Magnetic hyperthermia-radiotherapy system based on composite particles implanted via flexible ultrasonic endoscope

Abstract

The present application relates to the technical field of tumor radiotherapy and magnetic induction hyperthermia medical instruments, and discloses a magnetic hyperthermia-radiotherapy system based on composite particles implanted via a flexible ultrasonic endoscope. The system comprises the flexible ultrasonic endoscope and a puncture needle sliding in a working channel of the flexible ultrasonic endoscope, wherein one end of the puncture needle is connected to a particle channel, and the composite particles are loaded in the particle channel; and an advancement needle pushes the composite particles from the particle channel to the puncture needle. The present application enables sequential implantation of the composite particles, allowing for both magnetic hyperthermia and radiotherapy effects, realizing synergistic sensitization, more efficiently killing diseased tissues, and enhancing the therapeutic effect. Moreover, the system, guided by the flexible ultrasonic endoscope via natural orifice access, enables puncturing implantation of the composite particles into malignant tumors within human cavities such as the digestive tract, thereby expanding application scenarios of magnetic hyperthermia and radioactive particle therapy. Due to the self-temperature control characteristic of the composite particles, the system eliminates the need for temperature measurement and control devices, reducing device complexity while ensuring targeted, safe, and effective tumor treatment.

Description

Magnetic hyperthermia-radiotherapy system with composite particles implanted by soft endoscopic ultrasound TECHNICAL FIELD

[0001] The present patent relates to the technical field of tumor radiotherapy and magnetic induction hyperthermia medical devices, in particular to a magnetic induction hyperthermia-radiotherapy system based on magnetic hyperthermia radioactive composite particles. BACKGROUND

[0002] Magnetic hyperthermia is a physical therapy that selectively kills tumors implanted with magnetic medium without damaging normal tissues by using the characteristics of the magnetic medium to produce heat and rise in temperature under an alternating magnetic field. Compared with traditional chemotherapy or radiotherapy, magnetic hyperthermia has less trauma and can be treated multiple times with one intervention. However, due to the high mobility of magnetic medium particles, there is a risk of escaping from the treatment target area to the surrounding healthy tissues, which reduces the therapeutic effect and causes thermal damage to healthy tissues due to magnetic induction heating, and also produces additional toxic side effects. Particle implantation therapy is an internal radiotherapy minimally invasive therapy that implants radioactive particles in tumors to kill tumor cells by continuous release of radiation. Due to the low energy and short penetration distance of the radiation of radioactive particles, it is easy to protect, but at the same time, the killing power of tumor cells far from the radiation source is low, and the effective killing range is limited.

[0003] No matter magnetic hyperthermia or radioactive particle therapy, the particles need to be implanted into the predetermined position by soft tissue puncture method at present.

[0004] The existing technology, such as injecting a stream of magnetic medium particles into a lesion, uses an external magnetic field generator to generate a magnetic field for magnetic induction heating, and uses in-vivo multi-fiber temperature measurement and circulating water temperature control. Due to the high mobility of the stream of magnetic medium particles, there are problems of loss of magnetic medium particles and difficulty in temperature measurement and control of magnetic hyperthermia.

[0005] The existing technology, such as using a particle implantation device to implant radioactive particles into a lesion by percutaneous puncture. This separate particle internal radiotherapy has a limited effective killing range, and at present, due to the need for image guidance during the puncture surgery process, 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, and it is difficult to guide the implantation of particles for treatment under the conditions of the limitations of particle implantation therapy, which has not been extended to the treatment of malignant tumors in the digestive tract and other body cavities. SUMMARY

[0006] The purpose of the present disclosure is to provide a magnetic hyperthermia-radiotherapy system with composite particles implanted by soft endoscopic ultrasound.

[0007] The purpose of the present disclosure can be achieved by the following technical solutions:

[0008] The composite particle magnetotherapeutic-radiotherapeutic system implanted by soft endoscope includes a soft endoscope, the soft endoscope includes an ultrasonic probe; a puncture needle inserted into and sliding along the working channel of the soft endoscope, the puncture needle has a sharp part;

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

[0010] The end of the particle channel away from the puncture needle is provided with a push needle, and the push 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 embodiments, the material of the puncture needle is nickel-titanium alloy.

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

[0013] In some embodiments, a filler bin is included, and the filler bin is used to load the composite particles;

[0014] The particle channel is located in the filler bin, and the puncture needle is detachably connected with the filler bin.

[0015] In some embodiments, the filler bin is fixedly provided with a jacking rod elastically abutting against the composite particles in the filler bin, and the jacking rod abuts against the composite particles, and the composite particles have a tendency to move towards the particle channel.

[0016] In some embodiments, the filler bin is fixedly provided with a jacking block, and the jacking block has a movable bin; one end of the movable bin is closed, and the other end is open, the jacking rod passes out of the movable bin to the filler bin, the jacking rod is provided with a limiting block, a compression spring is installed in the movable bin between the limiting block and a lock catch, and the lock catch is detachably connected with the open end of the movable bin; the compression spring is elastically relaxed, so that the compression spring drives the jacking rod to abut against the composite particles.

[0017] In some embodiments, the lock catch is threadedly connected with the open end of the movable bin.

[0018] In some embodiments, the end of the puncture needle away from the sharp part is threadedly connected with the shell of the filler bin.

[0019] In some embodiments, the push needle passes out of the end of the working channel of the soft endoscope away from the ultrasonic probe.

[0020] In some embodiments, an alternating magnetic field generator is included, 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 generates heat through magnetic induction to kill cancer cells;

[0021] The alternating magnetic field generator is installed on a movable mechanical arm.

[0022] Advantages of the present disclosure:

[0023] The composite particles can be implanted in sequence, so that the magnetic hyperthermia and radiotherapy effects can be provided, the synergistic sensitization can be provided, the diseased tissue can be killed more efficiently, and the treatment effect can be improved; and the system is guided by a soft ultrasonic endoscope, is intervened through a natural cavity, and punctures and implants the composite particles in malignant tumors in a digestive tract and other cavities of a human body, so that the application scenarios of magnetic hyperthermia and radiotherapy are widened.

[0024] The system does not need a temperature measuring and controlling device due to the self-temperature control characteristics of the composite particles, the equipment complexity is reduced under the condition of ensuring the targeting, safety and curative effect of tumor treatment. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present disclosure or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced. Obviously, for those skilled in the art, other drawings can also be obtained without creative labor on the basis of these drawings.

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

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

[0028] Fig. 3 is a schematic diagram of the structure of the particle implanting device of the embodiment of the present disclosure;

[0029] Fig. 4 is a schematic diagram of the local structure of the particle implanting device of the embodiment of the present disclosure;

[0030] Fig. 5 is a workflow diagram of the embodiment of the present disclosure;

[0031] Fig. 6 is a flowchart of a material preparation method in the magnetic and radioactive composite particles according to an embodiment;

[0032] Fig. 7 is a flowchart of a preparation and assembly method in the magnetic and radioactive composite particles according to an embodiment;

[0033] Fig. 8 is a schematic diagram of the structure of the magnetic and radioactive composite particles according to an embodiment. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present disclosure will be clearly and completely described below with reference to the drawings 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 those of ordinary skill in the art without creative work fall within the protection scope of the present disclosure.

[0035] The composite particle magnetotherapeutic-radiotherapeutic system implanted by a soft endoscope includes a soft endoscope 4, the soft endoscope 4 including an ultrasonic probe 4-2; a puncture needle 3-1 extending into and sliding along a working channel 4-1 of the soft endoscope 4, the puncture needle 3-1 having a sharp portion;

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

[0037] The particle channel of the puncture needle 3-1 is provided with a push needle 3-3 at one end away from the puncture needle 3-1, the push needle 3-3 pushing the composite particles 3-4 in the particle channel into the puncture needle 3-1 until the composite particles 3-4 overflow from the sharp portion of the puncture needle 3-1.

[0038] In use, the composite particles 3-4 in the particle channel are pushed into the puncture needle 3-1 by the push needle 3-3 until the composite particles 3-4 overflow from the sharp portion of the puncture needle 3-1, at which time the composite particles 3-4 are implanted into a target site; since the push needle 3-3, the particle channel and the puncture needle 3-1 are all in the working channel 4-1 of the soft endoscope 4, in actual use, they are implanted into a tumor inside a digestive tract under the guidance of the soft endoscope 4. The radioactive particles in the composite particles 3-4 continuously emit rays to kill surrounding tumor cells within a half-life period; meanwhile, under the action of an alternating magnetic field generated by an external magnetic field generator, the magnetic nanoparticles in the composite particles 3-4 generate heat by magnetic induction to rise to a certain temperature to ablate tumor cells, and the two therapies are synergistically sensitized; during this period, the soft endoscope 4 simultaneously performs endoscopic optical imaging and intracavitary ultrasonic imaging to provide accurate imaging guidance for implantation of the composite particles 3-4, and the soft endoscope 4 provides guidance for the puncture path of the particle implantation device 3, so as to realize accurate 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 without any external temperature measurement and control system, accurate temperature control of magnetic induction thermotherapy can be realized.

[0039] In the embodiment, the puncture needle 3-1 is hollow in the center to form a puncture channel with an inner diameter of about 0.8-1.0 mm, which is slightly larger than the diameter of the composite particles 3-4 of 0.8 mm, just allowing the single composite particles 3-4 to pass through. By such design, it is ensured that the number of composite particles 3-4 pushed by the push needle 3-3 to the puncture channel is controllable each time, and further, 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 (forceps channel) of the soft ultrasound endoscope 4, which is usually about 2.0-3.5 mm. The needle tip is sharp and can puncture soft tissues to a certain depth. The needle body is made of nickel-titanium alloy and has a certain superelasticity, which can bend and advance along the working channel 4-1 of the soft ultrasound endoscope 4. The length of the puncture needle 3-1 is greater than the length of the soft ultrasound endoscope 4 to which it is adapted, so that the needle tip can extend out of the working channel 4-1 of the soft ultrasound endoscope 4 and puncture soft tissues.

[0040] In some disclosures, the particle loading device 3-2 includes a filler bin 3-2-1 for the composite particles 3-4. The filler bin 3-2-1 is fixedly installed with a jacking block 3-2-3, and the jacking block 3-2-3 has a movable bin inside. One end of the movable bin is closed, and the other end is open. A jacking rod 3-2-2 passes out of the movable bin to the filler bin 3-2-1. The jacking rod 3-2-2 has a limiting block thereon. A compression spring 3-2-4 is installed in the movable bin between the limiting block and a lock catch 3-2-5. The lock catch 3-2-5 is detachably connected with 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 jacking rod 3-2-2 to abut against the composite particles 3-4. The jacking rod 3-2-2 can push one composite particle 3-4 onto the particle channel each time under the elastic force of the compression spring 3-2-4.

[0041] In use, the push needle 3-3 passes out of one end of the working channel 4-1 of the soft ultrasound endoscope 4 away from the ultrasound probe 4-2. A doctor manually pushes the push needle 3-3 from back to front by hand, so as to push the composite particles 3-4 on the particle channel along the lumen of the puncture needle 3-1 to the target position. After the push needle 3-3 is withdrawn, the jacking rod 3-2-2 can again load one 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 catch 3-2-5 is threadedly connected with the open end of the movable bin. It is convenient to pre-tighten the compression spring 3-2-4 by the lock catch 3-2-5, or to detach the lock catch 3-2-5 for replacement of the compression spring 3-2-4.

[0043] The end of the puncture needle 3-1 is designed with a threaded joint, which can be screwed onto the shell of the (3-2-1) filler bin 3-2-1, and the lumen of the puncture needle 3-1 is coaxial with the particle channel of the (3-2-1) filler bin 3-2-1; the puncture needle 3-1 can be easily and detachably installed.

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

[0045] The movable mechanical arm 6: the front end of the mechanical arm is connected and fixed with the 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 site of the patient and stably hover at the target position.

[0046] The soft ultrasonic endoscope 4 is used to detect the position and shape of the tumor during the operation, to provide an intervention path for the puncture needle 3-1 of the particle implantation device 3, to guide the puncture needle 3-1 to puncture and insert into the inside of the tumor of the digestive tract mucosa through optical imaging, and to feedback the position of the needle tip of the puncture needle 3-1 and detect the arrangement position of the composite particles 3-4 implanted in the body through intracavitary ultrasonic imaging. The soft ultrasonic endoscope 4 is held by the operator when in use, and can be hung on the main box module 2 when not in use.

[0047] Of course, the main box module 2 is also included in the illustration, and the main box module 2: contains a movable base 2-1, a soft ultrasonic endoscope connector 2-2, a human-computer interaction platform mounting seat 2-3, a display stand 2-4, and a hanging rack 2-5. The movable base 2-1 is provided with casters 2-1, which can realize the movement of the position of the whole machine; the soft ultrasonic endoscope connector 2-2 is connected with the soft ultrasonic endoscope 4, which realizes the collection and transmission of the endoscopic image signal; the human-computer interaction platform mounting seat 2-3 and the display stand 2-4 respectively provide position installation and fixing for the human-computer interaction platform 1 and the display 5; the hanging rack 2-5 can place the soft ultrasonic endoscope 4 and the particle implantation device 3. The main box module 2 integrates the endoscopic imaging system, the endoscope light source, the ultrasonic imaging system, and the computer control system, etc., to supply power for each active module, and to input irradiation light for the soft ultrasonic endoscope 4, which can perform endoscopic image processing and ultrasonic image processing, and signal control for the alternating magnetic field generator 7.

[0048] The display 5: is hung on the main box module 2 through the display stand 2-4 or the rotating arm, which is used to display the endoscopic image and the ultrasonic image.

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

[0050] The workflow of the magnetothermal therapy-radiotherapy system of the present application is shown in Figure 5:

[0051] a Tumor localization: The size, shape and location of the tumor are determined and marked by CT detection before surgery.

[0052] b Planning of composite particle 3-4 implantation scheme: The tumor magnetothermal therapy-radiotherapy planning system of the computer helps to predict and select appropriate treatment parameters (magnetic field strength and frequency, treatment time, composite particle 3-4 arrangement scheme, etc.).

[0053] c Surgical preparation: Refer to the preoperative preparation of other tumor treatment procedures, and connect the monitor for whole-process vital sign monitoring.

[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 into the lesion through the natural cavity, and the endoscopic optical imaging observes the position, size, shape, etc. of the tumor, then adjusts the scope to make the ultrasonic probe 4-2 on the soft ultrasonic endoscope 4 stick to the surface of the digestive tract at a suitable angle, so that clear tumor ultrasonic images and endoscopic optical images are generated, and the working cavity port at the tip of the scope is aligned with the tumor.

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

[0056] f Puncture through the soft ultrasonic 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 ultrasonic endoscope 4 into the surface of the lesion, and under the guidance of imaging and the assistance of scope angle position adjustment, the puncture needle 3-1 is punctured from the surface of the lesion into the interior of the tumor.

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

[0058] h Combined treatment: After the composite particle 3-4 is implanted, radioactive treatment is started, then the alternating magnetic field generator 7 is moved to the target position by moving the mechanical arm, and the magnetothermal therapy is started according to the predetermined treatment parameters.

[0059] i Postoperative detection: After the end, CT detection is performed again to evaluate the tumor inactivation.

[0060] j Multiple treatments: The composite particle 3-4 remains in the target position, and subsequent treatment does not need to be implanted again, and can be repeated multiple times regularly for magnet-induced thermotherapy.

[0061] For the composite particles 3-4, as disclosed in some cases, the combination of nanoparticles and iodine-coated silver rods obtains a magnetothermal radioactive composite particle 3-4, which has both magnetothermal therapy and radioactive therapy effects, can kill diseased tissues more efficiently, and improve treatment effect; the magnetic nanoparticles of the composite particle 3-4 are wrapped in a titanium shell and do not directly contact with human tissues, which can reduce toxic side effects; and the material properties of the composite particle 3-4 can meet various imaging methods such as CT and MR, and the external imaging means when implanted or interposed in the human body is rich. As shown in FIG. 8, the surrounding layer 1, the iodine-coated silver rod 2 and the magnetothermal nanoparticles 3.

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

[0063] In some cases, the surrounding layer material is titanium, and in addition to the titanium shell, ceramic or other low-atomic-number metals such as stainless steel and aluminum can also be selected.

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

[0065] The volume ratio between the containing area and the volume of the iodine-coated silver rod is 6:1-12:1; which ensures that the ratio of magnetothermal nanoparticles and radionuclides is balanced, and the two treatment methods can synergistically enhance sensitivity.

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

[0067] The iodine-coated silver rod is located in the middle of the containing area; the iodine-coated silver rod is located at the center position, with a height deviation <0.5 mm and a radial deviation <0.15 mm. Attitude skew will cause uneven distribution of magnetic nanoparticles in the composite particle 3-4, resulting in uneven temperature field, but slight deviation has weak influence.

[0068] As shown in Figure 6 or Figure 7, in the present application, the particle size of the magnetic heat nanoparticles is 10-300 nm; the particle size of the magnetic heat nanoparticles is determined by the preparation method; as for the magnetic heat nanoparticles, its preparation is the prior art, the purpose is to form magnetic heat nanoparticles with heat production efficiency > 15 W / g and magnetic heat therapy temperature: 42-45℃, such as patent, preparation of high-heat self-controlled temperature type magnetic nanoparticles (CN108373174 A): magnetic heat nanoparticles, comprising: dissolving NaOH into deionized water, stirring to completely dissolve, forming an alkaline solution with a concentration of 3.5-4.5 mol, as a precipitant;

[0069] 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 are dissolved into 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 carry out a preliminary co-precipitation reaction to form a precursor suspension; the mixed solution needs to be continuously stirred during the addition of the precipitant to make the solution uniform;

[0071] The precursor suspension is moved to a high-pressure kettle and sealed, and after setting the rotation speed and hydrothermal temperature, heating is started; after the temperature in the high-pressure kettle rises to the set heating temperature, it is kept at this temperature for 6 hours, and then naturally cooled to room temperature, then the high-pressure kettle is opened, and the formed magnetic nanoparticle suspension is taken out; the rotation speed of the high-pressure kettle is set to 200 rad / min, and the hydrothermal temperature is 350℃;

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

[0073] After the washing is completed, the obtained precipitate is vacuum dried at a temperature of 80℃ 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 comprises: placing the surrounding layer in the groove of the magnetic base, then filling the magnetocaloric nanoparticles at the bottom of the containing area, such as filling the magnetocaloric nanoparticles with a weight of ≥1.05 mg. If the filling amount is too small, the magnetocaloric therapy time will increase, the surgical efficiency will decrease, and the tumor thermal ablation area will be smaller; the iodine-coated silver rod is placed in the containing area; continue to fill the magnetocaloric nanoparticles until the iodine-coated silver rod is completely wrapped and the containing area of the titanium shell is completely filled; and the surrounding layer is closed. Specifically, in some embodiments, it comprises: placing the titanium shell in the groove of the magnetic base; filling the magnetocaloric nanoparticles at the bottom of the titanium shell; continue to fill the magnetocaloric nanoparticles until the iodine-coated silver rod is completely wrapped and the inner cavity of the titanium shell is completely filled; and the titanium shell cover is installed at the gap of the titanium shell for packaging.

[0075] Embodiment one:

[0076] Magnetocaloric nanoparticle preparation process:

[0077] First step, preparation of precipitator. Dissolve 24 g of NaOH into 150 mL of deionized water, stir with a glass rod until it is completely dissolved, and prepare an alkaline solution as a precipitator.

[0078] Second step, preparation of metal salt ion solution. Dissolve 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%) into 80 mL of deionized water to form a metal salt ion solution.

[0079] Third step, dropwise addition of precipitator to generate precursor suspension. Slowly dropwise add the precipitator prepared in the first step to the metal salt ion solution prepared in the second step at room temperature to generate a precursor suspension by preliminary co-precipitation reaction. It should be noted that the mixed solution needs to be continuously stirred during the dropwise addition of the precipitator to ensure uniform mixing of the solution;

[0080] Fourth step, hydrothermal reaction to generate magnetic nanoparticle suspension. Move the precursor suspension prepared in the third step to a high-pressure kettle and seal it. After setting the rotation speed and hydrothermal temperature, start heating. After the temperature in the high-pressure kettle rises to the set heating temperature, keep it at that temperature for a certain period of time. Then naturally cool to room temperature, then open the high-pressure kettle and take out the formed magnetic nanoparticle suspension. The rotation speed is set to 200 rad / min, the hydrothermal temperature is 350℃, and the holding time is 6 hours;

[0081] Fifth step, post-processing. The magnetic nanoparticle suspension obtained in the fourth step is repeatedly rinsed with deionized water and anhydrous ethanol several times until it is neutral. After rinsing, the obtained precipitate is vacuum dried at a temperature of 80°C for 6 hours, and then naturally cooled to room temperature. The obtained magnetic solid is ground with a jade mortar to obtain the magnetic nanoparticles.

[0082] Iodine-coated silver rod preparation process:

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

[0084] ②Coating core: place the dried silver particles in the reaction bottle, and then move 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, the radioactive silver particles are taken out and dried.

[0085] Titanium shell and titanium shell cover are prepared by mechanical processing:

[0086] After the magnetic nanoparticles, iodine-coated silver rod, titanium shell and titanium shell cover are prepared, the magnetic-thermal radioactive composite particles 3-4 are assembled. As shown in FIG. 2, a. The titanium shell is installed in the groove of the magnetic base, and then the magnetic-thermal nanoparticles are filled at the bottom of the titanium shell. Due to the influence of the magnetic base, the magnetic-thermal nanoparticles are adsorbed at the bottom of the titanium shell; b. The iodine-coated silver rod is placed in the titanium shell; c. Continue to fill the magnetic-thermal nanoparticles until the iodine-coated silver rod is completely wrapped and the inner cavity of the titanium shell is completely filled; d. The titanium shell cover is installed at the gap of the titanium shell, and the composite particle 3-4 is packaged by welding or adhesive bonding. After the assembly of the magnetic-thermal radioactive composite particles 3-4 is completed, since the welding or adhesive bonding will have welding slag or adhesive on the surface of the titanium shell, the surface of the composite particle 3-4 needs to be polished.

[0087] In order to facilitate verification, the present application selects a magnetic-thermal radioactive composite particle 3-4 with a particle size of 0.8 mm and a length of 4.5 mm; the surrounding layer material is titanium; the thickness of the surrounding layer is 0.1 mm; the volume ratio between the containing area and the volume of the iodine-coated silver rod is 7.2:1; the filling degree of the magnetic-thermal nanoparticles in the containing area is 100%, and generally the iodine-coated silver rod is located at the center position; the particle size of the magnetic-thermal nanoparticles is 13.3 nm.

[0088] Verification example one: the composite particle 3-4 has both magnetic-thermal treatment and radioactive treatment functions, and has better killing and inhibiting effect on diseased cells

[0089] In other conditions, as shown in Table 1, the titanium shell is loaded with magnetic nanoparticles alone for magnetic hyperthermia treatment; the titanium shell is loaded with iodine-coated silver rods alone for radiotherapy; and the combination of magnetic nanoparticles and iodine-coated silver rods improves the killing range (radius) compared with single magnetic nanoparticles.

[0090] Table 1

[0091] Verification Example Two: The required implantation and interventional magnetic medium particles are concentrated in the titanium shell, which can reduce the toxic side effects while ensuring effective treatment.

[0092] In other conditions, as shown in Table 2, the titanium shell is loaded with magnetic nanoparticles alone for magnetic hyperthermia treatment; the titanium shell is loaded with iodine-coated silver rods alone for radiotherapy; and the combination of magnetic nanoparticles and iodine-coated silver rods improves the killing range (radius) compared with single magnetic nanoparticles.

[0093] Table 2

[0094] Verification Example Three:

[0095] In other conditions, as shown in Table 3, the titanium shell is loaded with magnetic nanoparticles alone, and the killing range (radius) of the titanium shell loaded with only magnetic nanoparticles is 1.8 mm; and the killing range (radius) of the structure of the present application is 2.4 mm, that is, the combination of magnetic nanoparticles and iodine-coated silver rods improves the killing range (radius) compared with single magnetic nanoparticles.

[0096] Table 3

[0097] Verification Example Four:

[0098] In other conditions, as shown in Table 4, the structure of the present application, but the filling degree of the magnetic nanoparticles is different; the higher the filling degree, the greater the killing range (radius) and the higher the heat production efficiency (J / S).

[0099] Table 4

[0100] In the description of the present specification, the description of the terms "one embodiment", "example", "specific example", and the like 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 the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials, or characteristics can be combined in any one or more embodiments or examples in a suitable manner.

[0101] 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 to the above-mentioned embodiments, and the above-mentioned embodiments and descriptions in the specification are only to illustrate the principles of the present disclosure, and various changes and improvements can be made to the present disclosure without departing from the spirit and scope of the present disclosure, and all such changes and improvements fall within the scope of the claimed present disclosure.

Claims

1. A composite particle hyperthermia-radiotherapy system implanted by a flexible endoscope, comprising a flexible endoscope, the flexible endoscope comprising an ultrasonic probe; characterized in that, a puncture needle extending into and sliding along a working channel of the flexible endoscope, the puncture needle having a sharp portion; the puncture needle having a puncture channel extending along a length direction of the puncture needle, a particle channel coaxially connected to an end of the puncture needle away from the sharp portion, the particle channel loaded with the composite particles; an advancing needle installed at an end of the particle channel away from the puncture needle, the advancing needle pushing the composite particles in the particle channel into the puncture needle until the composite particles overflow from the sharp portion of the puncture needle.

2. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 1, wherein, The puncture needle is made of nickel-titanium alloy.

3. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 1, wherein, The puncture channel has an inner diameter slightly larger than a particle diameter of the composite particles, and only allows a single composite particle to pass through.

4. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 1, wherein, The system comprises a filler bin for loading the composite particles; the particle channel is located in the filler bin, and the puncture needle is detachably connected to the filler bin.

5. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 4, wherein, The filler bin is fixedly installed with a jacking rod elastically abutting against the composite particles in the filler bin, the jacking rod abutting against the composite particles has a tendency to move towards the particle channel.

6. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 5, wherein, The filler bin is fixedly installed with a jacking block, the jacking block has a movable bin therein, one end of the movable bin is closed, and the other end is open, the jacking rod passes out of the movable bin to the filler bin, the jacking rod has a limiting block thereon, a compression spring is installed in the movable bin between the limiting block and a lock catch, the lock catch is detachably connected to the open end of the movable bin; the compression spring elastically relaxes, so that the compression spring drives the jacking rod to abut against the composite particles.

7. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 6, wherein, The lock catch is threadedly connected to the open end of the movable bin.

8. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 4, wherein, An end of the puncture needle away from the sharp portion is threadedly connected to a housing of the filler bin.

9. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 1, wherein, The advancing needle passes out of an end of the working channel of the flexible endoscope away from the ultrasonic probe.

10. The endoscopic ultrasound implanted composite particle hyperthermia- radiotherapy system of claim 1, wherein, The system comprises an alternating magnetic field generator for generating an alternating magnetic field with adjustable magnetic field strength and frequency, so that the magnetic medium of the composite particles implanted in a treatment target area generates heat by magnetic induction to kill cancer cells; The alternating magnetic field generator is installed on a movable mechanical arm.

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