WO2006059793A1 - 高強度パルス光照射により誘起される制御された音圧波による血管再狭窄予防治療用装置 - Google Patents
高強度パルス光照射により誘起される制御された音圧波による血管再狭窄予防治療用装置 Download PDFInfo
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- pulsed light
- sound pressure
- blood vessel
- intensity pulsed
- water vapor
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
- A61B18/26—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor for producing a shock wave, e.g. laser lithotripsy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
- A61B18/24—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor with a catheter
- A61B18/245—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor with a catheter for removing obstructions in blood vessels or calculi
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B2017/22001—Angioplasty, e.g. PCTA
- A61B2017/22002—Angioplasty, e.g. PCTA preventing restenosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
- A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
- A61B18/22—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
- A61B18/26—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor for producing a shock wave, e.g. laser lithotripsy
- A61B2018/263—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor for producing a shock wave, e.g. laser lithotripsy the conversion of laser energy into mechanical shockwaves taking place in a liquid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
- A61N2005/0602—Apparatus for use inside the body for treatment of blood vessels
Definitions
- the present invention relates to a device for preventing restenosis after percutaneous coronary angioplasty of a narrowed blood vessel by a sound pressure wave induced by irradiation with high-intensity pulsed light, and further, the sound pressure wave prevents restenosis. It relates to a device controlled to suit. Background art
- PTCA percutaneous coronary angioplasty
- PTCA percutaneous coronary angioplasty
- the restenosis rate after 3 months was as high as 30-40%.
- percutaneous coronary angioplasty by stent placement has been performed. According to this method, although the restenosis rate has decreased to 15 to 35%, there is a problem of in-stent restenosis, and stenting is not possible. If the sputum was in place, subsequent retreatment was difficult.
- Restenosis is caused by the vascular lumen being forcibly expanded by the balloon, and in the subsequent healing process, smooth muscle cells migrate and proliferate from the vascular media to the damaged site of the intima, or hematopoietic stem cells It has been reported that it is caused by adhesion to damaged blood vessels via adhesion factors, differentiation and proliferation into smooth muscle cells, and hyperplasia of the intima.
- a method using ultrasonic waves has been tried.
- smooth muscle cells using one or more anti-cytoskeletal agents such as cytochalasin B or cortisin.
- a method has also been developed to reduce restenosis by treating cells and irradiating them with an effective amount of ultrasonic energy to reduce smooth muscle cell migration, survival or adhesion (see Japanese Patent Publication No. 2002-502804). Gazette), the administration of an anti-cytoskeletal agent is essential.
- photodynamic therapy that suppresses neointimal thickening has also been attempted (W000 / 59505) I PDT drugs need to be administered to the patient in advance, and the time required for treatment is also a burden on the patient. Was also big.
- a method for preventing restenosis using a dispatch catheter having a drug administration means has been reported.
- a catheter is used, but a radiation source is provided at the distal end of the catheter, a heat generating means is provided in the catheter, or vibration for generating ultrasonic waves in the catheter. Since it was necessary to arrange a means for local administration of the source and drug, the catheter became thick and difficult to handle.
- Patent Document 1 Japanese Patent Laid-Open No. 7-289557
- Patent Document 2 Japanese Patent Publication No. 9-508038
- Patent Document 3 Japanese Patent Laid-Open No. 2001-46532
- Patent Literature 4 Special Table 2002-502804
- Patent Document 5 W000 / 59505 gazette Disclosure of Invention
- a high-intensity pulsed light irradiation means irradiates a blood vessel with high-intensity pulsed light to generate water vapor bubbles in the blood vessel, and a blood vessel that causes restenosis due to sound pressure waves generated when the bubbles contract or disappear It is a device that reduces the number of smooth muscle cells proliferating at the site of injury and suppresses the adhesion of hematopoietic stem cells.
- An object of the present invention is to provide an apparatus capable of controlling a sound pressure wave that can accurately prevent restenosis.
- restenosis causes damage to the blood vessel wall due to the forced expansion of the blood vessel lumen by the balloon, and cells, such as smooth muscle cells, migrate from the vascular media to the damaged site of the intima during the subsequent healing process.
- the present inventors have examined whether or not restenosis can be prevented by inhibiting the proliferation of smooth muscle cells and further preventing the adhesion of hematopoietic stem cells, and water vapor bubbles are generated when laser is irradiated in a liquid. Focusing on the phenomenon in which sound pressure waves are generated when the bubbles contract and disappear, a high-intensity pulsed light irradiation site is provided at the tip of the blood vessel catheter, and high-intensity pulsed light such as a laser is irradiated inside the blood vessel.
- a device capable of generating water vapor bubbles in a blood vessel is a device that requires means for irradiating a high-intensity pulsed light having a certain intensity and wavelength inside the blood vessel, and basically generates a high-intensity pulsed light. Only a device, a fiber for transmitting high-intensity pulsed light, and a means for transporting the fiber to the treatment site in the blood vessel are sufficient, and the maximum diameter portion to be inserted into the blood vessel is very small.
- the present inventors further examined conditions for generating water vapor bubbles that can generate sound pressure waves that can more reliably prevent restenosis.
- the present invention is as follows.
- a device for the prevention and treatment of vascular restenosis that reduces the number of proliferating cells in the treatment area after angioplasty by vascular dilatation due to pressure waves.
- a water vapor bubble having a size of 1/2 or more of the thickness of the water vapor, and the sound pressure wave induced by the collabs of the water vapor bubble hits the blood vessel wall to generate a water vapor bubble capable of damaging smooth muscle cells.
- the length of the water vapor bubble in the transverse direction relative to the direction of irradiation with high-intensity pulsed light is the length in the longitudinal direction.
- the length of the water vapor bubble in the transverse direction with respect to the direction of irradiation with the high-intensity pulsed light is not more than twice the inner diameter of the blood vessel, [1] or [2] Equipment,
- the lateral length of the water vapor bubbles with respect to the irradiation direction of the high-intensity pulsed light is 10 to 200% of the inner diameter of the blood vessel.
- the device for preventing and treating vascular restenosis according to any one of [1] to [5], wherein a high-intensity pulsed light transmission fiber including a catheter is disposed in the catheter,
- the internal structure of the distal end of the catheter is an internal structure that suppresses the rate at which water vapor bubbles are generated by irradiation with high-intensity pulsed light in the lateral direction.
- a water vapor bubble whose lateral length relative to the light irradiation direction is larger than the vertical length, and has a high sound pressure when a sound pressure wave induced by Collabs hits the blood vessel wall [ 6] to [8]
- the device for preventing and treating vascular restenosis is an internal structure that suppresses the rate at which water vapor bubbles are generated by irradiation with high-intensity pulsed light in the lateral direction.
- [2 1] The apparatus for preventing and treating vascular restenosis according to any one of [1] to [20], wherein the diameter of the catheter sheath portion inserted into the blood vessel is 2 mm or less.
- FIG. 1 shows the apparatus of the present invention.
- Figure 2 shows the process from the generation to the disappearance of water vapor generated by laser light irradiation.
- FIG. 3 shows a conceptual diagram of restenosis prevention treatment using the device of the present invention.
- Figure 4 shows the relationship between the intensity of the irradiation laser (J / pulse), the distance from the center of the bubble (mm), and the peak sound pressure (MPa).
- Figure 5 shows the sound pressure waveform at a distance of 5 mm from the center of the bubble when a laser intensity of 0.45 J / pulse was used.
- FIG. 6 is a diagram showing a method of a smooth muscle cell injury experiment using a laser-induced sound pressure wave.
- FIG. 7 is a diagram showing the results of a smooth muscle cell injury experiment using laser-induced sound pressure waves.
- FIG. 8 is a diagram and a photograph showing a method for preventing and treating restenosis using a rabbit.
- Figure 9 is a diagram and photograph showing the results of restenosis prevention treatment using a rabbit.
- FIG. 10 shows the relationship between laser energy and sound pressure.
- Fig. 11 is a photograph showing the shape of water vapor bubbles generated when the laser irradiation fiber is not inside the catheter. The shape of bubbles of 450mJ / pu l se is shown.
- Figure 12 is a photograph showing the shape of water vapor bubbles generated when the laser irradiation fiber is inside the catheter. The shape of bubbles of 450nJ / pulse when 3mm is inserted into the sheath is shown.
- the present invention is an apparatus for preventing and treating restenosis using high-intensity pulsed light.
- the apparatus of the present invention includes at least a high-intensity pulsed light irradiation means for irradiating a high-intensity pulsed light into a blood vessel, and further guides the high-intensity pulsed light irradiation part to a percutaneous coronary angioplasty site.
- a catheter may be included.
- Figure 1 shows a schematic diagram of the apparatus of the present invention.
- the high-intensity pulsed light irradiation means includes high-intensity pulsed light generation means (high-intensity pulsed light source), means for transmitting high-intensity pulsed light into the blood vessel, means for irradiating the high-intensity pulsed light into the blood vessel, etc.
- the portion that transmits the high-intensity pulsed light is an optical transmission fiber.
- the optical transmission fiber of the present invention may be inserted into a penetration lumen in a catheter used for percutaneous angioplasty (PTCA) by balloon expansion so that high-intensity pulsed light reaches the treatment site. In this case, treatment with the therapeutic apparatus of the present invention is performed immediately after percutaneous angioplasty by balloon expansion.
- PTCA percutaneous angioplasty
- an optical fiber for transmitting high-intensity pulsed light is pre-arranged in the balloon catheter used for the percutaneous angioplasty, and after the percutaneous angioplasty is performed, the balloon is deflated and the high-intensity pulse is transmitted.
- the treatment of the present invention may be carried out by irradiating the light. Therefore, the present invention provides a blood vessel that can prevent vascular restenosis by reducing cells that proliferate in an operation site after angioplasty by vasodilation, for example, smooth muscle cells, by sound pressure waves induced by irradiation with high-intensity pulsed light.
- the present invention may be a dedicated device for preventing and treating vascular restenosis, which is disposed as a high-intensity pulsed light transmission fiber in a catheter.
- vascular restenosis prevention treatment is performed.
- stent placement for example, self It can also be used to prevent restenosis after angioplasty.
- the means for irradiating the high-intensity pulsed light into the blood vessel is provided as a high-intensity pulsed light irradiation unit at the distal end of the optical transmission fiber.
- a member for changing the pulse light irradiation angle such as a prism may be arranged in the high-intensity pulsed light irradiation unit, but usually no special member is required and the distal end of the optical fiber has a high intensity. Can act as a pulsed light irradiator.
- the sound pressure wave refers to a wave accompanied by pressure fluctuation in a medium.
- the sound pressure wave is also referred to as an acoustic wave, but in the present invention, the generated acoustic wave may become an impact wave due to the nonlinearity of the medium.
- the sound pressure wave includes an ultrasonic wave having an audio frequency, an ultrasonic wave having an audio frequency higher than that, and an ultra-low frequency having an audio frequency lower than the audio frequency.
- the vascular catheter optionally included in the apparatus of the present invention is a tube for inserting a part of the apparatus of the present invention into a blood vessel, and is used as a guide when moving a part of the apparatus to a target site.
- a commonly used catheter can be used, and its diameter and the like are not limited, and can be appropriately designed according to the thickness of the blood vessel to be treated.
- the device of the present invention requires only one optical fiber for transmitting high-intensity pulsed light in the catheter, so that the diameter of the catheter can be reduced.
- the diameter of the catheter sheath portion is 2 mm or less. .
- High-intensity pulsed light includes pulsed light generated by a laser and an optical parametric oscillator (0P0; Optical Parametric Oscillator).
- the laser generation means an ordinary laser generator can be used, and the laser type is not limited as long as it is a laser having a wavelength band in which the absorption coefficient of water is lO lOOOcnf 1 , preferably lO lOOcm- 1 , and rare earth ions are used.
- a solid state laser using XeCl or an XeCl excimer laser can be used.
- the oscillation wavelength of the laser is 0.3 to 3 mm, preferably 1.5 to 32 mm, more preferably 1.5 to 2.5 / zm, and more preferably a wavelength near the maximum absorption wavelength of water (1.9 m).
- the laser is expressed by the ion of the element that generates the laser and the kind of the base material that holds the ion. Ho (holonium), Tm (thulium), Er (erbium), Nd (neodymium) and the like, and Ho and Tm are preferable.
- base materials include YAG, YSGG, and YV0.
- Ho YAG laser, Tm: YAG laser, Ho: YSGG laser, Tm: YSGG laser, Ho: YV0 laser, Tm: YV0 laser, and XeCl excimer laser (oscillation wavelength 308 ⁇ ) may be used. It can.
- the laser oscillation wavelength is preferably a water absorption wavelength maximum (1.
- Ho YAG laser (oscillation wavelength 2. l ⁇ m), TD YAG laser (oscillation wavelength 2.01 m) existing in the vicinity.
- Examples of the laser generator include LASER1-2-3 SCHWARTZ (manufactured by ELECTRO-OPTICS).
- Optical Parametric Oscillator (0P0) can continuously change the wavelength of pulsed light, and can select pulsed light in the wavelength band whose water absorption coefficient is 10 to 1 OOOcnr 1. For example, 0.3 to 3 ffl, preferably 1.5 to 3 mm, more preferably 1.5 to 2.5 / m, and even more preferably a wavelength near the absorption maximum of water (1.9 ⁇ m) may be selected.
- the means for transmitting the high-intensity pulsed light into the blood vessel are the means for irradiating the high-intensity pulsed light (high-intensity pulsed light irradiation part) and the high-intensity pulsed light with high intensity. It includes a stone fiber (one optical fiber) (high-intensity pulsed light transmission fiber) that is transmitted from a pulsed light generator to the high-intensity pulsed light irradiation means.
- near the distal end means a portion near the end opposite to the end (proximal end) connected to the high-intensity pulsed light generator, and the distal end and This refers to a part of several tens of centimeters from the distal end.
- the quartz fiber is connected at one end to a high-intensity pulsed light generator and at the other end. It is connected to high-intensity pulsed light irradiation means (high-intensity pulsed light irradiation part).
- the quartz fiber used in the present invention can be inserted into a blood vessel as it is, from a very thin fiber having a diameter of about 0.05 to 0.3 mm to a visible thickness, or inside a catheter. As long as it can be inserted into a blood vessel and transmit high-intensity pulsed light energy, a wide variety of diameters can be used.
- the high-intensity pulsed light irradiation means is a means for irradiating the blood vessel with high-intensity pulsed light, which is generated by an external high-intensity pulsed light generator (high-intensity pulsed light source) High-intensity pulsed light transmitted along the blood vessel through the transmission fiber) is irradiated into the blood vessel so that water vapor bubbles are formed in the blood.
- the direction of irradiation with high-intensity pulsed light is not limited.
- a plurality of high-intensity pulse light transmission fibers may be dispersed. The diameter of the fiber is preferably! ⁇ Between ⁇ ⁇ ⁇ .
- the distal end of the optical fiber for transmitting high-intensity pulsed light that is, the high-intensity pulsed light irradiation part at the tip of the optical fiber is more powerful than the tip of the catheter to prevent injury to the blood vessel wall by the tip. It is desirable to retract inside.
- the pulse width of the high-intensity pulsed light is not limited, but is 10 ns to 1 ms, preferably 100 / A S to 400 S.
- the pulse width is shown in full width at half maximum.
- the repetition frequency of the high intensity pulse light is not limited.
- FIG. 1 shows a conceptual diagram of restenosis prevention treatment using the device of the present invention.
- Water vapor bubbles are particularly effective in preventing restenosis when the shape and size of water vapor bubbles just before collaborating are constant.
- the shape of the water vapor bubbles is such that when the size of the direction in which the blood vessel advances is vertical and the direction perpendicular to the direction in which the blood vessel advances is horizontal, the shape of the water vapor bubble that expands in the horizontal direction is more horizontal.
- a large sound pressure wave can be generated in the direction. Therefore, the sound pressure wave conducts laterally from the water vapor generation point, and more reliably reduces the medial smooth muscle cells present laterally with respect to the water vapor bubbles.
- the sound pressure wave is large After that, normal cells in normal tissues are also damaged. Therefore, there is a certain range of sound pressure waves suitable for stenosis prevention.
- the device of the present invention produces a laterally spreading mushroom-shaped or western-less water vapor bubble that is effective in reducing medial smooth muscle cells but does not significantly damage vascular function. It is a device that can generate water vapor bubbles that generate sound pressure waves and do not expand the blood vessel wall to the extent that the blood vessel wall is damaged. Furthermore, since the peak sound pressure decreases as the distance from the center of the generated bubble increases, it is necessary to generate water vapor bubbles so that a thicker blood vessel induces a stronger sound pressure.
- the larger the arteriosclerotic treatment section the more smooth muscle cells that proliferate after treatment and the greater the severity of restenosis that is expected.
- the device of the present invention can appropriately adjust the sound pressure strongly or gently depending on the expected severity of restenosis.
- the generated steam bubble is preferably a steam bubble having a length in the transverse direction with respect to the direction of irradiation with the high-intensity pulsed light that is 1/2 or more of the length in the longitudinal direction, and is the same as or longer than the length in the longitudinal direction. Large steam bubbles are preferred. Furthermore, a water vapor bubble having a size that does not excessively expand the blood vessel wall and damage the blood vessel wall is preferable. For this purpose, the lateral length with respect to the high-intensity pulsed light irradiation direction is A water vapor bubble having a size not more than twice the inner diameter is preferred, and a water vapor bubble smaller than the inner diameter of the blood vessel is preferred.
- the generated steam bubbles have a length in the horizontal direction as defined above of 50% to 500%, preferably 75% to 500%, more preferably 100% to 500% of the length in the vertical direction. It is desirable to be.
- the lateral length varies depending on the thickness of the blood vessel to be treated, but is preferably 10% to 200%, preferably 10% to 150%, more preferably 10% to 100% of the inner diameter of the blood vessel. . For example, in the case of the coronary aorta, since the inner diameter of the blood vessel is about 3 mm, the lateral length of the water vapor bubble is reduced from about 0.3.
- the positional relationship between the position of the high-intensity pulsed light irradiation means at the distal end of the high-intensity pulsed light transmission means and the distal end of the catheter is adjusted. do it.
- water vapor bubbles are generated inside the catheter immediately in front of the high-intensity pulsed light irradiation means, and the inside of the catheter proceeds outward while being expanded and removed from the catheter. Get out.
- the shape of water vapor bubbles generated inside the blood vessel outside the catheter can also be adjusted by changing the shape inside the distal end of the catheter.
- the sound pressure wave generated in the transverse direction that is, the sound pressure wave applied to the smooth muscle cells can be adjusted.
- the high-intensity pulsed light irradiation part at the tip of the optical fiber within several nun from the distal end part of the catheter, it is possible to generate a water vapor bubble having a more appropriate shape.
- a higher sound pressure wave can be applied to the blood vessel wall.
- the high-intensity pulsed light irradiating part at the tip of the optical fiber is located within 0.5 to 5 mm, preferably 1 to 3 mnu, more preferably 1 to 2 mm inside the catheter with respect to the catheter tip. Is desirable. Also, the shape of the water vapor bubble can be adjusted by the shape inside the distal end of the catheter, and as a result, the sound pressure wave can be adjusted. When the high-intensity pulsed light irradiation part is present inside the catheter, water vapor bubbles are generated inside the catheter, and it goes out from the inside of the catheter while being expanded. At this time, the water vapor bubbles go outside inside the catheter.
- a convex portion that can suppress the expansion of water vapor bubbles in the longitudinal direction, a groove, or a continuous concave and convex portion may be provided inside the distal end of the catheter. Further, the structure may be changed so that the inner diameter of the distal end portion of the catheter becomes wider at the distal end portion.
- the magnitude of the sound pressure of the induced sound pressure wave differs by changing the position of the high-intensity pulse light irradiation part of the optical transmission fiber and the catheter tip. come.
- the higher the distance between the high-intensity pulsed light irradiation part of the optical transmission fiber and the distal end of the catheter The more the high-intensity pulsed light irradiation unit is retracted into the catheter, the higher the sound pressure of the induced sound pressure wave, even when the high-intensity pulsed light of the same energy is irradiated.
- the relationship between laser energy and sound pressure in the case of changing the position of the light irradiator in FIG. 10 is an example.
- the position of the light irradiator is appropriately adjusted according to the thickness of the catheter or optical transmission fiber, etc. Appropriate sound pressure waves can be generated.
- the sound pressure wave changes not only by the positional relationship between the catheter tip and the high-intensity pulsed light irradiation unit but also by the combination of the positional relationship and the intensity of the high-intensity pulsed light to be irradiated.
- the intensity of the high-intensity pulsed light to be irradiated is changed, the position of the irradiation part of the high-intensity pulsed light and the tip of the catheter is changed, or the internal structure of the distal end of the catheter is changed. It is a device that can adjust the size and / or shape of the water vapor bubbles to be generated and adjust the generation of sound pressure waves suitable for restenosis prevention.
- the sound pressure of the sound pressure wave can be adjusted as appropriate by changing the wavelength and pulse width of the high-intensity pulsed light.
- the number of irradiations of high-intensity pulsed light is increased, sound pressure waves are also induced many times, which is more effective in damaging smooth muscle cells.
- the number of irradiations can be appropriately selected depending on the expected severity of restenosis, the thickness of the blood vessel, etc. For example, 1 to 200 times, 1 to 100 times, 1 to 50 times, or 1 to 10 times It is.
- the sound pressure of the sound pressure wave inhibits the proliferation of smooth muscle cells in the arteriosclerosis treatment part, but is not damaged to the normal part of the treatment part and the surrounding normal tissue, and varies depending on the blood vessel used.
- 0.1 to 100 MPa preferably 0.1 to 50 MPa, more preferably 0.1 to 20 MPa, particularly preferably 0.1 to 10 MPa, and most preferably 0.1 to 4 MPa. If the expected severity of restenosis is low and avoid damage to normal cells, the sound pressure should be lowered, for example, 0.1 to 5 MPa, 0.1 to 4 MPa, 0.1 A sound pressure of ⁇ 2.5 MPa or 0.1 to I MPa may be applied to the arteriosclerosis treatment part.
- a liquid feeding means is incorporated in the catheter of the treatment apparatus of the present invention, and the liquid feeding means is used to perform the production.
- a saline solution or the like may be injected into the portion of the blood vessel where the high-intensity pulse light is irradiated, that is, in the vicinity of the irradiation portion of the high-intensity pulse light irradiation portion.
- the liquid feeding means is composed of a liquid feeding channel provided in the catheter, an inlet provided at the distal end of the liquid feeding channel, a liquid reservoir connected to the channel, a pump for feeding, and the like.
- a lumen may be provided in the catheter and the lumen may be used as the liquid supply channel, or a separate tube may be provided in the catheter.
- the high-intensity pulsed light from the high-intensity pulsed light irradiation means is introduced into the blood vessel in order to replace the local blood part where the high-intensity pulsed light is irradiated into the blood vessel and water vapor bubbles start to be generated with physiological saline.
- the part to be irradiated and the inlet of the liquid delivery means must be located close to each other.
- a lumen may be provided in the catheter, and a high-intensity pulse light transmission fiber may be passed through the lumen, and physiological saline or the like may be sent through the lumen.
- physiological saline to be delivered is not limited, but it is sufficient to use about 1/10 to 1/1000 of the amount of fluid delivered when using an endoscope that injects flash fluid and observes the lumen of blood vessels. .
- Blood flow is a pulsatile flow.
- the kinetic energy (dynamic pressure) of the blood flow is large, the generation of water vapor bubbles affects not only blood pressure (static pressure) but also dynamic pressure. Receive.
- the blood flow stops completely the blood is a non-Newtonian fluid, so the viscosity increases and water vapor bubbles are hardly generated.
- the timing can be detected by setting a delay time specific to the observation blood vessel in the heart rate information from the electrocardiogram.
- an electrocardiograph and a laser generator are connected electronically, and an electrocardiogram signal is generated through a delay generator so that high-intensity pulsed light is emitted when the pulsatile blood flow decreases. What is necessary is just to transmit to an apparatus. How much time delay is applied can be appropriately determined by a combination of an electrocardiograph, a delay generator, and a high-intensity pulsed light generator.
- the timing for transmitting a signal that emits high-intensity pulsed light when the pulsatile blood flow drops from the ECG is also appropriate.
- a person skilled in the art can easily determine the relationship from the known cardiac cycle, aortic blood flow velocity, and electrocardiogram. For example, in the case of coronary arteries, little blood flows during systole when the aortic blood flow rate is high, and blood flows during diastole when the aortic blood flow rate is low. Therefore, the blood flow velocity in the coronary artery is maximized during the appearance of the P wave after the appearance of the T wave in the electrocardiogram, and the irradiation intensity of the high intensity pulse light is between the appearance of the P wave and the disappearance of the QRS wave. desirable.
- a pressure sensor or the like is disposed on the catheter of the treatment apparatus of the present invention, and the pulsation of the blood flow is monitored by the sensor so that the high-intensity pulsed light is emitted when the pulsatile blood flow is reduced. May be. Also in this case, the pressure sensor and the high-intensity pulsed light generator are electronically connected, and the signal from the pressure sensor is transmitted to the high-intensity pulsed light generator with a delay.
- the device of the present invention is a device for preventing vascular restenosis after percutaneous angioplasty, and guides the high-intensity pulsed light irradiation unit of the present invention to the site where the percutaneous angioplasty is performed.
- the target blood vessel of the device of the present invention is not limited, and can be applied to any coronary artery or other smaller blood vessels.
- the angioplasty is usually performed in the common carotid artery and coronary artery.
- the device of the present invention can also be suitably used for treatment of these arteries after angioplasty.
- the high-intensity pulsed light irradiation part of the device of the present invention is inserted into the penetrating lumen, and treatment is performed. Treatment can be performed by transporting to the site.
- the device of the present invention is a dedicated device for preventing restenosis disposed in a dedicated catheter
- the device of the present invention A force taper is inserted into the blood vessel, and the treatment is performed with the high-intensity pulsed light irradiation part reaching the treatment site.
- the portion to be inserted into the blood vessel may be a small-diameter catheter containing one optical fiber for transmitting high-intensity pulsed light, so it is not from a large blood vessel such as a femoral artery blood vessel, but a radial artery. It can also be inserted from a thin blood vessel.
- the high-intensity pulsed light irradiation part of the device of the present invention is guided to the percutaneous angioplasty site, What is necessary is just to irradiate high-intensity pulsed light without closing the blood flow in the blood.
- high-intensity pulse light irradiation water vapor bubbles are generated at the irradiated end of the whole blood, and sound pressure waves are generated when the bubbles contract and disappear.
- the sound pressure wave propagates in the whole blood, propagates to the blood vessel wall, and reduces the smooth muscle cells of the media.
- a small amount of physiological saline or the like may be injected into the portion of the blood vessel irradiated with high-intensity pulsed light as described above.
- the optical transmission fiber within the catheter by moving the optical transmission fiber within the catheter and adjusting the position of the high-intensity pulsed light at the fiber tip with respect to the catheter tip, or changing the structure inside the catheter distal tip,
- the shape and size can be adjusted, and the size of the sound pressure wave that is induced by the water vapor bubble collabs and applied to the arteriosclerosis treatment part of the blood vessel wall can be adjusted.
- a sound pressure wave may be generated by irradiating a high-intensity pulsed light in advance at a site where an angioplasty is to be performed before angioplasty. Even if a sound pressure wave is generated before angioplasty is performed, smooth muscle cells in that portion can be reduced, and migration and colonization of smooth muscle cells at the site of vascular injury after angioplasty can be prevented. .
- Ho YAG laser generator 21 (LASER1-2-3SCHWARTZ (ELECTRO-OPTICS (USA)))
- the sound pressure was measured with a needle-type Hyde Mouth Phone (Model No. 7020, manufactured by Toray Techno Co., Ltd.) with the laser output and the distance from one end of the optical fiber as a parameter.
- the first was an outer diameter of 600 im and a core diameter of 400 im, which was irradiated with an intensity of 0.13 J / pulse, 0.27 J / pulse or 0.45 J / pulse,
- the sound pressure was measured at 5IM, 10mm and 15mm from the center
- Figure 4 shows the intensity of the irradiated laser (J / pulse), the distance from the bubble center (mm) and the peak sound pressure.
- proliferating smooth muscle cells (mouse-derived aortic smooth muscle cells P53LMAC01) were cultured in 96-well plates, and the sound pressure wave was peaked (approximately 1.20, 1.25, 1.46 MPa ) And the number of times (10, 20, 160 times) were changed.
- the laser light generator used for generating the sound pressure wave and the laser irradiation conditions were the same as in Example 1. The laser was applied at a distance of 6 mm from the bottom of the 96-well plate. The dead cell rate was measured by MTT assay 48 hours after application of the sound pressure wave. About 1.20 Mpa, 10 times, about 4%, 1.46 Mpa, about 20% dead cell rate at 20 times, and it was possible to give controllable damage to smooth muscle cells by laser irradiation conditions (Figure 7).
- a restenosis model was created in which a 2Fr. Balloon catheter was inserted from the femoral artery of a Japanese white rabbit under full anesthesia and the aorta was scratched. An optical fiber was inserted retrogradely from a 4Fr. Sheath placed in the femoral artery, and the aorta was irradiated with laser.
- Figure 8 shows the system used in this example. Six weeks later, they were sacrificed, and vascular tissue specimens were prepared by 11 ⁇ 1 ( ⁇ 11 ⁇ -£ 03 ⁇ (13 ⁇ 4) staining, and the therapeutic effect was evaluated.
- FIG. 9 shows a cross section of a blood vessel wall obtained by cutting and expanding a part of a blood vessel as shown in the figure, with the upper part on the inner membrane side and the lower part on the outer membrane side.
- the arrow in the figure indicates the inner elastic plate, and the smooth muscle cells proliferate on the intima side of the inner elastic plate.
- Each photo shows a normal blood vessel, a stenosis model blood vessel, and a laser beam of 0.06 J / pulse irradiated 20 times clockwise from the upper left.
- Ho: YAG laser (wavelength 2.10 m, pulse width 250 s, frequency 2 Hz) is irradiated in water.
- the sound pressure was measured using a needle-type hydrophone (Model No. NH7020, manufactured by Toray Techno Co., Ltd.) from two ends of the optical fiber in front of the thigh and three dishes in the horizontal direction.
- the outer diameter was 600 m and the core diameter was 400 m.
- Laser output was 85 to 570 mJ / pulse when irradiated using only one optical fiber (it is free in Fig. 10).
- the optical fiber was placed in the catheter (sheath), and the distance from the optical fiber tip to the catheter tip was set to lmm, 2mm, and 3mm
- Figure 10 shows the relationship between the position of the optical fiber, laser output, and sound pressure.
- the tip of the optical fiber is When the distance between the tip of the optical fiber and the catheter tip was 2 mm or less, a decrease in the sound pressure wave was observed when the laser output was increased, but it was 3 min.
- the maximum sound pressure measured was about 4 MPa When laser was irradiated in a blood vessel with an inner diameter of about 3 mm, the distance from the laser irradiation point to the blood vessel wall was not observed.
- Figures 1 and 12 show the shape of water vapor bubbles generated when a 450 mJ / pulse laser is irradiated.
- Fig. 11 shows the case where the laser irradiation fiber was irradiated without being put in the sheath (catheter), and
- Fig. 12 shows the case where the laser irradiation fiber was put in the sheath, and the tip of the fiber was the sheath.
- the generated bubble is larger in length in the transverse direction to the laser irradiation direction than in the longitudinal direction, and resembles a mashroom.
- the ratio of the vertical and horizontal lengths of the water vapor bubbles shown in Fig. 1 is 1: 0.8, and the vertical and horizontal lengths of the water vapor bubbles shown in Fig. 1 2 are as follows. The ratio is 1: 2.
- water vapor bubbles are generated by irradiating high-intensity pulsed light in the liquid.
- the sound pressure wave generated when bubbles are contracted and extinguished can inhibit the growth of smooth muscle cells.
- the sound pressure group The magnitude of the sound pressure in the blood vessel wall can be adjusted.
- the apparatus of the present invention is such that the length of the water vapor bubbles in the transverse direction with respect to the direction of irradiation with high-intensity pulsed light is at least half the length in the longitudinal direction (in the direction of irradiation with high-intensity pulsed light).
- the apparatus of the present invention irradiates high-intensity pulsed light at a blood vessel site where an angioplasty has been performed, and generates a sound pressure wave. By this sound pressure wave, proliferation of smooth muscle cells that migrate and settle in the blood vessel forming part is achieved. It can inhibit and prevent vascular restenosis.
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EP2477571A2 (en) * | 2009-09-18 | 2012-07-25 | Veniti, Inc. | Hot tip laser generated vapor vein therapy device |
US8715276B2 (en) | 2004-09-09 | 2014-05-06 | Covidien Lp | Methods and apparatus for treatment of hollow anatomical structures |
EP2373381B1 (en) * | 2008-12-02 | 2015-11-04 | Biolitec Pharma IP & Investment Ltd. | Laser induced vapor/plasma mediated medical device |
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Title |
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ERIKO SUGA ET AL: "Ho:Yag laser yuki onkyo o mochiita sai kyosa yobo no kiso kento (2)", THE JOURNAL OF JAPAN SOCIETY FOR LASER SURGERY AND MEDICINE, vol. 25, no. 3, 15 October 2004 (2004-10-15), pages 208, XP003007772 * |
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US8715276B2 (en) | 2004-09-09 | 2014-05-06 | Covidien Lp | Methods and apparatus for treatment of hollow anatomical structures |
EP2373381B1 (en) * | 2008-12-02 | 2015-11-04 | Biolitec Pharma IP & Investment Ltd. | Laser induced vapor/plasma mediated medical device |
EP2477571A2 (en) * | 2009-09-18 | 2012-07-25 | Veniti, Inc. | Hot tip laser generated vapor vein therapy device |
EP2477571A4 (en) * | 2009-09-18 | 2013-04-17 | Veniti Inc | VEIN THERAPY INSTRUMENT WITH STEAM THROUGH LASER WITH HOT TIP |
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