Self-powered, wireless, detachable optopharmaceutical syringe and its preparation method
By designing self-powered, wireless, and removable phototherapy syringes, the problem of difficulty in replacing Chinese medicines in implantable rhythmic photodynamic cancer treatment and being restricted by power supply areas is solved, and the replacement and supplementation of the medicines, as well as wirelessly controlled rhythmic photodynamic therapy is achieved, which improves the compliance and effect of treatment.
Patent Information
- Application Number
- CN202311116180.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-08-31
- Publication Date
- 2025-05-30
- Estimated Expiration
- 2043-08-31
AI Technical Summary
In the prior art, Chinese medicines for implantable rhythmic photodynamic cancer treatment are difficult to replace, and are limited by the power supply area, which affects the patient's compliance and treatment effect.
A self-powered, wireless, and removable photopharmaceutical syringe is designed, which is magnetically connected to the replaceable syringe through the implanted base, and the self-powered module is used to convert the mechanical energy of human body movement into electrical energy, promoting the injection of the agent and photodynamic therapy.
The in vitro replacement and supplementation of the agent is achieved, avoiding the risk of in vivo replacement, and without being restricted by the power supply area, rhythmic photodynamic treatment can be performed anytime and anywhere, improving patient compliance and treatment effect.
Smart Images

Figure CN118403256B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of rhythmic photodynamic therapy for cancer, and particularly relates to a self-powered, wireless, detachable optical drug syringe and a preparation method thereof. Background Art
[0002] Cancer is a well-recognized medical problem in the world, and early active treatment is extremely important for curing cancer. Rhythmic photodynamic therapy (abbreviated as mPDT) is a new type of photodynamic therapy technology that uses continuous, low-dose light irradiation and photosensitizers for treatment. Different from traditional photodynamic therapy, mPDT uses low-dose light irradiation and photosensitizers, requires continuous and multiple treatments, reduces the side effects of patients, and improves the treatment effect and duration at the same time.
[0003] To get rid of the limitation of large equipment on the treatment process, using integrated devices for mPDT is a feasible solution. Prior art one (DOI: 10.1002 / smll.201702479) provides a wireless, battery-free, implantable optofluidic device for optogenetic and pharmacological control. Researchers implanted it above the brain to simultaneously provide energy for wirelessly controllable drug release and light stimulation through radio frequency. Prior art two (DOI: 10.1038 / s41551-018-0261-7) provides implantable micro light emitting diodes (abbreviated as μLEDs) for photodynamic therapy based on radio frequency. However, cancer treatment is a long-term process. For implanted devices, when the internally released drugs are consumed, it is impossible to replenish the drugs, and surgery is required to replace the new device. Moreover, due to power supply limitations, the treatment process must be within the power supply area range, which is not conducive to improving patient compliance. Summary of the Invention
[0004] Aiming at the above deficiencies in the prior art, the self-powered, wireless, detachable optical drug syringe and the preparation method thereof provided by the present invention solve the problems of difficult replacement of drugs and limited power supply area range in implanted rhythmic photodynamic cancer treatment through the detachable magnetic connection between the implant base and the replaceable syringe, and converting the mechanical energy of human activities into electrical energy for pushing the medicine and performing rhythmic photodynamic therapy through the self-powered module.
[0005] In order to achieve the above invention purpose, the technical solution adopted by the present invention is as follows:
[0006] On the one hand, a self-powered, wireless, detachable optical drug syringe provided by the present invention includes an implant base, a replaceable injection actuator connected to the implant base, and a self-powered module connected to the replaceable injection actuator;
[0007] The self - power supply module is used to convert mechanical energy into electrical energy, supply power for the implanted base to emit light beams with a preset wavelength, and supply power for the replaceable injection actuator to push the medicine based on the principle of thermal expansion.
[0008] The implanted base is used to inject the medicine into the part to be treated, and emit light beams with a preset wavelength to the part to be subjected to rhythm photodynamic therapy, driving the photosensitizer to perform rhythm photodynamic therapy on tumor cells.
[0009] The replaceable injection actuator is used to store the medicine, and after receiving an infrared control signal, push the stored medicine into the implanted base through the principle of thermal expansion.
[0010] The beneficial effects of the present invention are as follows: A self - powered, wireless, and detachable optical medicine syringe provided by the present invention can convert the mechanical energy of human activities into electrical energy through the self - power supply module. The converted electrical energy can be used to push the medicine to the part to be subjected to rhythm photodynamic therapy and drive the micron - level LED to emit light beams with a preset wavelength for rhythm photodynamic therapy. It is no longer restricted by the power supply area and can perform rhythm photodynamic therapy on cancer cells at any time with the generation of human activities or mechanical energy. Through the magnetic attraction connection between the implanted base and the replaceable injection actuator, the present invention can replace the rhythm photodynamic therapy medicine outside the body, avoiding risks such as patient compliance and safety easily caused by replacing or supplementing the medicine in the body. Through infrared wireless remote control, a detachable and self - powered structure, the present invention realizes convenient rhythm photodynamic therapy for cancer patients to supplement the medicine without being restricted by the power supply area.
[0011] Further, the self - power supply module includes an arched stainless - steel sheet and a lead zirconate titanate piezoelectric ceramic fixedly connected to the arched stainless - steel sheet.
[0012] The beneficial effect of adopting the above - mentioned further solution is that the arched stainless - steel sheet can recover after being extruded. Combined with the piezoelectric ceramic, it can effectively convert the mechanical energy generated by human activities during extrusion into electrical energy to supply power for heating the nickel - chromium electrode and sending light beams with a preset wavelength by the micron - level LED.
[0013] Further, the implanted base includes a base main body, four first magnets fixedly embedded in the base main body at 90° intervals, a tubular fluid channel with one end passing through the center of the base main body along the lower side of the base main body, a micron - level LED arranged on the outer side of the other end of the tubular fluid channel, and a silver wire connecting the micron - level LED and two symmetrically arranged first magnets for conduction.
[0014] The beneficial effects of adopting the above further solution are as follows: The implant base provided by the present invention forms an injection head through the base body and the tubular fluid channel, and provides a basis for the detachable connection with the replaceable injection actuator through four first magnets. The setting of the four first magnets will neither cause leakage during the drug push due to insufficient magnetic suction or insufficient magnetic suction at each connection part, nor cause waste of resources and increase in cost due to excessive setting of magnets. Moreover, the first magnets and silver wires conduct electricity for the micron-level LED disposed at the tip of the injection position of the tubular fluid channel, effectively improving the space utilization rate and making use of the electrical conductivity of the first magnets.
[0015] Further, the tubular fluid channel is made of a tubular polyimide film.
[0016] The beneficial effects of adopting the above further solution are as follows: The polyimide film has good biocompatibility and glial cell adhesiveness. After disinfection and sterilization, it can be used for safe drug injection treatment.
[0017] Further, the replaceable injection actuator includes a tubular medicine storage body disposed opposite to the base body, two second magnets and two third magnets fixedly embedded in the tubular medicine storage body relative to the first magnets, and a circuit heating sub-module connected corresponding to the upper opening of the medicine storage body; one end of the tubular medicine storage body is magnetically attracted to the base body through the magnetic suction force between the two second magnets and two third magnets and the four first magnets.
[0018] The beneficial effects of adopting the above further solution are as follows: The replaceable injection actuator provided by the present invention stores the medicine through the tubular storage body, and realizes a reliable magnetic attraction connection between the replaceable injection actuator and the implant base through the two second magnets and two third magnets relative to the four first magnets respectively. Under the control heating of the circuit heating sub-module, the thermal expansion layer pushes the medicine in the tubular medicine storage body into the implant base due to the principle of thermal expansion, and injects it into the part to be subjected to rhythm photodynamic therapy, realizing the detachable connection of the syringe and the in vitro replacement and supplement of the medicine, and avoiding the thermal damage to the body tissue caused by the in-body heating of the circuit components.
[0019] Further, the circuit heating sub-module includes a circuit board, a control circuit unit disposed above the circuit board, and a nickel-chromium heating electrode disposed below the circuit board; the nickel-chromium heating electrode is wrapped in the thermal expansion layer to form a thermal-driven fluid pump; the thermal-driven fluid pump is connected to the tubular medicine storage body; the thermal-driven fluid pump is used to push the medicine in the tubular medicine storage body into the base body.
[0020] The beneficial effects of adopting the above further scheme are as follows: The control circuit is arranged above the circuit heating sub-module to facilitate the effective reception of infrared control signals, realizing the all-round wireless control of the optical medicine syringe. The nickel-chromium heating electrode can efficiently and sensitively conduct heat transfer, enabling the medicament in the tubular medicine storage body to be pushed under control.
[0021] Further, the control circuit unit is used to receive the electric energy and infrared control signals from the self-power supply module, and based on the infrared control signals and electric energy, control the nickel-chromium heating electrode to generate heat, and control the micron-level LED to emit a light beam with a preset wavelength through two second magnets, two first magnets opposite to the two second magnets, and a silver wire.
[0022] The beneficial effects of adopting the above further scheme are as follows: The control circuit unit provided by the present invention can, after receiving a wireless infrared control signal, control the nickel-chromium electrode to heat and the micron-level LED to emit a light beam with a preset wavelength for rhythm photodynamic therapy.
[0023] On the other hand, the present invention also provides a preparation method for a self-powered, wireless, and detachable optical medicine syringe, including the following steps:
[0024] S1. Obtain a base body and a tubular medicine storage body with the same outer diameter through three-dimensional printing, and use epoxy resin glue to evenly space, symmetrically fix, and penetrate and embed four first magnets into the base body;
[0025] S2. Use epoxy resin glue to thread one end of a tubular polyimide film through the center of one side of the base body as a tubular fluid channel;
[0026] S3. Use epoxy resin glue to fixedly connect the micron-level LED with polyimide as the substrate to the outer side of the other end of the tubular polyimide film, and use a silver wire to connect and conduct the micron-level LED with two first magnets;
[0027] S4. Use epoxy resin glue to fixedly embed two second magnets and two third magnets symmetrically arranged relative to the four first magnets into the tubular medicine storage body;
[0028] S5. Arrange the control circuit unit in the circuit heating sub-module on one side of the circuit board, and arrange the nickel-chromium heating electrode in the circuit heating sub-module on the other side of the circuit board, wherein the control circuit unit is connected to the self-power supply module;
[0029] S6. Add expansion particles to the mixture of polydimethylsiloxane and a curing agent, and stir evenly to form a thermal expansion layer;
[0030] S7. Use the thermal expansion to wrap the nickel-chromium heating electrode to form a thermal-driven fluid pump;
[0031] S8. Connect the circuit heating sub-module with the thermal drive fluid pump to one end of the tubular medicine cartridge body, weld one end of the two second magnets to the control circuit unit, and seal the connection between the thermal expansion layer and one end of the tubular medicine cartridge body with epoxy resin glue;
[0032] S9. Utilize the magnetic attraction between the second magnets and the third magnets and the first magnets to magnetically connect the other end of the tubular medicine cartridge body to the other side of the base body, so that the two second magnets, the two first magnets opposite to the two second magnets, and the silver wire conduct the control circuit unit and the micro-LED, completing the preparation of the self-powered, wireless, and detachable optical medicine syringe.
[0033] The beneficial effects of the present invention are as follows: A preparation method of a self-powered, wireless, and detachable optical medicine syringe provided by the present invention enables a reliable magnetic connection between the base body and the tubular medicine cartridge body by evenly spacing, symmetrically fixing, and penetrating and embedding four first magnets into the base body at intervals, and penetrating and embedding two second magnets and two third magnets corresponding to the four first magnets into the tubular medicine cartridge body; the present invention uses a polyimide film with biocompatibility to make a tubular fluid channel, and loads a micro-LED at the injection end of the tubular fluid channel, which can accurately apply medicine and light to the site of rhythm photodynamic therapy; the present invention not only utilizes the magnetic attraction of the magnets but also utilizes the conductivity of the magnets, and powers the micro-LED through the two second magnets, the two first magnets opposite to the two second magnets, and the silver wire; the present invention heats the thermal expansion layer through a nickel-chromium heating electrode, and through the principle of thermal expansion, pushes the medicine through the tubular medicine cartridge body, the base body, and the tubular fluid channel to the site of rhythm photodynamic therapy for precise treatment.
[0034] On the other hand, the present invention also provides a usage method of a self-powered, wireless, and detachable optical medicine syringe, including the following steps:
[0035] A1. Implant the tubular fluid channel implanted in the base into the site to be subjected to rhythm photodynamic therapy;
[0036] A2. Add medicine to the tubular medicine cartridge body, and utilize the magnetic attraction between the two second magnets and the two third magnets and the four first magnets to magnetically connect the tubular medicine cartridge body to the base body, realizing the connection between the replaceable injection actuator and the implanted base;
[0037] A3. Utilize the self-powered module to obtain the mechanical energy of human activities, convert the mechanical energy into electrical energy, and transmit the electrical energy to the circuit heating sub-module and the micro-LED;
[0038] A4. Use the infrared signal transmitter to control the control circuit unit in the circuit heating sub-module to drive the nickel-chromium heating electrode to heat;
[0039] A5. The control circuit unit in the heating sub-module of the circuit is controlled by an infrared signal transmitter to control the micron-level LED to emit a light beam with a preset wavelength through two second magnets, two first magnets opposite to the two second magnets, and a silver wire.
[0040] A6. The nickel-chromium heating electrode is used to heat the thermal expansion layer, and the medicament is pushed to the part to be subjected to rhythmic photodynamic therapy along the tubular medicine storage body through the base body and the tubular fluid channel by the principle of thermal expansion to perform rhythmic photodynamic therapy.
[0041] The beneficial effects of the present invention are as follows: A method for using a self-powered, wireless, and detachable optical medicine syringe provided by the present invention wirelessly controls the injection of the medicament and the micron-level LED to emit a light beam with a preset wavelength through an infrared control signal, uses the principle of thermal expansion to inject the medicament in the tubular medicine storage into the part to be subjected to rhythmic photodynamic therapy, and uses two second magnets, two third magnets, and four first magnets to connect the tubular medicine storage body and the base body through magnetic attraction, so that the photoelectric syringe is detachable, and the injected medicament can be replaced and supplemented.
[0042] Other advantages of the present invention will be analyzed in more detail in the subsequent embodiments. BRIEF DESCRIPTION OF THE DRAWINGS
[0043] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required to be used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can be obtained based on these drawings without creative efforts.
[0044] Figure 1 It is a schematic structural diagram of a self-powered, wireless, and detachable optical medicine syringe in Embodiment 1 of the present invention.
[0045] Figure 2 It is a flowchart of the preparation method of a self-powered, wireless, and detachable optical medicine syringe in Embodiment 2 of the present invention.
[0046] Figure 3 It is a flowchart of the use method of a self-powered, wireless, and detachable optical medicine syringe in Embodiment 3 of the present invention.
[0047] Figure 4 It is a comparison chart of the test results of mouse breast cancer xenograft tumors in Embodiment 3 of the present invention.
[0048] Wherein: 101, control circuit unit; 102, circuit board; 103, nickel-chromium heating electrode; 104, thermal expansion layer; 201, tubular medicine cartridge body; 202, second magnet; 203, third magnet; 301, base body; 302, first magnet; 303, tubular fluid channel; 304, silver wire; 305, microscale LED. Detailed implementation mode
[0049] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. The components of the embodiments of the present invention described and illustrated herein can be arranged and designed in various different configurations. Therefore, the detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely represents selected embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention. Embodiment 1
[0050] As Figure 1 shown, in an embodiment of the present invention, the present invention provides a self-powered, wireless, and detachable optical medicine syringe, including an implant base, a replaceable injection actuator connected to the implant base, and a self-powered module connected to the replaceable injection actuator;
[0051] The self-powered module is used to convert mechanical energy into electrical energy to supply power for the implant base to emit a light beam with a preset wavelength, and to supply power for the replaceable injection actuator to push the medicine based on the thermal expansion principle;
[0052] The self-powered module includes an arched stainless steel sheet and a lead zirconate titanate piezoelectric ceramic fixedly connected to the arched stainless steel sheet; the stainless steel sheet fixed with the lead zirconate titanate piezoelectric ceramic is arranged at the heel part of a person, and mechanical energy can be provided when the person moves and walks; the self-powered module converts the collected mechanical energy into electrical energy for power supply.
[0053] The implant base is used to inject the medicine into the treatment site to be treated, and emit a light beam with a preset wavelength to the site to be treated with rhythmic photodynamic therapy, and drive the photosensitizer to perform rhythmic photodynamic therapy on tumor cells.
[0054] In this embodiment, the preferably used medicament is the photosensitizer porphyrin. The preset wavelength of the light beam is 470 nm, and the light intensity is 2433 lux. The light beam with a wavelength of 470 nm can excite the photosensitizer porphyrin to generate reactive oxygen species (ROS), thereby killing tumor cells and treating cancer. When facing different types of tumor cells and in different treatment environments, the wavelength of the medicament and the light beam can be selectively targeted, adjusted, or replaced.
[0055] The implant base includes a base body 301, four first magnets 302 fixedly embedded in the base body 301 at 90° intervals, a tubular fluid channel 303 with one end passing through the center of the base body 301 along the lower side of the base body 301, a micro-LED 305 disposed outside the other end of the tubular fluid channel 303, and a silver wire 304 connecting the micro-LED 305 and two symmetrically arranged first magnets 302 for conduction.
[0056] The structural dimensions of the implant base are as follows:
[0057] The diameter of the base body 301 is 10 mm and the thickness is 1 mm; the diameter of the tubular fluid channel 303 is 5 mm and the thickness is 30 μm; the diameters of the four first magnets 302 are all 1 mm and the thicknesses are all 1 mm;
[0058] The tubular fluid channel 303 is made of a tubular polyimide film.
[0059] The replaceable injection actuator is used to store the medicament and, after receiving an infrared control signal, push the stored medicament into the implant base by the principle of thermal expansion.
[0060] The replaceable injection actuator includes a tubular medicine chamber body 201 disposed opposite to the base body 301, two second magnets 202 and two third magnets 203 fixedly embedded in the tubular medicine chamber body 201 opposite to the first magnets 302, and a circuit heating sub-module connected corresponding to the upper opening of the medicine chamber body; one end of the tubular medicine chamber body 201 is magnetically attracted to the base body 301 through the magnetic attraction between the two second magnets 202 and two third magnets 203 and the four first magnets 302. One end of the two second magnets 202 is connected to the control circuit unit 101 by welding.
[0061] The control circuit unit 101 is used to receive the electric energy and infrared control signals from the self-power supply module. Based on the electric energy provided by the self-power supply module, it controls the nickel-chromium heating electrode 103 to generate heat through the infrared control signal, and controls the micron-level LED 305 to emit a beam of a preset wavelength through two second magnets 202, two first magnets 302 opposite to the two second magnets 202, and a silver wire 304. The control circuit unit 101 uses a low-drop linear regulator of model WL2815 to regulate the electric energy generated by the self-power supply module. The WL2815 linear regulator ensures a stable output current under the condition of low cost of ceramic capacitors, and improves the efficiency to extend the power supply life of the self-power supply module; the control circuit unit 101 uses an infrared receiver of model TSOP37438 to receive the infrared control signals of external remote control; the control circuit unit 101 uses a microcontroller of model ATtiny84 to receive the regulated electric energy from the self-power supply module and process the infrared control signals received by the infrared receiver, so as to control the nickel-chromium heating electrode 103 to generate heat to push the drug and control the micron-level LED 305 to emit a beam of a preset wavelength.
[0062] The circuit heating sub-module includes a circuit board 102, a control circuit unit 101 arranged above the circuit board 102, and a nickel-chromium heating electrode 103 arranged below the circuit board 102; the nickel-chromium heating electrode 103 is wrapped in a thermal expansion layer 104 to form a thermal drive fluid pump; the thermal drive fluid pump is connected to the tubular medicine storage body 201; the thermal drive fluid pump is used to push the drug in the tubular medicine storage body 201 into the base body 301.
[0063] The structural dimensions of the replaceable injection actuator are as follows:
[0064] The thickness of the circuit board 102 is 0.6 mm; the outer diameter of the tubular medicine storage body is 10 mm, the thickness is 3 mm, and the capacity is about 30 microliters; the diameters of the two second magnets 202 are 1 mm, and the heights are 2.6 mm; the diameters of the two third magnets 203 are 1 mm and the heights are 2 mm. Embodiment 2
[0065] As Figure 2 shown, on the basis of Embodiment 1, in another embodiment of the present invention, the present invention also provides a preparation method for a self-powered, wireless, and detachable optical drug syringe, including the following steps:
[0066] S1. Obtain a base body 301 and a tubular medicine storage body 201 with the same outer diameter through three-dimensional printing, and use epoxy resin glue to evenly space, symmetrically fix, and penetrate and embed four first magnets 302 into the base body 301.
[0067] S2. Use epoxy resin glue to pass one end of the tubular polyimide film through the center of one side of the base body 301 as the tubular fluid channel 303;
[0068] S3. Use epoxy resin glue to fixedly connect the micro-LED 305 with polyimide as the substrate to the outer side of the other end of the tubular polyimide film, and use silver wire 304 to connect and conduct the micro-LED 305 with the two first magnets 302;
[0069] S4. Use epoxy resin glue to fixedly embed the two second magnets 202 and the two third magnets 203 symmetrically arranged relative to the four first magnets 302 into the tubular medicine storage body 201;
[0070] S5. Set the control circuit unit 101 in the circuit heating sub-module on one side of the circuit board 102, and set the nickel-chromium heating electrode 103 in the circuit heating sub-module on the other side of the circuit board 102, wherein the control circuit unit 101 is connected to the self-power supply module;
[0071] S6. Add the expansion particles to the mixture of polydimethylsiloxane and curing agent and stir evenly to form the thermal expansion layer 104;
[0072] As a preferred solution, the model of the expansion particles added in this embodiment is: Expancel 031 DU 40, AkzoNobel;
[0073] The thermal expansion layer 104 is made of polydimethylsiloxane with an elastomer-to-curing agent ratio of 10:1, and expansion microspheres, and is mixed in a mass ratio of 2:1;
[0074] S7. Use the thermal expansion layer 104 to wrap the nickel-chromium heating electrode 103 to form a thermally driven fluid pump;
[0075] S8. Connect the circuit heating sub-module with the thermally driven fluid pump to one end of the tubular medicine storage body 201, weld one end of the two second magnets 202 to the control circuit unit 101, and use epoxy resin glue to seal the connection between the thermal expansion layer 104 and one end of the tubular medicine storage body 201;
[0076] S9. Use the magnetic attraction force between the second magnets 202 and the third magnets 203 and the first magnets 302 to magnetically connect one end of the tubular medicine storage body 201 to the other side of the base body 301, so that the two second magnets 202, the two first magnets 302 opposite to the two second magnets 202, and the silver wire 304 conduct the control circuit unit and the micro-LED 305, and complete the preparation of the self-powered, wireless, and detachable optical medicine syringe.
[0077] In this embodiment, all components are sealed and connected with epoxy resin, and the part of the connection base body 301 in contact with human tissues is encapsulated with polydimethylsiloxane to prevent short circuits and meet biocompatibility requirements. Embodiment 3
[0078] As Figure 3 shown, based on Embodiment 1 and Embodiment 2, in another embodiment of the present invention, the present invention provides a method for using a self-powered, wireless, and detachable photo-drug syringe, including the following steps:
[0079] A1. Implant the tubular fluid channel 303 of the implant base into the part to be subjected to rhythm photodynamic therapy.
[0080] A2. Add the drug to the tubular drug chamber body 201, and use the magnetic attraction force between two second magnets 202 and two third magnets 203 and four first magnets 302 to magnetically connect the tubular drug chamber body 201 with the base body 301, realizing the connection between the replaceable injection actuator and the implant base.
[0081] A3. Use the self-powered module to obtain the mechanical energy of human activities, convert the mechanical energy into electrical energy, and transmit the electrical energy to the circuit heating sub-module and the micro-scale LED.
[0082] A4. Use the infrared signal transmitter to control the control circuit unit 101 in the circuit heating sub-module to drive the nickel-chromium heating electrode 103 to heat.
[0083] A5. Use the infrared signal transmitter to control the control circuit unit 101 in the circuit heating sub-module to control the micro-scale LED 305 to emit a light beam with a preset wavelength through two second magnets 202, two first magnets 302 opposite to the two second magnets 202, and the silver wire 304.
[0084] A6. Use the nickel-chromium heating electrode 103 to heat the thermal expansion layer 104, and push the drug along the tubular drug chamber body 201 through the base body 301 and the tubular fluid channel 303 to the part to be subjected to rhythm photodynamic therapy by the principle of thermal expansion, for rhythm photodynamic therapy.
[0085] In this embodiment, the emitted light beam is blue light with a wavelength of 470 nm, and the drug is 5,10,15,20-tetrakis(4-trimethylammonium)phenylporphyrin tetratosylate; turning on the blue light irradiation activates the porphyrin reaction to generate reactive oxygen species (ROS) to kill nearby tumor cells, realizing local photodynamic therapy; when the drugs and energy of the replaceable module are exhausted, a new actuator module can be simply and quickly replaced for the next treatment.
[0086] In the experiment of wireless-controlled local drug delivery and light-stimulated anti-tumor, the self-powered, wireless, and detachable photo-drug syringe provided by the present invention was used for the mouse breast cancer xenograft tumor test. The test included the following steps:
[0087] B1. Obtain several mouse breast cancer models;
[0088] The construction method of the mouse breast cancer model included the following steps:
[0089] B11. Collect tumor cells in logarithmic growth from female Balb / c mice (body weight ~20 g) at 6 - 8 weeks old;
[0090] B12. Place the collected tumor cells in 10 ml of serum-free matrix, centrifuge at 1500 revolutions per minute for 3 minutes, wash continuously 3 times after centrifugation, and mix with serum-free matrix to obtain a culture medium;
[0091] B13. Calculate the number of tumor cells in the culture medium using a counter, and adjust the density of 4T1-luc breast cancer cells in the culture medium to 5×106 cells / ml to obtain the tumor cell culture solution to be inoculated;
[0092] B14. Inoculate the tumor cell culture solution to be inoculated subcutaneously into the right thigh of several mice. After seven days, several mouse breast cancer models with palpable tumor nodules were obtained;
[0093] B2. Set a control group CTRL, a porphyrin group POR, a light irradiation group LED, and a rhythmic photodynamic therapy group mPDT to treat the mouse breast cancer models respectively;
[0094] The control group CTRL did not receive any treatment;
[0095] The porphyrin group POR started to inject 25 μl of porphyrin (2 mg / ml) near the tumor on the 7th day, once a day, for a total of 2 weeks of treatment;
[0096] The light irradiation group LED started to irradiate the tumor with blue light from the implanted device for 2 hours on the 8th day, once a day, for a total of 2 weeks of treatment;
[0097] The photodynamic therapy group PDT started to inject 25 μl of porphyrin (2 mg / ml) using the self-powered, wireless, and detachable photo-drug syringe provided by the present invention on the 7th day, and irradiated the tumor with blue light with a wavelength of 470 nm for 2 hours on the 8th day after 24 hours, once a day, for a total of 2 weeks of treatment;
[0098] B3. Measure the tumor size of each mouse in each mouse breast cancer model and draw a tumor growth curve before the mouse treatment experiment every day, and observe the survival period of the mice;
[0099] Such as Figure 4As shown, the tumor growth rate of mice in the rhythmic photodynamic therapy group (mPDT) was significantly lower than that in the control group (CTRL), the porphyrin group (POR), and the light irradiation group (LED), with significant statistical differences. Moreover, all mice did not show any abnormalities in eating and drinking during the experiment, and there were no abnormal changes in body weight.
[0100] As described above, the above are only specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention can easily think of changes or substitutions, which should all be covered within the protection scope of the present invention.
Claims
1. A self-powered, wireless, detachable optical drug syringe, characterized in that, it includes an implantation base, a replaceable injection actuator connected to the implantation base, and a self-powered module connected to both the implantation base and the replaceable injection actuator; the self-powered module is used to convert mechanical energy into electrical energy to power the implantation base to emit a light beam with a preset wavelength, and to power the replaceable injection actuator to push the drug based on the principle of thermal expansion; the implantation base is used to inject the drug into the treatment site to be treated, and to emit a light beam with a preset wavelength to the site to be treated with rhythmic photodynamic therapy, driving the photosensitizer to perform rhythmic photodynamic therapy on tumor cells; the replaceable injection actuator is used to store the drug, and after receiving an infrared control signal, it pushes the stored drug into the implantation base through the principle of thermal expansion; the implantation base includes a base body, four first magnets fixedly embedded in the base body at 90° intervals, a tubular fluid channel with one end passing through the center of the base body along the lower side of the base body, a micro-LED arranged outside the other end of the tubular fluid channel, and a silver wire connecting the micro-LED to two symmetrically arranged first magnets to conduct electricity.
2. The self-powered, wireless, detachable optical drug syringe according to claim 1, characterized in that, the self-powered module includes an arched stainless steel sheet and a lead zirconate titanate piezoelectric ceramic fixedly connected to the arched stainless steel sheet.
3. The self-powered, wireless, detachable optical drug syringe according to claim 1, characterized in that, the tubular fluid channel is made of tubular polyimide film.
4. The self-powered, wireless, detachable optical drug syringe according to claim 1, characterized in that, the replaceable injection actuator includes a tubular drug storage body arranged opposite to the base body, two second magnets and two third magnets fixedly embedded in the tubular drug storage body relative to the first magnets, and a circuit heating sub-module connected to the upper opening of the drug storage body; one end of the tubular drug storage body is connected to the base body through the magnetic attraction force between the two second magnets, the two third magnets and the four first magnets.
5. The self-powered, wireless, detachable optical drug syringe according to claim 4, characterized in that, the circuit heating sub-module includes a circuit board, a control circuit unit arranged above the circuit board, and a nickel-chromium heating electrode arranged below the circuit board; the nickel-chromium heating electrode is wrapped in a thermal expansion layer to form a thermal-driven fluid pump; the thermal-driven fluid pump is connected to the tubular drug storage body; the thermal-driven fluid pump is used to push the drug in the tubular drug storage body into the base body.
6. The self-powered, wireless, detachable optical drug syringe according to claim 5, characterized in that, the control circuit unit is used to receive the electrical energy and infrared control signal of the self-powered module, and based on the infrared control signal and electrical energy, control the nickel-chromium heating electrode to generate heat, and control the micro-LED to emit a light beam with a preset wavelength through the two second magnets, the two first magnets opposite to the two second magnets and the silver wire.
7. A preparation method of the self-powered, wireless, detachable optical drug syringe according to any one of claims 1-6, characterized in that, It includes the following steps: S1. Obtain a base body and a tubular medicine storage body with the same outer diameter through three-dimensional printing, and use epoxy resin glue to evenly space, symmetrically fix, and penetrate and embed four first magnets into the base body; S2. Use epoxy resin glue to pass one end of a tubular polyimide film through the center of one side of the base body as a tubular fluid channel; S3. Use epoxy resin glue to fixedly connect a micron-level LED with polyimide as the substrate to the outer side of the other end of the tubular polyimide film, and use silver wires to connect and conduct the micron-level LED with two first magnets; S4. Use epoxy resin glue to fixedly embed two second magnets and two third magnets symmetrically arranged relative to the four first magnets into the tubular medicine storage body; S5. Set the control circuit unit in the circuit heating sub-module on one side of the circuit board, and set the nickel-chromium heating electrode in the circuit heating sub-module on the other side of the circuit board, wherein the control circuit unit is connected to the self-power supply module; S6. Add expansion particles to the mixture of polydimethylsiloxane and a curing agent, and stir evenly to form a thermal expansion layer; S7. Use the thermal expansion to wrap the nickel-chromium heating electrode to form a thermally driven fluid pump; S8. Connect the circuit heating sub-module with the thermally driven fluid pump to one end of the tubular medicine storage body, weld one end of the two second magnets to the control circuit unit, and use epoxy resin glue to seal the connection between the thermal expansion layer and one end of the tubular medicine storage body; S9. Use the magnetic attraction between the second magnets and the third magnets and the first magnets to magnetically connect the other end of the tubular medicine storage body to the other side of the base body, so that the two second magnets, the two first magnets opposite to the two second magnets, and the silver wires conduct the control circuit unit and the micron-level LED, and complete the preparation of the self-powered, wireless, and detachable optical medicine syringe.
Citation Information
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