Patent Application
20230118399
The present invention relates to a drug solution injection needle for puncturing the myocardium of a patient and injecting a drug solution and a drug solution injection needle system provided with the drug solution injection needle.
In a known treatment method for regenerating cardiomyocytes, a drug solution such as a cardiac regenerative cell formulation is directly administered to cardiomyocytes losing their function due to a myocardial infarction or the like.
Note that diagnosis (mapping) with electrophysiology (EP) catheters or the like is performed to identify the target sites that require drug administration treatment prior to treatment.
To directly administer the drug solution to the cardiomyocytes, a hollow needle (drug solution injection needle) that punctures the myocardium of the patient and injects the drug solution is used (see Patent Document 1 below).
The drug solution injection needle is inserted into a sheath or guiding catheter and in this state is entered into a cavity (cardiac cavity) of a living body. When the distal end of the sheath or guiding catheter reaches at or near the target site, a needle tip of the drug solution injection needle is extended out from the leading end opening to puncture the target site (myocardium) and administer the drug solution to the cardiomyocytes.
Patent Document 1: WO 99/49926
However, in the case of drug administration treatment using a drug solution injection needle, it is important that the drug solution is reliably administered to the cardiomyocytes of the patient. Thus, when the drug solution is injected, the opening for drug solution injection in the needle tip of the drug solution injection needle needs to be located in the myocardium.
However, it is not easy to check whether the opening of the drug solution injection needle is located in the myocardium.
For example, as in the case of the drug solution injection needle described in Patent Document 1, even when cine imaging is used to check the position of a needle tip provided with a radiopaque band or the like, because the shape of the pulsating heart wall cannot be confirmed from the cine imaging, it is difficult to discern whether the needle tip is located inside the heart wall (myocardium) or located outside the heart wall (cardiac cavity).
The present invention has been made on the basis of the above-described circumstances.
The object of the present invention is to provide a drug solution injection needle that enables easy determination of whether an opening for drug solution injection is located inside a heart wall (myocardium) and that enables a drug solution to be reliably injected into the myocardium.
Another object of the present invention is to provide a drug solution injection needle system that enables a drug solution to be reliably injected into the myocardium.
A drug solution injection needle according to the present invention is a hollow needle for puncturing a myocardium of a patient and injecting a drug solution that includes a distal end member, the distal end member being a sharp member and made of metal; a connecting tube having electrical insulating properties connected to a base end side of the distal end member; a metal tube connected to a base end side of the connecting tube; and an insulating layer covering an outer circumferential surface of a base end portion of the metal tube, wherein the connecting tube and/or the distal end member includes at least one hole (outflow path for the drug solution) communicating with a cavity of the drug solution injection needle and open to an outer surface of the connecting tube or the distal end member; and an electrode configured to measure electric potential is formed by a distal end portion of the metal tube not covered by the insulating layer.
A drug solution injection needle system according to the present invention includes the drug solution injection needle according to the present invention and a notification unit configured to notify an operator that injection of the drug solution is possible when an electric potential measured by the electrode of the drug solution injection needle is equal to or greater than a predetermined value.
Embodiments will now be described, by way of example only, with reference to the accompanying drawings which are meant to be exemplary, not limiting, and wherein like elements are numbered alike in several Figures, in which:
The invention will now be described by reference to the preferred embodiments. This does not intend to limit the scope of the present invention, but to exemplify the invention.
(1) A drug solution injection needle according to the present invention is a hollow needle for puncturing a myocardium of a patient and injecting a drug solution that includes a distal end member, the distal end member being a sharp member and made of metal; a connecting tube having electrical insulating properties connected to a base end side of the distal end member; a metal tube connected to a base end side of the connecting tube; and an insulating layer covering an outer circumferential surface of a base end portion of the metal tube, wherein the connecting tube and/or the distal end member includes at least one hole (outflow path for the drug solution) communicating with a cavity of the drug solution injection needle and open to an outer surface of the connecting tube or the distal end member; and an electrode configured to measure electric potential is formed by a distal end portion of the metal tube not covered by the insulating layer.
According to the drug solution injection needle with such a configuration, when the electrode constituted by the distal end portion of the metal tube is entered inside the heart wall (myocardium), the electric potential measured by the electrode rapidly increases (an electric potential of equal to or greater than a certain value can be acquired). Thus, by detecting a rapid increase in the electric potential, it can be confirmed that the electrode has been entered inside the heart wall.
The electrode (distal end portion of the metal tube) is located on the base end side of the hole formed in the connecting tube and/or the distal end member. Thus, when the electrode is located inside the heart wall, the opening (opening for drug solution injection) of the hole is also located inside the heart wall (myocardium).
Accordingly, by checking whether the electric potential measured by the electrode is equal to or greater than the predetermined value, whether the opening for drug solution injection is located inside the heart wall can be easily determined, and by injecting the drug solution after confirming that the electric potential is equal to or greater than the predetermined value, the drug solution can be reliably injected from the opening of the hole to the myocardium.
Also, because the metal tube and the insulating layer covering the outer circumferential surface of the base end portion are provided, the distal end portion of the metal tube can be used as an electrode and the base end portion of the metal tube can be used as the lead of the electrode.
This removes the need for separately providing a ring-shaped electrode on the outer surface of the needle or providing a lead line of the electrode inside or outside the metal tube. This allows the diameter of the needle to be reduced and allows sufficient cavity space of the needle to be ensured.
Furthermore, the metal distal end member constituting the drug solution injection needle and the metal tube are electrically insulated from one another via the connecting tube, and the distal end member does not form an electrode. Thus, the electric potential does not increase at the stage when the distal end member and the connecting tube are entered inside the heart wall, and the distal end portion (electrode) of the metal tube is not entered.
(2) In the drug solution injection needle according to the present invention, preferably, a distal end of the distal end member is closed, and a tube wall of the connecting tube includes a plurality of side holes communicating with the cavity of the needle (cavity of the connecting tube) and open to the outer circumferential surface of the connecting tube.
According to the drug solution injection needle with such a configuration, compared to a drug solution injection needle with a side hole formed in the distal end member, the length of the distal end portion of the needle with poor flexibility can be reduced.
(3) In the drug solution injection needle according to (2), preferably, side hole groups including the plurality of side holes arranged in an axial direction of the connecting tube are disposed at even angular intervals apart in a circumferential direction of the connecting tube.
According to a drug solution injection needle with such a configuration, the drug solution can be injected evenly in the axial direction (direction of the wall thickness of the myocardium) of the connecting tube and the circumferential direction of the connecting tube.
(4) In the drug solution injection needle according to (3), preferably, the side holes of the side hole groups located on a distal end side have a larger diameter than the side holes located on the base end side.
According to a drug solution injection needle with such a configuration, the drug solution can be injected further evenly in the axial direction of the connecting tube (direction of the wall thickness of the myocardium).
(5) In the drug solution injection needle according to the present invention, preferably, a helical slit is formed in a distal end region of the base end portion of the metal tube.
According to a drug solution injection needle with such a configuration, the stiffness of the distal end region of the base end portion of the metal tube is somewhat reduced by the helical slit, giving the injection needle flexibility.
(6) In the drug solution injection needle according to the present invention, preferably, the drug solution is a cardiac regenerative cell formulation.
(7) A drug solution injection needle system according to the present invention includes the drug solution injection needle according to the present invention and a notification unit configured to notify an operator that injection of the drug solution is possible when an electric potential measured by the electrode of the drug solution injection needle is equal to or greater than a predetermined value.
A drug solution injection needle 100 of the embodiment illustrated in
The drug solution injection needle 100 of the present embodiment is provided with the metal distal end member 10, the connecting tube 20 having electrical insulating properties, the metal tube 30, and the insulating layer 40.
As illustrated in
The gripping portion 50 constituting the drug solution injection needle device is made of a resin, a rubber, an elastomer, or the like.
The gripping portion 50 is provided with an injection port 51 for supplying a drug solution to the cavity of the drug solution injection needle 100 and a connector 53 electrically connected with the electrode of the drug solution injection needle 100 via a lead welded to the base end of the metal tube 30.
The effective length (L100 illustrated in
The outer diameter of the drug solution injection needle 100 typically ranges from 0.3 to 1.5 mm and in a preferable example is 0.8 mm.
The inner diameter of the drug solution injection needle 100 typically ranges from 0.1 to 1.3 mm and in a preferable example is 0.6 mm.
The drug solution injection needle 100 of the present embodiment is a hollow needle for puncturing the myocardium of a patient and injecting a drug solution to the cardiomyocytes.
Here, the term “drug solution” can include cell formulations such as a cardiac regenerative cell formulation and gene transfer agents.
As illustrated in
The length (L10 illustrated in
If the length of the distal end member 10 is too short, the puncture performance may be impaired, or the joining strength with the connecting tube 20 may be decreased.
On the other hand, if the length of the distal end member 10 is too long, the ability of the drug solution injection needle 100 to follow a blood vessel may be impaired and entering the connecting tube 20 connected to the base end side of the distal end member 10 and the distal end portion 31 (electrode) of the metal tube 30 into the myocardium may be difficult.
Any known metal used in drug solution injection needles can be used as the metal constituting the distal end member 10, with examples including stainless steel, NiTi, β titanium, and platinum iridium.
Additionally, a portion or all of the distal end member 10 may be constituted by a radiopaque metal. This allows the position of the distal end member 10 up to the target site to be checked via cine imaging. Examples of a radiopaque metal include platinum and its alloys, gold, tungsten, and tantalum.
The connecting tube 20 constituting the drug solution injection needle 100 is made of a material having electrical insulating properties and is a member that connects the distal end member 10 and the metal tube 30 while ensuring the electrical insulating properties of both.
In some embodiments, the distal end member 10 and the metal tube 30 are connected via the connecting tube 20, but no such limitation is intended. As illustrated in
As illustrated in
The length (L20 illustrated in
If the length of the connecting tube 20 is too short, the distal end member 10 and the metal tube 30 may not be sufficiently insulated.
On the other hand, if the length of the connecting tube 20 is too long, the ability of the distal end portion of the drug solution injection needle 100 to follow a blood vessel may be impaired.
The electrically insulating material constituting the connecting tube 20 is not particularly limited, but preferably a resin material or a ceramic material is used. Using a resin material is particularly preferable because of its good electrical insulating properties and heat insulating properties and ease of forming.
The resin constituting the connecting tube 20 may be a thermoplastic resin or a thermosetting resin. Also, resin includes in its meaning ebonite. Specific examples include cyclic olefin-based resin, polyphenylene sulfide, polyether ether ketone (PEEK), polybutylene terephthalate, poly carbonate, polyamide, polyacetal, modified polyphenylene ether, polyester-based resin, polytetrafluoroethylene, fluororesin, sulfone-based resin, polyetherimide, poly ethersulfone, polyetherketone, polyether lactone, liquid crystal polyester, polyamideimide, polyimide, polyether nitrile, polypropylene, polyethylene, epoxy resin, unsaturated polyester resin, phenol resin, urea resin, melamine resin, and polyurethane resin. Of these, polyether ether ketone, polycarbonate, polyphenylsulfone, polyamide, and polyacetal are preferable.
In the connecting tube 20, as outflow paths for the drug solution to be injected, the ten side holes 25 (251 to 259, 25X) communicating with the cavity of the connecting tube 20 (drug solution injection needle 100) and open to the outer circumferential surface of the connecting tube 20 are formed.
As illustrated in
Accordingly, the drug solution can be injected evenly in the axial direction (direction of the wall thickness of the myocardium) of the connecting tube 20 and the circumferential direction of the connecting tube 20.
Regarding the diameters of the side holes in the first side hole group, the side hole 251 located on the distal end side has the largest diameter, the side hole 252 located next in the middle region has a large diameter, and the side hole 253 located on the base end side has the smallest diameter.
Regarding the diameters of the side holes in the second side hole group, the side hole 254 located on the distal end side has a larger diameter than the side hole 255 located on the base end side.
Regarding the diameters of the side holes in the third side hole group, the side hole 256 located on the distal end side has the largest diameter, the side hole 257 located next in the middle region has a large diameter, and the side hole 258 located on the base end side has the smallest diameter.
Regarding the diameters of the side holes in the fourth side hole group, the side hole 259 located on the distal end side has a larger diameter than the side hole 25X located on the base end side.
As described above, by making the diameter of the side holes located on the distal end side larger than the diameter of the side holes located on the base end side, the discharge amount of the drug solution from the side holes in the same side hole group can be made even, and the drug solution can also be evenly injected in the axial direction (direction of the wall thickness of the myocardium) of the connecting tube 20.
For example, regarding to diameters of the side holes 25 (251 to 259, 25X), the diameter of the side hole 251 and the side hole 256 is 0.27 mm, the diameter of the side hole 252 and the side hole 257 is 0.23 mm, the diameter of the side hole 253 and the side hole 258 is 0.20 mm, the diameter of the side hole 254 and the side hole 259 is 0.30 mm, and the diameter of the side hole 255 and the side hole 25X is 0.25 mm.
The metal tube 30 constituting the drug solution injection needle 100 is made of a tubular member provided with a cavity that communicates with the cavity of the connecting tube 20.
The length (L100-L10-L20) of the metal tube 30 typically ranges from 800 to 2500 mm and in a preferable example is 1283.5 mm.
The metal tube 30 requires the stiffness (particularly bending stiffness) and elasticity (particularly bending elasticity) required for a typical drug solution injection needle.
The metal constituting the metal tube 30 can be the same metal as that used for the distal end member 10, for example. Additionally, a portion or all of the distal end portion 31 of the metal tube 30 may be constituted by a radiopaque metal. This allows the position of the electrode up to the target site to be checked via cine imaging.
As illustrated in
Note that the slit 33 is a through-slit that extends from the outer circumferential surface of the metal tube to the inner circumferential surface. However, in another example, the slit may be formed not extending through to the inner circumferential surface.
The length (L33 illustrated in
The pitch of the slit 33 is formed so as to become continuously narrower toward the distal end direction. This allows the stiffness of distal end region of the base end portion 32 to be continuously (smoothly) reduced toward the distal end direction. Accordingly, the ease of controlling the drug solution injection needle 100 when guiding it into the target site can be improved. However, the slit formed in the distal end region of the base end portion may be formed having the same pitch.
The insulating layer 40 constituting the drug solution injection needle 100 is a layer made of an electrical insulation material that covers the outer circumferential surface of the base end portion 32 of the metal tube 30.
Since the outer circumferential surface of the base end portion 32 of the metal tube 30 is covered by the insulating layer 40, the distal end portion 31 of the metal tube 30 not covered by the insulating layer 40 can function as an electrode for measuring electric potential and the base end portion 32 of the metal tube 30 can function as the lead of the electrode.
This removes the need for separately providing a ring-shaped electrode on the outer surface of the needle or providing a lead line of the electrode inside or outside the metal tube. This allows the diameter of the drug solution injection needle 100 to be reduced and allows sufficient cavity space to be ensured.
Also, because the insulating layer 40 can close up the slit 33 formed in the distal end region of the base end portion 32 of the metal tube 30, the liquid-tightness of the drug solution injection needle 100 can be ensured.
The length (L31 illustrated in
Note that the insulating layer 40 does not need to cover the outer circumferential surface across the entire length (L100-L10-L20-L31) of the base end portion 32 of the metal tube 30, and in the present embodiment, the region from the distal end of the base end portion 32 extending a certain length is covered by the insulating layer 40.
The length (L40 illustrated in
The insulating layer 40 can be formed by shrinking a heat-shrinkable resin tube in which the base end portion 32 of the metal tube 30 is inserted inside.
Examples of the heat-shrinkable resin tube for forming the insulating layer 40 include polyethylene terephthalate (PET) and polyether block amide copolymer resin (PEBAX (trademark)).
The film thickness of the insulating layer 40 ranges from 10 to 100 μm and in a preferable example is 20 μm.
The drug solution injection needle 100 of the present embodiment together with the gripping portion 50 (the injection port 51 and the connector 53) form the drug solution injection needle device, and a drug solution is injected into the myocardium of a patient using the drug solution injection needle device.
When the drug solution injection needle device is used to inject a drug solution, a syringe containing the drug solution to be supplied to the cavity of the drug solution injection needle 100 is connected to the injection port 51 and the connector 53 is connected to an electrocardiogram device.
The drug solution injection needle 100 of the present embodiment is inserted into a sheath or guiding catheter and in this state is entered into a cavity (cardiac cavity) of a living body. When the distal end of the sheath or guiding catheter reaches at or near the target site specified by mapping, a needle tip of the drug solution injection needle 100 is extended out from the leading end opening to puncture the target site (myocardium).
At this stage, the remaining portion (base end portion) of the connecting tube 20 including the region where the side holes 25 are formed is located inside the cardiac cavity. Thus, even if an operation is performed to inject the drug solution at this stage, the drug solution would leak out inside the cardiac cavity, meaning that the drug solution cannot be injected in the myocardium.
However, in the state illustrated in
At this stage, the connecting tube 20 where the side holes 25 are formed is located in the myocardium. Thus, by performing an operation to inject the drug solution at this stage, the drug solution can be injected in the myocardium.
Also, in the state illustrated in
An embodiment of the present invention has been described above. However, the drug solution injection needle of the present invention is not limited thereto, and various changes may be made.
For example, a cavity that communicates with the cavity of the connecting tube and the cavity of the metal tube may be formed in the distal end member, and a hole that communicates with the cavity of the distal end member and opens to the outer surface (distal end surface or outer circumferential surface) of the distal end member may be formed. In this case, the side holes may or may not be formed in the outer circumferential surface of the connecting tube.
An example of such a drug solution injection needle is illustrated in
A drug solution injection needle system 200 of the present embodiment illustrated in
As illustrated in
The indifferent electrode 72 is provided on an electrode catheter (not illustrated) different from the guiding catheter 60 and is disposed in the vena cava of the patient P in a manner that does not pick up the cardiac potential of the patient P.
This makes it possible to measure the electric potential between the electrode of the drug solution injection needle 100 and the indifferent electrode 72 and to sequentially input the measured electric potential information to the electrocardiogram device 70.
The guiding catheter 60 constituting the drug solution injection needle system 200 guides the distal end portion of the drug solution injection needle 100 to the cardiac cavity H of the patient P, with the distal end being first inserted and positioned at or near the target site.
The notification unit 80 constituting the drug solution injection needle system 200 constantly determines whether the electric potential measured via the electrode of the drug solution injection needle 100 is equal to or greater than the predetermined value. When the electric potential is equal to or greater than the predetermined value, the notification unit 80 notifies the operator OP that the drug solution can be injected (the drug solution can be injected in the myocardium).
Here, how the operator OP is notified is not particularly limited and examples include and are not limited to a display of a message on a monitor or the like, a lamp lighting up or blinking, and a buzzer or audio message.
According to the drug solution injection needle system 200 of the present embodiment, by performing an injection operation to supply the drug solution from the syringe 55 into the cavity of the drug solution injection needle 100 after a notification is received from the notification unit 80, the drug solution can be reliably injected to the myocardium of the patient without the need for constantly monitoring via a monitor the electric potential measured by the electrode.
This application is based upon and claims the benefit of priority from the International Patent Application No. PCT/JP2020/014251, filed on Mar. 27, 2020, the entire content of each of which is incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2020/014251 | 3/27/2020 | WO |
