Composite particle magnetic hyperthermia-radiotherapy system implanted via flexible endoscopic ultrasound

Abstract

The present application relates to the technical field of tumor radiotherapy and magnetic induction hyperthermia medical devices, and discloses a composite particle magnetic hyperthermia-radiotherapy system implanted via a soft ultrasonic endoscope, comprising a soft ultrasonic endoscope, a puncture needle sliding in a working channel of the soft ultrasonic endoscope, one end of the puncture needle being connected to a particle channel, the particle channel being loaded with composite particles; a propulsion needle pushing the composite particles in the particle channel to the puncture needle; the present application can sequentially implant composite particles, so that it can have magnetic hyperthermia and radiotherapy effects, synergistically enhance sensitivity, and can more efficiently kill diseased tissues and improve treatment effects; and the system is guided by a soft ultrasonic endoscope and intervenes through natural cavities to puncture and implant composite particles in malignant tumors in human cavities such as the digestive tract, thereby broadening the application scenarios of magnetic hyperthermia and radioactive particle therapy; due to the self-temperature-control characteristics of the composite particles, the system does not require a temperature measurement and control device, thereby reducing the complexity of the equipment while ensuring the targeting, safety and efficacy of tumor treatment.

Description

Technical Field

[0001] This patent relates to the technical field of tumor radiotherapy and magnetic induction hyperthermia medical devices, and specifically to a magnetic induction hyperthermia-radiotherapy system based on magnetothermal radioactive composite particles. Background Art

[0002] Magnetic hyperthermia is a physical therapy that uses the characteristics of magnetic media generating heat and heating under an alternating magnetic field to selectively kill tumors implanted with magnetic media without damaging normal tissues. Compared with traditional chemotherapy or radiotherapy, magnetic hyperthermia is less invasive and can be used for multiple treatments in one intervention. However, due to the high fluidity of magnetic medium particles, there is a risk of escaping from the treatment target area to the surrounding healthy tissues, reducing the efficacy and causing thermal damage to healthy tissues due to magnetic induction heating, while also producing additional toxic side effects. Particle implantation therapy is an internal radiation minimally invasive therapy that implants radioactive particles in the tumor and uses them to continuously release radiation to kill tumor cells. Since radioactive particle radiation has low energy and short penetration distance, it is easy to protect, but at the same time, it has low lethality to tumor cells far away from the radiation source, and the effective killing range is limited.

[0003] Whether it is magnetic hyperthermia or radioactive particle therapy, it is currently necessary to use soft tissue puncture to implant the particles into the predetermined location.

[0004] Existing technologies, such as injecting magnetic medium particle flow into the lesion, using an external magnetic field generator to generate a magnetic field for magnetic induction heating, and using multiple optical fibers arranged in the body for temperature measurement and circulating water for temperature control. Due to the high fluidity of the magnetic medium particle flow, there are problems such as magnetic medium particle loss and difficulty in measuring and controlling the temperature of magnetic hyperthermia.

[0005] Existing technologies, such as using a particle implantation device to implant radioactive particles into the lesion through percutaneous puncture. This single intra-particle radiotherapy has a limited effective killing range, and currently, due to the need for image guidance during the puncture operation, CT and MRI images cannot be imaged in real time and are generally used for preoperative treatment planning; ultrasound has good real-time performance, but is affected by the acoustic window, and the imaging quality of hollow organs (such as malignant tumors of the esophagus and gastrointestinal tract) is poor, which makes it difficult to guide the implantation of particles for treatment. Due to the limited conditions, particle implantation therapy has not yet been extended to the treatment of malignant tumors in the digestive tract and other human cavities. Summary of the invention

[0006] The purpose of the present disclosure is to provide a composite particle magnetic hyperthermia-radiotherapy system implanted via a flexible endoscopic ultrasound.

[0007] The purpose of this disclosure can be achieved through the following technical solutions:

[0008] A composite particle magnetic hyperthermia-radiotherapy system implanted via a soft ultrasound endoscope comprises a soft ultrasound endoscope, wherein the soft ultrasound endoscope comprises an ultrasound probe; a puncture needle extending into and sliding along a working channel of the soft ultrasound endoscope, wherein the puncture needle has a sharp thorn portion;

[0009] The puncture needle has a puncture channel extending along the length direction of the puncture needle, and one end of the puncture needle away from the puncture portion is coaxially connected to a particle channel, and the particle channel is loaded with composite particles;

[0010] A propulsion needle is installed at one end of the particle channel away from the puncture needle, and the propulsion needle pushes the composite particles in the particle channel into the puncture needle until the composite particles overflow from the sharp part of the puncture needle.

[0011] In some disclosures, the puncture needle is made of nickel-titanium alloy.

[0012] In some disclosures, the inner diameter of the puncture channel is slightly larger than the particle size of the composite particle, and only a single composite particle is allowed to pass through.

[0013] In some disclosures, a filling bin is included, the filling bin being used to load the composite particles;

[0014] The particle channel is located in the filling chamber, and the puncture needle is detachably connected to the filling chamber.

[0015] In some disclosures, a lifting rod is installed in the filling bin to elastically resist the composite particles in the filling bin. The lifting rod resists the composite particles, and the composite particles have a tendency to move toward the particle channel.

[0016] In some disclosures, a filling bin is fixedly installed with a lifting block, and a movable bin is provided inside the lifting block; one end of the movable bin is closed, and the other end is open, a lifting rod passes through the movable bin to the filling bin, and a limit block is provided on the lifting rod, and a compression spring is installed in the movable bin between the limit block and the lock, and the lock is detachably connected to the open end of the movable bin; the compression spring elastically expands, so that the compression spring drives the lifting rod to resist the composite particles.

[0017] In some disclosures, the lock buckle is threadedly connected to the open end of the movable cartridge.

[0018] In some disclosures, one end of the puncture needle facing away from the puncture portion is threadedly connected to the housing of the filling bin.

[0019] In some disclosures, the pusher needle is passed through an end of a working channel of a flexible ultrasound endoscope that is away from the ultrasound probe.

[0020] In some disclosures, an alternating magnetic field generator is included for generating an alternating magnetic field with adjustable magnetic field strength and frequency, so that the magnetic medium of the composite particles implanted in the treatment target area is heated up by magnetic induction heat generation, thereby killing cancer cells;

[0021] The alternating magnetic field generator is installed on the movable robotic arm.

[0022] Beneficial effects of the present disclosure:

[0023] Composite particles can be implanted in sequence, so that they can have the effects of magnetic hyperthermia and radioactive therapy, synergistically enhance sensitivity, and kill diseased tissues more efficiently, improving the treatment effect; and the system is guided by a soft ultrasound endoscope and intervenes through natural cavities to puncture and implant composite particles in malignant tumors in the digestive tract and other human cavities, broadening the application scenarios of magnetic hyperthermia and radioactive particle therapy;

[0024] Due to the self-temperature controlling characteristics of the composite particles, the system does not require a temperature measurement and control device, thus reducing the complexity of the equipment while ensuring the targeting, safety and efficacy of tumor treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0026] Figure 1 is a schematic diagram of an overall module of an embodiment of the present disclosure;

[0027] Figure 2 is a schematic diagram of the overall structure of an embodiment of the present disclosure;

[0028] Figure 3 is a schematic structural diagram of a particle implantation device according to an embodiment of the present disclosure;

[0029] Figure 4 A schematic diagram of a partial structure of a particle implantation device according to an embodiment of the present disclosure;

[0030] Figure 5 is a workflow diagram of an embodiment of the present disclosure;

[0031] Figure 6 A flow chart of a method for preparing materials in magnetocaloric radioactive composite particles according to an embodiment;

[0032] Figure 7 A flow chart of a method for preparing and assembling a magnetocaloric radioactive composite particle according to an embodiment;

[0033] Figure 8 The figure is a schematic diagram of the structure of a magnetocaloric radioactive composite particle according to an embodiment. DETAILED DESCRIPTION

[0034] The following will be combined with the drawings in the embodiments of the present disclosure to clearly and completely describe the technical solutions in the embodiments of the present disclosure. Obviously, the described embodiments are only part of the embodiments of the present disclosure, rather than all the embodiments. Based on the embodiments in the present disclosure, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present disclosure.

[0035] The composite particle magnetic hyperthermia-radiotherapy system implanted via a flexible ultrasonic endoscope comprises a flexible ultrasonic endoscope 4, wherein the flexible ultrasonic endoscope 4 comprises an ultrasonic probe 4-2; a puncture needle 3-1 extending into and sliding along a working channel 4-1 of the flexible ultrasonic endoscope 4, wherein the puncture needle 3-1 has a sharp spike portion;

[0036] The puncture needle 3-1 has a puncture channel extending along the length direction of the puncture needle 3-1, and one end of the puncture needle 3-1 away from the puncture portion is coaxially connected to a particle channel, and the particle channel is loaded with composite particles 3-4;

[0037] A propulsion needle 3-3 is installed at one end of the particle channel away from the puncture needle 3-1, and the propulsion needle 3-3 pushes the composite particles 3-4 in the particle channel into the puncture needle 3-1 until the composite particles 3-4 overflow from the spike portion of the puncture needle 3-1.

[0038] When in use, the composite particles 3-4 in the particle channel are pushed into the puncture needle 3-1 by the advancement needle 3-3 until the composite particles 3-4 overflow from the sharp part of the puncture needle 3-1, and the composite particles 3-4 are implanted into the targeted part; since the advancement needle 3-3, the particle channel and the puncture needle 3-1 are all in the working channel 4-1 of the soft ultrasound endoscope 4, in actual use, they are implanted into the tumor through the digestive tract under the guidance of the soft ultrasound endoscope 4. The radioactive particles in the composite particles 3-4 continuously emit radiation during their half-life to kill surrounding tumor cells. At the same time, under the action of the alternating magnetic field generated by the external magnetic field generator, the magnetic nanoparticles in the composite particles 3-4 generate heat by magnetic induction, rising to a certain temperature to ablate tumor cells, and the two therapies synergistically enhance sensitivity. During this period, the soft ultrasonic endoscope 4 simultaneously performs endoscopic optical imaging and intracavitary ultrasonic imaging to provide precise imaging guidance for the implantation of the composite particles 3-4, and the soft ultrasonic endoscope 4 provides guidance for the puncture path of the particle implantation device 3, thereby achieving precise positioning of the composite particles 3-4. Since the Curie point of the magnetic nanoparticles of the composite particles 3-4 is within the clinically required treatment temperature range, under the action of the alternating magnetic field, the temperature is automatically constant within the clinically required treatment temperature range, and precise temperature control of magnetic induction hyperthermia can be achieved without any external temperature measurement or temperature control system.

[0039] In this embodiment, the center of the puncture needle 3-1 is a cavity, forming a puncture channel with an inner diameter of about 0.8-1.0 mm, the purpose of which is to be slightly larger than the diameter of the composite particle 3-4 of 0.8 mm, just allowing a single composite particle 3-4 to pass through. Through such a design, it is ensured that the number of composite particles 3-4 pushed into the puncture channel each time the needle 3-3 is pushed is controllable, and further ensured that the number of composite particles 3-4 implanted into the target position is controllable; the outer diameter of the puncture needle 3-1 is slightly smaller than the diameter of the working channel 4-1 (clamp channel) of the soft ultrasonic endoscope 4, usually about 2.0-3.5 mm; the needle tip is sharp and can puncture soft tissue to a certain depth; the needle body is made of nickel-titanium alloy, has a certain superelasticity, and can bend and advance along the working channel 4-1 of the soft ultrasonic endoscope 4; the length of the puncture needle 3-1 is greater than the length of the adapted soft ultrasonic endoscope 4, so that its needle tip can extend out of the working channel 4-1 of the soft ultrasonic endoscope 4 and puncture the soft tissue.

[0040] In some disclosures, a particle filling device 3-2 is included, the particle filling device 3-2 includes a filling bin 3-2-1, the filling bin 3-2-1 is used for composite particles 3-4; the filling bin 3-2-1 is fixedly installed with a lifting block 3-2-3, and the lifting block 3-2-3 has a movable bin; one end of the movable bin is closed and the other end is open, the lifting rod 3-2-2 passes from the movable bin to the filling bin 3-2-1, and the lifting rod 3-2-2 has a limit block, and the limit block A compression spring 3-2-4 is installed in the movable bin between the block and the lock buckle 3-2-5, and the lock buckle 3-2-5 is detachably connected to the open end of the movable bin; the compression spring 3-2-4 elastically relaxes, so that the compression spring 3-2-4 drives the lifting rod 3-2-2 to resist the composite particle 3-4; the lifting rod 3-2-2 can push one composite particle 3-4 onto the particle channel each time under the elastic force of the (3-2-4) compression spring 3-2-4.

[0041] When in use, the push needle 3-3 passes through the working channel 4-1 end of the soft ultrasonic endoscope 4 away from the ultrasonic probe 4-2. The doctor holds the push needle 3-3 and manually pushes it from back to front, so that the composite particles 3-4 on the particle channel can be pushed to the target position along the cavity of the puncture needle 3-1. After the push needle 3-3 is withdrawn, the (3-2-2) lifting rod 3-2-2 can load another composite particle 3-4 onto the particle channel, and the cycle is repeated to implant a certain number of composite particles 3-4 into the lesion.

[0042] In some disclosures, the lock buckle 3-2-5 is threadedly connected to the open end of the movable chamber; it is convenient to pre-tighten the compression spring 3-2-4 through the lock buckle 3-2-5, or to disassemble the lock buckle 3-2-5 to facilitate the replacement of the compression spring 3-2-4.

[0043] The end of the puncture needle 3-1 is designed with a threaded connector, which can be screwed onto the shell of the (3-2-1) filling chamber 3-2-1. The cavity of the puncture needle 3-1 is coaxial with the particle channel of the (3-2-1) filling chamber 3-2-1, which facilitates the detachable installation of the puncture needle 3-1.

[0044] In some disclosures, an alternating magnetic field generator 7 is included: connected and fixed at the front end of a movable mechanical arm 6; used to generate an alternating magnetic field with adjustable magnetic field strength and frequency, so that the magnetic medium implanted in the treatment target area can generate heat through magnetic induction and heat up, thereby killing cancer cells.

[0045] Movable mechanical arm 6: The front end of the mechanical arm is connected to the fixed alternating magnetic field generator 7, and the end is fixed on the main box module 2. The operator can manually drag the mechanical arm to make the alternating magnetic field generator 7 close to any treatment part of the patient and stably hover at the target position.

[0046] The soft ultrasound endoscope 4 is used to detect the location and morphology of the tumor during surgery, provide an intervention path for the puncture needle 3-1 of the particle implantation device 3, guide the puncture needle 3-1 to puncture and insert into the digestive tract mucosal tumor through optical imaging, and feedback the needle tip position of the puncture needle 3-1 through intracavitary ultrasound imaging and detect the arrangement position of the composite particles 3-4 implanted in the body. When in use, the soft ultrasound endoscope 4 is held by the operator at the position to be detected, and can be mounted on the main chassis module 2 when idle.

[0047] Of course, the diagram also includes a main box module 2, which includes a movable base 2-1, a flexible ultrasonic endoscope connector 2-2, a human-machine interactive platform mounting seat 2-3, a display column 2-4, and a bracket 2-5. The movable base 2-1 has casters 2-1, which can realize the movement of the entire machine; the flexible ultrasonic endoscope connector 2-2 is connected to the body of the flexible ultrasonic endoscope 4 to realize the collection and transmission of endoscopic image signals; the human-machine interactive platform mounting seat 2-3 and the display column 2-4 respectively provide the human-machine interactive platform 1 and the display 5 with a fixed position; the bracket 2-5 can place the flexible ultrasonic endoscope 4 and the particle implantation device 3. The main box module 2 integrates the endoscopic imaging system, the endoscopic light source, the ultrasonic imaging system and the computer control system, etc., supplies power to each active module, and inputs irradiation light to the flexible ultrasonic endoscope 4, which can perform endoscopic image processing and ultrasonic image processing, and perform signal control on the alternating magnetic field generator 7.

[0048] Display 5: mounted on the main chassis module 2 via display columns 2-4 or a rotating arm, used to display endoscopic images and ultrasound images.

[0049] Human-computer interaction platform 1: fixed on the main box module 2 by the human-computer interaction platform mounting base 2-3, used for setting treatment parameters and command control of treatment actions.

[0050] The working process of the magnetic hyperthermia-radiotherapy system of the present invention is as follows: Figure 5 As shown:

[0051] aTumor localization: Before surgery, CT scan is used to determine and mark the size, shape and location of the tumor.

[0052] b. Plan the composite particle 3-4 implantation plan: Use a computer-based tumor magnetic hyperthermia-radiotherapy planning system to help predict and select appropriate treatment parameters (magnetic field strength and frequency, treatment time, composite particle 3-4 arrangement plan, etc.).

[0053] c. Surgical preparation: Refer to other tumor treatment procedures for preoperative preparation and connect the monitor to monitor vital signs throughout the process.

[0054] d Soft ultrasonic endoscope 4 exploration: The soft ultrasonic endoscope 4 is connected to the main box, and the doctor operates the scope to intervene in the lesion through the natural cavity. Endoscopic optical imaging is used to observe the location, size, shape, etc. of the tumor. The scope is then adjusted so that the ultrasonic probe 4-2 on the soft ultrasonic endoscope 4 is attached to the surface of the digestive tract at a suitable angle, so as to produce clear tumor ultrasonic images and endoscopic optical images, and the working cavity opening at the front end of the scope is aligned with the tumor.

[0055] e Loading of composite particles 3-4: The puncture needle 3-1, the particle filling device 3-2, and the push needle 3-3 are quickly assembled together to form the particle implantation device 3 as a whole. The composite particles 3-4 are loaded into the particle filling device 3-2 and loaded into the particle channel by the loading mechanism.

[0056] f Puncture through the soft ultrasound endoscope 4: The doctor pushes the puncture needle 3-1 of the particle implantation device 3 along the working channel 4-1 of the soft ultrasound endoscope 4 into the surface of the lesion, and under the guidance of imaging and the assistance of the angle position adjustment of the endoscope, punctures the puncture needle 3-1 from the surface of the lesion into the interior of the tumor.

[0057] g Implantation of composite particles 3-4: The push needle 3-3 of the particle implantation device 3 pushes the composite particles 3-4 in the particle channel along the cavity of the puncture needle 3-1 into the tumor; the push needle 3-3 moves back and forth until a sufficient number of composite particles 3-4 are implanted. After the implantation is completed, the particle implantation device 3 and the soft ultrasonic endoscope 4 are withdrawn in sequence.

[0058] h Combined treatment: After the composite particles 3-4 are implanted, radiotherapy is started, and then the robot arm is moved to move the alternating magnetic field generator 7 to the target position, and magnetic hyperthermia is started according to the predetermined treatment parameters.

[0059] iPostoperative testing: CT scans were performed again after the completion of the procedure to assess the extent of tumor inactivation.

[0060] j Multiple treatments: The composite particles 3-4 remain at the target location and do not need to be re-implanted for subsequent treatments. The magnetic induction thermal therapy can be repeated multiple times at regular intervals.

[0061] Regarding the composite particle 3-4, as disclosed in some publications, the nanoparticles and the radioactive particles of the iodine-plated silver rod are combined to obtain a magnetic thermal radioactive composite particle 3-4, which has both magnetic thermal therapy and radioactive therapy effects, and can more efficiently kill diseased tissues and improve the treatment effect; the magnetic nanoparticles of the composite particle 3-4 are wrapped in a titanium shell and do not directly contact human tissues, which can reduce toxic side effects; and the material properties of the composite particle 3-4 can meet a variety of imaging methods such as CT and MR, and there are abundant in vitro imaging methods when implanted or intervened in the human body. Figure 8 As shown, there is a surrounding layer 1, iodine-coated silver rods 2 and magnetocaloric nanoparticles 3.

[0062] In some cases, the size of the magnetocaloric radioactive composite particles 3-4 can be selected from conventional sizes, such as a particle diameter of 0.8 mm and a length of 4.5 mm.

[0063] In some cases, the surrounding layer is made of titanium. In addition to the titanium shell, ceramics or other metals with low atomic numbers, such as stainless steel and aluminum, can also be used.

[0064] In some cases, the thickness of the surrounding layer is 0.05-0.1 mm; 0.05-0.1 mm, ensuring that the composite particle 3-4 accommodation area is sufficient and that its structural strength meets the requirements of the particle implantation surgery;

[0065] The volume of the containing area and the volume of the iodine-coated silver rod are in a ratio of 6:1 to 12:1, ensuring a balanced ratio of magnetocaloric nanoparticles to radioactive nuclides. The two treatment methods can synergistically enhance sensitivity.

[0066] The filling degree of the magnetic thermal nanoparticles in the containing area is ≥ 70%; the filling degree is ≥ 70% to ensure that the number of magnetic thermal nanoparticles is sufficient, otherwise it will lead to a long magnetic thermal therapy time and poor therapeutic effect.

[0067] The iodine-plated silver rod is in the middle of the containing area; the iodine-plated silver rod is located in the center, with a height deviation of <0.5mm and a radial deviation of <0.15mm. The posture deviation will cause uneven distribution of magnetic nanoparticles in the composite particles 3-4 and an uneven temperature field, but a slight deviation will have a weak effect.

[0068] like Figure 6 or Figure 7As shown, in the present application, the particle size of the magnetocaloric nanoparticles is 10-300nm; 10-300nm, the particle size of the magnetocaloric nanoparticles is determined by the preparation method; for magnetocaloric nanoparticles, the preparation thereof is the prior art, and the purpose is to form magnetocaloric nanoparticles with a heat generation efficiency of >15W / g and a magnetic hyperthermia temperature of 42°C-45°C, such as the patent, a preparation of a high heat generation self-controlling magnetic nanoparticles. CN108373174 A): Magnetocaloric nanoparticles, comprising: dissolving NaOH in deionized water, stirring to completely dissolve it, and forming an alkaline solution with a concentration of 3.5-4.5mol as a precipitant;

[0069] Dissolving 6.3-6.5 parts by weight of FeCl3·6H2O, 2.3-2.5 parts by weight of CrCl3·6H2O, 1.7-1.9 parts by weight of CoCl2·6H2O and 1.1-1.3 parts by weight of ZnCl2 in 78-85 parts by weight of deionized water to form a metal salt ion solution;

[0070] The precipitant is slowly added dropwise to the metal salt ion solution at room temperature to perform a preliminary coprecipitation reaction to generate a precursor suspension; during the process of adding the precipitant, the mixed solution needs to be continuously stirred to make the solution evenly mixed;

[0071] The precursor suspension was transferred to an autoclave and sealed. After setting the rotation speed and hydrothermal temperature, heating and heating began. After the temperature in the autoclave reached the set heating temperature, it was kept at this temperature for 6 hours, then naturally cooled to room temperature, and then the autoclave was opened to take out the formed magnetic nanoparticle suspension. The rotation speed of the autoclave was set to 200 rad / min and the hydrothermal temperature was set to 350°C.

[0072] The obtained magnetic nanoparticle suspension is washed to neutrality;

[0073] After the washing is completed, the obtained precipitate is vacuum dried at a temperature of 80° C. for 6 hours, and then naturally cooled to room temperature to obtain a magnetic solid; the magnetic solid is fully ground to obtain magnetic nanoparticles.

[0074] The preparation method of the above-mentioned magnetocaloric radioactive composite particles 3-4 includes: placing the surrounding layer in the groove of the magnetic base, and then filling the bottom of the receiving area with magnetocaloric nanoparticles, such as the weight of the filled magnetocaloric nanoparticles ≥ 1.05 mg. If the filling amount is too small, the magnetic hyperthermia time will increase, the surgical efficiency will decrease, and the tumor thermal ablation area will be smaller; placing the iodine-plated silver rod in the receiving area; continuing to fill the magnetocaloric nanoparticles until the iodine-plated silver rod is completely wrapped and the receiving area of ​​the titanium shell is completely filled; and sealing the surrounding layer. Specifically, in some embodiments, it includes: placing the titanium shell in the groove of the magnetic base; filling the magnetocaloric nanoparticles at the bottom of the titanium shell; continuing to fill the magnetocaloric nanoparticles until the iodine-plated silver rod is completely wrapped and the inner cavity of the titanium shell is completely filled; installing the titanium shell cover at the gap of the titanium shell for packaging.

[0075] Embodiment 1:

[0076] Magnetocaloric nanoparticles preparation process:

[0077] The first step is to prepare a precipitant. Dissolve 24 g of NaOH in 150 mL of deionized water and stir with a glass rod to completely dissolve it to prepare an alkaline solution as a precipitant.

[0078] The second step is to prepare a metal salt ion solution. 6.467 g of FeCl3·6H2O (≥99%), 2.418 g of CrCl3·6H2O (≥99%), 1.805 g of CoCl2·6H2O (≥99%) and 1.214 g of ZnCl2 (≥98%) are dissolved in 80 mL of deionized water to form a metal salt ion solution.

[0079] The third step is to drop a precipitant to generate a precursor suspension. The precipitant prepared in the first step is slowly added drop by drop to the metal salt ion solution prepared in the second step at room temperature to perform a preliminary coprecipitation reaction to generate a precursor suspension. It should be noted that the mixed solution needs to be continuously stirred during the process of dropping the precipitant to ensure that the solution is evenly mixed;

[0080] The fourth step is to generate a suspension of magnetic nanoparticles by hydrothermal reaction. Move the precursor suspension prepared in the third step to the autoclave and seal it. Set the rotation speed and hydrothermal temperature and start heating. After the temperature in the autoclave reaches the set heating temperature, keep it at this temperature for a certain period of time. Then cool it naturally to room temperature, then open the autoclave and take out the formed suspension of magnetic nanoparticles. Set the rotation speed to 200rad / min, the hydrothermal temperature to 350℃, and the holding time to 6 hours;

[0081] Step 5: Post-treatment. The magnetic nanoparticle suspension obtained in step 4 is repeatedly rinsed with deionized water and anhydrous ethanol several times until it is neutral. After rinsing, the obtained precipitate is vacuum dried at 80°C for 6 hours and then naturally cooled to room temperature. The obtained magnetic solid is fully ground with an agate mortar to obtain magnetic nanoparticles.

[0082] Preparation process of iodine-plated silver rod:

[0083] ① Halogenation: transfer the silver particles and the mixed solution of hydrochloric acid and sodium chlorate into the reaction bottle, rotate and react for about 2 hours, take out the halogenated silver particles and absorb them dry.

[0084] ② Core plating: Place the dried silver particles into a reaction bottle, transfer the KI-NaOH solution, iodine [125I] source and NaOH solution into the reaction bottle, and react for 10-18 hours. After the reaction is completed, take out the radioactive silver particles and dry them.

[0085] Titanium shells and titanium shell covers are prepared by machining:

[0086] After the magnetic nanoparticles, iodine-coated silver rods, titanium shells and titanium shell caps are prepared, the magnetocaloric radioactive composite particles 3-4 are assembled. Figure 2 As shown, a. install the titanium shell in the groove of the magnetic base, and then fill the bottom of the titanium shell with magnetocaloric nanoparticles. Due to the influence of the magnetic base, the magnetocaloric nanoparticles are adsorbed on the bottom of the titanium shell; b. place the iodine-plated silver rod into the titanium shell; c. continue to fill the magnetocaloric nanoparticles until the iodine-plated silver rod is completely wrapped and the inner cavity of the titanium shell is completely filled; d. install the titanium shell cover at the notch of the titanium shell, and weld it with a welder or glue it to encapsulate the composite particles 3-4. After the magnetocaloric radioactive composite particles 3-4 are assembled, since welding or glue bonding will leave welding slag or glue on the surface of the titanium shell, the surface of the composite particles 3-4 needs to be polished.

[0087] For the convenience of verification, this application uses magnetocaloric radioactive composite particles 3-4 with a particle size of 0.8mm and a length of 4.5mm; the material of the surrounding layer is titanium; the thickness of the surrounding layer is 0.1mm; the volume of the containing area and the volume of the iodine-plated silver rod account for 7.2:1; the filling degree of the magnetocaloric nanoparticles in the containing area is 100%, and generally, unless otherwise specified, the iodine-plated silver rod is located in the center; the particle size of the magnetocaloric nanoparticles is 13.3nm.

[0088] Verification Example 1: The composite particle 3-4 has both magnetic heat therapy and radiotherapy functions, and has a better killing and inhibition effect on diseased cells

[0089] Under the same other conditions, as shown in Table 1, magnetocaloric nanoparticles are loaded alone in the titanium shell for magnetic hyperthermia therapy; iodine-plated silver rods are loaded alone in the titanium shell for radioactive therapy; the combination of magnetocaloric nanoparticles and radioactive particles of iodine-plated silver rods increases the killing range (radius) relative to a single magnetocaloric nanoparticle.

[0090] Table 1

[0091] Treatment Magnetic Hyperthermia Radiation therapy Magnetic hyperthermia + radiotherapy Killing range (radius) 1.8mm 1.6mm 2.4mm

[0092] Verification Example 2: The required implantation and intervention magnetic medium particles are concentrated in the titanium shell, which can ensure effective treatment while reducing toxic side effects

[0093] Under the same other conditions, as shown in Table 2, the magnetic medium particles are concentrated in the titanium shell, which can reduce toxic side effects while ensuring effective treatment.

[0094] Table 2

[0095]

[0096] Verification Example 3:

[0097] Under the same other conditions, magnetocaloric nanoparticles are loaded separately in the titanium shell, as shown in Table 3, wherein only magnetocaloric nanoparticles are loaded in the titanium shell, and the killing range (radius) thereof is 1.8 mm; while the structure of the present application has a killing range (radius) of 2.4 mm, that is, the present application utilizes a combination of magnetocaloric nanoparticles and radioactive particles of iodine-plated silver rods to increase the killing range (radius) thereof relative to a single magnetocaloric nanoparticle.

[0098] Table 3

[0099] Comparative performance Titanium shell + magnetocaloric nanoparticles Composite particles 3-4 of the present invention Killing range (radius) 1.8mm 2.4mm

[0100] Verification Example 4:

[0101] Under the same other conditions, as shown in Table 4, the structure of the present application, but the filling degree of magnetocaloric nanoparticles is different; the higher the filling degree, the larger the killing range (radius) and the higher the heat generation efficiency (J / S).

[0102] Table 4

[0103] Filling 50％ 70％ 100％ Heat generation efficiency (J / S) 0.05 0.07 0.11 Killing range (radius) 1.8mm 2.1mm 2.4mm

[0104] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present disclosure. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0105] The above shows and describes the basic principles, main features and advantages of the present disclosure. Those skilled in the art should understand that the present disclosure is not limited by the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present disclosure. Without departing from the spirit and scope of the present disclosure, the present disclosure may have various changes and improvements, and these changes and improvements fall within the scope of the present disclosure to be protected.

Claims

1. A composite particle magnetic hyperthermia-radiotherapy system implanted via a soft ultrasound endoscope, comprising a soft ultrasound endoscope, wherein the soft ultrasound endoscope comprises an ultrasound probe; characterized in that: A puncture needle inserted into and slid along the working channel of the flexible ultrasonic endoscope, wherein the puncture needle has a sharp thorn portion; The puncture needle has a puncture channel extending along the length direction of the puncture needle, and one end of the puncture needle away from the puncture portion is coaxially connected to a particle channel, and the particle channel is loaded with composite particles; A propulsion needle is installed at one end of the particle channel away from the puncture needle, and the propulsion needle pushes the composite particles in the particle channel into the puncture needle until the composite particles overflow from the spike portion of the puncture needle; The material of the puncture needle is nickel-titanium alloy; The composite particles are obtained by combining nanoparticles and radioactive particles of iodine-plated silver rods, and specifically include an enveloping layer (1), an iodine-plated silver rod (2) and magnetocaloric nanoparticles (3); the iodine-plated silver rod (2) is located at the center of the composite particle accommodation area, with a height deviation of <0.5 mm and a radial deviation of <0.15 mm; the enveloping layer (1) is made of titanium, with a thickness of 0.05 to 0.1 mm; the volume of the composite particle accommodation area and the volume of the iodine-plated silver rod (2) are in a ratio of 6:1 to 12:1; and the filling degree of the magnetocaloric nanoparticles (3) in the composite particle accommodation area is ≥70%; It includes an alternating magnetic field generator, which is used to generate an alternating magnetic field with adjustable magnetic field strength and frequency, so that the magnetic medium of the composite particles implanted in the treatment target area is heated by magnetic induction to kill cancer cells; The alternating magnetic field generator is installed on the movable robotic arm.

2. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 1, characterized in that: The inner diameter of the puncture channel is slightly larger than the particle size of the composite particle, and only a single composite particle is allowed to pass through.

3. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 1, characterized in that: It includes a filling bin, and the filling bin is used for loading composite particles; The particle channel is located in the filling chamber, and the puncture needle is detachably connected to the filling chamber.

4. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 3, characterized in that: A lifting rod is installed in the filling bin to elastically resist the composite particles in the filling bin. The lifting rod resists the composite particles, and the composite particles have a tendency to move toward the particle channel.

5. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 4, characterized in that: A lifting block is fixedly installed in the filling bin, and a movable bin is arranged inside the lifting block; one end of the movable bin is closed and the other end is open, a lifting rod passes through the movable bin to the filling bin, a limit block is arranged on the lifting rod, a compression spring is installed in the movable bin between the limit block and the lock, and the lock is detachably connected to the open end of the movable bin; the compression spring elastically expands, so that the compression spring drives the lifting rod to resist the composite particles.

6. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 5, characterized in that: The lock buckle is threadedly connected to the open end of the movable bin.

7. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 3, characterized in that: One end of the puncture needle away from the puncture portion is threadedly connected to the shell body of the filling bin.

8. The composite particle magnetic hyperthermia-radiotherapy system implanted via soft endoscopic ultrasound according to claim 1, characterized in that: The push needle passes through the working channel end of the flexible ultrasound endoscope away from the ultrasound probe.

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