member 4 slides toward the open end 32a side of the second cylindrical portion 32. At this time, the flange portion 42 abuts on the upper end 3A of the first cylindrical portion 31, and the extruded portion 43 reaches the vicinity of the open end portion 32a of the second cylindrical portion 32. Along with this, the cell structure 5 is pushed out by the extrusion portion 43, so that the cell structure 5 is detached from the cylinder 3 (second cylindrical portion 32). After that, the forceps 61 can be pulled out by releasing the grip of the handle portion 44 by the forceps 61. As a result, the cell structure 5 can be reliably transported and supplied to the bronchial stump fistula S.

Then, as illustrated in FIG. 8, the fistula treatment instrument 1 of the present invention can remain in the bronchial stump for a predetermined period after supplying the cell structure 5 to the bronchial stump fistula S. As a result, the fistula treatment instrument 1 acts as a weight stone, and the cell structure 5 supplied to the supplied bronchial stump fistula S can be stabilized. After the improvement of the bronchial stump fistula S is confirmed, the bronchoscope 6 is introduced again, and the fistula treatment instrument 1 is recovered by grasping and pulling out the handle 44 of the fistula treatment instrument 1 with forceps 61. be able to.

As described above, the fistula treatment instrument 1 of the present invention has an exterior portion 2 having a substantially cylindrical through hole 21 and a bottomless cylindrical cylindrical body 3 inserted into the through hole 21 of the exterior portion 2. And an extrusion member 4 that is slidable in the internal axial direction of the cylindrical body 3. One end of the cylindrical body 3 projects to the outside of the exterior portion 2, and the cylindrical body 3 can hold the solidified cell structure 5 inside the other end side. When the extrusion member 4 is slid from one end side to the other end side, the cell structure 5 held inside the other end side is pushed out and can be detached from the cylindrical body 3. Therefore, the cell structure 5 for closing the fistula can be reliably transported and supplied to a predetermined position, and various diseases associated with the fistula can be effectively treated.

The fistula treatment device and the assembly kit thereof of the present invention are not limited to the above embodiments. For example, the cylindrical portion may be capable of holding a solidified cell structure inside, and is not limited to the form composed of the first cylindrical portion and the second cylindrical portion described above. Further, the extruded member is not limited to the above-mentioned form as long as it is slidable in the axial direction inside the cylindrical body and can extrude the cell structure.

1 Treatment instrument for fistula 2 Exterior part 21 Through hole 3 Cylindrical body 31 First cylindrical part 31a Protruding part 32 Second cylindrical part 4 Extruded member 41 Main body part 42 Flange part 43 Extruded part 44 Handle part 5 Cell structure

Claims (5)

A fistula treatment device for transporting and supplying a cell structure for closing a fistula to a predetermined position.
An exterior part with a substantially columnar through hole and
A bottomless cylindrical cylinder inserted into the through hole of the exterior portion, and
An extruded member that can slide inside the cylinder in the axial direction,
With
The cylindrical body has one end side protruding to the outside of the exterior portion and can hold a solidified cell structure inside the other end side.
When the extrusion member is slid from the one end side of the cylinder toward the other end side, the cell structure held inside the other end side is pushed out and can be detached from the cylinder. A treatment instrument for a fistula, which is characterized by being. The cylindrical body includes a first cylindrical portion and a second cylindrical portion having a diameter larger than that of the first cylindrical portion.
The first cylindrical portion is provided with a protruding portion projecting to the outside of the exterior portion at one end, and the other end is connected to the second cylindrical portion.
The treatment instrument for a fistula according to claim 1, wherein the second cylindrical portion is inserted into the through hole and can hold the cell structure inside. The extruded member
A substantially cylindrical body portion inserted into the first cylindrical portion and the second cylindrical portion, and a substantially cylindrical main body portion.
A substantially disk-shaped flange portion provided at one end of the main body portion and exposed to the outside of the first cylindrical portion, and a substantially disk-shaped flange portion.
A substantially disk-shaped extruded portion provided at the other end of the main body portion and located inside the second cylindrical portion, and
With
The fistula treatment instrument according to claim 2, wherein the outer diameters of the flange portion and the extruded portion are larger than the inner diameter of the first cylindrical portion. The treatment instrument for a fistula according to claim 3, wherein the extruded member includes a handle portion protruding from the vicinity of the center of the flange portion. An assembly kit for a fistula treatment device according to claim 1.
An exterior part with a substantially columnar through hole and
A bottomless cylindrical cylinder inserted into the through hole of the exterior portion, and
An extruded member that can slide inside the cylinder in the axial direction,
An assembly kit characterized by being equipped with.

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