WO2022270494A1 - コラーゲン分解装置およびコラーゲン分解装置の作動方法 - Google Patents

コラーゲン分解装置およびコラーゲン分解装置の作動方法 Download PDF

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WO2022270494A1
WO2022270494A1 PCT/JP2022/024660 JP2022024660W WO2022270494A1 WO 2022270494 A1 WO2022270494 A1 WO 2022270494A1 JP 2022024660 W JP2022024660 W JP 2022024660W WO 2022270494 A1 WO2022270494 A1 WO 2022270494A1
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collagen
heat source
stress
source device
irradiation
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PCT/JP2022/024660
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English (en)
French (fr)
Japanese (ja)
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一平 八木
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東京都公立大学法人
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Priority to JP2023530476A priority Critical patent/JPWO2022270494A1/ja
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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
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • 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
    • A61N5/067—Radiation therapy using light using laser light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the present invention relates to a collagen decomposing device and a method of operating the collagen decomposing device.
  • Fibrous stenosis in which stenosis occurs due to the progress of fibrosis in the treated area after treatment of the gastrointestinal tract, is known. Fibrous strictures can be surgically resected.
  • balloon dilatation is known, in which a balloon catheter is placed at a site of stenosis in the gastrointestinal tract and the balloon is inflated to dilate the site of stenosis.
  • balloon ablation in which a balloon is guided to a lesion area and the balloon is heated to cauterize the lesion area (see, for example, Patent Document 1).
  • An object of the present invention is to provide a collagen degradation device and a method of operating the collagen degradation device that can selectively destroy collagen fibers while suppressing damage to cells.
  • a collagen degradation device includes a stress applying device that applies stress to a first area of a target tissue, and a second area that has at least a portion that overlaps with the first area and applies thermal energy to the second area. and a heat source device that supplies heat.
  • a method for operating a collagen decomposing device is the method for operating a collagen decomposing device according to the first aspect, wherein the control device causes the heat source device to heat in the second range.
  • the step of outputting a heating start instruction to start the step of the control device outputting an addition start instruction to cause the stress applying device to start applying stress to the first range after the heating start instruction, the step of controlling a step of the device outputting a heating stop instruction to the heat source device to stop heating; and a step of the control device outputting an addition stop instruction to the stress applying device to stop applying the stress after the heating stop instruction. and including.
  • the collagen degrading device can selectively destroy collagen fibers while suppressing damage to cells.
  • FIG. 10 is a diagram showing Young's modulus-stress characteristics for different temperatures obtained from the results of the first experiment;
  • FIG. 4 is a diagram showing the relationship between temperature and Young's modulus obtained as a result of a first experiment;
  • FIG. 10 is a diagram showing the relationship between the traction force and the elongation rate of the test piece I according to the second experiment;
  • FIG. 10 is a diagram showing the relationship between the traction force and the elongation rate of the test piece I according to the second experiment;
  • FIG. 10 is a diagram showing the relationship between the traction force and the elongation rate of the test piece II according to the second experiment; It is a figure which shows the relationship between the traction force of the test piece and elongation rate which concern on a 3rd experiment.
  • FIG. 10 is a diagram showing the relationship between the internal pressure of the balloon and the diameter of the stenosis model according to the fourth experiment; FIG. 11 shows the results of a fifth experiment;
  • FIG. 12 is a diagram showing the relationship between the diameter of the balloon and the diameter of the stenosis model without heating according to the sixth experiment.
  • FIG. 10 is a diagram showing the relationship between the diameter of a balloon and the diameter of a heated stenosis model according to the sixth experiment.
  • FIG. 11 is a diagram showing changes in the state of tissue according to the seventh experiment
  • Fig. 3 is a perspective view showing the configuration of a collagen decomposing device 1 according to a second embodiment
  • Fig. 2 is a cross-sectional view of a collagen decomposing device 1 according to a second embodiment
  • FIG. 1 is a diagram showing the configuration of a gastrointestinal tract expansion device 2 according to the first embodiment.
  • the gastrointestinal tract expansion device 2 according to the first embodiment is a device for dilating a constricted portion of the gastrointestinal tract while suppressing the possibility of restenosis.
  • the balloon catheter 23 has an inner shaft 231 , a balloon 232 and an outer shaft 233 .
  • the inner shaft 231 is provided from the proximal end to the distal end of the balloon catheter 23 .
  • the inner shaft 231 has a hollow structure for passing a guide wire for guiding the balloon 232 to a desired position.
  • the balloon 232 is provided near the distal end of the balloon catheter 23 so as to cover the inner shaft 231 .
  • the tip of the inner shaft 231 may protrude outside the balloon 232 or may be covered with the balloon 232 .
  • the outer shaft 233 is provided so as to cover the inner shaft 231 from the proximal end of the balloon catheter 23 to the proximal end of the balloon 232 .
  • the outer shaft 233 has a hollow structure.
  • a first lumen L1 for supplying the heat medium to the balloon 232 and a second lumen L2 for recovering the heat medium from the balloon 232 are provided between the outer shaft 233 and the inner shaft 231 .
  • a first lumen L1 connects the pump 22 and the balloon 232 .
  • a second lumen L2 connects the balloon 232 and the tank 21 .
  • the maximum diameter of the balloon catheter 23 when stored is narrower than the inner diameter of the forceps channel of the endoscope.
  • the maximum diameter of the balloon catheter 23 when stored is 3.2 mm or less.
  • the gastrointestinal tract expansion device 2 After positioning the balloon 232 at the constricted part of the gastrointestinal tract, the gastrointestinal tract expansion device 2 supplies a heated heat medium to heat the constricted part and pressurize the constricted part from the inside to the outside. .
  • the temperature of the narrowed portion rises to near the denaturation temperature of the collagen fibers due to heat exchange between the narrowed portion and the heat medium, part of the collagen fibers is denatured into gelatin.
  • Gelatin has a random coil structure, whereas collagen fibers have a triple-stranded helix structure. Therefore, gelatin has low strength compared to collagen fibers. Specifically, the material strength of collagen is about 1.3N, while the material strength of gelatin is about 0.6N.
  • the balloon 232 pressurizes the stenotic site to expand it, but the stenotic site is softened due to the denaturation of part of the collagen fibers into gelatin, which causes destruction of the cell tissue of the gastrointestinal tract wall. can be suppressed.
  • the gastrointestinal tract expansion device 2 is an example of a collagen degradation device.
  • FIG. 2 is a flow chart showing a control method for the gastrointestinal tract expansion device 2 according to the first embodiment.
  • a user for example, a doctor
  • the gastrointestinal tract expansion device 2 first inserts the endoscope into the patient's body and positions the distal end of the endoscope near the stenotic site.
  • the user injects a contrast agent into the stenotic site through the forceps channel of the endoscope, and obtains information such as the length and diameter of the stenotic site by imaging with X-rays.
  • the user passes the balloon catheter 23 through the forceps channel of the endoscope and advances the balloon catheter 23 so that the balloon 232 resides across the stenosis.
  • the user operates the control device 24 to start extended control by the control device 24.
  • the controller 24 supplies power to the temperature controller 211 to heat the heat medium (step S1).
  • the temperature of the heat medium required to apply the desired heat to the constricted portion can be obtained in advance using the specifications (thermal conductivity, thickness, surface area, etc.) of the balloon 232 and the outer shaft 233 .
  • the required temperature of the heat medium in the balloon 232 can be obtained by solving the equation (1).
  • Equation ( 1 ) Q is the amount of heat that passes through, T h is the temperature of the heat medium in the balloon 232, T c is the temperature of the constriction (body temperature), h1 is the heat transfer coefficient between the heat medium and the balloon 232 , and h2 is the heat transfer coefficient between the constricted portion and the balloon 232, ⁇ is the heat conductivity of the balloon 232, L is the thickness of the balloon 232, and A is the surface area of the balloon 232.
  • the temperature of the heat medium in the balloon 232 is T h should be about 90°C.
  • the control device 24 drives the pump 22 so as to discharge the heat medium at the first flow rate, and supplies the heat medium to the balloon 232 (step S2).
  • Heat transfer medium is supplied to the balloon 232 through the first lumen L1 and returns to the tank 21 through the second lumen L2.
  • the internal pressure of balloon 232 is determined by the first flow rate.
  • the first flow rate is such that the balloon 232 is in contact with the stenotic site, and the flow rate is such that the stress (for example, less than 100 kPa) is applied to the extent that the stenotic site does not expand (crack does not occur).
  • the controller 24 continues supplying the heat medium at the first flow rate for a certain period of time (for example, 60 seconds) (step S3). During this time, it can be expected that the constricted site is heated by heat exchange between the heat medium and the constricted site, and the collagen fibers are denatured into gelatin.
  • the control device 24 drives the pump 22 so as to discharge the heat medium at the second flow rate (step S4).
  • the second flow rate is larger than the first flow rate, and is a flow rate that gives a predetermined stress (for example, a stress of 40 kPa or more and 500 kPa or less) to the constricted portion.
  • a predetermined stress for example, a stress of 40 kPa or more and 500 kPa or less
  • the narrowed portion is pressed from the inside to the outside, and the narrowed portion can be expanded.
  • a stress of 100 kPa or more and 500 kPa or less is applied, but according to the gastrointestinal dilation device according to the first embodiment, the stricture can be expanded even in a range of 40 kPa or more and less than 100 kPa. be able to. Since the collagen fibers are denatured into gelatin, the Young's modulus at the stenosis site is reduced, and the possibility of cracking at the stenosis
  • the control device 24 cools the heat medium (step S5).
  • the temperature controller 211 is a heater
  • the control device 24 stops the heating of the heat medium by stopping the heater.
  • the control device 24 cools the heat medium by supplying the heat exchanger with a low-temperature refrigerant (for example, below the gelling temperature of gelatin).
  • the controller 24 continues supplying the heat medium at the second flow rate for a certain period of time (for example, 60 seconds) (step S6).
  • the gastrointestinal tract expansion device 2 cools the constricted site while dilating the constricted site.
  • the control device 24 stops the pump 22 and stops the supply of the heat medium (step S7). After the heat medium is recovered from the balloon catheter 23, the user pulls out the balloon catheter 23 from the forceps channel of the endoscope.
  • the gastrointestinal tract expansion device 2 applies thermal energy to the constricted portion of the gastrointestinal tract and further applies stress.
  • the gastrointestinal tract expansion device 2 can dilate the constricted site while reducing the Young's modulus by denaturing the collagen fibers at the constricted site to gelatin.
  • collagen fibers can be prevented from being ruptured, so that collagen fibers can be selectively destroyed while suppressing damage to the cell tissue of the gastrointestinal tract wall.
  • the gastrointestinal tract expansion device 2 can expand the constricted site without causing cracks in the constricted site.
  • the gastrointestinal tract expansion device 2 heats the fluid for expanding the balloon 232 to supply thermal energy to the constricted portion. Accordingly, the temperature controller 211 is provided outside the balloon catheter 23, and the size of the balloon catheter 23 can be reduced. This allows the balloon catheter 23 to pass through the forceps channel of the endoscope. Note that in other embodiments, a heater or the like may be provided inside the balloon.
  • the gastrointestinal tract expansion device 2 supplies thermal energy to the constricted portion by supplying a heated heat medium to the balloon 232, but the present invention is not limited to this.
  • heat energy may be supplied to the stenotic portion from the outside of the balloon catheter 23 by means of waves (for example, electromagnetic waves such as near-infrared light).
  • the gastrointestinal tract expansion device 2 according to the first embodiment presses the constricted portion with the balloon 232, but the present invention is not limited to this.
  • pressing may be performed using other devices such as bougies.
  • a test piece of collagen fiber was immersed in water at different temperatures for 5 minutes and pulled until it broke, and the relationship between load and displacement was measured.
  • bovine Achilles tendons embedded in silicone resin and sliced to a thickness of 1.0 ⁇ 0.1 mm were used as collagen fiber test pieces.
  • similar specimens were used for tensile tests.
  • FIG. 3 is a diagram showing Young's modulus-stress characteristics by temperature obtained from the results of the first experiment. As a result of the first experiment, it was found that there is no large difference in Young's modulus up to 4 MPa at 25°C and 60°C, but the Young's modulus drops significantly at 70°C.
  • FIG. 4 is a diagram showing the relationship between temperature and Young's modulus obtained as a result of the first experiment.
  • the Young's modulus exceeds 30 kPa when the temperature of the water is 60°C or lower, while the Young's modulus becomes 10 kPa or lower when the temperature exceeds 65°C.
  • the Young's modulus at 65°C was 1/5 of the Young's modulus at 60°C. From these results, it can be read that denaturation of collagen fibers occurs at around 65°C.
  • FIG. 5 is a diagram showing the procedure of the second experiment.
  • a tensile test was performed on the test piece I with a pulling force of 4 N (0.8 MPa) (T1). After that, the test piece I was immersed in water at 65° C. for 10 minutes, and then subjected to a tensile test with a traction force of 4N (T2). After that, the test piece I was immersed in water at 35° C.
  • FIG. 6 is a diagram showing the relationship between the traction force and the elongation rate of the test piece I according to the second experiment.
  • the test piece elongates during traction regardless of the temperature, but returns to its original length when the traction is stopped. For this reason, conventionally, it was necessary to expand until collagen fibers were broken, and it can be said that there was no choice but to give damage to cell tissues.
  • the length of the test piece is shortened by about 20% by heating. This is considered to be due to shrinkage due to thermal denaturation of the collagen tissue. In other words, it can be seen from the second experiment that the stricture cannot be dilated simply by applying heat.
  • FIG. 7 is a diagram showing the relationship between the traction force and the elongation rate of the test piece II according to the second experiment. As shown in FIG. 7, it can be seen that the length of the specimen was shortened by heating, but the length of the specimen was elongated by continuing to apply a traction force during cooling. When the traction was stopped after cooling, the length was shortened, but it was elongated by about 80% compared to when the test was started. From this, it can be seen that the collagen fibers are fixed while maintaining the state at the time of being pulled by cooling while applying a pulling force.
  • a specimen of collagen fibers was immersed in water at 65°C for 10 minutes, then the specimen was immersed in water at 35°C for 5 minutes while applying a traction force, and the specimen was subjected to a tensile test with the same traction force.
  • the traction force during cooling was varied from 0.8 MPa, 2 MPa, 4 MPa, 5 MPa, 6 MPa and 7 MPa. Note that the traction force was set to 4 N (0.8 MPa) during the tensile test.
  • FIG. 8 is a diagram showing the relationship between the traction force and elongation rate of the test piece according to the third experiment.
  • the tensile force is less than 4 MPa
  • the elongation rate of the test piece after cooling is less than the elongation rate before heating.
  • the tensile force is 4 MPa
  • the elongation rate of the test piece after cooling is approximately the same as the elongation rate before heating.
  • the tensile force exceeds 4 MPa
  • the elongation of the specimen after cooling is greater than that before heating.
  • a pressure greater than 4 MPa should be applied when dilating the stricture.
  • a test piece of collagen fibers was rolled into a cylindrical shape and fixed to a diameter of 4 mm with a cyanoacrylate adhesive to create a stricture model simulating an esophageal stricture.
  • a balloon catheter was passed through the stenosis model, and the internal pressure of the balloon was gradually increased.
  • the internal pressure of the balloon reached 30 kPa, the balloon was put into hot water, and then the internal pressure of the balloon was further increased.
  • FIG. 9 is a diagram showing the relationship between the internal pressure of the balloon and the diameter of the stenosis model according to the fourth experiment. As shown in FIG. 9, it can be seen that the diameter of the constricted model changes significantly before and after hot water injection. On the other hand, when the stenosis model was observed after the fourth experiment, it was confirmed that fibrous structures remained in the stenosis model. Then, when the sample removed from the balloon catheter was put into hot water again, contraction of the stenosis model was confirmed. It is presumed that this is because many collagen fibers that were not denatured into gelatin remained during the experiment. In other words, it is presumed that even if heating is performed while a traction force is being applied, denaturation of the collagen fibers does not progress easily.
  • FIG. 10 is a diagram showing the results of the fifth experiment. As shown in FIG. 10, it can be seen that the denaturation of collagen fibers progresses by heating, and that the denaturation progresses greatly by applying a traction force after heating. In addition, as hypothesized above, there was no significant difference when heating was performed halfway through traction compared to heating only. From the results of the fifth experiment, it can be seen that in order to effectively denature the collagen fibers, it is preferable to apply traction force after heating the collagen fibers.
  • ⁇ Sixth experiment ⁇ The inventor conducted a sixth experiment in order to confirm the expansion effect of the balloon catheter when heating was performed.
  • a balloon catheter was passed through a stenosis model at 37° C. (equivalent to body temperature) and a stenosis model heated to 70° C., the internal pressure of the balloon was gradually increased, and the diameter of the balloon and the diameter of each stenosis model were adjusted. compared.
  • FIG. 11 is a diagram showing the relationship between the diameter of the balloon and the diameter of the stenosis model without heating according to the sixth experiment.
  • the diameter of all stenosis models without heating was well below the diameter of the balloon until the internal pressure of the balloon was 100 kPa.
  • all stenosis models ruptured when the internal pressure of the balloon reached 160 kPa. Plots that greatly exceed the balloon diameter in FIG. 11 indicate rupture.
  • FIG. 12 is a diagram showing the relationship between the diameter of the balloon and the diameter of the heated stenosis model according to the sixth experiment.
  • the diameters of all of the heated stenosis models became almost equal to the diameter of the balloon. This indicates that the stenosis model has expanded sufficiently to follow the diameter of the balloon.
  • all constriction models with heating were expanded to 160 kPa without breaking.
  • a sixth experiment confirmed that application of traction followed by heating can expand the diameter of the stenosis to the balloon diameter without causing rupture of the stenosis.
  • a bovine Achilles tendon was HE-stained, heated at 70° C. for 15 minutes, then pulled so that a stress of 6 MPa was applied, and observed before heating, after heating, and after pulling.
  • FIG. 13 is a diagram showing changes in tissue state according to the seventh experiment.
  • cell nuclei were stained bluish purple (dark gray in FIG. 13), and collagen fibers were stained red (light gray in FIG. 13). Heating turned the unstained area (white in FIG. 13) red. This is because the fibrous structure was destroyed by the denaturation of collagen fibers into gelatin.
  • focusing on the cell nucleus it can be seen that the cell nucleus remains both after heating and after pulling. In other words, no morphological change in cells was observed within the range of heat load/stress load of the method according to the first embodiment. From this, it can be seen that according to the first embodiment, it is possible to selectively destroy collagen fibers while suppressing damage to cells.
  • HIFU High Intensity Focused Ultrasound
  • An object of the second embodiment is to provide a collagen decomposition device and a method of operating the collagen decomposition device that can selectively destroy collagen fibers in a range narrower than the irradiation range of ultrasonic waves.
  • FIG. 14 is a perspective view showing the configuration of the collagen decomposing device 1 according to the second embodiment.
  • FIG. 15 is a cross-sectional view of the collagen decomposing device 1 according to the second embodiment.
  • Collagen degradation device 1 includes housing 11 , gel pad 12 , ultrasonic irradiation device 13 , laser device 14 and control device 15 .
  • the housing 11 is configured in a substantially cylindrical shape having a through hole 111 . That is, the housing 11 has a disk-shaped bottom surface with a hole in the center.
  • Gel pad 12 is provided to cover the bottom surface of housing 11 .
  • the gel pad 12 is made of polyurethane gel, for example.
  • the gel pad 12 does not have to have through-holes at locations corresponding to the through-holes 111 of the housing 11 .
  • the ultrasonic irradiation device 13 is provided inside the housing 11 .
  • the ultrasonic irradiation device 13 irradiates ultrasonic waves from the bottom surface of the housing 11 .
  • the laser device 14 is provided inside the through hole 111 of the housing 11 .
  • Laser device 14 irradiates laser light through through hole 111 and gel pad 12 .
  • the control device 15 controls outputs of the ultrasonic irradiation device 13 and the laser device 14 .
  • the collagen decomposition apparatus 1 brings the bottom surface of the housing 11 and an object T (for example, a living body) into close contact with each other via the gel pad 12, and irradiates the object T with laser light and ultrasonic waves. , selectively destroys collagen fibers at target locations of the object T, resulting in tissue softening.
  • an object T for example, a living body
  • water or jelly may be used instead of the gel pad 12 .
  • the ultrasonic irradiation device 13 uses the bottom surface of the housing 11 as an opening surface. Therefore, the irradiation range R1 of the ultrasonic waves covers at least the range obtained by extending the bottom surface of the housing 11 in the direction of irradiation of the ultrasonic waves.
  • the ultrasonic irradiation device 13 irradiates ultrasonic waves having a frequency of 200 kHz or more and 10 MHz or less, a power of 0.4 kW/cm 2 or more and 10 kW/cm 2 or less, and a sound pressure of 1 MPa or more and 150 MPa or less.
  • the sound pressure of the ultrasonic waves is preferably 1 MPa or more and 25 MPa or less.
  • the ultrasonic irradiation device 13 applies ultrasonic waves under the conditions of 250 kHz, 0.4 kW/cm 2 and 3.5 MPa. Under these conditions, the ultrasonic waves emitted by the ultrasonic irradiation device 13 do not damage non-target tissues such as skin, muscles, blood vessels, and nerves among living tissues, and collagen fibers are thermally denatured. gelatin can be selectively destroyed. If the frequency of the ultrasonic wave is less than 200 kHz, the focal area becomes large with respect to the living tissue, so the damage to the non-target tissue becomes large.
  • the ultrasonic irradiation device 13 irradiates ultrasonic waves having a frequency that generates cavitation having an intensity capable of destroying gelatin without destroying living tissue.
  • the laser device 14 emits laser light having an absorption wavelength of collagen fibers. Specifically, the laser device 14 emits laser light with a wavelength of 400 nm or more and 900 nm or less. Laser light is an example of thermal energy.
  • the irradiation range R2 of the laser light output by the laser device 14 is narrower than the irradiation range R1 of the ultrasonic irradiation device 13 .
  • a wavelength of 400 nm or more and 900 nm or less is a wavelength at which the absorption coefficient of collagen is higher than that of hemoglobin, lipid, and water, which are components of biological tissue having relatively high absorption coefficients.
  • the control device 15 is connected to the ultrasonic irradiation device 13 and the laser device 14 via cables, and outputs control signals to the ultrasonic irradiation device 13 and the laser device 14 . Further, the control device 15 may supply power for driving the ultrasonic irradiation device 13 and the laser device 14 through cables. When the collagen decomposition device 1 is operated, the control device 15 starts irradiation of ultrasonic waves by the ultrasonic irradiation device 13 and irradiation of laser light by the laser device 14 .
  • the control device 15 controls the laser device 14 so as to repeat irradiation of pulsed light with a pulse time width of 1 ns or more and 20 ms or less at a frequency of 0.1 Hz or more and 100 kHz or less. Irradiation of pulsed light is preferably performed at a frequency of 0.1 Hz or more and 1 kHz or less and a pulse time width of 1 ns or more and 1 ms or less.
  • the controller 15 can raise the temperature of the collagen fibers irradiated with the laser beam to near the denaturation temperature (45° C.), thereby partially denaturing the collagen fibers into gelatin. That is, the laser device 14 irradiates thermal energy with a power that raises the temperature of the collagen fibers present within the irradiation range R2 of the laser light to a temperature near the denaturation temperature of collagen.
  • the controller 15 can suppress the occurrence of thermal diffusion of the laser light. That is, the laser device 14 irradiates heat energy for a period of time shorter than the period of time required for the temperature of collagen fibers existing outside the irradiation range R2 of the laser light to rise to the denaturation temperature due to thermal diffusion. Preferably, the laser device 14 irradiates laser light under the conditions of 532 nm and 1 mJ/mm 2 .
  • ⁇ Action and effect of collagen decomposition device 1>> When the user inputs an irradiation instruction to the control device 15 while the bottom surface of the housing 11 is in close contact with the object T, the control device 15 outputs a laser light irradiation instruction to the laser device 14, and simultaneously emits ultrasonic waves. An ultrasonic wave irradiation instruction is output to the irradiation device 13 . That is, the control device 15 outputs an irradiation instruction to the ultrasonic irradiation device 13 at least while the laser device 14 is operating.
  • the object T is irradiated with the laser light from the laser device 14, the temperature of the collagen fibers present in the irradiation range R2 rises.
  • the temperature of the collagen fibers reaches the denaturation temperature, some of the collagen fibers are denatured into gelatin.
  • Gelatin has a random coil structure, whereas collagen fibers have a triple-stranded helix structure. Therefore, gelatin has low strength compared to collagen fibers. Specifically, the material strength of collagen is about 1.3N, while the material strength of gelatin is about 0.6N. Therefore, cavitation caused by ultrasonic waves emitted from the ultrasonic irradiation device 13 is often generated in locations where gelatin in which collagen fibers are denatured exists. When cavitation caused by ultrasound expands and ruptures, weak gelatin is destroyed, while collagen fibers and other living tissues, which are stronger than gelatin, are not damaged.
  • the acoustic energy of ultrasonic waves damages gelatin, which is weak in intensity, but does not damage collagen fibers and other living tissues.
  • gelatin which is weak in intensity, but does not damage collagen fibers and other living tissues.
  • cavitation bursting or acoustic energy portions of collagen fibers irradiated with laser light are selectively destroyed.
  • cavitation expands and ruptures between the tangled collagen fibers, so that a force can be generated in the direction of separating the collagen fibers from each other. As a result, even if the irradiation of the laser light is stopped and the heating of the collagen fibers is stopped, the flexibility of the fibers as a whole can be maintained.
  • the laser beam partially denatures collagen existing in a portion narrower than the irradiation range R1 of the ultrasonic wave to gelatin, and then irradiates the collagen with the ultrasonic wave. .
  • the collagen degradation device 1 can selectively destroy collagen fibers in a range narrower than the ultrasonic wave irradiation range.
  • the collagen decomposition device 1 according to the second embodiment is provided with a laser device 14 in the through hole 111 of the housing 11, and the ultrasonic irradiation device 13 irradiates laser light to the center of the ultrasonic irradiation range.
  • the irradiation direction of ultrasonic waves and the irradiation direction of laser light may not match.
  • the collagen decomposition device 1 may be provided with the ultrasonic irradiation device 13 and the laser device 14 so that the irradiation range of ultrasonic waves and the irradiation range of laser light intersect.
  • the collagen decomposition device 1 according to the second embodiment includes one laser device 14 and one ultrasonic irradiation device 13, the present invention is not limited to this.
  • the collagen degradation device 1 according to another embodiment may include multiple laser devices 14 and ultrasonic irradiation devices 13 .
  • the collagen decomposition device 1 according to another embodiment is provided with a plurality of laser devices 14 so that the laser beams intersect at one point, so that the collagen fibers at the points where the laser beams intersect can be denatured into gelatin. may be configured.
  • the control device 15 may adjust the angle of the laser device 14 to change the depth to the epidermis of the point where the laser beams intersect.
  • the collagen decomposition device 1 instead of the laser device 14, another heat source device capable of irradiating thermal energy to a range narrower than the range of ultrasonic wave irradiation may be used.
  • the collagen decomposing device 1 according to another embodiment may be equipped with a heater by thermal radiation.
  • the control device 15 includes a processor, a memory, an auxiliary storage device, etc. connected via a bus, and functions as the control device 15 that controls the ultrasonic irradiation device 13 and the laser device 14 by executing a program.
  • processors include CPUs (Central Processing Units), GPUs (Graphic Processing Units), microprocessors, and the like.
  • the program may be recorded on a computer-readable recording medium.
  • a computer-readable recording medium is, for example, a storage device such as a magnetic disk, a magneto-optical disk, an optical disk, or a semiconductor memory.
  • the program may be transmitted over telecommunications lines.
  • All or part of each function of the control device 15 may be realized using a custom LSI (Large Scale Integrated Circuit) such as an ASIC (Application Specific Integrated Circuit) or a PLD (Programmable Logic Device).
  • PLDs include PAL (Programmable Array Logic), GAL (Generic Array Logic), CPLD (Complex Programmable Logic Device), and FPGA (Field Programmable Gate Array).
  • PAL Programmable Array Logic
  • GAL Generic Array Logic
  • CPLD Complex Programmable Logic Device
  • FPGA Field Programmable Gate Array
  • the collagen degrading device can selectively destroy collagen fibers while suppressing damage to cells.

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PCT/JP2022/024660 2021-06-21 2022-06-21 コラーゲン分解装置およびコラーゲン分解装置の作動方法 WO2022270494A1 (ja)

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* Cited by examiner, † Cited by third party
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JP2014533130A (ja) * 2011-10-04 2014-12-11 べシックス・バスキュラー・インコーポレイテッド ステント内再狭窄を治療するための装置及び方法
JP2021510614A (ja) * 2018-01-16 2021-04-30 エルメディカル リミテッドＥｌｍｅｄｉｃａｌ Ｌｔｄ． 体内組織の熱治療のためのデバイス、システム、および方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014533130A (ja) * 2011-10-04 2014-12-11 べシックス・バスキュラー・インコーポレイテッド ステント内再狭窄を治療するための装置及び方法
JP2021510614A (ja) * 2018-01-16 2021-04-30 エルメディカル リミテッドＥｌｍｅｄｉｃａｌ Ｌｔｄ． 体内組織の熱治療のためのデバイス、システム、および方法

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