JP6730956B2 - Medical equipment - Google Patents

Description

The present disclosure relates to medical devices.

BACKGROUND ART Cancer immunotherapy that enhances immunity to treat cancer has been conventionally known. Among cancer immunotherapy, there is immune cell therapy for treating cancer by enhancing the function of immune cells of a patient. In this immune cell therapy, the immune cells of a patient are taken out of the body, cultured and activated, and then returned to the body of the patient to enhance immunity to cancer cells and treat cancer. Patent Document 1 describes an example of cancer immunotherapy.

Japanese Patent Publication No. 2017-503472

By the way, a medical device or a cell administration method for locally administering predetermined cells such as immune cells toward a target tissue transvascularly has not been established.

The present disclosure aims to provide a medical device capable of locally administering cells transvascularly to a target tissue.

The medical device according to the first aspect of the present invention is a medical device that is placed in a vessel, and a hollow needle portion that pierces the peripheral wall of the vessel in the vessel and communicates the inside and outside of the vessel, An embolus portion that is disposed in the blood vessel downstream of the hollow needle portion in the extending direction of the blood vessel and that embolizes the blood vessel by contacting body fluid in the blood vessel.

The medical device according to one embodiment of the present invention includes an urging portion that moves or deforms the hollow needle portion in the vessel from a state in which the hollow needle portion does not pierce the peripheral wall to a state in which the hollow needle portion pierces the peripheral wall.

As one embodiment of the present invention, the urging portion includes an expansion portion that is expandable in a radial direction of the blood vessel in the blood vessel, and the hollow needle portion follows expansion of the expansion portion. It moves and pierces the said surrounding wall.

As one embodiment of the present invention, a plurality of the hollow needle portions are provided in a circumferential direction of the vascular vessel while being left in the vascular vessel.

As one embodiment of the present invention, a plurality of the hollow needle portions are provided in the extending direction of the vascular vessel while being left in the vascular vessel.

As one embodiment of the present invention, the embolus portion contains a thrombus-forming substance that has a function of swelling by contact with body fluid in the vessel or coagulation of body fluid in the vessel.

As one embodiment of the present invention, the embolus unit includes an expansion body that holds the thrombus-generating substance and expands in the vessel in the radial direction of the vessel.

In one embodiment of the present invention, the expansion body is a mesh member.

According to the present disclosure, it is possible to provide a medical device capable of locally administering cells to a target tissue transvascularly.

It is a figure which shows the outline of an example of cancer immunotherapy. It is a figure which shows the single body of the medical device as one Embodiment of this invention. It is a figure which shows the state in which the medical device shown in FIG. 2 was left in the blood vessel. It is a figure which shows a mode that the medical instrument shown in FIG. 2 is conveyed to a predetermined position in a blood vessel.

Hereinafter, an embodiment of a medical device according to the present invention will be described with reference to FIGS. In the drawings, common members and parts are designated by the same reference numerals.

FIG. 1 is a diagram showing an outline of an example of cancer immunotherapy. In the cancer immunotherapy shown in FIG. 1, immune cells X are taken out from the blood of the patient P, activated, cultured, and returned to the blood of the patient P again. As a result, the immunity of the patient P can be enhanced, and elimination of cancer cells and suppression of cancer cell development can be realized.

2 and 3 are diagrams showing a medical device 1 according to the present embodiment, which can be used for the cancer immunotherapy shown in FIG. FIG. 2 shows the medical device 1 alone. FIG. 3 shows a state in which the medical device 1 is placed in the blood vessel BV as a blood vessel. More specifically, FIG. 3 shows a state in which the medical device 1 is placed at a position near the upstream side of the blood vessel BV with respect to the target tissue T that is the target of cancer treatment. The medical device 1 of FIG. 2 is a side view, and the medical device 1 of FIG. 3 is a sectional view.

As shown in FIGS. 2 and 3, the medical device 1 includes a hollow needle portion 2, an embolus portion 3, and a biasing portion 4.

As shown in FIG. 3, the hollow needle portion 2 is capable of piercing the blood vessel wall, which is the peripheral wall of the blood vessel BV, inside the blood vessel BV as a blood vessel, and communicating the inside and outside of the blood vessel BV. In FIG. 3, the hollow needle portion 2 shows a state in which the peripheral wall of the blood vessel BV is pierced, and in this state, the inside and outside of the blood vessel BV are communicated by the flow path 2 a of the hollow needle portion 2.

In addition, the hollow needle portion 2 of the present embodiment is provided in plural in the circumferential direction of the blood vessel BV while being left in the blood vessel BV. Furthermore, as shown in FIG. 3, the hollow needle portions 2 of the present embodiment are provided in plural in the extending direction of the blood vessel BV while being left in the blood vessel BV. As described above, by arranging a plurality of hollow needle portions 2 penetrating the peripheral wall of the blood vessel BV in a state where the medical device 1 is placed in the blood vessel BV, in the peripheral direction and the extending direction of the blood vessel BV, In comparison with the configuration in which a single cell is placed in the blood vessel BV, more cells such as immune cells X are passed from the blood vessel BV to the outside of the blood vessel BV with respect to the target tissue T that is the target of cancer treatment and is located on the downstream side of the blood vessel BV. It can be administered.

The material for forming the hollow needle portion 2 is preferably a biocompatible material, and may be biocompatible resin, silicon, metal, ceramic, or the like. Of these, biocompatible resins include, for example, medical grade silicone, polylactic acid, polyglycolic acid, polycarbonate, and PEEK material, and biocompatible metals include stainless steel, titanium, and manganese. And so on. Also, biocompatible ceramics include alumina, zirconia, silicon carbide, silicon nitride, and the like. When the hollow needle portion 2 contains a drug and is dissolved by a solution applied to the hollow needle portion 2 from the outside, the material for forming the hollow needle portion 2 may be a water-soluble polymer.

Further, the length of the hollow needle portion 2 is preferably, for example, about several hundred μm to several mm. The width of the hollow needle portion 2 is preferably about several tens μm to several hundreds μm. The length of the hollow needle portion 2 of the present embodiment means a protruding length L (see FIG. 2) from the outer surface of the annular member serving as an expansion portion of the biasing portion 4 described later. In addition, the width of the hollow needle portion 2 of the present embodiment means the maximum width D (see FIG. 2) of the hollow needle portion 2.

As shown in FIG. 3, the embolus portion 3 is arranged in the blood vessel BV more downstream than the hollow needle portion 2 in the extending direction of the blood vessel BV. Then, the embolus unit 3 forms an embolus such as a thrombus by contacting blood as a body fluid in the blood vessel BV, and embolizes the blood vessel BV.

Specifically, the embolus unit 3 of the present embodiment contains a thrombus-forming substance that swells in the blood vessel BV as a blood vessel by being in contact with blood as a body fluid. Examples of such thrombus-forming substance include hydrogel. However, a thrombus-forming substance having an action of coagulating blood in the blood vessel BV may be used.

More specifically, the embolus part 3 of the present embodiment is provided with an expansion body that holds a thrombus-generating substance and is expandable inside the blood vessel BV in the radial direction outside the blood vessel BV. The expandable body of this embodiment is a self-expanding mesh member. 2 and 3 show the mesh member in an expanded state. This mesh member is a lump formed of wire rods, and a large number of internal spaces are formed between the wire rods. The mesh member can be in a contracted state so that the internal space between the wires is reduced, and the contracted mesh member can be housed in the delivery catheter 5 (see FIG. 4) described later. While being accommodated in the delivery catheter 5 (see FIG. 4) in the contracted state, the delivery catheter 5 is carried to a predetermined position in the vessel. The thrombus-forming substance described above is retained on the surface of the wire rod that constitutes the mesh member as the expander.

Various metal materials, polymer materials, and the like are used for the wire material forming the mesh member as the expansion body of the embolus portion 3. Examples include metal materials such as stainless steel, tantalum, nickel-titanium alloys (including nitinol), biodegradable magnesium alloys and cobalt alloys (including cobalt-chromium-nickel alloys).

As the polymer material, polyethylene, polypropylene, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, crosslinkable ethylene-vinyl acetate copolymer, polyvinyl chloride, polyamide elastomer, polyurethane, polyester, polyary. Examples include thermoplastic resins such as lane sulfide. Of these, biodegradable polymer materials that are decomposed in vivo and the decomposed products do not show toxicity are preferable. Examples of the polymeric material that decomposes in vivo include polylactic acid, poly(lactic acid-glycolic acid), polyglycolic acid, poly(lactic acid-ε-caprolactone), poly(glycolic acid-ε-caprolactone), poly-p. -Dioxanone, poly(glycolic acid-trimethylene carbonate), poly-β-hydroxybutyric acid and the like.

The mesh member as the expandable body of the embolus part 3 of the present embodiment is a self-expanding type in which the shape is memorized in a predetermined shape. The configuration may be combined with the expansion type. Examples of the surface treatment method for the wire material constituting the mesh member include chemical treatment with an oxidizing agent or fluorine gas, surface graft polymerization, plasma discharge treatment, corona discharge treatment, UV/ozone treatment, electron beam irradiation and the like.

The urging portion 4 moves or deforms the hollow needle portion 2 in the blood vessel BV from a state where it does not penetrate the peripheral wall of the blood vessel BV to a state where it penetrates. More specifically, the urging portion 4 includes an expansion portion that can be expanded radially outside the blood vessel BV inside the blood vessel BV, and the hollow needle portion 2 moves following the expansion of the expansion portion and moves as described above. Pierce the perimeter wall. The expansion part of the urging part 4 of the present embodiment is configured by an annular member that supports the hollow needle part 2 on the outer surface and is expandable and contractible in the radial direction of the blood vessel BV. Therefore, the hollow needle portion 2 moves outward in the radial direction of the blood vessel BV as the annular member serving as the expanded portion of the biasing portion 4 expands and deforms radially outward in the blood vessel BV. As a result, the hollow needle portion 2 can be moved from the state in which the peripheral wall of the blood vessel BV is not pierced to the state in which it is pierced. The annular member serving as the expansion portion of the biasing portion 4 in the present embodiment is formed of a self-expanding stent, and is formed of the same material as the mesh member serving as the expansion body of the embolus portion 3 described above. You can In this way, the urging portion 4 may be composed of only the self-expanding expansion portion.

Hereinafter, a method for indwelling the medical device 1 of this embodiment in the blood vessel BV shown in FIG. 3 will be described.

FIG. 4 is a diagram showing how the medical device 1 is carried to a predetermined position in the blood vessel BV. As shown in FIG. 4, the medical device 1 is carried to a predetermined position in the blood vessel BV while being housed in the delivery catheter 5. Then, the medical device 1 is discharged from the delivery catheter 5 into the blood vessel BV at a predetermined position of the blood vessel BV. As a result, the self-expanding mesh member of the embolus portion 3 of the medical device 1 and the self-expanding stent of the biasing portion 4 of the medical device 1 expand toward the radial outside of the blood vessel BV. As a result, the medical device 1 can be brought into the state shown in FIG. When the medical device 1 is delivered and left in the blood vessel, an inner delivery catheter that extends and is arranged in at least a part of the inner cavity of the medical device 1 can be used. The inner delivery catheter is not shown in FIG. After delivering the medical device 1 to a predetermined site, the inner delivery catheter is retrieved. As the inner delivery catheter, a delivery catheter for a self-expandable stent or a balloon catheter for a balloon-expandable stent can be used.

Further, when the state of FIG. 4 is changed to the state of FIG. 3, the thrombus-forming substance held by the mesh member as the expansion body of the embolus portion 3 comes into contact with the blood in the blood vessel BV. As a result, the thrombus-forming substance swells and fills a large number of internal spaces formed between the wire rods forming the mesh member. Therefore, a plug is formed by the net-like member and the swollen thrombus-forming substance, and the blood vessel BV is plugged at the position of the embolus portion 3, and the blood flow can be stopped or weakened.

Hereinafter, as shown in FIG. 3, the medical device 1 is placed in the blood vessel BV in the vicinity of the target tissue T, and a predetermined cell such as an immune cell X, which is executed in a state where the blood vessel BV is embolized by the embolization unit 3, is passed through. A cell administration method for locally administering the target tissue T vascularly will be described.

As shown in FIG. 3, by leaving the medical device 1 in the indwelling state, the blood flow of the blood vessel BV can be stopped or weakened. Further, as shown in FIG. 3, the inside and outside of the blood vessel BV are in communication with each other by the hollow needle portion 2. In this state, the tubular member 6 is inserted into the blood vessel BV, and the opening 6a formed at the distal end of the tubular member 6 is advanced to near the placement position of the medical device 1 (see FIG. 3). Then, through the tubular member 6, predetermined cells such as immune cells X used for cancer treatment of the target tissue T are discharged from the opening 6a. As described above, the predetermined cells discharged in the vicinity of the indwelling position of the medical device 1 can move from the inside of the blood vessel BV to the outside of the blood vessel BV through the flow path 2a of the hollow needle portion 2. That is, a predetermined cell such as the immune cell X can be administered to a position outside the blood vessel BV and near the target tissue T. Thus, by using the medical device 1 of the present embodiment, it becomes possible to locally administer predetermined cells such as immune cells X to the target tissue T transvascularly.

After performing the above-described cell administration, in order to stop the outflow of blood to the outside of the blood vessel BV through the flow path 2a of the hollow needle portion 2, for example, a treatment of embolizing the upstream side of the blood vessel BV with respect to the medical device 1. I do. However, the outflow of blood to the outside of the blood vessel BV through the flow path 2a of the hollow needle portion 2 may be stopped by another method.

Further, the predetermined cells to be locally administered in the above-mentioned cell administration method are set according to the target tissue T and its purpose. Therefore, the predetermined cells to be locally administered are not limited to blood cells that are immune cells X (for example, lymphocytes (T cells, B cells, NK cells), red blood cells, granulocytes, monocytes, platelets), For example, hematopoietic stem cells, myoblasts, cardiomyocytes, fibroblasts, mesenchymal stem cells, synovial cells, embryonic stem cells, epithelial cells, endothelial cells and the like may be used. Further, the above-mentioned predetermined cells include allogeneic donor cells, xenogeneic donor cells, syngeneic donor cells, genetically engineered cells, established cell lines, patient-derived cells, and the like.

The medical device according to the present disclosure is not limited to the items described in the above embodiments, and various modifications and variations can be made without departing from the scope of the claims.

The present disclosure relates to medical devices.

1: Medical device 2: Hollow needle portion 2a: Flow path 3: Embolization portion 4: Energizing portion 5: Delivery catheter 6: Tubular member 6a: Opening BV: Blood vessel D: Hollow needle portion width L: Hollow needle portion Length P: patient T: target tissue X: immune cells

Claims (8)

A medical device placed in a vessel,
Penetrating the peripheral wall of the vessel in the vessel, a hollow needle portion that communicates the inside and outside of the vessel,
A medical device comprising: an embolus portion disposed in the blood vessel, downstream of the hollow needle portion in the extending direction of the blood vessel, and embolizing the blood vessel by contacting body fluid in the blood vessel. The medical device according to claim 1, further comprising: a biasing portion that moves or deforms the hollow needle portion from a state of not piercing the peripheral wall to a state of piercing the peripheral wall within the vessel. The urging portion includes an expansion portion that is expandable in a radial direction outside the vessel in the vessel,
The medical device according to claim 2, wherein the hollow needle portion moves following the expansion of the expansion portion to pierce the peripheral wall. The medical device according to any one of claims 1 to 3, wherein a plurality of the hollow needle portions are provided in the vessel in the circumferential direction while being left in the vessel. The medical device according to any one of claims 1 to 4, wherein a plurality of the hollow needle portions are provided in the extending direction of the vascular vessel while being left in the vascular vessel. 6. The medical device according to claim 1, wherein the embolus portion contains a thrombus-forming substance that swells in contact with a body fluid in the vessel or has a function of coagulating the body fluid in the vessel. Instrument. The medical device according to claim 6, wherein the embolus portion includes an expansion body that holds the thrombus-generating substance and expands in the vessel in a radial direction of the vessel. The medical device according to claim 7, wherein the expansion body is a mesh member.

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