Collagen decomposition device and method of operating the collagen decomposition device

Abstract

This collagen decomposition device comprises: a stress application device for applying stress to a first range of a subject tissue; and a heat source device for imparting thermal energy to a second range, at least a portion of which overlaps the first range.

Description

[Technical Field]

[0001] This invention relates to a collagen decomposition device and a method for operating a collagen decomposition device. This application claims priority to Japanese Patent Application No. 2021-102278, filed in Japan on June 21, 2021, the contents of which are incorporated herein by reference. [Background technology]

[0002] Fibrous strictures are known to occur after treatment of the gastrointestinal tract due to the progression of fibrosis in the treated area. Fibrous strictures can be surgically removed. Another non-invasive treatment method for fibrous strictures is balloon dilation, in which a balloon catheter is placed in the narrowed area of ​​the gastrointestinal tract and the narrowed area is expanded by inflating the balloon.

[0003] Furthermore, balloon ablation, a treatment method using a balloon catheter, is also known, in which a balloon is guided to the lesion and the lesion is cauterized by heating the balloon (see, for example, Patent Document 1). [Prior art documents] [Non-patent literature]

[0004] [Patent Document 1] Japanese Patent Publication No. 2007-229095 [Overview of the project] [Problems that the invention aims to solve]

[0005] Even if a narrowed area is surgically removed, it is known that inflammation often occurs in the same area after surgery, leading to further fibrosis and restenosis in the same location. Furthermore, even with non-invasive balloon dilation, collagen fibers are rigid, and balloon dilation can cause cracks in the digestive tract wall at the dilated area, often resulting in restenosis similar to surgical intervention. In other words, it is thought that dilation damages cells, causing inflammation, which in turn leads to the formation of collagen fibers and subsequent restenosis. The object of the present invention is to provide a collagen degradation device and a method for operating the collagen degradation device that can selectively destroy collagen fibers while minimizing damage to cells. [Means for solving the problem]

[0006] According to a first aspect of the present invention, the collagen decomposition apparatus comprises a stress application device for applying stress to a first range of target tissue, and a heat source device for supplying thermal energy to a second range having at least a portion overlapping with the first range.

[0007] According to a second aspect of the present invention, a method for operating a collagen decomposition apparatus is a method for operating a collagen decomposition apparatus according to a first aspect, comprising the steps of: the control device outputting a heating start instruction to the heat source device to start heating in the second range; the control device outputting an addition start instruction to the stress addition device after the heating start instruction to start adding stress to the first range; the control device outputting a heating stop instruction to the heat source device to stop heating; and the control device outputting an addition stop instruction to the stress addition device after the heating stop instruction to stop adding stress. [Effects of the Invention]

[0008] According to at least one of the above embodiments, the collagen decomposition device can selectively destroy collagen fibers while minimizing damage to cells. [Brief explanation of the drawing]

[0009] [Figure 1] This figure shows the configuration of the gastrointestinal dilator 2 according to the first embodiment. [Figure 2] This is a flowchart showing the control method for the gastrointestinal dilator 2 according to the first embodiment. [Figure 3] This figure shows the Young's modulus-stress properties at different temperatures, obtained from the results of the first experiment. [Figure 4]FIG. 1 is a diagram showing the relationship between temperature and Young's modulus obtained as a result of a first experiment. [Figure 5] FIG. 2 is a diagram showing the procedure of a second experiment. [Figure 6] FIG. 3 is a diagram showing the relationship between traction force and elongation rate for test piece I according to the second experiment. [Figure 7] FIG. 4 is a diagram showing the relationship between traction force and elongation rate for test piece II according to the second experiment. [Figure 8] FIG. 5 is a diagram showing the relationship between traction force and elongation rate for a test piece according to a third experiment. [Figure 9] FIG. 6 is a diagram showing the relationship between the internal pressure of a balloon and the diameter of a stenosis model according to a fourth experiment. [Figure 10] FIG. 7 is a diagram showing the results of a fifth experiment. [Figure 11] FIG. 8 is a diagram showing the relationship between the diameter of a balloon and the diameter of an unheated stenosis model according to a sixth experiment. [Figure 12] FIG. 9 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. [Figure 13] FIG. 10 is a diagram showing changes in the state of tissue according to a seventh experiment. [Figure 14] FIG. 11 is a perspective view showing the configuration of a collagen decomposition apparatus 1 according to a second embodiment. [Figure 15] FIG. 12 is a cross-sectional view of the collagen decomposition apparatus 1 according to the second embodiment. MODE FOR CARRYING OUT THE INVENTION

[0010] First Embodiment FIG. 1 is a diagram showing the configuration of a gastrointestinal dilator 2 according to a first embodiment. The gastrointestinal dilator 2 according to the first embodiment is an apparatus for dilating a stenotic site in the gastrointestinal tract while suppressing the possibility of restenosis occurring.

[0011] Configuration of Gastrointestinal Dilator 2 The gastrointestinal dilator 2 comprises a tank 21, a pump 22, a balloon catheter 23, and a control device 24. The tank 21 is filled with a heat transfer medium (e.g., diluted contrast agent, distilled water, etc.) to be supplied to the balloon catheter 23. Inside the tank 21 is a temperature controller 211 for heating the heat transfer medium. The temperature controller 211 may be a heater or a heat exchanger. The pump 22 pumps the heat transfer medium filled in the tank 21 to the balloon catheter 23.

[0012] The balloon catheter 23 comprises an inner shaft 231, a balloon 232, and an outer shaft 233. The inner shaft 231 is provided extending from the proximal end to the tip of the balloon catheter 23. The inner shaft 231 has a hollow structure through which a guide wire passes to guide the balloon 232 to the desired position. The balloon 232 is positioned near the tip of the balloon catheter 23 so as to cover the inner shaft 231. The tip of the inner shaft 231 may be outside the balloon 232 or may be covered by 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. Between the outer shaft 233 and the inner shaft 231, there is a first lumen L1 for supplying a heat transfer medium to the balloon 232 and a second lumen L2 for recovering the heat transfer medium from the balloon 232. The first lumen L1 connects the pump 22 and the balloon 232. The second lumen L2 connects the balloon 232 and the tank 21.

[0013] The maximum diameter of the balloon catheter 23 when retracted is narrower than the inner diameter of the endoscope's forceps channel. For example, the maximum diameter of the balloon catheter 23 when retracted is 3.2 mm or less.

[0014] The gastrointestinal dilator 2 positions the balloon 232 at a narrowed area of ​​the gastrointestinal tract and then supplies heat to a heated heat transfer medium, thereby heating the narrowed area and pressurizing it from the inside out. Through heat exchange between the narrowed area and the heat transfer medium, when the temperature of the narrowed area rises to near the denaturation temperature of collagen fibers, some of the collagen fibers denature into gelatin. Collagen fibers have a triple-stranded helix structure, while gelatin has a random coil structure. Therefore, gelatin has lower strength compared to collagen fibers. Specifically, the material strength of collagen is about 1.3 N, while the material strength of gelatin is about 0.6 N. The narrowed area is expanded by the pressurization of the balloon 232, but because the narrowed area is softened due to the denature of some of the collagen fibers into gelatin, the destruction of the cellular tissue of the gastrointestinal wall can be suppressed. The gastrointestinal dilator 2 is an example of a collagen decomposition device.

[0015] Control method for gastrointestinal dilator 2 Figure 2 is a flowchart showing the control method for the gastrointestinal dilator 2 according to the first embodiment. The user of the gastrointestinal dilator 2 (for example, a physician) first inserts the endoscope into the patient's body and positions the tip of the endoscope near the narrowed area. The user injects contrast agent into the narrowed area through the endoscope's forceps channel and obtains information such as the length and diameter of the narrowed area by imaging it with X-rays. Next, the user passes the balloon catheter 23 through the endoscope's forceps channel and advances the balloon catheter 23 so that the balloon 232 extends across the narrowed area.

[0016] The user operates the control device 24 to start the extended control by the control device 24. The control device 24 supplies power to the temperature controller 211 and heats the heat transfer medium (step S1). The temperature of the heat transfer medium required to provide the desired heat to the constricted area can be determined in advance using the specifications of the balloon 232 and the outer shaft 233 (thermal conductivity, thickness, surface area, etc.). For example, since the heat transport between the balloon 232 and the constricted area is shown by the following equation (1), the required temperature of the heat transfer medium in the balloon 232 can be determined by solving equation (1).

[0017]

number

[0018] Next, the control device 24 drives the pump 22 to discharge the heat transfer medium at a first flow rate, supplying the heat transfer medium to the balloon 232 (step S2). The 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 the balloon 232 is determined by the first flow rate. The first flow rate is such that the balloon 232 is in contact with the constricted area and applies a stress (e.g., less than 100 kPa) that does not cause the constricted area to expand (cracks do not occur). The control device 24 continues to supply the heat transfer medium at the first flow rate for a certain period of time (e.g., 60 seconds) (step S3). During this time, heat exchange between the heat transfer medium and the constricted area is expected to heat the constricted area and cause the collagen fibers to denature into gelatin.

[0019] Next, the control device 24 drives the pump 22 to discharge the heat transfer medium at a second flow rate (step S4). The second flow rate is greater than the first flow rate and is set to apply a predetermined stress (for example, a stress of 40 kPa to 500 kPa) to the narrowed area. This causes the narrowed area to be pressed from the inside to the outside, and the narrowed area can be expanded. In conventional balloon dilation, a stress of 100 kPa to 500 kPa is applied, but with the gastrointestinal dilation device according to the first embodiment, expansion of the narrowed area can be achieved even in the range of 40 kPa to less than 100 kPa. Because the collagen fibers have been denatured into gelatin, the Young's modulus of the narrowed area is reduced, and the possibility of cracks occurring in the narrowed area is low.

[0020] Next, the control device 24 cools the heat transfer medium (step S5). If the temperature controller 211 is a heater, the control device 24 stops heating the heat transfer medium by stopping the heater. If the temperature controller 211 is a heat exchanger, the control device 24 cools the heat transfer medium by supplying a coolant at a low temperature (for example, below the gelation temperature of gelatin) to the heat exchanger. The control device 24 continues to supply the heat transfer medium at the second flow rate for a certain period of time (for example, 60 seconds) (step S6). In other words, the gastrointestinal dilator 2 cools the narrowed area while keeping it dilated. This allows for a phase change from the sol state to the gel state of gelatin, and re-denaturation from gelatin to collagen fibers, while the narrowed area is dilated. By denaturing into collagen fibers while dilated, it is expected that the dilated diameter will be maintained even after the compression by the balloon 232 is stopped.

[0021] The control device 24 stops the pump 22 and ceases the supply of the heat transfer medium (step S7). After the heat transfer medium has been recovered from the balloon catheter 23, the user removes the balloon catheter 23 from the forceps channel of the endoscope.

[0022] As described above, the gastrointestinal dilator 2 according to the first embodiment applies thermal energy to the narrowed area of ​​the gastrointestinal tract and further applies stress. As a result, the gastrointestinal dilator 2 can dilate the narrowed area by denaturing the collagen fibers in the narrowed area into gelatin and lowering the Young's modulus. This prevents the rupture of collagen fibers, and thus selectively destroys collagen fibers while minimizing damage to the cellular tissue of the gastrointestinal wall. As a result, the gastrointestinal dilator 2 can dilate the narrowed area without causing cracks in the narrowed area.

[0023] Furthermore, the gastrointestinal dilation device 2 according to the first embodiment supplies thermal energy to the narrowed portion by heating the fluid used to expand the balloon 232. This allows the temperature controller 211 to be placed outside the balloon catheter 23, thereby enabling miniaturization of the balloon catheter 23. This makes it possible to pass the balloon catheter 23 through the forceps channel of an endoscope. In other embodiments, a heater or the like may be provided inside the balloon.

[0024] The gastrointestinal dilator 2 according to the first embodiment supplies thermal energy to the narrowed portion by supplying a heated heat transfer medium to the balloon 232, but is not limited to this. For example, in another embodiment, thermal energy may be supplied to the narrowed portion from outside the balloon catheter 23 by wave (e.g., electromagnetic waves such as near-infrared light). Furthermore, the gastrointestinal dilator 2 according to the first embodiment applies pressure to the narrowed portion using a balloon 232, but is not limited to this. For example, in other embodiments, pressure may be applied using other devices such as a bougie.

[0025] The following describes experimental results that support the effectiveness of the gastrointestinal dilator 2 according to the first embodiment.

[0026] Experiment 1 The inventor conducted a first experiment to verify the change in Young's modulus of collagen fibers with respect to temperature. In the first experiment, collagen fiber specimens were immersed in water at different temperatures for 5 minutes and then pulled until they broke, and the relationship between load and displacement was measured. In the first experiment, bovine Achilles tendons embedded in silicone resin and sliced ​​to a thickness of 1.0 ± 0.1 mm were used as collagen fiber specimens. The same specimens were used for tensile tests in the following experiments.

[0027] Figure 3 shows the Young's modulus-stress properties at different temperatures, obtained from the results of the first experiment. The results of the first experiment showed that there was no significant difference in Young's modulus up to 4 MPa at 25°C and 60°C, but the Young's modulus decreased significantly at 70°C.

[0028] Figure 4 shows the relationship between temperature and Young's modulus obtained from the first experiment. The results of the first experiment showed that the Young's modulus of water exceeds 30 kPa when the temperature is below 60°C, but falls below 10 kPa when the temperature exceeds 65°C. The Young's modulus at 65°C was 1 / 5 of the Young's modulus at 60°C. These results suggest that collagen fiber degeneration occurs at around 65°C.

[0029] Experiment 2 The inventor hypothesized that collagen fibers would solidify when heated, subjected to tensile force, and then cooled, and conducted a second experiment to verify this hypothesis. Figure 5 shows the procedure for the second experiment. In the second experiment, test piece I of collagen fibers was immersed in 35°C water for 5 minutes, and then subjected to a tensile test with a tensile force of 4N (0.8MPa) (T1). Subsequently, test piece I was immersed in 65°C water for 10 minutes, and then subjected to a tensile test with a tensile force of 4N (T2). Subsequently, test piece I was immersed in 35°C water for 5 minutes, and then subjected to a tensile test with a tensile force of 4N (T3). In addition, test piece II of collagen fibers was immersed in 35°C water for 5 minutes, and then subjected to a tensile test with a tensile force of 4N (T1). Subsequently, test piece II was immersed in 65°C water for 10 minutes, and then subjected to a tensile test with a tensile force of 4N (T2). Subsequently, specimen II was immersed in 35°C water for 5 minutes while a manual tensile force of 30N was applied, and then a tensile test was performed on specimen II with a tensile force of 4N (T3).

[0030] Figure 6 shows the relationship between the tensile force and elongation rate of specimen I in the second experiment. As shown in Figure 6, regardless of temperature, the specimen elongates during tensile force, but returns to its original length when tensile force is removed. For this reason, conventional methods required expansion until collagen fibers ruptured, which inevitably damaged the cell tissue. Also, Figure 6 shows that heating shortens the length of the specimen by about 20%. This is thought to be due to shrinkage caused by thermal denaturation of the collagen tissue. In other words, the second experiment shows that simply applying heat is not enough to expand the constricted area.

[0031] Figure 7 shows the relationship between the tensile force and elongation rate of specimen II in the second experiment. As shown in Figure 7, the length of the specimen shortens with heating, but the length of the specimen elongates when the tensile force is continued to be applied during cooling. When the tension is stopped after cooling, the length shortens, but it has still elongated to about 80% of its initial length. From this, it can be seen that collagen fibers are fixed in place while maintaining their state when cooled with tensile force applied.

[0032] Experiment 3 The inventor conducted a third experiment to investigate the tensile force required for the elongation of collagen fibers. In the third experiment, a collagen fiber specimen was immersed in 65°C water for 10 minutes, then immersed in 35°C water for 5 minutes while applying a tensile force, and a tensile test was performed on the specimen with the same tensile force. In the third experiment, the tensile force during cooling was varied to 0.8 MPa, 2 MPa, 4 MPa, 5 MPa, 6 MPa, and 7 MPa. The tensile force during the tensile test was set to 4 N (0.8 MPa).

[0033] Figure 8 shows the relationship between the tensile force and elongation rate of the test specimen in the third experiment. As shown in Figure 8, when the tensile force is less than 4 MPa, the elongation rate of the test specimen after cooling is less than the elongation rate before heating. When the tensile force is 4 MPa, the elongation rate of the test specimen after cooling is about the same as the elongation rate before heating. When the tensile force exceeds 4 MPa, the elongation rate of the test specimen after cooling is greater than the elongation rate before heating. In other words, from the third experiment, it can be seen that a pressure of more than 4 MPa should be applied when expanding a constricted area.

[0034] Experiment 4 The inventor conducted a fourth experiment to confirm the dilation effect of the balloon catheter. In the fourth experiment, a test piece of collagen fiber was rolled into a tube 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 then passed through this stricture model, and the internal pressure of the balloon was gradually increased. When the internal pressure of the balloon reached 30 kPa, the balloon was immersed in hot water, and then the internal pressure of the balloon was further increased.

[0035] Figure 9 shows the relationship between the internal pressure of the balloon and the diameter of the stenosis model in the fourth experiment. As shown in Figure 9, it can be seen that the diameter of the stenosis model changes significantly before and after the introduction of hot water. 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. When the sample removed from the balloon catheter was put back into the hot water, contraction of the stenosis model was observed. This is presumed to be because many collagen fibers that did not denature into gelatin during the experiment remained. In other words, it is presumed that even if heating is performed while a tensile force is applied, the denaturation of collagen fibers does not progress easily.

[0036] Experiment 5 Based on the findings from the fourth experiment, the inventor hypothesized that, in order to effectively denature collagen fibers, it is preferable to apply tensile force after heating the collagen fibers. To verify this hypothesis, the inventor conducted a fifth experiment. In the fifth experiment, the degree of collagen fiber denaturation was examined for each of the following test specimens: specimen A (no traction or heating), specimen B (tension but no heating), specimen C (tension followed by heating), and specimen D (heating followed by traction). The degree of collagen fiber denaturation was determined by fluorescence detection of CHP (Collagen Hybridizing Peptide) added to the test specimens. CHP is a probe that specifically binds to damaged collagen chains.

[0037] Figure 10 shows the results of the fifth experiment. As shown in Figure 10, it was found that heating accelerates the denaturation of collagen fibers, and that applying tensile force after heating further accelerates the denaturation. Furthermore, as hypothesized above, there was no significant difference when tensile force was applied and then heating was added, compared to heating alone. From the results of the fifth experiment, it can be seen that applying tensile force after heating the collagen fibers is preferable in order to effectively denature the collagen fibers.

[0038] Experiment 6 The inventor conducted a sixth experiment to confirm the expansion effect of the balloon catheter when heated. In the sixth experiment, a balloon catheter was passed through a stenosis model heated to 37°C (equivalent to body temperature) and a stenosis model heated to 70°C, and the internal pressure of the balloon was gradually increased. The diameter of the balloon was then compared with the diameter of each stenosis model.

[0039] Figure 11 shows the relationship between the balloon diameter and the diameter of the unheated constriction model in the sixth experiment. Up to a balloon internal pressure of 100 kPa, the diameter of all unheated constriction models was significantly smaller than the balloon diameter. Furthermore, all constriction models ruptured by the time the balloon internal pressure reached 160 kPa. In Figure 11, plots significantly exceeding the balloon diameter indicate rupture.

[0040] Figure 12 shows the relationship between the diameter of the balloon and the diameter of the heated constriction model in the sixth experiment. When the internal pressure of the balloon exceeded 40 kPa, the diameter of all heated constriction models became approximately equal to the diameter of the balloon. This indicates that the constriction models expanded sufficiently and followed the diameter of the balloon. Furthermore, all heated constriction models expanded up to 160 kPa without rupturing. The sixth experiment confirmed that by applying tensile force after heating, the diameter of the constricted portion could be expanded to the balloon diameter without causing rupture of the constricted portion.

[0041] Experiment 7 The inventor conducted a seventh experiment to confirm the changes in tissue condition due to heating and traction. In the seventh experiment, bovine Achilles tendons were stained with HE, heated at 70°C for 15 minutes, and then traction was applied to create a stress of 6 MPa. Observations were made before heating, after heating, and after traction.

[0042] Figure 13 shows the changes in the tissue state related to the seventh experiment. In Figure 13, cell nuclei were stained blue-violet (dark gray in Figure 13) and collagen fibers were stained red (light gray in Figure 13) by HE staining. Upon heating, the unstained areas (white in Figure 13) turned red. This is because the fibrous structure was destroyed due to the denaturation of collagen fibers into gelatin. On the other hand, focusing on the cell nuclei, it can be seen that the cell nuclei remained intact both after heating and after traction. In other words, no morphological changes in cells were observed within the range of heat load and stress load of the method according to the first embodiment. From this, it can be seen that according to the first embodiment, collagen fibers can be selectively destroyed while suppressing damage to cells.

[0043] <Second Embodiment> A technique called HIFU (High-Intensity Focused Ultrasound) is known, which achieves therapeutic effects by selectively destroying biological tissue non-invasively using ultrasound. While techniques exist to soften tissue containing collagen fibers by cutting some of the high-strength collagen fibers, there is a need for a non-invasive technique to soften collagen-containing tissue.

[0044] The destructive range of HIFU is determined by the aperture area of ​​the ultrasonic transmitter and the wavelength of the ultrasound. Therefore, the destructive range of HIFU is at least 5 mm. 3 Collagen fibers are of a certain size. They are randomly distributed on a micrometer scale, and nerves and blood vessels run near them. Therefore, it has been difficult to selectively destroy collagen fibers using ultrasound without damaging unintended biological tissues. The objective of the second embodiment is to provide a collagen decomposition device and a method for operating the collagen decomposition device that can selectively destroy collagen fibers in a range narrower than the irradiation range of ultrasound.

[0045] Configuration of Collagen Decomposition Device 1 The embodiments will be described in detail below with reference to the drawings. Figure 14 is a perspective view showing the configuration of the collagen decomposition apparatus 1 according to the second embodiment. Figure 15 is a cross-sectional view of the collagen decomposition apparatus 1 according to the second embodiment. The collagen decomposition apparatus 1 comprises a housing 11, a gel pad 12, an ultrasonic irradiation device 13, a laser device 14, and a control device 15. The housing 11 is configured in a substantially cylindrical shape with a through hole 111. That is, the housing 11 has a disc-shaped bottom surface with a hole in the center. The gel pad 12 is provided so as to cover the bottom surface of the housing 11. The gel pad 12 is made of, for example, polyurethane gel. The gel pad 12 does not need to have a through hole in the location corresponding to the through hole 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. The laser device 14 irradiates laser light through the through hole 111 and the gel pad 12. The control device 15 controls the output of the ultrasonic irradiation device 13 and the laser device 14.

[0046] In the second embodiment, the collagen decomposition device 1 can selectively destroy collagen fibers at a target location in the target object T by bringing the bottom surface of the housing 11 into close contact with the target object T (e.g., living tissue) via a gel pad 12, and irradiating the target object T with laser light and ultrasound, thereby softening the tissue. In other embodiments, water or jelly may be used instead of the gel pad 12.

[0047] The ultrasonic irradiation device 13 has an opening at the bottom of the housing 11. Therefore, the ultrasonic irradiation range R1 extends at least from the bottom of the housing 11 in the direction of ultrasonic irradiation. The ultrasonic irradiation device 13 operates at a frequency of 200 kHz to 10 MHz and a power output of 0.4 kW / cm². 2 More than 10kW / cm 2 The device irradiates with ultrasound having the following power and sound pressure of 1 MPa to 150 MPa. Preferably, the sound pressure of the ultrasound is 1 MPa to 25 MPa. More preferably, the ultrasonic irradiation device 13 has a frequency of 250 kHz and a frequency of 0.4 kW / cm².2 Ultrasound is irradiated under the condition of 3.5 MPa. With such conditions, the ultrasound irradiated by the ultrasound irradiation device 13 can selectively destroy gelatin formed by heat denaturation of collagen fibers without damaging non-target tissues such as skin, muscles, blood vessels and nerves in biological tissues. When the frequency of the ultrasound is lower than 200 kHz, the focal area becomes larger relative to the biological tissue, which increases the damage caused to non-target tissues. The power is 10 kW / cm 2 2 or when the sound pressure of the ultrasound exceeds 150 MPa, the number of cavitations generated becomes excessive, which increases the damage caused to non-target tissues. In addition, when the frequency of the ultrasound exceeds 10 MHz or the power is 0.4 kW / cm 2 2, the ultrasound irradiated from outside the body is attenuated in the living body, so it falls below the cavitation generation threshold, resulting in reduced destructive power against gelatin. Furthermore, when the sound pressure of the ultrasound is lower than 1 MPa, the number of cavitations generated becomes too small, resulting in reduced destructive power against gelatin. In other words, the ultrasound irradiation device 13 irradiates ultrasound at a frequency that generates cavitations having an intensity capable of destroying gelatin without destroying biological tissues.

[0048] The laser device 14 irradiates laser light with an absorption wavelength of collagen fibers. Specifically, the laser device 14 irradiates 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 ultrasound 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 compared to hemoglobin, lipids, and water, which are components with relatively high absorption coefficients in biological tissues.

[0049] The control device 15 is connected to the ultrasound irradiation device 13 and the laser device 14 via a cable, and outputs control signals to the ultrasound irradiation device 13 and the laser device 14. The control device 15 may also supply electric power for driving the ultrasound irradiation device 13 and the laser device 14 via a cable. When the collagen decomposition device 1 is activated, the control device 15 starts irradiating with ultrasound using the ultrasonic irradiation device 13 and also starts irradiating with laser light using the laser device 14. The control device 15 controls the laser device 14 to repeatedly irradiate with pulsed light at a frequency of 0.1 Hz to 100 kHz and a pulse duration of 1 ns to 20 ms. The pulsed light irradiation is preferably performed at a frequency of 0.1 Hz to 1 kHz and a pulse duration of 1 ns to 1 ms. As a result, the control device 15 raises the temperature of the collagen fibers irradiated with laser light to near the denaturation temperature (45°C), and partially denatures the collagen fibers into gelatin. In other words, the laser device 14 irradiates with thermal energy of a power that raises the temperature of the collagen fibers present within the laser irradiation range R2 to a temperature near the collagen denaturation temperature.

[0050] Furthermore, since the denaturation to gelatin is limited to the laser irradiation range R2, the temperature drops during periods when the laser is not irradiated, and the material returns to collagen fibers. In the object T, thermal diffusion outside the laser irradiation range R2 occurs in approximately 20 ms. Therefore, the control device 15 can suppress thermal diffusion of the laser light by setting the pulse duration of the laser light to 20 ms or less. In other words, the laser device 14 irradiates thermal energy for a time shorter than the time it takes for the temperature of collagen fibers outside the laser irradiation range R2 to rise to the denaturation temperature due to thermal diffusion. Preferably, the laser device 14 has a wavelength of 532 nm and a density of 1 mJ / mm². 2 The laser beam is irradiated under these conditions.

[0051] 《Mechanism and Effects of Collagen Decomposition Device 1》 With the bottom surface of the housing 11 in close contact with the object T, when the user inputs an irradiation command to the control device 15, the control device 15 outputs an irradiation command for laser light to the laser device 14 and simultaneously outputs an irradiation command for ultrasound to the ultrasound irradiation device 13. In other words, the control device 15 outputs an irradiation command to the ultrasound irradiation device 13 at least while the laser device 14 is operating. When the laser light from the laser device 14 is irradiated onto the object T, the temperature of the collagen fibers present in the irradiation range R2 rises. When the temperature of the collagen fibers reaches the denaturation temperature, some of the collagen fibers are denatured into gelatin. Collagen fibers have a triple-stranded helix structure, while gelatin has a random coil structure. Therefore, gelatin has lower 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 ultrasound irradiated from the ultrasound irradiation device 13 occurs more frequently in areas where gelatin, which is the denatured collagen fiber, is present. When cavitation generated by ultrasound expands and bursts, weaker gelatin is destroyed, while stronger collagen fibers and other biological tissues remain undamaged. Similarly, the acoustic energy of ultrasound damages weaker gelatin while not damaging collagen fibers or other biological tissues. The selective destruction of gelatin by cavitation bursting and acoustic energy selectively destroys the parts of the collagen fibers that are irradiated with laser light. Furthermore, the expansion and bursting of cavitation between intertwined collagen fibers generates a force that separates the collagen fibers. This allows the overall flexibility of the fibers to be maintained even after laser irradiation is stopped and the collagen fibers are no longer heated.

[0052] Thus, according to the collagen decomposition apparatus 1 of the second embodiment, the collagen present in a region narrower than the ultrasonic irradiation range R1 is partially denatured into gelatin by laser light, and then ultrasonic waves are irradiated. As a result, the collagen decomposition apparatus 1 can selectively destroy collagen fibers in a region narrower than the ultrasonic irradiation range.

[0053] <Other Embodiments> Although one embodiment has been described in detail with reference to the drawings above, the specific configuration is not limited to that described above, and various design changes are possible.

[0054] In the collagen decomposition apparatus 1 according to the second embodiment, a laser device 14 is provided in a through hole 111 of the housing 11, and the laser light is irradiated to the center of the ultrasonic irradiation range of the ultrasonic irradiation device 13. On the other hand, the configuration is not limited to this in other embodiments. For example, in the collagen decomposition apparatus 1 according to other embodiments, the direction of ultrasonic irradiation and the direction of laser light irradiation do not have to coincide. In this case, for example, the collagen decomposition apparatus 1 may be provided with the ultrasonic irradiation device 13 and the laser device 14 such that the ultrasonic irradiation range and the laser light irradiation range intersect.

[0055] Furthermore, the collagen decomposition apparatus 1 according to the second embodiment includes one laser device 14 and one ultrasonic irradiation device 13, but is not limited thereto. For example, the collagen decomposition apparatus 1 according to another embodiment may include multiple laser devices 14 and ultrasonic irradiation devices 13. For example, the collagen decomposition apparatus 1 according to another embodiment may be configured so that multiple laser devices 14 intersect at a single point, thereby denaturing the collagen fibers at the point where the laser beams intersect into gelatin. In this case, the control device 15 may adjust the angle of the laser devices 14 to change the depth of the point where the laser beams intersect in relation to the epidermis.

[0056] Furthermore, in other embodiments of the collagen decomposition apparatus 1, a heat source device capable of irradiating thermal energy over a narrower area than the ultrasonic irradiation range may be used instead of the laser device 14. For example, in other embodiments of the collagen decomposition apparatus 1, a heater using thermal radiation may be provided.

[0057] <Computer Configuration> The control device 15 includes a processor, memory, and auxiliary storage device connected by a bus, and functions as a control device 15 that controls the ultrasonic irradiation device 13 and the laser device 14 by executing a program. Examples of processors include a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), and a microprocessor. The program may be recorded on a computer-readable recording medium. Computer-readable recording media include, for example, magnetic disks, magneto-optical disks, optical disks, and semiconductor memory. The program may also be transmitted via a telecommunications line.

[0058] Furthermore, all or part of the functions of the control device 15 may be implemented using custom LSIs (Large Scale Integrated Circuits) such as ASICs (Application Specific Integrated Circuits) or PLDs (Programmable Logic Devices). Examples of PLDs include PALs (Programmable Array Logic), GALs (Generic Array Logic), CPLDs (Complex Programmable Logic Devices), and FPGAs (Field Programmable Gate Arrays). Such integrated circuits are also included as examples of processors. [Industrial applicability]

[0059] According to at least one of the above embodiments, the collagen decomposition device can selectively destroy collagen fibers while minimizing damage to cells. [Explanation of symbols]

[0060] 1...Collagen decomposition device 11...Housing 12...Gel pad 13...Ultrasonic irradiation device 14...Laser device 15...Control device

Claims

1. A stress application device that applies stress to a first range of the target tissue, A heat source device that provides thermal energy to a second range having at least a portion overlapping with the first range, A control device for controlling the stress application device and the heat source device, Equipped with, The control device is The heat source device is given an instruction to start heating. After heating by the heat source device is started, a first stress application start instruction is output to the stress application device to apply a first stress capable of selectively destroying the thermally denatured parts of the collagen fibers. The heat source device is given a command to stop heating. After the heating by the heat source device is stopped, an instruction to stop the stress application by the stress application device is output. Collagen decomposition device.

2. The stress application device applies stress to a first range that selectively destroys areas where collagen fibers have undergone thermal denaturation without damaging non-target tissue within the target tissue. The collagen decomposition apparatus according to claim 1.

3. The stress application device applies a stress of 40 kPa or more and 500 kPa or less to the first range. The collagen decomposition apparatus according to claim 2.

4. The heat source device provides thermal energy with enough power to raise the temperature of the collagen fibers within the second range to above the collagen denaturation temperature. A collagen decomposition apparatus according to any one of claims 1 to 3.

5. The stress-applying device presses the tubular organ, which is the target tissue, from the inside outward in the radial direction. A collagen decomposition apparatus according to any one of claims 1 to 3.

6. Equipped with a balloon that inflates by the supply of fluid, The first range and the second range are the ranges of the tubular organ that the balloon contacts, The stress-applying device presses the tubular organ radially outward from the inside by supplying the fluid to the balloon. The heat source device provides thermal energy to the tubular organ by heating the fluid. The collagen decomposition apparatus according to claim 5.

7. The system includes a control device for controlling the stress application device and the heat source device, The control device is Prior to the output of the heating start instruction, a second stress application start instruction is output to the stress application device, which applies a second stress that does not damage the non-target tissue within the target tissue. A collagen decomposition apparatus according to any one of claims 1 to 3.

8. The heat source device outputs the thermal energy using waves as a medium. The aforementioned waves are irradiated so as to converge on the areas of the target tissue where collagen fibers are present. A collagen decomposition apparatus according to any one of claims 1 to 3.

9. The second range is narrower than the first range. A collagen decomposition apparatus according to any one of claims 1 to 3.

10. An ultrasonic irradiation device that irradiates the first irradiation area with ultrasound at a frequency that generates cavitation with an intensity capable of destroying gelatin without destroying biological tissue, A heat source device that irradiates thermal energy to a second irradiation range which is inside the first irradiation range and narrower than the first irradiation range, A collagen decomposition device equipped with the following features.

11. The heat source device irradiates the second irradiation range with laser light having a wavelength of 400 nm to 900 nm. The collagen decomposition apparatus according to claim 10.

12. The heat source device irradiates the second irradiation range with laser light having a wavelength of 400 nm to 900 nm with a pulse time width of 1 ns to 20 ms. The collagen decomposition apparatus according to claim 11.

13. The heat source device irradiates thermal energy with enough power to raise the temperature of the collagen fibers present in the second irradiation range to a temperature near the collagen denaturation temperature. A collagen decomposition apparatus according to any one of claims 10 to 12.

14. The heat source device irradiates thermal energy for a period of time shorter than the time it takes for the temperature of collagen fibers outside the second irradiation range to rise to the denaturation temperature due to thermal diffusion. The collagen decomposition apparatus according to claim 13.

15. The ultrasonic irradiation device irradiates ultrasound with a frequency of 200 kHz or more and 10 MHz or less, at a power of 0.4 kW / cm² or more and 10 kW / cm² or less. A collagen decomposition apparatus according to any one of claims 10 to 12.

16. It comprises a housing having a disc-shaped bottom surface with a hole in the center, The ultrasonic irradiation device irradiates the ultrasonic waves from the bottom surface of the housing, The heat source device irradiates the thermal energy through the hole. A collagen decomposition apparatus according to any one of claims 10 to 12.

17. A method for operating a collagen decomposition apparatus comprising an ultrasonic irradiation device, a heat source device, and a control device, The control device outputs an irradiation instruction to the heat source device to irradiate the second irradiation range with thermal energy. The control device outputs an irradiation instruction to the ultrasonic irradiation device during the operation of the heat source device, which instructs the device to irradiate a first irradiation range that includes the second irradiation range and is wider than the second irradiation range with ultrasound at a frequency that generates cavitation with an intensity capable of destroying gelatin without destroying biological tissue. A method for operating a collagen decomposition device, including the device itself.

18. A method for operating a collagen decomposition apparatus according to any one of claims 1 to 3, The control device outputs a heating start instruction to the heat source device to start heating in the second range, The control device outputs an instruction to start stress application to the stress application device after the heating start instruction, which causes the device to start applying a first stress to the first range that is capable of selectively destroying the parts of the collagen fibers that have undergone thermal denaturation. The control device outputs a heating stop instruction to the heat source device to stop heating, The control device, after the heating stop instruction, outputs an addition stop instruction to the stress application device to stop applying the stress, A method for operating a collagen decomposition device having the following characteristics.

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