WO2021100316A1 - 薬液拡散システムおよび薬液拡散促進装置 - Google Patents

薬液拡散システムおよび薬液拡散促進装置 Download PDF

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Publication number
WO2021100316A1
WO2021100316A1 PCT/JP2020/036226 JP2020036226W WO2021100316A1 WO 2021100316 A1 WO2021100316 A1 WO 2021100316A1 JP 2020036226 W JP2020036226 W JP 2020036226W WO 2021100316 A1 WO2021100316 A1 WO 2021100316A1
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Prior art keywords
ultrasonic wave
chemical
ultrasonic
drug solution
unit
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PCT/JP2020/036226
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English (en)
French (fr)
Japanese (ja)
Inventor
俊彦 宇都
船村　重彰
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株式会社カネカ
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Priority to JP2021558192A priority Critical patent/JPWO2021100316A1/ja
Publication of WO2021100316A1 publication Critical patent/WO2021100316A1/ja

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/158—Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body

Definitions

  • the present invention relates to a system for diffusing a drug solution injected into the body and a drug solution diffusion promoting device in the treatment of cancer or the like.
  • Patent Document 1 describes light transmission / reception means for transmitting / receiving light to a living body, electroacoustic conversion means for transmitting / receiving ultrasonic waves to a living body, and light.
  • a control means for controlling the direction of ultrasonic wave transmission / reception and a drug administration means for administering a drug in the vicinity of a living body irradiated with therapeutic ultrasonic waves are provided, and the drug administration means is a catheter-type applicator.
  • Patent Document 2 discloses an ultrasonic catheter system for providing treatment to a treatment site at one or more positions of a subject, and the system includes a tubular member, a microbubble reservoir, and an ultrasonic wave.
  • An energy source, the ultrasonic energy is adapted to imaging the treatment site and bursting the microbubbles, and is electrically connected to the ultrasonic energy source and the ultrasonic energy source. It is disclosed to include a control circuit configured to send activation.
  • an object of the present invention is to provide a chemical solution diffusion system and a chemical solution diffusion promoting device capable of appropriately diffusing a chemical solution.
  • a drug solution diffusion system for diffusing a drug solution to a target tissue in a living body, and includes a drug solution injection tube pierced by the target tissue.
  • a two-dimensional or three-dimensional target tissue that is provided in the chemical injection tube and is connected to the first ultrasonic generator that generates the first ultrasonic wave for diffusing the chemical solution and the first ultrasonic generator.
  • It has an ultrasonic control unit that controls the irradiation conditions of the first ultrasonic wave according to the image, and the ultrasonic control unit has a propagation direction, intensity, and oscillation of the first ultrasonic wave generated by the first ultrasonic wave generating unit.
  • the gist is to control at least one of the frequencies.
  • at least one of the propagation direction, intensity and oscillation frequency of the first ultrasonic wave is controlled according to the two-dimensional or three-dimensional image of the target tissue, so that the target tissue is in a state of being affected.
  • the drug solution can be appropriately diffused to the required site. Therefore, it is possible to shorten the irradiation time of ultrasonic waves required for treatment, which contributes to the reduction of the burden on the patient and the operator.
  • the chemical diffusion system is connected to a second ultrasonic generation unit that generates a second ultrasonic wave having an oscillation frequency different from that of the first ultrasonic wave and an ultrasonic control unit, and irradiates the target tissue with the second ultrasonic wave. It is preferable to further have an image forming unit that forms an image using the reflected wave of the time, and a storage unit that is connected to the ultrasonic control unit and stores the image formed by the image forming unit.
  • the chemical solution diffusion system further has a processing unit connected to an ultrasonic control unit, and the processing unit further includes an image of the target tissue before the chemical solution injection and after the chemical solution injection and after the irradiation of the first ultrasonic wave.
  • the image of the target tissue is compared, and the ultrasonic control unit preferably controls the irradiation conditions of the first ultrasonic wave by using the comparison result in the processing unit.
  • the drug solution diffusion system further has a data storage unit and a processing unit connected to the ultrasonic control unit, respectively, and the data storage unit is provided with data on the diffusion pattern of the drug solution according to the type of tumor.
  • the pattern table is stored, and the processing unit compares the reference result of the diffusion pattern table with the image of the target tissue after the injection of the chemical solution and after the irradiation of the first ultrasonic wave, and the ultrasonic control unit. It is preferable to control the irradiation conditions of the first ultrasonic wave by using the comparison result in the processing unit.
  • the chemical diffusion system further includes a measuring unit connected to an ultrasonic control unit, and the measuring unit is at least one of the shape, size, spread, and hardness of the tumor from the image before injection of the chemical solution. It is preferable that the ultrasonic control unit controls the irradiation condition of the first ultrasonic wave by using the measurement result of the measurement unit.
  • the chemical solution diffusion system further has a processing unit connected to an ultrasonic control unit, and the processing unit further includes an image of the target tissue after the chemical solution injection and before the irradiation of the first ultrasonic wave, and after the chemical solution injection. Therefore, the images of the target tissue after the irradiation of the first ultrasonic wave are compared, and it is preferable that the ultrasonic control unit controls the irradiation condition of the first ultrasonic wave by using the comparison result in the processing unit.
  • the chemical solution diffusion system further has a third ultrasonic wave generating unit that generates a third ultrasonic wave for heating the target tissue at an oscillation frequency different from that of the first ultrasonic wave.
  • the first ultrasonic wave generator is different from the first ultrasonic wave, the second ultrasonic wave having an oscillation frequency different from that of the first ultrasonic wave and used for image formation for diagnosis, and the first ultrasonic wave. It is preferable to generate a third ultrasonic wave having an oscillation frequency for heating the target tissue.
  • the chemical solution diffusion system further includes a liquid supply unit connected to a proximal portion of the chemical solution injection tube to supply the chemical solution into the chemical solution injection tube, and a cooling unit connected to the liquid supply unit to cool the chemical solution. Is preferable.
  • the chemical solution diffusion system further includes a liquid supply unit connected to the proximal portion of the chemical solution injection tube and supplying the chemical solution into the chemical solution injection tube, and a data storage unit connected to the ultrasonic control unit to provide data.
  • the storage unit has a drug solution table containing data on the type of drug solution and a tumor table containing data indicating the state of the tumor diagnosed in the past, and the ultrasonic control unit uses the reference result of the tumor table as a reference result. Based on this, it is preferable to select the type of chemical solution from the chemical solution table and issue a command signal to the liquid supply unit to supply the selected type of chemical solution into the chemical solution injection tube.
  • the data storage unit further has a frequency table containing data on the oscillation frequency of the first ultrasonic wave
  • the ultrasonic control unit further has a frequency table from the frequency table based on the reference result of the tumor table. It is preferable to select the value of the oscillation frequency of the sound wave and emit a command signal to generate the first ultrasonic wave of the selected oscillation frequency to the first ultrasonic wave generation unit.
  • the first ultrasonic wave generating section includes at least two oscillators, and the two oscillators are provided on the side wall portion of the chemical solution injection pipe.
  • the first ultrasonic wave generating portion is provided in the cavity of the chemical solution injection tube and has a rotation axis parallel to the longitudinal axis direction of the chemical solution injection tube.
  • the first ultrasonic wave generating unit emits the first ultrasonic wave toward the outside in the radial direction of the chemical solution injection tube.
  • the chemical diffusion system further includes a measuring unit connected to an ultrasonic control unit, and the measuring unit is at least one of the shape, size, spread, and hardness of the tumor from the image before injection of the chemical solution.
  • the ultrasonic control unit uses the measurement results of the tumor in the measurement unit to measure the intensity of the first ultrasonic wave with respect to the first ultrasonic wave generating unit depending on the position in the circumferential direction of the drug solution injection tube. It is preferable to emit a command signal that changes at least one of the oscillation frequency and the oscillation frequency.
  • the ultrasonic control unit gives a command to increase the intensity of the first ultrasonic wave in the circumferential direction of the chemical injection tube as the radial distance from the center of the longitudinal axis of the chemical injection tube to the outer edge of the tumor becomes longer. It is preferable to emit a signal.
  • the ultrasonic control unit lowers the oscillation frequency of the first ultrasonic wave in the circumferential direction of the chemical injection tube as the radial distance from the center of the longitudinal axis of the chemical injection tube to the outer edge of the tumor becomes longer. It is preferable to emit a command signal.
  • the chemical solution preferably contains fine bubbles.
  • the present invention also provides a chemical solution diffusion promoting device.
  • One embodiment of the drug solution diffusion promoting device of the present invention used in the above drug solution diffusion system is provided in a drug solution injection tube pierced by a target tissue and a drug solution injection tube, and is provided with a first ultrasonic wave for diffusing the drug solution.
  • the first ultrasonic wave generating unit includes at least two vibrators, and the two ultrasonic wave generators are provided on the side wall portion of the chemical injection pipe.
  • the first ultrasonic wave generating portion is provided in the cavity of the chemical solution injection tube and has a rotation axis parallel to the longitudinal axis direction of the chemical solution injection tube.
  • the state of the target tissue is adjusted. Therefore, the drug solution can be appropriately diffused to the required site. Therefore, it is possible to shorten the irradiation time of ultrasonic waves required for treatment, which contributes to the reduction of the burden on the patient and the operator. Further, according to the above-mentioned chemical solution diffusion promoting device, the irradiation direction, irradiation position, intensity and the like of ultrasonic waves can be changed without moving the first ultrasonic wave generating unit.
  • FIG. 1 A cross-sectional side view showing the structure of the chemical solution diffusion promoting device of the chemical solution diffusion system shown in FIG. 1 is shown.
  • a cross-sectional view taken along the line III-III of the chemical solution diffusion promoting device shown in FIG. 2 is shown.
  • a cross-sectional side view showing a modified example of the chemical solution diffusion promoting device shown in FIG. 2 is shown.
  • a cross-sectional side view showing another modification of the chemical solution diffusion promoting device shown in FIG. 2 is shown.
  • a cross-sectional view taken along the line VI-VI of the chemical solution diffusion promoting device shown in FIG. 5 is shown.
  • FIG. 2 shows an image of an ultrasonic diagnostic image when the drug solution injection tube and the ultrasonic wave generating portion of the drug solution diffusion promoting device shown in FIG. 2 are punctured into the tumor.
  • the figure which shows an example of the treatment flow in the drug solution diffusion system shown in FIG. 1 is shown.
  • a diagram showing another example of the treatment flow in the drug solution diffusion system shown in FIG. 1 is shown.
  • FIG. 6 shows a diagram showing still another example of the treatment flow in the drug solution diffusion system shown in FIG.
  • the block diagram of the chemical solution diffusion system which concerns on other embodiment of this invention is shown.
  • the block diagram of the chemical solution diffusion system which concerns on still another Embodiment of this invention is shown.
  • the figure which shows an example of the treatment flow in the drug solution diffusion system shown in FIG. 12 is shown.
  • the block diagram of the chemical solution diffusion system which concerns on still another Embodiment of this invention is shown.
  • One embodiment of the drug solution diffusion system of the present invention is a drug solution diffusion system for diffusing a drug solution to a target tissue in a living body, and is provided in a drug solution injection tube pierced by the target tissue and a drug solution injection tube.
  • the first ultrasonic wave generating part that generates the first ultrasonic wave for diffusing the chemical solution and the first ultrasonic wave generating part are connected to the first ultrasonic wave according to the two-dimensional or three-dimensional image of the target tissue. It has an ultrasonic control unit that controls irradiation conditions, and the ultrasonic control unit controls at least one of the propagation direction, intensity, and oscillation frequency of the first ultrasonic wave generated by the first ultrasonic wave generating unit.
  • the drug solution diffusion system is used to spread a drug solution locally administered to a target tissue such as a tumor in a living body in drug therapy, which is one of the treatment methods for tumors such as cancer.
  • the drug solution is administered into the target tissue using a drug solution injection tube, and is diffused into the target tissue by ultrasonic waves emitted from the ultrasonic wave generating part.
  • the drug solution administered to the target tissue can include an anticancer drug.
  • anticancer agents include cytotoxic anticancer agents such as antimetabolites, microtubule inhibitors and antitumor antibiotics; endocrine therapeutic agents; molecular targeted agents such as immune checkpoint inhibitors; oncolytic virus.
  • a virus therapeutic drug or the like containing a sex virus or the like can be used.
  • the drug solution may contain absolute ethanol, which is used as an anticancer agent in percutaneous ethanol therapy.
  • the chemical solution may contain an ultrasonic contrast agent such as perflubutane or a mixture of galactose and palmitic acid.
  • the chemical solution preferably contains fine bubbles.
  • a fine bubble is a bubble having a sphere-equivalent diameter of 100 ⁇ m or less.
  • the bubble diameter of the fine bubble, the type of gas in the bubble, and the presence or absence of a shell for the gas core can be appropriately selected according to the condition of the tumor.
  • the type of gas in the bubble of the fine bubble is not particularly limited, but for example, an inert gas such as air, oxygen, nitrogen, carbon dioxide, hydrogen, helium, argon, xenon, krypton, carbon fluoride, sulfur hexafluoride, etc. Can be mentioned. Only one of these may be used, or two or more thereof may be used in combination.
  • an inert gas such as air, oxygen, nitrogen, carbon dioxide, hydrogen, helium, argon, xenon, krypton, carbon fluoride, sulfur hexafluoride, etc. Can be mentioned. Only one of these may be used, or two or more thereof may be used in combination.
  • Examples of the material constituting the shell for the gas core include phospholipids, polycationic lipids, proteins, higher fatty acids, sugars, sterols, surfactants, natural or synthetic molecules and the like. Only one of these may be used, or two or more thereof may be used in combination.
  • FIG. 1 shows a block diagram of a chemical solution diffusion system according to an embodiment of the present invention.
  • FIG. 2 shows a cross-sectional side view showing the structure of the chemical solution diffusion promoting device of the chemical solution diffusion system shown in FIG.
  • FIG. 3 shows a cross-sectional view of the chemical solution diffusion promoting device shown in FIG. 2 along lines III-III.
  • 4 to 5 show cross-sectional side views showing a modified example of the chemical solution diffusion promoting device shown in FIG.
  • FIG. 6 shows a cross-sectional view of the chemical solution diffusion promoting device shown in FIG. 5 along the VI-VI line.
  • FIG. 1 shows a block diagram of a chemical solution diffusion system according to an embodiment of the present invention.
  • FIG. 2 shows a cross-sectional side view showing the structure of the chemical solution diffusion promoting device of the chemical solution diffusion system shown in FIG.
  • FIG. 3 shows a cross-sectional view of the chemical solution diffusion promoting device shown in FIG. 2 along lines III-III.
  • 4 to 5 show cross-
  • FIG. 7 shows an image of an ultrasonic diagnostic image when the drug solution injection tube and the ultrasonic wave generating portion of the drug solution diffusion promoting device shown in FIG. 2 are punctured into the tumor.
  • FIG. 8 shows an example of a treatment flow in the drug solution diffusion system shown in FIG.
  • the chemical solution diffusion system 1 includes a chemical solution injection tube 3, a first ultrasonic wave generation unit 11, and an ultrasonic wave control unit 20.
  • a chemical solution diffusion promoting device 2 is provided in a chemical solution injection tube 3 that is pierced into a target tissue and a chemical solution injection tube 3, and a first ultrasonic wave that generates a first ultrasonic wave for diffusing the drug solution.
  • An example having the generation unit 11 is shown.
  • the chemical injection pipe 3 has a first end and a second end in the longitudinal axis direction. It can be said that the first end is the distal end and the second end is the proximal end.
  • the distal side is the first end side in the longitudinal axis direction of the drug solution injection tube 3 and refers to the treatment target side.
  • the proximal side is the second end side of the drug solution injection tube 3 in the longitudinal axis direction and refers to the hand side of the user (operator).
  • the proximal side may be referred to as a proximal portion and the distal side may be referred to as a distal portion.
  • the left side represents the distal side and the right side represents the proximal side.
  • the inside of the drug solution diffusion promoting device 2 refers to a direction toward the center of the longitudinal axis of the drug solution injection tube 3 in the radial direction of the drug solution injection tube 3, and the outside refers to a radiation direction opposite to the inside. Point.
  • the drug solution injection tube 3 is a tubular member that is punctured by the target tissue in the living body, and has a function of locally administering the drug solution into the target tissue.
  • the drug solution injection tube 3 has a distal portion and a proximal portion, and a puncture portion 3a to be inserted into the target tissue of the patient is provided in the distal portion.
  • the chemical solution injection tube 3 has one or a plurality of lumens 3b extending in the longitudinal axis direction thereof, and at least one lumen 3b functions as a flow path through which the chemical solution flows.
  • the distal end of the drug solution injection tube 3 is provided with an opening 3c that communicates with the outside, and the drug solution can be discharged to the outside of the drug solution injection tube 3 from the opening 3c.
  • the opening 3c may be provided so as to face the distal side as shown in FIG. 2, or may be provided on the side wall portion 3d of the chemical solution injection pipe 3 (not shown).
  • the drug solution injection tube 3 having the puncture portion 3a As the drug solution injection tube 3 having the puncture portion 3a, as shown in FIG. 2, the drug solution injection tube 3 is formed in a needle shape, and the tip of the needle is located on the distal side.
  • the puncture portion 3a is not particularly limited as long as it is formed so as to easily puncture the tissue, but it is preferable that the puncture portion 3a has an inclined opening edge 3e at the distal end of the drug solution injection tube 3 as shown in FIG. ..
  • a first grip portion 9 gripped by the operator is preferably connected to the proximal portion of the drug solution injection tube 3.
  • the chemical injection tube 3 is a hollow coil formed by spirally winding one or a plurality of metal wires, a hollow coil or at least one of the inner or outer surfaces of the hollow body coated with resin, and a tubular shape. Resin tubes of the above, or those in which these are connected in the longitudinal axis direction can be mentioned.
  • the chemical injection tube 3 is a tubular resin tube
  • the chemical injection tube 3 can be composed of a single layer or a plurality of layers, and a part in the longitudinal direction or the circumferential direction is composed of a single layer, and the like.
  • the unit may be composed of a plurality of layers.
  • the chemical injection tube 3 is preferably made of resin or metal.
  • the resin constituting the chemical injection tube 3 include polyamide-based resin, polyester-based resin, polyurethane-based resin, polyolefin-based resin, fluorine-based resin, vinyl chloride-based resin, silicone-based resin, and natural rubber. Only one of these may be used, or two or more thereof may be used in combination. Of these, polyamide-based resins, polyester-based resins, polyurethane-based resins, polyolefin-based resins, and fluororesins are preferably used.
  • the metal constituting the chemical injection tube 3 examples include stainless steel such as SUS304 and SUS316, platinum, nickel, cobalt, chromium, titanium, tungsten, gold, Ni—Ti alloy, Co—Cr alloy, or a combination thereof. Can be mentioned.
  • the wire made of Ni—Ti alloy has excellent shape memory and high elasticity.
  • the wire rod may be a fiber material such as the above-mentioned metal, polyarylate fiber, aramid fiber, ultra-high molecular weight polyethylene fiber, PBO fiber, carbon fiber and the like. The fiber material may be monofilament or multifilament.
  • a tubular body made of resin on which a reinforcing material such as a metal wire is arranged may be used as the chemical injection pipe 3.
  • the chemical solution diffusion promoting device 2 has an outer tube 5 capable of accommodating the chemical solution injection tube 3.
  • the drug solution injection tube 3 can be arranged in the lumen 5b of the outer tube 5 so as not to damage the non-treatment tissue site or the inside of the forceps channel of the endoscope.
  • the outer tube 5 is a member having a distal portion and a proximal portion. Further, the outer tube 5 has a first end (distal end) and a second end (proximal end) in the longitudinal axis direction. The outer tube 5 communicates with the outside through an opening 5a provided on the distal side thereof.
  • a second grip portion 10 for the operator to grip may be provided in the proximal portion of the outer tube 5.
  • the second grip portion 10 can be formed in a tubular shape, for example.
  • the description of the constituent materials of the chemical injection tube 3 can be referred to.
  • the material of the outer tube 5 may be the same as or different from the material of the chemical injection tube 3.
  • the outer tube 5 is a tubular body, a metal tube, or a combination thereof formed by arranging a resin tube, a single wire or a plurality of wires, and a stranded wire in a specific pattern. Can be used.
  • the first ultrasonic wave generating unit 11 is provided in the chemical solution injection pipe 3 and is a portion that generates the first ultrasonic wave for diffusing the chemical solution.
  • the first ultrasonic wave is a therapeutic ultrasonic wave for diffusing a drug solution.
  • the oscillation frequency and ultrasonic output of the first ultrasonic wave generated by the first ultrasonic wave generating unit 11 can be appropriately set according to the type of treatment, the type and dose of the chemical solution.
  • Examples of the ultrasonic scanning method in the first ultrasonic wave generating unit 11 include an electronic scanning type and a mechanical scanning type.
  • a piezoelectric method and an electrostatic method can be mentioned.
  • the oscillation frequency of the first ultrasonic wave is preferably 1 kHz or more, more preferably 10 kHz or more, further preferably 100 kHz or more, preferably 10 MHz or less, and preferably 1 MHz or less. Is more preferable, and 500 kHz or less is further preferable. By setting the oscillation frequency in this way, the chemical solution can be effectively diffused.
  • Ultrasonic output Ispta of the first ultrasonic wave is preferably 100 mW / cm 2 or more, more preferably 300 mW / cm 2 or more, still more preferably 500 mW / cm 2 or more, also, 10 W / preferably cm 2 or less, more preferably 5W / cm 2 or less, and more preferably 1W / cm 2 or less.
  • the first sound wave generating unit 11 emits the first ultrasonic wave toward the outer side in the radial direction of the chemical injection tube 3.
  • the propagation direction of the first ultrasonic wave is shown in the direction z.
  • the first ultrasonic wave generating unit 11 may emit ultrasonic waves toward the distal side of the drug solution injection tube 3.
  • the first ultrasonic wave generating unit 11 can include an ultrasonic probe.
  • the ultrasonic probe converts an electric signal into an ultrasonic wave to transmit and receive an ultrasonic wave.
  • the ultrasonic probe may be a single oscillator type probe or a dual oscillator type probe having a transmitting oscillator and a receiving oscillator.
  • the oscillator can have, for example, a configuration having two electrodes and a piezoelectric material sandwiched between the two electrodes.
  • the piezoelectric material is a crystalline substance exhibiting piezoelectricity, and is a substance that generates a voltage when a mechanical strain is applied, or conversely, a material that generates a mechanical strain when a voltage is applied.
  • As the piezoelectric material barium titanate (BaTIO 3 ), lead zirconate titanate (PZT), polyvinylidene fluoride (PVDF), 1-3 composite composite piezoelectric material and the like can be used.
  • the first ultrasonic wave generating portion 11 is provided on the side wall portion 3d of the chemical solution injection pipe 3. This facilitates the irradiation of the target tissue in the living body with ultrasonic waves. It is more preferable that the first ultrasonic wave generating portion 11 is provided in the puncturing portion 3a of the chemical solution injection tube 3. As a result, the first ultrasonic wave generating portion 11 can be inserted into the target tissue, and the drug solution diffusion effect can be further enhanced.
  • the first ultrasonic wave generating unit 11 includes at least two oscillators 11A, and the two oscillators 11A are provided on the side wall portion 3d of the chemical injection pipe 3.
  • the first ultrasonic wave generating unit 11 includes at least two single-oscillator type probes, and the vibrators 11AB of at least two single-oscillator type probes are provided on the side wall portion 3d of the chemical injection pipe 3. Is more preferable.
  • the ultrasonic irradiation direction, irradiation position, intensity, etc. can be changed without moving the first ultrasonic wave generating unit 11 itself.
  • the array method can be used.
  • the first ultrasonic wave generating unit 11 includes at least two oscillators 11A, the two oscillators 11A are provided on the side wall portion 3d of the chemical injection tube 3, and the phase of the ultrasonic waves generated from the two oscillators 11A is It is preferable that they are offset from each other. As a result, the irradiation direction, irradiation position, intensity, and the like of the ultrasonic waves can be changed without moving the first ultrasonic wave generation unit 11 itself.
  • the phases of the ultrasonic waves generated from the two vibrators 11A are preferably T / 4 or more, more preferably T / 3 or more, and further preferably 2T / 5 or more.
  • the deviation is preferably 3T / 4 or less, more preferably 2T / 3 or less, and further preferably T / 2 or less.
  • T is the vibration period (unit: s) of the ultrasonic wave.
  • the two vibrators 11A which are out of phase with each other, are arranged next to each other in the circumferential direction of the chemical injection pipe 3. By arranging the vibrators 11A in this way, it becomes easier to control the interference of the ultrasonic wavefronts of the two vibrators 11A.
  • the first ultrasonic wave generating unit 11 includes at least two oscillators 11A, and the two oscillators 11A are provided on the side wall portion 3d of the chemical injection pipe 3, and the intensity of the ultrasonic waves generated from the two oscillators 11A is high. It is preferable that each is controlled so as to be different. By configuring the first ultrasonic wave generation unit 11 in this way, it is possible to change the ultrasonic wave irradiation direction, irradiation position, intensity, and the like without moving the first ultrasonic wave generation unit 11 itself.
  • the vibrator 11A can be formed into, for example, a polygonal shape such as a rectangular shape or a strip shape, a ring shape, or the like. With such a shape, a plurality of oscillators 11A can be arranged in an array, that is, regularly.
  • a polygonal shape such as a rectangular shape or a strip shape
  • the vibrator 11A into a ring shape ultrasonic waves can be generated over a wide range at one time, so that the chemical solution injected into the target tissue can be easily diffused in the circumferential direction.
  • the plurality of ring-shaped vibrators 11A can be easily arranged side by side in the longitudinal axis direction of the chemical injection pipe 3.
  • the number of vibrators 11A provided in the first ultrasonic wave generating unit 11 is not particularly limited, but it is more preferable that 8 or more are provided, 16 or more are further preferably provided, and 32 or more are provided. It is even more preferable that 64 or more are provided, and 256 or less may be provided, or 128 or less may be provided. By setting the number of oscillators 11A in this way, it is possible to accurately control the irradiation direction, irradiation position, intensity, and the like of ultrasonic waves.
  • the first ultrasonic wave generating unit 11 includes a plurality of vibrators 11A, and the plurality of vibrators 11A are continuously arranged.
  • the two oscillators 11A are arranged adjacent to each other in the circumferential direction of the chemical injection pipe 3.
  • the vibrator 11A is provided in this way, it is possible to construct an image in the 360-degree direction by sequentially receiving diagnostic ultrasonic waves in the circumferential direction.
  • the intensity of ultrasonic waves and the oscillation frequency can be changed depending on the position of the chemical injection tube 3 in the circumferential direction.
  • the arrangement of the plurality of oscillators 11A is not particularly limited, and may be arranged side by side in the longitudinal axis direction of the chemical solution injection tube 3, or arranged side by side in the longitudinal axis direction and the circumferential direction of the chemical solution injection tube 3. You may.
  • FIG. 4 is a cross-sectional side view showing a modified example of the chemical solution diffusion promoting device 2 shown in FIG.
  • the side wall portion 3d of the chemical solution injection pipe 3 is provided with a recess 3g.
  • at least a part of the first ultrasonic wave generating portion 11 is arranged in the recess 3g.
  • the recess 3g As a result, at least a part of the first ultrasonic wave generating portion 11 can be accommodated in the recess 3g, so that it is possible to prevent the first ultrasonic wave generating portion 11 from excessively protruding outward in the radial direction of the chemical solution injection pipe 3. it can. Therefore, it becomes easy to puncture the target tissue of the drug solution injection tube 3.
  • the outer end of the first ultrasonic wave generating unit 11 is at the same position as the outer end of the chemical injection pipe 3, or is inward of the outer end of the chemical injection pipe 3. It is preferably located at.
  • the first ultrasonic wave generating unit 11 does not protrude outward in the radial direction from the surface of the chemical solution injection tube 3, so that the target tissue of the chemical solution injection tube 3 is reached. It becomes easier to puncture.
  • the chemical solution diffusion promoting device 2 as shown in FIG. 4, an embodiment in which the entire first ultrasonic wave generating unit 11 is arranged in the recess 3g of the chemical solution injection pipe 3 can be mentioned.
  • the first ultrasonic wave generating portion 11 is arranged outside the outer surface of the side wall portion 3d of the chemical solution injection pipe 3, but as shown in FIG. 4, the first ultrasonic wave generating portion 11 is arranged. 1 At least a part of the ultrasonic wave generating portion 11 may be arranged in the wall of the side wall portion 3d. Further, although not shown, at least a part of the first ultrasonic wave generating portion 11 may be arranged in the lumen of the side wall portion 3d.
  • the sound absorbing material 11B is provided inward of the vibrator 11A in the radial direction of the chemical injection pipe 3.
  • the oscillator 11A is preferably supported by the sound absorbing material 11B.
  • the vibrator 11A is supported from the back surface by the sound absorbing material 11B, so that the deformation of the vibrator 11A can be suppressed.
  • the sound absorbing material 11B may be made of a material having an appropriate ultrasonic attenuation rate and acoustic impedance, and is made of, for example, a mixture containing a base material and a filler.
  • a base material include resins such as natural rubber, synthetic rubber, epoxy resin, and vinyl chloride resin.
  • the filler material include metal oxides and ceramic fine particles.
  • the vibrator 11A is arranged outside the chemical injection pipe 3 in the radial direction of the chemical injection pipe 3 and the specific gravity of the chemical injection pipe 3 is 1 or less. Since the specific gravity of the living tissue is approximately 1, the ultrasonic waves radiated inward from the vibrator can be attenuated by imparting the sound absorbing effect to the chemical injection tube 3 itself in this way.
  • the first ultrasonic wave generating unit 11 may have directivity in the propagation direction of ultrasonic waves. In that case, since it is not necessary to provide a plurality of vibrators 11A in the chemical injection pipe 3, it is possible to suppress an increase in the diameter of the chemical injection pipe 3 in the portion where the first ultrasonic wave generating portion 11 is provided. As a result, the burden on the patient for puncturing the drug solution injection tube 3 into the target tissue can be reduced.
  • the acoustic matching layer 11C may be provided on the outer side in the radial direction from the vibrator 11A. This makes it easier for the ultrasonic waves from the first ultrasonic wave generating unit 11 to enter the tumor. Further, from the viewpoint of focusing ultrasonic waves, it is preferable that the first ultrasonic wave generating unit 11 is provided with an acoustic lens on the outer side in the radial direction with respect to the vibrator 11A. The acoustic lens can be provided on the outer side in the radial direction with respect to the acoustic matching layer 11C.
  • the oscillator 11A and an energy supply source such as a power supply can be connected by a conducting wire.
  • the conducting wire can be arranged inside the side wall portion 3d of the chemical solution injection pipe 3 or on the outer surface or the inner surface of the side wall portion 3d.
  • Examples of the conducting wire include those using a conductor of electric energy or light energy, and the surface may be coated.
  • a conducting wire in which the core of the conductive material is coated with a non-conductive material, an optical fiber, or the like can be used.
  • a large diameter portion having the above may be provided.
  • a ring-shaped member provided on the outer side in the radial direction of the chemical solution injection pipe 3 can be mentioned. Due to the presence of the large diameter portion, even if the drug solution injected into the target tissue flows back to the proximal side, it can be blocked.
  • a second chemical injection tube that punctures the target tissue in the living body is further provided in the lumen 3b of the chemical injection tube 3 in which the first ultrasonic wave generating portion 11 is provided on the side wall portion 3d. You may be.
  • the drug solution can be discharged not only from the drug solution injection tube 3 but also from the second drug solution injection tube, so that the drug solution can be easily distributed throughout the tumor, and the therapeutic effect of the drug solution can be enhanced.
  • the description of the chemical injection tube 3 can be referred to.
  • the configuration of the second chemical injection tube may be the same as or different from the configuration of the chemical injection tube 3.
  • the type of the chemical solution supplied into the second chemical solution injection tube may be the same as or different from the type of the chemical solution supplied into the chemical solution injection tube 3.
  • the second chemical injection pipe can be moved in the longitudinal axis direction of the chemical injection pipe 3 with respect to the chemical injection pipe 3. Thereby, the discharge position of the chemical solution from the second chemical solution injection tube can be adjusted according to the shape of the target tissue or the like.
  • the distal end of the second drug solution injection tube is located distal to the distal end of the drug solution injection tube 3. It is preferable to do so.
  • the drug solution can be discharged from the second drug solution injection tube at a position distal to the drug solution injection tube 3, so that the drug solution can easily reach the distal side of the target tissue and the therapeutic effect of the drug solution is enhanced. be able to.
  • an ultrasonic wave generating part (hereinafter referred to as a "fourth ultrasonic wave generating part") may be provided on the side wall of the second chemical injection pipe.
  • the fourth ultrasonic wave generating unit is a portion that generates the fourth ultrasonic wave for diffusing the chemical solution, similarly to the first ultrasonic wave generating unit 11.
  • the oscillation frequency and ultrasonic output of the fourth ultrasonic wave can be appropriately set according to the type of treatment, the type and dose of the drug solution.
  • the oscillation frequency and ultrasonic output of the fourth ultrasonic wave may be the same as or different from that of the first ultrasonic wave.
  • the description of the first ultrasonic wave generating unit 11 can be referred to.
  • the fourth ultrasonic wave generating portion When the fourth ultrasonic wave generating portion is provided on the side wall portion of the second chemical solution injection tube, the fourth ultrasonic wave is generated when the second chemical solution injection tube is moved to the most distal side with respect to the chemical solution injection tube 3.
  • the distal end of the generating portion is preferably located distal to the distal end of the first ultrasonic generating portion 11.
  • the fourth ultrasonic wave for diffusing the drug solution can be generated by the fourth ultrasonic wave generator at a position distal to the drug solution injection tube 3, so that the drug solution can be easily spread throughout the tumor, and the treatment with the drug solution is performed. The effect can be enhanced.
  • FIG. 5 shows a cross-sectional side view showing a modified example of the chemical solution diffusion promoting device shown in FIG. 2, and FIG. 6 shows a cross-sectional view of the chemical solution diffusion promoting device shown in FIG. 5 along the VI-VI line.
  • the first ultrasonic wave generating unit 11 is provided in the cavity 3b of the chemical injection pipe 3, and has a rotation shaft 11d parallel to the longitudinal axis direction of the chemical injection pipe 3. You may have. In that case, it is preferable that the first ultrasonic wave generating unit 11 rotates 360 degrees around the rotation axis 11d. By providing the first ultrasonic wave generating unit 11 in this way, the mechanical scanning type chemical solution diffusion promoting device 2 can be obtained. The same configuration as the chemical solution diffusion promoting device 2 shown in FIGS. 2 to 4 will not be described.
  • the first ultrasonic wave generating unit 11 When the first ultrasonic wave generating unit 11 is provided in the cavity 3b of the chemical solution injection tube 3 and has a rotation axis 11d parallel to the longitudinal axis direction of the chemical solution injection tube 3, the first ultrasonic wave is generated. It is preferable that the portion 11 has directivity in the propagation direction of the ultrasonic wave. This makes it easier to irradiate the necessary portion of the target tissue with ultrasonic waves from the first ultrasonic wave generating unit 11.
  • the specific gravity of the chemical solution injection tube 3 is preferably 1 or more.
  • the specific gravity of at least a part of the chemical injection pipe 3 in the longitudinal axis direction is preferably 1 or more.
  • the specific gravity of the portion of the chemical injection pipe 3 that overlaps with the first ultrasonic wave generating portion 11 in the longitudinal direction is It is more preferably 1 or more.
  • the chemical solution diffusion promoting device 2 further includes an interpolation member 4 arranged in the lumen 3b of the chemical injection tube 3.
  • An embodiment in which the first ultrasonic wave generating portion 11 is held at the distal end portion of the interpolation member 4 can be mentioned.
  • the chemical solution can flow to the outside of the interpolation member 4 in the lumen 3b of the chemical solution injection tube 3.
  • the interpolation member 4 is arranged in the hollow shaft 4A extending in the longitudinal axis direction of the chemical injection pipe 3 and the lumen of the shaft 4A, and is arranged in the lumen of the shaft 4A, and is the longitudinal length of the shaft 4A. It can be configured to have a support member 4B extending in the axial direction. In that case, the first ultrasonic wave generating portion 11 can be fixed to the distal portion of the support member 4B.
  • the support member 4B may be fixed to the shaft 4A or may not be fixed to the shaft 4A.
  • the distal end of the shaft 4A is preferably closed in order to prevent the chemical solution from entering the lumen of the shaft 4A.
  • the material of the shaft 4A may be the same as or different from the material of the chemical injection tube 3.
  • the shaft 4A is a tubular body, a metal tube, or a combination thereof formed by arranging a resin tube, a single wire or a plurality of wires, and a stranded wire in a specific pattern, similarly to the chemical injection pipe 3. Can be used.
  • the specific gravity of the portion of the shaft 4A that overlaps with the first ultrasonic wave generating unit 11 in the longitudinal axis direction Is preferably 1 or more.
  • the method of fixing the first ultrasonic wave generating portion 11 to the distal portion of the support member 4B is not particularly limited, and as shown in FIG. 5, a flat portion 4Ba is provided at the distal portion of the support member 4B, and the flat portion 4Ba is provided with the flat portion 4Ba.
  • the first ultrasonic wave generating unit 11 may be fixed. Further, the first ultrasonic wave generating portion 11 may be connected to the distal end portion of the support member 4B. The first ultrasonic wave generating portion 11 may be provided on the distal side of the support member 4B.
  • Examples of the support member 4B include a rod-shaped member and a torque wire.
  • Examples of the torque wire include a coil body formed by spirally winding one or a plurality of wires.
  • the support member 4B is a torque wire. As a result, the rotational torque on the proximal side can be efficiently transmitted to the first ultrasonic wave generating unit 11.
  • the shaft 4A when the support member 4B is fixed to the shaft 4A, the shaft 4A may be rotated on the hand side in order to change the propagation direction of ultrasonic waves. Therefore, in this case, it is preferable that the wire rods are arranged on the shaft 4A in a specific pattern. By configuring the shaft 4A in this way, it is possible to efficiently transmit the rotational torque on the proximal side to the first ultrasonic wave generating unit 11.
  • the interpolation member 4 is movable with respect to the chemical injection pipe 3 in the longitudinal axis direction of the chemical injection pipe 3. As a result, the irradiation position of the first ultrasonic wave from the first ultrasonic wave generating unit 11 can be adjusted according to the shape of the target tissue and the like.
  • the distal end of the insertion member 4 is located on the distal side of the distal end of the drug solution injection tube 3. Is preferable.
  • the first ultrasonic wave can be generated at a position distal to the drug solution injection tube 3, so that the drug solution can be easily distributed throughout the tumor, and the therapeutic effect of the drug solution can be enhanced.
  • the interpolation member 4 as shown in FIGS. 5 to 6 may be provided in the lumen 3b of the chemical solution injection tube 3 shown in FIGS. 2 to 4. That is, the first ultrasonic wave generating portion 11 is provided on the side wall portion 3d of the chemical liquid injection pipe 3, and the second insertion member is arranged in the lumen 3b of the chemical liquid injection pipe 3, and the second insertion member of the second insertion member.
  • An ultrasonic wave generating part (hereinafter referred to as a “fifth ultrasonic wave generating part”) may be held at the distal end portion.
  • the fifth ultrasonic wave generating unit is a portion that generates the fifth ultrasonic wave for diffusing the chemical solution, similarly to the first ultrasonic wave generating unit 11.
  • the oscillation frequency and ultrasonic output of the fifth ultrasonic wave can be appropriately set according to the type of treatment, the type and dose of the drug solution.
  • the oscillation frequency and ultrasonic output of the fifth ultrasonic wave may be the same as or different from that of the first ultrasonic wave.
  • the configuration of the fifth ultrasonic wave generating unit the description of the first ultrasonic wave generating unit 11 can be referred to.
  • the second insertion member When the fifth ultrasonic generator is held at the distal end of the second insertion member, the second insertion member is moved to the most distal side with respect to the drug solution injection tube 3.
  • the distal end of the insertion member is preferably located distal to the distal end of the drug solution injection tube 3, and the distal end of the fifth ultrasonic generator is far from the first ultrasonic generator 11. It is more preferably located distal to the position end.
  • the fifth ultrasonic wave for diffusing the drug solution can be generated by the fifth ultrasonic wave generator at a position distal to the drug solution injection tube 3, so that the drug solution can be easily spread throughout the tumor, and the treatment with the drug solution is performed. The effect can be enhanced.
  • the ultrasonic control unit 20 is connected to the first ultrasonic wave generation unit 11 and controls the irradiation conditions of the first ultrasonic wave according to the two-dimensional or three-dimensional image of the target tissue. Specifically, at least one of the propagation direction, intensity, and oscillation frequency of the first ultrasonic wave generated by the first ultrasonic wave generating unit 11 is controlled. According to the chemical diffusion system 1, at least one of the propagation direction, intensity, and oscillation frequency of the first ultrasonic wave is controlled according to the two-dimensional or three-dimensional image of the target tissue, so that the state of the target tissue is adjusted. Therefore, the drug solution can be appropriately diffused to the required site.
  • the irradiation conditions of the first ultrasonic wave can be appropriately set according to the shape, size, spread, hardness, etc. of the tumor, such as when the distance between the two differs depending on the position of the drug solution injection tube 3 in the circumferential direction. it can. Therefore, the drug solution can be easily spread over the entire tumor, and the therapeutic effect of the drug solution can be enhanced. In addition, it is possible to shorten the irradiation time of ultrasonic waves required for treatment, which contributes to reducing the burden on the patient and the operator.
  • the ultrasonic control unit 20 changes at least one of the propagation direction, intensity, and oscillation frequency of the ultrasonic waves generated by the first ultrasonic wave generation unit 11 with respect to the time with respect to the first ultrasonic wave generation unit 11. It is preferable to issue a command signal to make the sound wave. By changing the ultrasonic conditions over time in this way, the diffusion promoting effect of the chemical solution can be enhanced.
  • a two-dimensional or three-dimensional image of the target tissue can be obtained by using an image forming unit 23 preferably included in the chemical diffusion system 1 or an external device not included in the system 1.
  • the ultrasonic control unit 20 controls the irradiation conditions of the first ultrasonic wave according to the acquired two-dimensional or three-dimensional image of the target tissue.
  • the ultrasonic control unit 20 commands the first ultrasonic wave generation unit 11 to change at least one of the intensity of the first ultrasonic wave and the oscillation frequency depending on the position in the longitudinal axis direction or the circumferential direction of the chemical solution injection pipe 3. A signal may be emitted. This makes it possible to set the irradiation conditions of the first ultrasonic wave according to the condition of the tumor and the degree of penetration of the drug solution into the tumor before the irradiation of the first ultrasonic wave, and it is possible to enhance the diffusion effect of the drug solution. It becomes.
  • FIG. 7 is an image diagram of an ultrasonic diagnostic image when the drug solution injection tube 3 and the first ultrasonic wave generating portion 11 shown in FIG. 2 are punctured into the tumor 100. As shown in FIG.
  • the ultrasonic control unit 20 is the first in the circumferential direction of the drug solution injection tube 3 as the radial distance from the longitudinal axis center 3f of the drug solution injection tube 3 to the outer edge 101 of the tumor 100 is longer.
  • a command signal may be issued to increase the intensity x of the sound wave. This makes it easier for the drug solution to spread throughout the tumor, so that the therapeutic effect of the drug solution can be enhanced.
  • the fact that the intensity distribution of the first ultrasonic wave is unevenly distributed from the center 3f of the longitudinal axis of the chemical injection tube 3 means that the intensity x of the ultrasonic wave differs depending on the position in the circumferential direction of the chemical injection tube 3.
  • the ultrasonic control unit 20 lowers the oscillation frequency of the first ultrasonic wave in the circumferential direction of the chemical injection tube 3 as the radial distance from the center 3f of the longitudinal axis of the chemical injection tube 3 to the outer edge 101 of the tumor 100 is longer.
  • a command signal may be issued.
  • a program for performing each process of at least one of the ultrasonic control unit 20 and the processing unit 30 described later may be recorded on a computer-readable medium. This allows you to install the above program on your computer.
  • the computer-readable medium on which the program is recorded may be a non-transient recording medium. Examples of the non-transient recording medium include a recording medium such as a CD-ROM.
  • the chemical diffusion system 1 can include a processor for executing the above program in at least one of the ultrasonic control unit 20 and the processing unit 30 described later.
  • Processors include microprocessors mounted on integrated circuits.
  • the computer may include a processor and a storage device described below.
  • on-off control may be used, variable PI control may be used, or PID control may of course be used.
  • FIG. 8 shows an example of the treatment flow in the drug solution diffusion system 1 shown in FIG. Using the drug solution diffusion system 1 of FIG. 1, the following procedure can be performed.
  • the drug solution injection tube 3 is punctured into the target tissue (step S1).
  • step S1 it is preferable that the first ultrasonic wave generating unit 11 is arranged in the target tissue.
  • the drug solution is injected into the target tissue (step S2).
  • the ultrasonic control unit 20 controls the irradiation conditions of the first ultrasonic wave according to the two-dimensional or three-dimensional image of the target tissue (step S3).
  • step S3 at least one of the propagation direction, intensity, and oscillation frequency of the first ultrasonic wave generated by the first ultrasonic wave generating unit 11 is controlled.
  • the first ultrasonic wave is irradiated to the target tissue using the first ultrasonic wave generating unit 11 (step S4).
  • a two-dimensional or three-dimensional image of the target tissue may be obtained after the irradiation of the first ultrasonic wave in step S4 (step S5). It is preferable to confirm the diffusion state of the drug solution using the image obtained in step S5 (step S6). When it is determined in step S6 that the diffusion state of the chemical solution has not reached the target value, it is preferable to return to step S3 to control the irradiation conditions of the first ultrasonic wave and carry out step S4 and subsequent steps. If it is determined in step S6 that the diffusion state of the drug solution has reached the target value, the treatment is terminated.
  • the chemical diffusion system 1 may further include a second ultrasonic wave generating unit 12 that generates a second ultrasonic wave having an oscillation frequency different from that of the first ultrasonic wave.
  • a two-dimensional or three-dimensional image of the target tissue can be formed by using the reflected wave when the target tissue is irradiated with the second ultrasonic wave. That is, the second ultrasonic wave can be used to generate a diagnostic image.
  • the image formed by using the reflected wave when the target tissue is irradiated with the second ultrasonic wave may be a two-dimensional image or a three-dimensional image. Further, the image formed by using the reflected wave may be a still image or a moving image.
  • the oscillation frequency and ultrasonic output of the second ultrasonic wave generated by the second ultrasonic wave generating unit 12 can be appropriately set according to the type of treatment, the type and dose of the chemical solution.
  • the oscillation frequency of the second ultrasonic wave may be higher than the oscillation frequency of the first ultrasonic wave.
  • the oscillation frequency of the second ultrasonic wave is preferably 20 MHz or more, more preferably 30 MHz or more. It is more preferably 40 MHz or more, more preferably 100 MHz or less, more preferably 90 MHz or less, and even more preferably 80 MHz or less.
  • the ultrasonic output Ispta of the second ultrasonic wave is preferably 30 mW / cm 2 or more, more preferably 50 mW / cm 2 or more, further preferably 100 mW / cm 2 or more, and 720 W / cm 2 or more. preferably cm 2 or less, more preferably 500 W / cm 2 or less, and more preferably 300 W / cm 2 or less.
  • the second ultrasonic wave generating unit 12 may be provided in the chemical solution injection pipe 3 as shown in FIGS. 1 to 2, but may be provided in the outer tube 5, and is separate from the chemical solution diffusion promoting device 2. It may be provided. Further, the first ultrasonic wave generating unit 11 may also serve as the second ultrasonic wave generating unit 12. That is, the first ultrasonic wave generating unit 11 may generate the first ultrasonic wave and the second ultrasonic wave.
  • the description of the first ultrasonic wave generating unit 11 can be referred to.
  • the ultrasonic control unit 20 determines the type of the chemical solution supplied to the chemical solution injection tube 3 or It is preferable to control the amount. As a result, the drug solution can be appropriately administered to the target tissue.
  • the chemical diffusion system 1 is connected to the ultrasonic control unit 20 and has an image forming unit 23 that forms an image using the reflected wave when the target tissue is irradiated with the second ultrasonic wave.
  • a storage unit 25 which is connected to the ultrasonic control unit 20 and stores an image formed by the image forming unit 23.
  • the image formed by using the reflected wave when the target tissue is irradiated with the second ultrasonic wave visualizes the state of the target tissue before, after the injection of the chemical solution, after the irradiation, etc., and can be used for diagnosis. ..
  • the image for diagnosis is stored in the storage unit 25, the data can be appropriately read out when the data is processed in the processing unit described later, so that the validity of the treatment can be verified and a further treatment policy can be formulated. Can contribute to.
  • the image forming unit 23 forms a two-dimensional or three-dimensional image of the target tissue by using the reflected wave when the target tissue is irradiated with the second ultrasonic wave.
  • the image forming unit 23 is preferably connected to the storage unit 25.
  • the image formed by the image forming unit 23 can be transmitted to the storage unit 25, so that the image can be read out from the storage unit 25 when the irradiation conditions are set.
  • a processor preferably provided in the chemical solution diffusion system 1 may execute the program of the image forming unit 23.
  • the image forming unit 23 may be connected to a processing unit 30 described later. As a result, the processing unit 30 can perform processing necessary for grasping the state of the target tissue, such as comparison between images, using the image formed by the image forming unit 23.
  • the storage unit 25 may be a main storage device such as a RAM or ROM included in the computer, or an auxiliary storage device such as a hard disk.
  • the chemical diffusion system 1 is connected to a receiving unit that receives the reflected wave when the target tissue is irradiated with the second ultrasonic wave, and the second ultrasonic wave is applied to the target tissue. It may further have a display unit for displaying an image formed by using the reflected wave when irradiated.
  • the image forming unit 23 is preferably connected to the receiving unit. As a result, the reflected wave when the target tissue is irradiated with the second ultrasonic wave through the receiving unit can be transmitted to the image forming unit 23.
  • the chemical solution diffusion system 1 further has a processing unit 30 connected to the ultrasonic control unit 20.
  • the processing unit 30 can perform various processes such as calculation and comparison for grasping the state of the target organization.
  • the processing unit 30 compares the image of the target tissue before the injection of the chemical solution with the image of the target tissue after the injection of the chemical solution, and the ultrasonic control unit 20 uses the comparison result of the processing unit 30 to make a first comparison. 1 It is preferable to control the ultrasonic irradiation conditions. This makes it possible to set appropriate irradiation conditions based on the comparison result of the state of the target tissue before and after the injection of the drug solution.
  • the processing unit 30 compares the image of the target tissue before the chemical solution injection with the image of the target tissue after the chemical solution injection and after the irradiation of the first ultrasonic wave, and the ultrasonic control unit 20 is the processing unit. It is preferable to control the irradiation condition of the first ultrasonic wave by using the comparison result in No. 30. Thereby, based on the comparison result of the state of the target tissue before the injection of the chemical solution and after the injection of the chemical solution and after the irradiation of the first ultrasonic wave, it is determined whether or not the irradiation of the additional first ultrasonic wave is necessary. be able to.
  • the processing unit 30 compares the image of the target tissue after the injection of the chemical solution and before the irradiation of the first ultrasonic wave with the image of the target tissue after the injection of the chemical solution and after the irradiation of the first ultrasonic wave. It is preferable that the ultrasonic control unit 20 controls the irradiation conditions of the first ultrasonic wave by using the comparison result of the processing unit 30. Thereby, based on the comparison result of the state of the target tissue after the injection of the chemical solution and before and after the irradiation of the first ultrasonic wave, it is possible to determine whether or not the irradiation of the additional first ultrasonic wave is necessary.
  • the processing unit 30 includes an image of the target tissue after the injection of the chemical solution and after the nth irradiation of the first ultrasonic wave, and an image of the target tissue after the injection of the chemical solution and after the n + 1th irradiation of the first ultrasonic wave. It is preferable that the ultrasonic control unit 20 controls the irradiation condition of the first ultrasonic wave n + 2 by using the comparison result in the processing unit 30. Note that n is an integer of 1 or more. Thereby, the irradiation condition of the n + 2nd first ultrasonic wave can be appropriately set according to the state of the target tissue.
  • FIG. 9 shows another example of the treatment flow in the drug solution diffusion system 1 shown in FIG.
  • the flow shown in FIG. 9 is a two-dimensional or three-dimensional image using the reflected wave when the second ultrasonic wave is generated by the second ultrasonic wave generating unit 12 and the second ultrasonic wave is applied to the target tissue.
  • the flow is different from that shown in FIG. 8 in that the formed image is used for controlling the irradiation condition of the first ultrasonic wave and determining the diffusion state of the chemical solution.
  • the drug solution injection tube 3 is punctured into the target tissue (step S11).
  • step S11 it is preferable that the first ultrasonic wave generating unit 11 and the second ultrasonic wave generating unit 12 are arranged in the target tissue.
  • the second ultrasonic wave generation unit 12 generates a second ultrasonic wave, and a two-dimensional or three-dimensional image is formed by using the reflected wave when the target tissue is irradiated with the second ultrasonic wave (step S12). This makes it possible to visualize the state of the target tissue before injecting the drug solution.
  • the drug solution is injected into the target tissue (step S13).
  • the second ultrasonic wave is generated by the second ultrasonic wave generator 12, and the reflected wave when the second ultrasonic wave is applied to the target tissue is used to make the target tissue two-dimensional or tertiary after the injection of the chemical solution.
  • the original image may be formed (step S14).
  • the ultrasonic control unit 20 controls the irradiation condition of the first ultrasonic wave according to the two-dimensional or three-dimensional image of the target tissue at least before or after the drug solution injection (step S15). According to the irradiation conditions set in step S15, the first ultrasonic wave is irradiated to the target tissue using the first ultrasonic wave generating unit 11 (step S16).
  • the second ultrasonic wave is generated by the second ultrasonic wave generating unit 12, and the reflected wave when the second ultrasonic wave is irradiated to the target tissue is used to inject the chemical solution and the target tissue after the irradiation of the first ultrasonic wave.
  • Form a two-dimensional or three-dimensional image of (step S17). It is preferable to confirm the diffusion state of the drug solution using the image formed in step S17 (step S18). When it is determined in step S18 that the diffusion state of the chemical solution has not reached the target value, it is preferable to return to step S15 to control the irradiation conditions of the first ultrasonic wave and carry out step S16 and subsequent steps.
  • step S18 when it is determined that the diffusion state of the drug solution has reached the target value and the diffusion state of the drug solution has reached the target value, the treatment is terminated.
  • FIG. 10 shows another example of the treatment flow in the drug solution diffusion system 1 shown in FIG. Using the drug solution diffusion system 1 of FIG. 1, the following procedure may be performed.
  • steps S21 to S27 shown in FIG. 10 are the same as steps S11 to S17 shown in FIG. 9, description thereof will be omitted.
  • step S27 in the processing unit 30, a two-dimensional or three-dimensional image of the target tissue formed in step S22 before injection of the chemical solution and after injection of the chemical solution formed in step S27.
  • the two-dimensional or three-dimensional images of the target tissue after irradiation with the first ultrasonic waves are compared (step S28).
  • step 28 when it is determined that the diffusion state of the chemical solution has not reached the target value based on the comparison result of the images, the process returns to step S25 to control the irradiation condition of the first ultrasonic wave, and steps S26 and subsequent steps are performed. It is preferable to carry out.
  • step S28 when it is determined that the diffusion state of the drug solution has reached the target value based on the comparison result of the images, the treatment is terminated.
  • FIG. 11 shows a block diagram showing a modified example of the chemical solution diffusion system 1 shown in FIG.
  • the second ultrasonic wave generating unit 12 may be provided outside the chemical injection pipe 3. That is, the chemical solution diffusion system 1 may have a diagnostic ultrasonic wave generator having a second ultrasonic wave generator 12 in addition to the chemical solution diffusion promoting device 2.
  • the treatment can be performed in the same flow as the chemical solution diffusion system 1 of FIG.
  • the chemical solution diffusion system 1 may have an image forming portion 23. The same applies to the aspects shown below.
  • FIG. 12 shows a block diagram showing another modification of the drug solution diffusion system 1 shown in FIG.
  • the chemical solution diffusion system 1 has a chemical solution injection pipe 3, an ultrasonic control unit 20, a processing unit 30, and a data storage unit 35 connected to the ultrasonic control unit 20. May be good.
  • the data storage unit 35 can store reference data necessary for setting the irradiation conditions of the first ultrasonic wave.
  • the data storage unit 35 may be a main storage device such as a RAM or ROM included in the computer, or an auxiliary storage device such as a hard disk. That is, the storage unit 25 and the data storage unit 35 can be provided in the main storage device and the auxiliary storage device.
  • the data storage unit 35 stores a diffusion pattern table containing data on the diffusion pattern of the drug solution according to the type of tumor.
  • the processing unit 30 compares the reference result of the diffusion pattern table with the image of the target tissue after the injection of the chemical solution and after the irradiation of the first ultrasonic wave, and the ultrasonic control unit 20 processes. It is preferable to control the irradiation condition of the first ultrasonic wave by using the comparison result in the part 30. As a result, whether or not additional first ultrasonic wave irradiation is necessary based on the reference result of the diffusion pattern table and the comparison result of the state of the target tissue after the chemical solution injection and after the first ultrasonic wave irradiation. Can be determined.
  • the tumor type data stored in the diffusion pattern table includes the site where the tumor is formed, the shape, the size, the spread, the hardness, and the like.
  • the diffusion pattern data of the drug solution stored in the diffusion pattern table is formed by using the reflected wave when the target tissue is irradiated with ultrasonic waves for diagnosis before injecting the drug solution into the tumor in the past cases.
  • a two-dimensional or three-dimensional image of the image can be mentioned.
  • the chemical solution diffusion system 1 may have a storage unit 25 and a data storage unit 35. This makes it possible to compare the image stored in the storage unit 25 with the data stored in the data storage unit 35.
  • the chemical solution diffusion system 1 is connected to a proximal portion of the chemical solution injection pipe 3 and is connected to a liquid supply unit 40 for supplying the chemical solution into the chemical solution injection tube 3 and an ultrasonic control unit 20. It may further have a data storage unit 35 and the like.
  • the data storage unit 35 has a drug solution table containing data on the type of the drug solution, and a tumor table containing data indicating the state of the tumor diagnosed in the past, and the ultrasonic control unit 20 has the ultrasonic control unit 20. It is preferable to select the type of the drug solution from the drug solution table based on the reference result of the tumor table and issue a command signal to the liquid supply unit 40 to supply the selected type of drug solution into the drug solution injection tube 3. As a result, an appropriate type of drug solution suitable for the type of tumor can be selected, so that the drug solution diffusion effect can be further enhanced.
  • the liquid supply unit 40 is a member for supplying the chemical solution to the cavity 3b of the chemical solution injection tube 3, and for example, an injection pump controlled by a syringe or a motor can be used.
  • the data storage unit 35 further has a frequency table including data of the oscillation frequency of the first ultrasonic wave.
  • the ultrasonic control unit 20 selects the value of the oscillation frequency of the first ultrasonic wave from the frequency table based on the reference result of the tumor table, and the selected oscillation with respect to the first ultrasonic wave generation unit 11. It is preferable to emit a command signal that generates a first ultrasonic wave of frequency. As a result, an appropriate oscillation frequency of the first ultrasonic wave can be selected according to the type of tumor, so that the drug solution diffusion effect in the target tissue can be further enhanced.
  • FIG. 13 shows an example of the treatment flow in the drug solution diffusion system 1 shown in FIG. Using the drug solution diffusion system 1 of FIG. 12, the following procedure can be performed.
  • steps S31 to S37 shown in FIG. 13 are the same as steps S11 to S17 shown in FIG. 9, description thereof will be omitted.
  • the flow shown in FIG. 13 differs from the flow of FIG. 9 in that the processing unit 30 has a diffusion pattern table provided with data on the diffusion pattern of the drug solution according to the type of tumor stored in the data storage unit 35.
  • the reference result of (step S38) is being compared with the image formed in step S37 after injection of the chemical solution and after irradiation with the first ultrasonic wave (step S38).
  • step S38 If it is determined that the diffusion state of the drug solution has not reached the target value based on the comparison result in step S38, the process returns to step S35 to control the irradiation condition of the first ultrasonic wave, and steps S36 and subsequent steps are performed. Is preferable. If it is determined that the diffusion state of the drug solution has reached the target value based on the comparison result in step S38, the treatment is terminated.
  • FIG. 14 shows a block diagram showing still another modification of the drug solution diffusion system 1 shown in FIG.
  • the chemical solution diffusion system 1 may further include a measuring unit 45 connected to the ultrasonic control unit 20.
  • the measuring unit 45 measures at least one of the shape, size, spread, and hardness of the tumor from the image before the injection of the drug solution
  • the ultrasonic control unit 20 is the measuring unit 45. It is preferable to control the irradiation condition of the first ultrasonic wave by using the measurement result of. As a result, the irradiation conditions of the first ultrasonic wave can be appropriately set according to the state of the tumor, so that the effect of diffusing the drug solution in the target tissue can be enhanced.
  • the measuring unit 45 is a part that analyzes the shape, size, spread, and hardness of the tumor before irradiation with the first ultrasonic wave by using a two-dimensional or three-dimensional image of the target tissue before injecting the drug solution. Is preferable. In that case, a processor preferably provided in the chemical solution diffusion system 1 may execute the program of the measuring unit 45.
  • the measuring unit 45 may be a device that directly measures various parameters such as the shape and size of the tumor.
  • a device for directly measuring the hardness of a tumor for example, an ultrasonic hardness meter can be mentioned.
  • the first ultrasonic wave generating unit 11 By generating ultrasonic waves having a frequency in a range suitable for measuring hardness, which is different from the first ultrasonic wave, the first ultrasonic wave generating unit 11 also serves as the measuring unit 45. can do.
  • the measurement unit 45 shows the shape, size, spread and hardness of the tumor from the image before the drug solution injection.
  • the ultrasonic control unit 20 measures the circumference of the drug solution injection tube 3 with respect to the first ultrasonic wave generating unit 11 by using the measurement result of the tumor in the measuring unit 45. It is preferable to emit a command signal that changes at least one of the intensity of the first ultrasonic wave and the oscillation frequency depending on the position in the direction. As a result, the irradiation conditions of the first ultrasonic wave can be appropriately set according to the state of the tumor, so that the effect of diffusing the drug solution in the target tissue can be further enhanced.
  • the harder the tumor the stronger the intensity of the ultrasonic waves generated by the first ultrasonic wave generating unit 11. This makes it easier for the drug solution to spread to the hard part of the tumor, so that the therapeutic effect of the drug solution can be enhanced.
  • the chemical diffusion system 1 further includes a third ultrasonic wave generating unit 13 that generates a third ultrasonic wave for heating the target tissue at an oscillation frequency different from that of the first ultrasonic wave. It is preferable to have.
  • the thermal effect the drug solution diffusion effect and the immunity enhancing effect in the target tissue can be further enhanced.
  • the oscillation frequency and ultrasonic output of the third ultrasonic wave can be appropriately set according to the type of treatment, the type and dose of the drug solution.
  • the oscillation frequency of the third ultrasonic wave may be lower than the oscillation frequency of the second ultrasonic wave, and is set to, for example, 10 kHz or more, 100 kHz or more, or 1 MHz or more, and 100 MHz or less, 10 MHz or less, 5 MHz or less. Is also acceptable. By setting the oscillation frequency in this way, the thermal effect can be exhibited.
  • the description of the first ultrasonic wave generating unit 11 can be referred to.
  • the first ultrasonic wave generating unit 11 may also serve as a second ultrasonic wave generating unit 12 for generating a second ultrasonic wave having an oscillation frequency different from that of the first ultrasonic wave and a third ultrasonic wave generating unit 13. That is, the first ultrasonic wave generating unit 11 has an oscillation frequency different from that of the first ultrasonic wave, the first ultrasonic wave, and the second ultrasonic wave used for image formation for diagnosis, and an oscillation frequency different from the first ultrasonic wave.
  • a third ultrasonic wave may be generated to heat the target tissue.
  • the chemical solution diffusion system 1 is connected to a proximal portion of the chemical solution injection pipe 3 and is connected to a liquid supply unit 40 for supplying the chemical solution into the chemical solution injection pipe 3 and a liquid supply unit 40. It is preferable to have a cooling unit 50 for cooling the chemical solution. As a result, the chemical solution whose temperature has been adjusted by the cooling unit 50 can be supplied into the chemical solution injection pipe 3, so that excessive heating of the chemical solution can be prevented.
  • the cooling unit 50 may directly cool the chemical solution, but it is preferable to cool the container in which the chemical solution is stored.
  • a cooler having fins formed around the container and air-cooled by a blower, a heat pump type cooler, a cooler using a Peltier element, or the like can be used.

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  • Animal Behavior & Ethology (AREA)
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  • Vascular Medicine (AREA)
  • Surgical Instruments (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
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PCT/JP2020/036226 2019-11-18 2020-09-25 薬液拡散システムおよび薬液拡散促進装置 WO2021100316A1 (ja)

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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001025467A (ja) * 1999-07-14 2001-01-30 Olympus Optical Co Ltd 超音波散布チューブ
JP2002521118A (ja) * 1998-07-29 2002-07-16 ファーマソニックス，インコーポレイテッド 薬物注射の超音波処理増強
JP2010520871A (ja) * 2007-03-09 2010-06-17 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 超音波感知粒子により搬送される物質の放出を制御する方法
JP2011500288A (ja) * 2007-10-26 2011-01-06 ユニバーシティ オブ バージニア パテント ファウンデーション 超音波エネルギーおよびマイクロバブルを使用する治療およびイメージング用システムおよびその関連方法
US20130046230A1 (en) * 2010-03-05 2013-02-21 Cornell University Ultrasound-assisted convection enhanced delivery of compounds in vivo with a transducer cannula assembly
JP2013517847A (ja) * 2010-01-26 2013-05-20 エイ． エヴァンズ，マイケル 除神経のための方法、装置、及び薬剤
WO2015049886A1 (ja) * 2013-10-03 2015-04-09 国立大学法人東北大学 薬剤注入装置および薬剤注入方法
JP2017502715A (ja) * 2013-11-18 2017-01-26 コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． 血栓分散方法及び装置

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002521118A (ja) * 1998-07-29 2002-07-16 ファーマソニックス，インコーポレイテッド 薬物注射の超音波処理増強
JP2001025467A (ja) * 1999-07-14 2001-01-30 Olympus Optical Co Ltd 超音波散布チューブ
JP2010520871A (ja) * 2007-03-09 2010-06-17 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 超音波感知粒子により搬送される物質の放出を制御する方法
JP2011500288A (ja) * 2007-10-26 2011-01-06 ユニバーシティ オブ バージニア パテント ファウンデーション 超音波エネルギーおよびマイクロバブルを使用する治療およびイメージング用システムおよびその関連方法
JP2013517847A (ja) * 2010-01-26 2013-05-20 エイ． エヴァンズ，マイケル 除神経のための方法、装置、及び薬剤
US20130046230A1 (en) * 2010-03-05 2013-02-21 Cornell University Ultrasound-assisted convection enhanced delivery of compounds in vivo with a transducer cannula assembly
WO2015049886A1 (ja) * 2013-10-03 2015-04-09 国立大学法人東北大学 薬剤注入装置および薬剤注入方法
JP2017502715A (ja) * 2013-11-18 2017-01-26 コーニンクレッカ フィリップス エヌ ヴェＫｏｎｉｎｋｌｉｊｋｅ Ｐｈｉｌｉｐｓ Ｎ．Ｖ． 血栓分散方法及び装置

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