JP4090795B2 - Thermal stent and intraluminal surface fixation / stabilization device using the same - Google Patents

Description

[0001]
[Industrial application fields]
The present invention relates to a thermal stent and an apparatus for fixing and stabilizing an intraluminal surface in vivo using the thermal stent, and in particular, there are various lumens such as blood vessels, bile ducts, pancreatic ducts, urethra in vivo. The present invention relates to a thermal stent that heats and stabilizes the local surface in the lumen by a magnetic field induction method that can be used to treat stenosis, occlusion, plaque formation, and malignant tumor growth.
[0002]
In particular, the present invention relates to a thermal stent that can not only prevent restenosis after placement of a thermal stent, but also stabilize plaque in a vascular stenosis.
[0003]
[Prior art]
It is disclosed in JP-A-6-63154 and JP-A-6-63155 that tumor cells are heated to a temperature higher than the body temperature by an alternating magnetic field, and the tumor cells are killed and treated using the heat of the generated stent. It is disclosed in the publication. The techniques disclosed in these publications can be used to insert a stent into a tubular organ that has progressed beyond the scope of conventional stent insertion, and perform local heating to form a void, or a thermosensitive polymer and By applying the drug to the stent and dissolving the polymer by local heating to release the drug, the stent is prevented from narrowing or occlusion due to tumor infiltration into the stent or compression of the tumor from around the stent, The effectiveness can be maintained for a long time.
[0004]
However, these techniques are based on the condition that there is no circulatory system around the tumor cells, and as is clear from the description of the specification, the heating of the stent is caused by physiological saline, that is, physiological saline is retained. It is not evaluated in a system that is constantly circulating like blood. Such a conventional technique misses that the body temperature is constantly maintained at a constant temperature by circulating blood. In other words, it means that the stent is constantly cooled to a temperature close to body temperature in the circulating system, and a thermal stent that does not overcome this cooling action is not practical in the vascular system.
[0005]
In addition, since the heating means of the prior art uses an alternating magnetic field with a high frequency of 200 KHz, there is a drawback that temperature control becomes difficult because eddy currents are generated in the cylindrical body or induction heating occurs. It was a thing.
[Problems to be solved by the present invention]
The present invention relates to a thermal stent that can effectively generate heat even if it is placed in a circulatory system and can maintain a temperature higher than body temperature, and an in-vivo luminal surface fixation / stabilization device using the same.
[0006]
The present invention relates to a cylindrical body made of palladium-nickel or nickel-based low Curie temperature type ferromagnetic alloy that generates heat by an alternating magnetic field of 10 KHz to 50 KHz, and the outer surface of the cylindrical body is a lumen in a living body. its intraluminal surface and low Curie temperature type ferromagnetic alloy when placed together with a surface in direct contact with the heat insulating film the inner surface of the tubular body that is not in contact with the intraluminal surface is plastic coated A thermal stent used by being placed in a lumen in a living body, and
The cylindrical body is heated to a temperature higher than the living body temperature by applying an alternating magnetic field to the thermal stent from the outside of the thermal stent, and comprises a device that maintains this state for a predetermined time,
The apparatus comprises: coil means capable of accommodating a living body portion on which the thermal stent is disposed and applying an alternating magnetic field to the thermal stent;
The AC magnetic field is 10 KHz to 50 KHz, and means for supplying electric energy to the coil means so that the magnetic flux density of the environment surrounding the thermal stent is 5 mT or more;
Means for maintaining the supply of electrical energy for a predetermined time,
An intraluminal surface fixation / stabilization device using a thermal stent.
[0007]
Further, the present invention provides a thermal stent comprising a tubular body of a palladium / nickel-based low Curie temperature type ferromagnetic alloy and a heat insulating film covering the inner surface of the tubular body in a lumen of a living body. The cylindrical body is heated to a temperature higher than the living body temperature by applying an alternating magnetic field to the thermal stent from the outside of the thermal stent, and is contacted with the cylindrical body by the heated cylindrical body An apparatus for fixing and stabilizing an inner surface of a lumen by a thermal stent, wherein the inner surface of the lumen is fixed.
[0008]
In the present invention, the alternating magnetic field is preferably 10 KHz to 50 KHz.
If the alternating magnetic field is less than 10 KHz, it is difficult to warm up to a treatable temperature range, and if it exceeds 50 KHz, induction heating by electromagnetic waves occurs, and temperature control becomes difficult.
[0009]
In the present invention, the temperature higher than the living body temperature is 38 to 44 ° C, preferably 41 to 44 ° C. If the temperature higher than the living body temperature is less than 38 ° C, the effect of heating cannot be expected, and if it exceeds 44 ° C, the living body may be adversely affected.
[0010]
Next, the present invention is Ru using a palladium-nickel or nickel-based tubular body that generates heat by an alternating magnetic field is 10KHz~50KHz of low Curie temperature type ferromagnetic alloy is disposed within the lumen in vivo In the thermal stent, and an apparatus that generates heat to a temperature higher than the living body temperature by applying an alternating magnetic field to the thermal stent from the outside of the thermal stent and maintains this state for a predetermined time, Coil means that can accommodate a living body portion on which the stent is disposed and applies an AC magnetic field of 10 KHz to 50 KHz to the thermal stent, and the coil means so that the magnetic flux density in the environment surrounding the thermal stent is 5 mT or more Means for supplying electric energy to the battery, and means for maintaining the supply of electric energy for a predetermined time, and is in contact with the cylindrical body by the heated cylindrical body Fixing the by and within the lumen surface is fixed and stabilizer of the tube lumen surface by thermal stent according to claim. The magnetic flux density is preferably 5 mT to 15 mT. If the magnetic flux density is lower than 5 mT, the temperature of the thermal stent of the present invention cannot be sufficiently increased. Further, when the magnetic flux density exceeds 15 mT, not only is energy wasted, but a magnetic field is unnecessarily applied to the living body.
[0011]
Next, the present invention relates to a thermal stent comprising a cylindrical body made of a palladium / nickel-based low Curie temperature type ferromagnetic alloy and a heat insulating film covering the inner surface of the cylindrical body. is there.
[0012]
In the present invention, it is preferable that the cylindrical body has a wall formed in a linear pattern, and a hole other than the linear pattern forms a hole penetrating the wall. As the linear pattern, (1) the whole zigzag or corrugated strip is spirally connected and adjacent zigzags or corrugations are connected, and (2) zigzags or corrugated strips are arranged side by side in a plurality of axial directions. Examples include matching zigzags or waveforms connected together.
[0013]
Moreover, the cylindrical body used for this invention may cut | disconnect the cylindrical body to the axial direction, and may be C-shaped in cross section. In this case, before inserting the cylindrical body into the living body, the cylindrical body is rolled and fixed in advance so as to be wound, and after being inserted into the living body, the fixation is released to restore the original cylindrical body. To do.
[0014]
In the present invention, the ferromagnetic alloy preferably has a palladium to nickel ratio of 70 to 80 to 30 to 20. When the ratio of palladium is less than 70, heat is excessively generated beyond the treatable temperature range, and when it exceeds 80, sufficient heat generation cannot be obtained.
[0015]
In the present invention, the heat insulating film is preferably a plastic. The plastic is particularly preferably a material that does not affect the living body, and is preferably silicone, polyethylene, polypropylene, polytetrafluoroethylene, ethylenetetrafluoroethylene, or the like.
[0016]
In the present invention, the thermal stent is preferably self-expanding or balloon-expanding. In the case of the self-expanding type, the cross section may be folded into a star shape or a triple shape, and in the case of the balloon expansion type, a structure that can be easily expanded by expansion of the balloon and does not contract after expansion.
[0017]
In the thermal stent of the present invention, it is desirable that the material for covering the cylindrical body with the heat insulating film is inert to the living body for a long time, and preferably has a low thermal conductivity. The heat insulating effect can be adjusted by the film thickness, and fine air particles may be dispersed in the film. In order to coat the inner surface of the cylindrical body with the heat insulating film, the inner surface of the cylindrical body may be plastic-coated by spraying or dipping in a plastic solution while covering the outer surface of the cylindrical body. Also, the inner surface of the cylindrical body can be coated by plasma polymerization in a vacuum vessel.
[0018]
Next, a description will be given of a device for fixing and stabilizing the inner surface of the lumen by the thermal stent of the present invention. The device first requires a coil of a size that can be inserted into a living body at a site where a thermal stent is to be placed. This is because an alternating magnetic field is generated from the coil and the thermal stent is heated by the alternating magnetic field.
Since the strength of the alternating magnetic field generated from the coil can be measured by measuring the energy sent to the coil in advance, it is not necessary to measure the temperature when actually heating the thermal stent.
[0019]
A frequency generator is connected to the coil via an amplifier. As long as the frequency generator can be varied from 10 KHz to 50 KHz, an optimal frequency can be selected depending on the difference in tissue around the thermal stent in the living body. The frequency generator may generate a fixed frequency.
[0020]
Next, a method for fixing and stabilizing the intraluminal surface by the thermal stent of the present invention will be described. In the case of a self-expanding stent, it can be introduced into a target site of a living body by sandwiching a contracted thermal stent between inner and outer catheters at the distal end of a double catheter that has been conventionally used. When the distal end of the double catheter reaches the target site, the thermal stent is released by pulling the outer catheter back to the hand, and expands and restores the original shape. When the thermal stent is expanded, the double catheter is removed from the living body.
[0021]
In the case of a balloon expandable stent, a thermal stent is crowned on the balloon of a conventional PTCA balloon expandable catheter, inserted through the guiding catheter toward the target site of the living body, and beyond the tip of the guiding catheter. Then, the thermal stent is expanded by advancing the balloon portion of the PTCA balloon expansion catheter to the target site of the living body and expanding the balloon. For example, the stenosis site is expanded to a normal inner diameter. Once the thermal stent is expanded, the PTCA balloon dilatation catheter is removed from the body. At this time, the guiding catheter may be removed as necessary, but if it is necessary to place the stent again, it is left as it is.
[0022]
Next, the living body at the site where the thermal stent is placed is positioned in the coil, an alternating magnetic field is generated at a predetermined magnetic flux density, and the cylindrical body of the thermal stent is heated to generate a predetermined temperature at 42 ° C. to 44 ° C. Keep time. At this time, blood circulates in the blood vessel due to the expansion of the stenotic site, but the cooling of the cylindrical body is suppressed by the presence of the heat insulating film provided on the cylindrical body, and the inner surface of the stenotic site is heated at a stable temperature. Can do. As a result, the plaque is also fixed and the stenosis site is maintained at the original inner diameter for a long time.
[0023]
In addition, since the heating method depends on the magnetic field from outside the body, it can be done with a simple operation without placing a burden on the living body. Suppresses the proliferation of cells and the occurrence of plaque. Thus, the initial state can be maintained by repeated overheating.
[0024]
Although the above explanation has been given focusing on the stenosis site of the blood vessel, it can also be used for the bile duct, pancreatic duct, ureter, and tumor cell site where the influence of circulation is small.
[0025]
[Effects of the Invention]
In this way, the present invention provides a tubular body of a thermal stent when the tubular body of the thermal stent and the heat insulating film provided on the inner surface thereof act synergistically to generate an alternating magnetic field with a predetermined magnetic flux density. Generates heat and rises to a temperature of 42 ° C to 44 ° C. At this time, the thermal stent is cooled by the blood flow, but the cylindrical body is stably maintained at 42 ° C. to 44 ° C. without being cooled by the presence of the heat insulating film. At this time, the heating time can be adjusted according to the condition of the stenosis site. The stenosis part is stably fixed by the heat at this time.
[0026]
【Example】
[Example 1]
The thermal stent 1 of the present invention comprises a cylindrical body 2 made of a low Curie temperature type ferromagnetic alloy having a ratio of palladium to nickel of 76:24, and a plastic film 3 covering the inner surface of the cylindrical body 2. . The outer diameter of the thermal stent 1 is 4 mm, the inner diameter is 3 mm, and the length is 20 mm. The inner surface of the thermal stent 1 is coated with a plastic film 3 having a thickness of 0.3 mm. This film 3 has a function of preventing the thermal stent 1 from being cooled by a circulating flow of blood or the like.
<Evaluation Test 1>
Next, the thermal stent 1 of the present invention and the method of using the same will be described using the pseudo blood vessel model shown in FIG.
[0027]
A silicone tube 4 having an inner diameter of 4 mm was used as a pseudo blood vessel. The thermal stent 1 of the present invention having a reduced outer diameter was inserted into a catheter (not shown) having an outer diameter of 3 mm. This catheter is inserted into the silicone tube 4, a rod-like body is inserted from the proximal end side of the catheter, the thermal stent 1 of the present invention is pushed out of the catheter, and the thermal stent 1 of the present invention is placed in a predetermined position within the silicone tube 4. Left in place. After placement of the thermal stent 1 of the present invention, the catheter and rod-like body were removed from the silicone tube 4.
[0028]
A thermocouple 7 for temperature measurement was fixed around the silicone tube 4 in which the thermal stent 1 of the present invention was placed so that the temperature of the thermal stent 1 of the present invention could be measured. Further, the outside of the silicone tube 4 was surrounded by an agar layer 5. A coil 6 was arranged so as to surround the silicone tube 4 with a gap provided outside the agar layer 5. The agar layer 5 contained 0.9 w% NaCl and 5 w% agar. The outer diameter of the agar layer 5 was 20 mm. The agar layer 5 is provided on the tissue around the blood vessel.
[0029]
A thermocouple 7 was connected to the recorder 10 so that the temperature measured continuously could be recorded.
The coil 6 was connected to an oscillator 8 (Hewlett Packard Oscillator 33120A) via an RF amplifier 9 (ENI RF Amplifier 1040). One side of the silicone tube 4 is provided with a tube pump (Master Flex L / S) for circulating physiological saline. The other end of the silicone tube 4 and the open end of the tube pump are inserted into a physiological saline maintained at a constant temperature of 36 ° C. in a thermostatic bath.
[0030]
In order to observe changes in body temperature with this circulatory system, physiological saline was circulated from 34 ° C to 38 ° C and tested. The temperature of the thermal stent 1 was measured by circulating physiological saline at a flow rate of 17 to 145 ml / min. An alternating current with a frequency of 25 KHz generated by the oscillator 8 was amplified by the RF amplifier 9 and passed through the coil 6, and an alternating magnetic field was applied to the thermal stent 1.
[0031]
The temperature of the thermal stent 1 of the present invention was measured using a thermocouple 7. The magnetic flux density at the center of the magnetic field was measured with a solenoid type magnetic flux density meter. The magnetic flux density was measured between 0 and 15 mT.
[0032]
The thermal stent 1 of the present invention was evaluated at a circulating physiological saline temperature of 36 ° C. and a flow rate at that time of 58 ml / min.
[0033]
The temperature of the thermal stent 1 of the present invention reached thermal equilibrium after about 500 seconds when an AC magnetic field having a magnetic flux density of 10 mT was applied. Further, after 500 seconds, the temperature of the thermal stent 1 of the present invention was maintained at 42 ° C to 43 ° C.
[0034]
It was also found that the temperature of the thermal stent 1 of the present invention reached thermal equilibrium about 500 seconds after applying an alternating magnetic field having a magnetic flux density of 5 mT or more while circulating physiological saline at 36 ° C. Moreover, when the temperature of the thermal stent 1 of the present invention was circulated at a flow rate of 17 to 145 ml / min at the same physiological saline temperature, it remained at a thermal equilibrium of 42.6 ° C. in an alternating magnetic field with a magnetic flux density of 10 mT. In addition, when the temperature of the circulating physiological saline was changed from 34 ° C. to 38 ° C., the temperature of the thermal stent 1 of the present invention slightly increased with the increase of the physiological saline temperature. The temperature change of the thermal stent 1 was very slight with respect to the temperature change of the physiological saline, 0.05 when expressed by the temperature change of the type stent 1 / temperature change of the physiological saline. This remarkably indicates that the effect of the heat insulating film 3 of the present invention appears.
<Comparative evaluation test 1>
A thermal stent 1 of Example 1 having no heat insulating film 3 was prepared as a comparative stent. The heating conditions were the same as in Example 1 above, but could not be raised to 42 ° C, rather than 40 ° C.
<Evaluation Test 2>
Next, the thermal stent 1 of the present invention was implanted in the livers of five black mice under anesthesia in order to evaluate the increase in temperature in the living body using the thermal stent 1 of the present invention in an alternating magnetic field. Next, the abdomen of each mouse was covered with a coil. In this state, an alternating magnetic field of 25 KHz was applied to the thermal stent 1 of the present invention for 25 minutes at a magnetic flux density of 10 mT. At this time, the temperature of the embedded thermal stent 1 of the present invention was monitored using a thermocouple 7 during the heating period.
[0035]
The thermal stent 1 of the present invention embedded in the liver of the mouse was kept uniformly at a thermal equilibrium temperature of 43 ° C. during the heating period of the alternating magnetic field.
[0036]
【The invention's effect】
As described above, the thermal stent of the present invention uses a cylindrical body that generates heat by an alternating magnetic field of 10 KHz to 50 KHz made of a palladium-nickel or nickel-based low Curie temperature type ferromagnetic alloy. Heating was stable with a low-frequency AC magnetic field, and the elevated temperature was stable with little temperature change. The outer surface of the cylindrical body forms a surface where the inner surface of the tubular body and the low Curie temperature type ferromagnetic alloy are in direct contact with each other when placed in the lumen of the living body. Further, the insulation film plastic coat provided on the inner surface of the tubular body that is not in contact with the lumen surface, the stable temperature without When embedding the thermal stent of the present invention are also cooled to the circulation portion Can keep. In addition, the use of a plastic that is compatible with the living body for the heat insulating membrane prevents the proliferation of endothelial cells. In addition, since the thermal stent of the present invention has a structure that can be easily heated, it is possible to prevent neointimal proliferation for a long period of time by periodically heating repeatedly, and to suppress the occurrence of plaque, which is suitable for prevention of restenosis. It is.
[0037]
Next, the device for fixing / stabilizing the intraluminal surface by the thermal stent of the present invention has a simple structure and takes up little space because the part into which the living body is inserted is made of a coil.
[0038]
Furthermore, since the device for fixing and stabilizing the intraluminal surface by the thermal stent of the present invention has a simple structure, the operation is simple, and there is no trouble of measuring the temperature in a living body during heating.
[Brief description of the drawings]
FIG. 1 is a diagram showing an evaluation test apparatus for a thermal stent according to the present invention.
2 is a cross-sectional view of a portion where the thermal stent of the present invention is embedded in FIG.
[Explanation of symbols]
1 Thermal stent 2 Tubular body 3 Plastic film (heat insulation film)
4 Silicone tube 5 Agar layer 6 Coil 7 Thermocouple 8 Oscillator 9 RF amplifier 10 Recorder

Claims (10)

A cylindrical body made of palladium / nickel or a nickel-based low Curie temperature type ferromagnetic alloy that generates heat by an alternating magnetic field of 10 KHz to 50 KHz, and an outer surface of the cylindrical body is disposed in a lumen in a living body. The inner surface of the tubular body and the low Curie temperature type ferromagnetic alloy are in direct contact with each other, and the inner surface of the cylindrical body that does not contact the inner surface of the lumen is made of a heat-insulating film coated with plastic. A thermal stent that is used by being placed in a lumen in a living body. 2. The thermal stent according to claim 1, wherein the tubular body has a wall formed in a linear pattern, and a hole other than the linear pattern forms a hole penetrating the wall. The thermal stent according to claim 2, wherein the ferromagnetic alloy has a palladium to nickel ratio of 70 to 80 to 30 to 20. The thermal stent according to any one of claims 1 to 3, wherein the heat insulating film is plastic. The thermal stent according to any one of claims 1 to 4, wherein the thermal stent is self-expanding or balloon expandable. A cylindrical body made of palladium / nickel or nickel-based low Curie temperature type ferromagnetic alloy that generates heat by an alternating magnetic field of 10 KHz to 50 KHz, and an outer surface of the cylindrical body is disposed in a lumen in the living body. The inner surface of the tubular body and the low Curie temperature type ferromagnetic alloy are in direct contact with each other, and the inner surface of the cylindrical body that does not contact the inner surface of the lumen is made of a heat insulating film made of plastic. A thermal stent for use in a body lumen;
The cylindrical body is heated to a temperature higher than the living body temperature by applying an alternating magnetic field to the thermal stent from the outside of the thermal stent, and comprises a device that maintains this state for a predetermined time,
The apparatus comprises: coil means capable of accommodating a living body portion on which the thermal stent is disposed and applying an alternating magnetic field to the thermal stent;
The AC magnetic field is 10 KHz to 50 KHz, and means for supplying electric energy to the coil means so that the magnetic flux density of the environment surrounding the thermal stent is 5 mT or more;
Means for maintaining the supply of electrical energy for a predetermined time,
A device for fixing and stabilizing the inner surface of a lumen by a thermal stent. The tubular body has a wall formed in a linear pattern, and a hole other than the linear pattern forms a hole penetrating the wall. apparatus. 8. The device for fixing and stabilizing an intraluminal surface by a thermal stent according to claim 7, wherein the ferromagnetic alloy has a palladium to nickel ratio of 70 to 80 to 30 to 20. Thermal insulation film, fixed-stabilizer of intraluminal surface by thermal stent according to any one of claims 6-8 is plastic. The device for fixing and stabilizing an intraluminal surface with a thermal stent according to any one of claims 6 to 9, wherein the thermal stent is a self-expanding type or a balloon expansion type.

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