KR102576604B1 - Medical precision drug injection and electroporation fusion electrode - Google Patents

Abstract

A sheath for vascularity, one side of which is inserted into the human body at a predetermined depth; and a plurality of needle members located inside the trocar sheath and having a tip region protruding from one side of the trocar sheath and positioned around a cell membrane to which a drug is to be injected, wherein the tip region comprises the cell membrane Provides a precision drug injection and electroporation fusion electrode for medical use, characterized in that a perforated electrode forming a nanoperforation and a drug release hole positioned around the perforated electrode and injecting a drug into the nanoperforation.

Description

Medical precision drug injection and electroporation fusion electrode}

The present invention relates to a precision drug injection and electroporation fusion electrode for medical use, which can minimize drug spread in surrounding tissues by continuously performing electroporation and drug injection into a deep tumor, and has fewer side effects than conventional resection and normal recovery. It is about a high-potential medical precision drug injection and electroporation fusion electrode.

Methods of treating tumors so far include surgical resection, thermal resection, chemotherapy, radiation therapy, particle therapy, and the like.

In the case of surgical resection, damage to organ tissue occurs due to extensive removal of surrounding tissue, resulting in a long recovery period and making normal life difficult. Because of the treatment method, thermal ablation may have limited application depending on the location of the tumor and may cause complications due to thermal injury. Particle therapy, known as a dream treatment because it can kill tumors precisely and has few side effects, has limitations in introducing the technology due to space and cost issues due to the construction of particle accelerator facilities to accelerate protons and neutrons, and limitations in the countries in which it can be introduced. It may be difficult to apply to tissues with irregular and continuous movement, such as the lungs or stomach.

In 2009, Angiodynamics' Nanoknife was approved for use in tissue killing and began irreversible electroporation (IRE), which induces apoptosis by applying a high-voltage electric shock to cells to create nano holes in the cell membrane. Therefore, it can be applied to various cancer treatments, including pancreatic cancer. The efficacy and safety of this device have been proven through clinical trials on patients with stage 1 and 2 pancreatic cancer, and the U.S. Food and Drug Administration has approved clinical trials on patients with stage 3 pancreatic cancer. Clinical trials are in progress, and various cancer treatments will be available in the future. Research is underway to apply it.

However, when only irreversible electroporation is performed as described above, side effects such as incomplete death and effects on surrounding tissues due to high-voltage electric shock have been reported, which means that the shock voltage cannot be unconditionally increased for complete death. can do. In other words, existing irreversible electroporation has a high possibility of thermal cauterization of tissues at the electrode site due to high instantaneous voltage, and the electric field formation energy of tissues far from the electrode is low, which may lower the possibility of tumor death.

On the other hand, reversible electroporation is a non-thermal treatment with lowered electric shock voltage, which can minimize the effect of surrounding tissue and solve the problem of incomplete death through drug injection. However, reversible electroporation to date is a method of applying electroporation after extensively injecting apoptotic drugs into the tumor site. Side effects may occur due to anticancer drugs spreading to surrounding tissues other than the tumor. When reversible electroporation is applied to a tumor deep in the living body, targeting precision may be reduced during the process of inserting a needle for drug injection and reinserting an electrode for electroporation.

Korean Patent No. 10-1872408 (registration date: June 22, 2018) Korean Patent No. 10-1097511 (registration date: December 15, 2011)

The technical problem to be achieved by the present invention is to provide a medical precision drug injection and electroporation fusion electrode capable of reversible electroporation and tumor removal in a three-dimensional manner by injecting a minimum amount of drug into a deep tumor.

In addition, another technical problem to be achieved by the present invention is to provide a medical precision drug injection and electroporation fusion electrode capable of minimizing drug spread in surrounding tissues by continuously performing electroporation and drug injection into a deep tumor. There is.

Furthermore, another technical problem to be achieved by the present invention is to provide a medical precision drug injection and electroporation fusion electrode that can provide various treatment methods by injecting drugs in the middle of application of an electric pulse signal for electroporation. There is.

The purpose of the present invention is not limited to the purposes mentioned above, and other purposes not mentioned will be clearly understood by those skilled in the art from the description below.

In order to solve the above problem, the present invention includes a sheath for trowels, one side of which is inserted into the human body at a predetermined depth; And a plurality of needle members located inside the diaphragm sheath and having a tip region that protrudes from one side of the diaphragm sheath and is located around the cell membrane into which the drug is to be injected, wherein the tip region is located on the cell membrane. It is possible to provide a medical precision drug injection and electroporation fusion electrode, characterized in that a perforation electrode forming a nanoperforation, and a drug release hole located around the perforation electrode for injecting a drug into the nanoperforation are formed.

The medical precision drug injection and electroporation fusion electrode may be inserted into the human body at two or more positions among the front, side, or rear surface of the human body.

The needle member may be made of a flexible non-metallic material.

The perforation electrode may be formed in a spiral shape to surround the outer peripheral surface of the tip area.

The perforation electrode may be formed in a straight line on the outer peripheral surface in a direction parallel to the central axis of the tip area.

The needle member may be formed such that a channel connected to the drug release hole and providing the drug passes through the inside along a central axis.

The perforation electrode applies an electrical pulse signal to the cell membrane to form nanoperforations, and the electrical pulse signal may be a combination of pulses having an electric field strength of 500 V/cm to 1500 V/cm and an amplitude of 50 μs to 200 μs. there is.

The electric pulse signal may be a pulse train consisting of 8 to 10 pulses applied at intervals of 1 Hz within 15 minutes.

The medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention can perform tumor removal with reversible electroporation and minimal amount of drug injection into a deep tumor, and can continuously perform electroporation and drug injection into a deep tumor. This has the effect of minimizing the spread of the drug to surrounding tissues. Furthermore, it is possible to provide various treatment methods by injecting drugs in the middle of application of an electric pulse signal for electroporation, and has the advantage of having fewer side effects and a higher possibility of normal recovery than conventional ablation.

1 and 2 are perspective views showing a precision medical drug injection and electroporation fusion electrode according to an embodiment of the present invention;
Figures 3 and 4 are side views showing the needle member of the medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention;
5 is a cross-sectional view showing a needle member of a precision medical drug injection and electroporation fusion electrode according to an embodiment of the present invention;
Figure 6 is a diagram showing the expansion angle of the needle member of the medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings. The embodiments introduced below are provided as examples to sufficiently convey the spirit of the present invention to those skilled in the art. Accordingly, the present invention is not limited to the embodiments described below and may be embodied in other forms. Also, in the drawings, the length and thickness of layers and regions may be exaggerated for convenience. Like reference numerals refer to like elements throughout the specification.

Figures 1 and 2 are perspective views showing a medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention, and Figures 3 and 4 are needles of a medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention. A side view showing the member, Figure 5 is a cross-sectional view showing the needle member of the medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention, and Figure 6 is a medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention. This is a diagram showing the expansion angle of the needle member.

1 to 6, the medical precision drug injection and electroporation fusion electrode 10 according to the present invention includes a trocar sheath 100, one side of which is inserted into the human body at a predetermined depth; and a plurality of needle members (200) having tip regions (T) positioned inside the trocar sheath (100) and protruding from one side of the trocar sheath (100) and positioned around the cell membrane to which the drug is to be injected. ), wherein the tip region T includes a perforated electrode 210 forming nanoperforations 3h in the cell membrane, and a drug positioned around the perforated electrode 210 and injecting a drug into the nanoperforation. An emission hole 220 may be formed. The medical precision drug injection and electroporation fusion electrode 10 is flexible to be easily inserted and mounted inside the curved human body 1, and is preferably formed to be biocompatible so as not to cause a toxic reaction even when worn for a long time.

In detail, the trocar sheath 100, whose one side is inserted into the human body 1 at a predetermined depth, is inserted through a small hole cut in the patient's human body 1 and is adjusted with an auxiliary tool to provide treatment. When the position needs to be adjusted, it is preferably made of a soft material whose diameter can be changed by external force. For example, it may be made of soft silicone or natural rubber. In addition, when precise position control is required while being directly inserted through the human body, it is preferable that the device is made of a hard material whose diameter cannot be changed by external force. For example, it may be made of a hard biocompatible alloy or composite.

The plurality of needle members 200 located inside the sheath 100 have a tip area T, and the tip area T protrudes from one side of the sheath 100 to inject the drug. It can be located around the cell membrane of the desired deep tumor (3).

For example, the medical precision drug injection and electroporation fusion electrode 10 may be inserted into the human body 1 at two or more positions among the front, side, or back of the human body, as shown in FIG. 2. That is, the trocar sheath 100 is inserted at two or more positions among the front, side, or back of the human body, and a plurality of needle members 200 in each sheath 100 are inserted into the deep tumor 3 in three dimensions. Being accessible has the advantage of being able to accurately locate the area where drug injection is needed. For example, the tumor 3 may be a variety of tumors that occur in the deep area, such as breast cancer, lung cancer, pancreatic cancer, prostate cancer, liver cancer, etc.

The tip area (T) includes a perforation electrode 210 that forms a nanoperforation (3h) in the cell membrane, and a drug release hole 220 located around the perforation electrode 210 and injecting the drug into the nanoperforation. This may have been formed. That is, a nano-poration is induced in the cell membrane of the tumor 3 through an instantaneous voltage shock to the perforation electrode 210, thereby allowing the drug to be absorbed into the cell membrane. Therefore, tumor removal can be performed by simultaneously performing reversible electroporation and injection of a minimum amount of drug into the deep tumor (3), and by continuously performing electroporation and drug injection into the deep tumor (3), anticancer drugs are delivered to the surrounding tissue. It has the effect of minimizing the spread.

Furthermore, the medical precision drug injection and electroporation fusion electrode 10 may have a handle (not shown) connected to the other end for handling, and the handle may be adjusted to the expansion angle (θ1, θ2 in FIG. 6) of the needle member 200. ) may be provided with a control unit that can adjust. Accordingly, the plurality of needle members 200 may be spread widely or narrowly according to the size of the tumor to be operated, and the applied instantaneous voltage shock may be adjusted differently depending on the expansion angle. That is, the expansion angle of the needle member 200 and the length of the tip region T can be adjusted according to the size of the target tumor, and accordingly, the degree of reversible electroporation and the amount of drug absorbed can be adjusted, so that the surrounding tissue This has the advantage of minimizing drug spread and minimizing side effects.

For example, in the needle member 200, a thin film electrode having flexibility is formed on the entire outer circumferential surface, and then an electrode exposed portion for electroporation, that is, an area other than the tip area T, is made of Parylene, which has high biocompatibility and can be electrically shielded. It may be coated. Also, as another example, the needle member 200 may be formed of a flexible non-metallic material, and only the tip region T may have a perforated electrode formed thereon.

In the above case, the perforated electrode 210 may be formed in a spiral shape to surround the outer circumferential surface of the tip region T as shown in FIG. 3, or may be formed parallel to the central axis of the tip region T as shown in FIG. It may be formed in a straight line on the outer circumferential surface in the direction, and the drug release hole 220 is located around the perforated electrode 210 and can inject the drug into the nano perforation. At this time, the needle member 200 may be formed such that a channel 230 connected to the drug release hole 220 and providing the drug passes through the inside along the central axis.

The needle member 200 may be formed through a MEMS process. In this case, the perforation electrode 210 may be composed of a micro thin film electrode or multiple micro thin film electrodes, and may be wound and coupled at regular intervals along the outer peripheral surface of the needle member 200, or parallel to the axial direction of the needle member 200. It may be connected to the outer circumferential surface to do so.

For example, the needle member 200 may be formed of flexible polydimethylsiloxane (PDMS), and preferably has a diameter of 600 μm to 2,000 μm, but is not limited thereto.

For example, a tube with a drug injection channel 230 inside is manufactured using a molding method using a biocompatible polymer such as polydimethylsiloxane, and a micro thin film electrode or multiple micro thin film electrodes are formed on the substrate and then separated from the substrate. Separate, wind micro thin film electrodes or multiple micro thin film electrodes spaced apart at regular intervals along the outer peripheral surface of the tube having the drug injection channel 230, fix and fuse them, and package them with molding to form the perforated electrode 210. This formed needle member 200 may be provided.

The perforation electrode 210 applies an electric pulse signal to the cell membrane to form a nanoperforation (3h), and the electric pulse signal has an electric field strength of 500V/cm to 1500V/cm and an amplitude of 50㎲ to 200㎲. It may be a combination of pulses. As an example, considering that the maximum applied tumor diameter is 3cm or less, a voltage of 1500V to 4500V can be said to be instantaneously applied to the cell membrane of the tumor, and nanoporations are induced in the cell membrane through this instantaneous high voltage shock. Thus, the drug released from the drug release hole 220 can be injected into the tumor.

Furthermore, the electric pulse signal may be a pulse train consisting of 8 to 10 pulses applied at intervals of 1 Hz within 15 minutes. When the pulse train is applied for 3 minutes or more, it is preferable that the time is within the above time period because it may affect surrounding tissues. In addition, the treatment procedure may be performed differently according to the state of the tumor in various ways by changing the section in which the drug is injected in the middle of the application of the electric pulse signal for electroporation.

In other words, the medical precision drug injection and electroporation fusion electrode (10) enables drug injection in micro units due to the above method, and forms nano-perforations in the tumor cell membrane with the perforation electrode (210), thereby causing short-term cell death. A very small amount of drug (anti-cancer agent) can be administered, which can induce self-death of tumor (3) cells and thus treat the patient. In addition, the side effects of anticancer drugs can be minimized by injecting a very small amount of short-acting anticancer drugs, and unlike tissue resection, RF cauterization, and refrigerant cauterization, which extensively excise and cauterize surrounding tissues, medical precision drug injection and electroporation fusion electrodes (10) Electroporation using can preserve blood vessels, lymph nodes, and nerves around tumor cells (3), and can also shorten the recovery period after treatment.

The medical precision drug injection and electroporation fusion electrode according to an embodiment of the present invention can perform tumor removal through reversible electroporation of deep tumors and injection of a minimum amount of drug, and continuously electroporation and drug injection into deep tumors. This has the effect of minimizing the spread of the drug to surrounding tissues. Furthermore, it is possible to provide a variety of surgical procedures by injecting drugs during the application of the electric pulse signal for electroporation, and has the advantage of fewer side effects and a higher possibility of normal recovery than conventional resection.

Although the present invention has been described above with reference to preferred embodiments, those skilled in the art may make various modifications and changes to the present invention without departing from the spirit and scope of the present invention as set forth in the claims below. You will understand that you can do it.

One; anatomy
3; tumor
3h; nano perforation
10; Medical precision drug injection and electroporation fusion electrode
100; sheath for bushing
200; Needle member
210; perforated electrode
220; drug release hall
230; channel
T; tip area

Claims (8)

a trocar sheath, one side of which is inserted into the human body at a predetermined depth; and
It is located inside the tube sheath, and includes a plurality of needle members having a tip area that protrudes from one side of the tube sheath and is located around the cell membrane into which the drug is to be injected,
The tip area is formed with a perforation electrode that forms a nanoperforation in the cell membrane, and a drug release hole that is located around the perforation electrode and injects the drug into the nanoperforation,
The medical precision drug injection and electroporation fusion electrode, which includes the tubing sheath and a plurality of needle members, is inserted into the human body at two or more positions among the front, side, or back of the human body, and can be accurately located in the area where drug injection is required. The plurality of needle members in each of the trocar sheaths three-dimensionally approach the deep tumor,
The needle member is made of a flexible non-metallic material, and is manufactured using a biocompatible polymer containing polydimethylsiloxane to create a tube with a channel for drug injection inside by molding, and is a micro thin film electrode or multiple micro thin film electrodes. After being formed on a substrate, it is separated from the substrate, and micro thin film electrodes or multiple micro thin film electrodes are wound along the outer peripheral surface of the tube having the drug injection channel at regular intervals, and then fixed and fused through molding. The needle member in which the perforated electrode is formed is manufactured in a packaging manner
Medical precision drug injection and electroporation fusion electrode.
delete delete According to claim 1,
A medical precision drug injection and electroporation fusion electrode, characterized in that the perforation electrode is formed in a spiral shape to surround the outer peripheral surface of the tip area.
According to claim 1,
The perforation electrode is a medical precision drug injection and electroporation fusion electrode, characterized in that the perforation electrode is formed in a straight line on the outer peripheral surface in a direction parallel to the central axis of the tip area.
According to claim 1,
The needle member is a medical precision drug injection and electroporation fusion electrode, characterized in that the drug injection channel, which is connected to the drug release hole and supplies the drug, penetrates the inside along the central axis.
According to claim 1,
The perforation electrode applies an electric pulse signal to the cell membrane to form a nanoperforation,
The electric pulse signal is a medical precision drug injection and electroporation fusion electrode, characterized in that it is a combination of an electric field strength of 500V/cm to 1500V/cm and a pulse with an amplitude of 50㎲ to 200㎲.
According to claim 7,
The electric pulse signal is a medical precision drug injection and electroporation fusion electrode, characterized in that the pulse train consisting of 8 to 10 pulses is applied within 15 minutes at 1 Hz intervals.