技术领域Technical Field
本发明属于节律光动力治疗癌症技术领域，尤其涉及一种自供电、无线、可拆卸的光药注射器及其制备方法。The present invention belongs to the technical field of rhythmic photodynamic therapy for cancer, and in particular relates to a self-powered, wireless, detachable photomedicine injector and a preparation method thereof.
背景技术Background Art
癌症是世界公认的医学难题，早期积极治疗对治愈癌症极为重要。节律光动力治疗(Metronomic photodynamic therapy，简称mPDT)是一种新型的光动力治疗技术，它采用连续、低剂量的光照和光敏剂治疗。与传统的光动力治疗不同，mPDT使用低剂量的光照和光敏剂，需要连续、多次治疗，减轻了患者的副作用，同时提高治疗的效果和持续时间。Cancer is a medical problem recognized by the world, and early and active treatment is extremely important for curing cancer. Metronomic photodynamic therapy (mPDT) is a new photodynamic therapy technology that uses continuous, low-dose light and photosensitizers for treatment. Unlike traditional photodynamic therapy, mPDT uses low-dose light and photosensitizers and requires continuous, multiple treatments, which reduces the side effects of patients while improving the effectiveness and duration of treatment.
为摆脱大型设备对治疗过程的限制，使用集成化器件进行mPDT是一种可行的方案。现有技术一（DOI：10.1002/smll.201702479）提供了一种用于光遗传学和药理学控制的无线、无电池、植入式光流控设备，研究人员将它植入到大脑上方，通过射频实现无线可控的药物的释放和光刺激同时提供能量。现有技术二（DOI：10.1038/s41551-018-0261-7）提供了基于射频的用于光动力治疗的植入式微发光二极管（micro light emitting diode，简称μLED）。但是，癌症治疗是一个长期的过程，对于植入器件，当内部释放的药物消耗完之后，无法对药物进行补充，需要进行手术才能更换新的器件，并且由于供电限制，治疗过程必须处于供电区域范围内，不利于提高患者的依从性。In order to get rid of the limitation of large equipment on the treatment process, the use of integrated devices for mPDT is a feasible solution. Prior art 1 (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 achieve wireless controllable drug release and light stimulation through radio frequency while providing energy. Prior art 2 (DOI: 10.1038/s41551-018-0261-7) provides an implantable micro light emitting diode (μLED) for photodynamic therapy based on radio frequency. However, cancer treatment is a long process. For implanted devices, when the internal released drugs are consumed, the drugs cannot be replenished. Surgery is required to replace new devices. In addition, due to power supply limitations, the treatment process must be within the power supply area, which is not conducive to improving patient compliance.
发明内容Summary of the invention
针对现有技术中的上述不足，本发明提供的自供电、无线、可拆卸的光药注射器及其制备方法，通过植入底座与可更换注射器的可拆卸磁吸连接，并通过自供电模块将人体活动的机械能转化为推送药剂和进行节律光动力治疗的电能，解决了植入式节律光动力癌症治疗中药剂难以更换以及受供电区域范围限制的问题。In view of the above-mentioned deficiencies in the prior art, the self-powered, wireless, detachable photomedicine injector and its preparation method provided by the present invention have a detachable magnetic connection between the implanted base and the replaceable syringe, and a self-powered module that converts the mechanical energy of human activities into electrical energy for pushing medicines and performing rhythmic photodynamic therapy, thereby solving the problems of difficulty in replacing medicines and being limited by the power supply area in implantable rhythmic photodynamic cancer therapy.
为了达到上述发明目的，本发明采用的技术方案为：In order to achieve the above-mentioned object of the invention, the technical solution adopted by the present invention is:
一方面，本发明提供的一种自供电、无线、可拆卸的光药注射器，包括植入底座、与植入底座连接的可更换注射执行器，以及与可更换注射执行器均连接的自供电模块；In one aspect, the present invention provides a self-powered, wireless, detachable optical medicine injector, comprising an implant base, a replaceable injection actuator connected to the implant base, and a self-powered module connected to both the replaceable injection actuators;
所述自供电模块，用于将机械能转换为电能，为植入底座发射预设波长的光束供电，以及为可更换注射执行器基于热胀原理推送药剂供电；The self-powered module is used to convert mechanical energy into electrical energy, to provide power for the implant base to emit a light beam of a preset wavelength, and to provide power for the replaceable injection actuator to push the medicine based on the principle of thermal expansion;
所述植入底座，用于将药剂注射入待治疗部位，并对待进行节律光动力治疗部位发射预设波长的光束，驱动光敏剂对肿瘤细胞进行节律光动力治疗；The implant base is used to inject the drug into the part to be treated, and emit a light beam of a preset wavelength to the part to be treated with rhythmic photodynamic therapy, so as to drive the photosensitizer to perform rhythmic photodynamic therapy on tumor cells;
所述可更换注射执行器，用于存储药剂，以及接收红外控制信号后，通过热胀原理将存储的药剂推送入植入底座。The replaceable injection actuator is used to store medicines and, after receiving an infrared control signal, push the stored medicines into the implant base through the principle of thermal expansion.
本发明的有益效果为：本发明提供的一种自供电、无线、可拆卸的光药注射器，通过自供电模块能够将人体活动的机械能转换为电能，转换得到的电脑能够用于推送药剂至待节律光动力治疗部位，以及驱动微米级LED发射预设波长的光束进行节律光动力治疗，无需再受供电区域限制，能够随人体活动或机械能的产生，随时随地对癌细胞进行节律光动力治疗；本发明通过植入底座与可更换注射执行器间的磁吸连接，既实现了体外可更换节律光动力治疗药剂，避免了体内更换或补充药剂易引发的患者依从性、安全性等风险；本发明通过红外无线遥控，可拆卸且自供电的结构，实现了对癌症患者补充药剂方便且不受供电区域限制的节律光动力治疗。The beneficial effects of the present invention are as follows: the present invention provides a self-powered, wireless, detachable photomedicine injector, which can convert the mechanical energy of human activities into electrical energy through a self-powered module. The converted electrical energy can be used to push the medicine to the site to be treated with rhythmic photodynamic therapy, and drive the micron-level LED to emit a light beam of a preset wavelength for rhythmic photodynamic therapy. It is no longer restricted by the power supply area and can perform rhythmic photodynamic therapy on cancer cells anytime and anywhere as human activities or mechanical energy are generated. The present invention realizes replaceable rhythmic photodynamic therapy medicine in vitro through a magnetic connection between an implanted base and a replaceable injection actuator, thereby avoiding the risks of patient compliance, safety, etc. that are easily caused by replacing or supplementing medicine in vivo. The present invention realizes rhythmic photodynamic therapy that is convenient for cancer patients to supplement medicine and is not restricted by the power supply area through infrared wireless remote control and a detachable and self-powered structure.
进一步地，所述自供电模块包括拱形不锈钢片，以及与拱形不锈钢片固定连接的锆钛酸铅压电陶瓷。Furthermore, the self-powered module includes an arched stainless steel sheet and lead zirconate titanate piezoelectric ceramics fixedly connected to the arched stainless steel sheet.
采用上述进一步方案的有益效果为：拱形不锈钢片受到挤压后能够复原，结合压电陶瓷能够有效将人体活动挤压产生的机械能转化为电能，为镍铬电极加热和微米级LED发送预设波长光束供电。The beneficial effects of adopting the above further scheme are: the arched stainless steel sheet can recover after being squeezed, and combined with piezoelectric ceramics, it can effectively convert the mechanical energy generated by human activity into electrical energy, which is used to heat the nickel-chromium electrode and send a preset wavelength light beam to the micron-sized LED.
进一步地，所述植入底座包括底座主体、90°间隔固定嵌入底座主体的四个第一磁铁、一端沿底座主体下侧穿射于底座主体中心的管状流体通道、设置于管状流体通道另一端外侧的微米级LED，以及将微米级LED与两个对称设置的第一磁铁连接导通的银线。Furthermore, the implant base includes a base body, four first magnets fixedly embedded in the base body at 90° intervals, a tubular fluid channel with one end extending along the lower side of the base body and extending through the center of the base body, a micron-sized LED arranged on the outside of the other end of the tubular fluid channel, and a silver wire connecting the micron-sized LED and two symmetrically arranged first magnets.
采用上述进一步方案的有益效果为：本发明提供的植入底座通过底座主体和管状流体通道构成注射头，并通过四个第一磁铁为与可更换注射执行器的可拆卸连接提供基础，四个第一磁铁的设置既不会因磁吸力不足、各连接部磁吸力不足导致药剂推送时渗漏，也不会因过量设置磁铁造成资源浪费和成本增加，且通过第一磁铁和银线为设置于管状流体通道注射位置尖端的微米级LED导电，有效提升了空间利用率，也利用了第一磁铁的导电性能。The beneficial effects of adopting the above further scheme are as follows: the implant base provided by the present invention constitutes an injection head through the base body and the tubular fluid channel, and provides a basis for a detachable connection with a replaceable injection actuator through four first magnets. The arrangement of the four first magnets will not cause leakage of the medicine during pushing due to insufficient magnetic attraction and insufficient magnetic attraction of the connecting parts, nor will it cause waste of resources and increase in costs due to excessive arrangement of magnets. Moreover, the first magnets and silver wires are used to conduct electricity to the micron-sized LED arranged at the tip of the injection position of the tubular fluid channel, which effectively improves the space utilization rate and also utilizes the conductive properties of the first magnets.
进一步地，所述管状流体通道采用管状聚酰亚胺薄膜。Furthermore, the tubular fluid channel adopts a tubular polyimide film.
采用上述进一步方案的有益效果为：聚酰亚胺薄膜具有较好的生物相容性和胶质细胞粘附性，经消毒灭菌后，能够用于安全的药剂注射治疗。The beneficial effect of adopting the above further scheme is that the polyimide film has good biocompatibility and glial cell adhesion, and can be used for safe drug injection therapy after disinfection and sterilization.
进一步地，所述可更换注射执行器包括与底座主体相对设置的管状药仓主体、相对第一磁铁固定嵌入管状药仓主体中的两个第二磁铁和两个第三磁铁、与药仓主体上端开口对应连接电路加热子模块；所述管状药仓主体的一端与底座主体通过两个第二磁铁和两个第三磁铁与四个第一磁铁间的磁吸力连接。Furthermore, the replaceable injection actuator includes a tubular medicine chamber body arranged opposite to the base body, two second magnets and two third magnets fixedly embedded in the tubular medicine chamber body relative to the first magnet, and a circuit heating submodule connected corresponding to the upper opening of the medicine chamber body; one end of the tubular medicine chamber body is connected to the base body through the magnetic attraction between the two second magnets and the two third magnets and the four first magnets.
采用上述进一步方案的有益效果为：本发明提供的可更换注射执行器通过管状仓主体存放药剂，并通过两个第二磁铁和两个第三磁铁分别相对四个第一磁铁实现可更换注射执行器与植入底座间的可靠磁吸连接，在电路加热子模块的控制加热下，热膨胀层因热胀原理将管状药仓主体内的药剂推送至植入底座内，射入待进行节律光动力治疗部位，实现了注射器的可拆卸连接和药剂的体外更换和补充，避免了电路元件在体内加热对身体阻止造成的热损伤。The beneficial effects of adopting the above-mentioned further scheme are as follows: the replaceable injection actuator provided by the present invention stores medicines through the tubular magazine body, and realizes a reliable magnetic connection between the replaceable injection actuator and the implant base through two second magnets and two third magnets respectively relative to the four first magnets. Under the controlled heating of the circuit heating submodule, the thermal expansion layer pushes the medicine in the tubular medicine magazine body into the implant base due to the principle of thermal expansion, and injects it into the site to be treated with rhythmic photodynamic therapy, thereby realizing the detachable connection of the syringe and the in vitro replacement and replenishment of the medicine, and avoiding thermal damage to the body caused by heating of the circuit components in the body.
进一步地，所述电路加热子模块包括电路板、设置于电路板上方的控制电路单元，以及设置于电路板下方的镍铬加热电极；所述镍铬加热电极包裹于热膨胀层内，形成热驱动流体泵；所述热驱动流体泵与管状药仓主体连接；所述热驱动流体泵用于将管状药仓主体内的药物推送至底座主体内。Furthermore, the circuit heating submodule 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 heat-driven fluid pump; the heat-driven fluid pump is connected to the tubular medicine chamber body; the heat-driven fluid pump is used to push the medicine in the tubular medicine chamber body into the base body.
采用上述进一步方案的有益效果为：电路加热子模块的上方设置控制电路便于有效接收的红外控制信号，实现光药注射器的全方位无线控制，采用镍铬加热电极能够高效敏感地进行热传递使得管状药仓主体内的药剂能够受控制的被推送。The beneficial effects of adopting the above further scheme are: a control circuit is arranged above the circuit heating submodule to facilitate the effective reception of infrared control signals, thereby realizing all-round wireless control of the optical medicine injector, and the use of nickel-chromium heating electrodes can efficiently and sensitively transfer heat so that the medicine in the tubular medicine chamber body can be pushed out in a controlled manner.
进一步地，所述控制电路单元用于接收自供电模块的电能和红外控制信号，并基于红外控制信号和电能控制镍铬加热电极发热，以及通过两个第二磁铁、与两个第二磁铁相对的两个第一磁铁和银线控制微米级LED发射预设波长的光束。Furthermore, the control circuit unit is used to receive electrical energy and infrared control signals from the power supply module, and control the heating of the nickel-chromium heating electrode based on the infrared control signal and electrical energy, and control the micron-sized LED to emit a light beam of a preset wavelength through two second magnets, two first magnets opposite to the two second magnets, and silver wires.
采用上述进一步方案的有益效果为：本发明提供的控制电路单元能够在接收无线红外控制信号后，控制镍铬电极加热以及微米级LED发射预设波长的光束进行节律光动力治疗。The beneficial effect of adopting the above further scheme is that the control circuit unit provided by the present invention can control the heating of the nickel-chromium electrode and the micron-level LED to emit a light beam of a preset wavelength for rhythmic photodynamic therapy after receiving the wireless infrared control signal.
另一方面，本发明还提供一种自供电、无线、可拆卸的光药注射器的制备方法，包括如下步骤：On the other hand, the present invention also provides a method for preparing a self-powered, wireless, detachable optical medicine injector, comprising the following steps:
S1、通过三维打印得到外径相同的底座主体和管状药仓主体，并利用环氧树脂胶将四个第一磁铁均匀间隔、对称固定、贯穿嵌入底座主体中；S1. Obtain a base body and a tubular medicine chamber body with the same outer diameter by three-dimensional printing, and evenly space and symmetrically fix four first magnets by epoxy resin glue, and embed them into the base body;
S2、利用环氧树脂胶将管状聚酰亚胺薄膜一端穿设于底座主体一侧中心作为管状流体通道；S2, using epoxy resin glue to penetrate one end of the tubular polyimide film into the center of one side of the base body as a tubular fluid channel;
S3、利用环氧树脂胶将聚酰亚胺作为基底的微米级LED固定连接至管状聚酰亚胺薄膜的另一端外侧，并利用银线将微米级LED与两个第一磁铁连接导通；S3, using epoxy resin glue to fix the micron-sized LED with polyimide as the base to the outer side of the other end of the tubular polyimide film, and using silver wire to connect the micron-sized LED to the two first magnets;
S4、利用环氧树脂胶将相对四个第一磁铁对称设置的两个第二磁铁和两个第三磁铁固定嵌入管状药仓主体中；S4. Using epoxy resin glue, two second magnets and two third magnets symmetrically arranged relative to the four first magnets are fixedly embedded in the tubular medicine chamber body;
S5、将电路加热子模块中的控制电路单元设置于电路板的一侧，并将电路加热子模块中的镍铬加热电极设置于电路板的另一侧，其中，控制电路单元与自供电模块连接；S5, disposing the control circuit unit in the circuit heating submodule on one side of the circuit board, and disposing the nickel-chromium heating electrode in the circuit heating submodule on the other side of the circuit board, wherein the control circuit unit is connected to the self-power supply module;
S6、将膨胀微粒添加至聚二甲基硅氧烷与固化剂的混合物中，并搅拌均匀，形成热膨胀层；S6, adding the expandable particles to the mixture of polydimethylsiloxane and the curing agent, and stirring evenly to form a thermal expansion layer;
S7、利用热膨胀包裹镍铬加热电极，形成热驱动流体泵；S7, wrapping the nickel-chromium heating electrode by thermal expansion to form a heat-driven fluid pump;
S8、将带有热驱动流体泵的电路加热子模块与管状药仓主体的一端连接，并将两个第二磁铁的一端与控制电路单元焊接，且利用环氧树脂胶将热膨胀层与管状药仓主体的一端连接处密封；S8, connecting the circuit heating submodule with the heat-driven fluid pump to one end of the tubular medicine chamber body, welding one end of the two second magnets to the control circuit unit, and sealing the connection between the heat expansion layer and one end of the tubular medicine chamber body with epoxy resin glue;
S9、利用第二磁铁和第三磁铁与第一磁铁间的磁吸力，将管状药仓主体的另一端与底座主体另一侧磁吸连接，使得两个第二磁铁、与两个第二磁铁相对的两个第一磁铁和银线将控制电路单元和微米级LED导通，完成自供电、无线、可拆卸的光药注射器的制备。S9. Utilize the magnetic attraction between the second magnet and the third magnet and the first magnet to magnetically connect the other end of the tubular medicine chamber 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 turn on the control circuit unit and the micron-sized LED, completing the preparation of a self-powered, wireless, and detachable optical medicine injector.
本发明的有益效果为：本发明提供的一种自供电、无线、可拆卸的光药注射器的制备方法，通过将四个第一磁铁均匀间隔、对称固定、贯穿嵌入底座主体中，并将两个第二磁铁和两个第三磁铁对应四个第一磁铁贯穿嵌入管状药仓主体中，使得底座主体和管状药仓主体间可靠磁吸连接；本发明采用具有生物相容性的聚酰亚胺薄膜制成管状流体通道，在管状流体通道注射端负载微米级LED，能够准确对待节律光动力治疗部位施药和光照；本发明不仅利用了磁铁的磁吸性还利用了磁铁的导电性，通过两个第二磁铁、与两个第二磁铁相对的两个第一磁铁和银线实现了为微米级LED供电；本发明通过镍铬加热电极对热膨胀层加热，通过热胀原理，将药剂经管状药仓主体、底座主体和管状流体通道推送至待节律光动力治疗部位，精准治疗。The beneficial effects of the present invention are as follows: the present invention provides a method for preparing a self-powered, wireless, and detachable photomedicine injector, by evenly spacing, symmetrically fixing, and penetrating and embedding four first magnets into the base body, and penetrating and embedding two second magnets and two third magnets corresponding to the four first magnets into the tubular medicine chamber body, so that the base body and the tubular medicine chamber body are reliably magnetically connected; the present invention adopts a biocompatible polyimide film to make a tubular fluid channel, and loads a micron-level LED at the injection end of the tubular fluid channel, which can accurately administer medicine and illuminate the rhythmic photodynamic therapy site; the present invention not only utilizes the magnetic attraction of the magnet but also utilizes the conductivity of the magnet, and realizes power supply for the micron-level LED through two second magnets, two first magnets opposite to the two second magnets, and 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 chamber body, the base body, and the tubular fluid channel to the site to be treated with rhythmic photodynamic therapy, and accurately treats.
另一方面，本发明还提供一种自供电、无线、可拆卸的光药注射器的使用方法，包括如下步骤：On the other hand, the present invention also provides a method for using a self-powered, wireless, detachable optical medicine injector, comprising the following steps:
A1、将植入底座的管状流体通道植入待进行节律光动力治疗部位；A1. Implanting the tubular fluid channel of the implant base into the site to be treated with rhythmic photodynamic therapy;
A2、添加药剂至管状药仓主体，并利用两个第二磁铁和两个第三磁铁与四个第一磁铁间的磁吸力，将管状药仓主体与底座主体磁吸连接，实现可更换注射执行器与植入底座的连接；A2. Add medicine to the tubular medicine chamber body, and use the magnetic attraction between the two second magnets and the two third magnets and the four first magnets to magnetically connect the tubular medicine chamber body with the base body, thereby realizing the connection between the replaceable injection actuator and the implant base;
A3、利用自供电模块获取人活动的机械能，并将机械能转换为电能，且将电能传输至电路加热子模块和微米级LED；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 submodule and the micron-level LED;
A4、利用红外信号发送器控制电路加热子模块中的控制电路单元驱动镍铬加热电极加热；A4, using the control circuit unit in the infrared signal transmitter control circuit heating submodule to drive the nickel-chromium heating electrode for heating;
A5、利用红外信号发送器控制电路加热子模块中的控制电路单元通过两个第二磁铁、与两个第二磁铁相对的两个第一磁铁和银线控制微米级LED发射预设波长的光束；A5. Using the infrared signal transmitter to control the control circuit unit in the circuit heating submodule to control the micron-sized LED to emit a light beam of a preset wavelength through two second magnets, two first magnets opposite to the two second magnets, and a silver wire;
A6、利用镍铬加热电极对热膨胀层加热，通过热胀原理将药剂沿管状药仓主体经底座主体和管状流体通道推送至待进行节律光动力治疗部位，进行节律光动力治疗。A6. Use the nickel-chromium heating electrode to heat the thermal expansion layer, and push the medicine along the tubular medicine chamber body through the base body and the tubular fluid channel to the site to be treated with rhythmic photodynamic therapy through the principle of thermal expansion, so as to perform rhythmic photodynamic therapy.
本发明的有益效果为：本发明提供的一种自供电、无线、可拆卸的光药注射器的使用方法，通过红外控制信号无线控制药剂注入和微米级LED发射预设波长光束，利用热胀原理使得管状药仓内的药剂注入至待节律光动力治疗部位，利用两个第二磁铁、两个第三磁铁和四个第一磁铁通过磁吸力连接管状药仓主体和底座主体，使得光电注射器可拆卸，注射的药剂可替换和补充。The beneficial effects of the present invention are as follows: the present invention provides a method for using a self-powered, wireless, and detachable optical medicine injector, which wirelessly controls the injection of medicine and the emission of a preset wavelength light beam by a micron-level LED through an infrared control signal, utilizes the principle of thermal expansion to inject the medicine in the tubular medicine chamber into the site to be treated with rhythmic photodynamic therapy, and utilizes two second magnets, two third magnets, and four first magnets to connect the tubular medicine chamber body and the base body through magnetic attraction, so that the photoelectric injector is detachable and the injected medicine can be replaced and supplemented.
针对于本发明还具有的其他优势将在后续的实施例中进行更细致的分析。Other advantages of the present invention will be analyzed in more detail in subsequent embodiments.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
为了更清楚地说明本发明实施例的技术方案，下面将对实施例中所需要使用的附图作简单地介绍，应当理解，以下附图仅示出了本发明的某些实施例，因此不应被看作是对范围的限定，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他相关的附图。In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.
图1为本发明实施例1中自供电、无线、可拆卸的光药注射器的结构示意图。FIG1 is a schematic diagram of the structure of a self-powered, wireless, detachable optical medicine injector in Example 1 of the present invention.
图2为本发明实施例2中自供电、无线、可拆卸的光药注射器的制备方法的步骤流程图。FIG2 is a flow chart showing the steps of a method for preparing a self-powered, wireless, detachable optical medicine injector in Example 2 of the present invention.
图3为本发明实施例3中自供电、无线、可拆卸的光药注射器的使用方法的步骤流程图。FIG3 is a flowchart showing the steps of a method for using a self-powered, wireless, detachable optical medicine injector in Embodiment 3 of the present invention.
图4为本发明实施例3中小鼠乳腺癌移植瘤试验结果对照图。FIG. 4 is a comparison chart of the test results of breast cancer transplanted tumors in mice in Example 3 of the present invention.
其中：101、控制电路单元；102、电路板；103、镍铬加热电极；104、热膨胀层；201、管状药仓主体；202、第二磁铁；203、第三磁铁；301、底座主体；302、第一磁铁；303、管状流体通道；304、银线；305、微米级LED。Among them: 101, control circuit unit; 102, circuit board; 103, nickel-chromium heating electrode; 104, thermal expansion layer; 201, tubular medicine chamber body; 202, second magnet; 203, third magnet; 301, base body; 302, first magnet; 303, tubular fluid channel; 304, silver wire; 305, micron-level LED.
具体实施方式DETAILED DESCRIPTION
下面将结合本发明实施例中附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。通常在此处附图中描述和示出的本发明实施例的组件可以以各种不同的配置来布置和设计。因此，以下对在附图中提供的本发明的实施例的详细描述并非旨在限制要求保护的本发明的范围，而是仅仅表示本发明的选定实施例。基于本发明的实施例，本领域技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the 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 generally described and shown in the drawings here can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present invention provided in the drawings is not intended to limit the scope of the claimed invention, but merely represents the selected embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present invention.
实施例1Example 1
如图1所示，在本发明的一个实施例中，本发明提供一种自供电、无线、可拆卸的光药注射器，包括植入底座、与植入底座连接的可更换注射执行器，以及与可更换注射执行器均连接的自供电模块；As shown in FIG1 , in one embodiment of the present invention, the present invention provides a self-powered, wireless, detachable optical medicine injector, comprising an implant base, a replaceable injection actuator connected to the implant base, and a self-powered module connected to both the replaceable injection actuators;
所述自供电模块，用于将机械能转换为电能，为植入底座发射预设波长的光束供电，以及为可更换注射执行器基于热胀原理推送药剂供电；The self-powered module is used to convert mechanical energy into electrical energy, to provide power for the implant base to emit a light beam of a preset wavelength, and to provide power for the replaceable injection actuator to push the medicine based on the principle of thermal expansion;
所述自供电模块包括拱形不锈钢片，以及与拱形不锈钢片固定连接的锆钛酸铅压电陶瓷；将固定有锆钛酸铅压电陶瓷的不锈钢片设置于人的足跟部位，在人体运动、行走时即可提供机械能；自供电模块将采集到的机械能转化为电能供电。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 set on the heel of a person to provide mechanical energy when the person moves or walks; the self-powered module converts the collected mechanical energy into electrical energy for power supply.
所述植入底座，用于将药剂注射入待治疗部位，并对待进行节律光动力治疗部位发射预设波长的光束，驱动光敏剂对肿瘤细胞进行节律光动力治疗。The implant base is used to inject the medicine into the part to be treated, and emit a light beam of a preset wavelength to the part to be treated with rhythmic photodynamic therapy, so as to drive the photosensitizer to perform rhythmic photodynamic therapy on tumor cells.
本实施例中优选采用的药剂为光敏剂卟啉，光束的预设波长为470nm，光照强度为2433勒克斯，通过470nm波长的光束能够激发光敏剂卟啉产生活性氧ROS，进而杀死肿瘤细胞，治疗癌症。在面对不同类型的肿瘤细胞以及在不同的治疗环境中时，药剂与光束的波长是可针对性选择、调整或替换的。The preferred agent used in this embodiment is photosensitizer porphyrin, the preset wavelength of the light beam is 470nm, and the light intensity is 2433 lux. The light beam with a wavelength of 470nm can excite the photosensitizer porphyrin to produce 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 agent and the light beam can be selected, adjusted or replaced in a targeted manner.
所述植入底座包括底座主体301、90°间隔固定嵌入底座主体301的四个第一磁铁302、一端沿底座主体301下侧穿射于底座主体301中心的管状流体通道303、设置于管状流体通道303另一端外侧的微米级LED305，以及将微米级LED305与两个对称设置的第一磁铁302连接导通的银线304。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 extending along the lower side of the base body 301 and extending through the center of the base body 301, a micrometer-sized LED 305 arranged on the outside of the other end of the tubular fluid channel 303, and a silver wire 304 connecting the micrometer-sized LED 305 to the two symmetrically arranged first magnets 302.
所述植入底座的结构尺寸为：The structural dimensions of the implant base are:
所述底座主体301的直径为10mm，厚度为1mm；所述管状流体通道303的直径为5mm，厚度为30μm；所述四个第一磁铁302的直径均为1mm，厚度均为1mm；The base body 301 has a diameter of 10 mm and a thickness of 1 mm; the tubular fluid channel 303 has a diameter of 5 mm and a thickness of 30 μm; the four first magnets 302 have diameters of 1 mm and thicknesses of 1 mm;
所述管状流体通道303采用管状聚酰亚胺薄膜。The tubular fluid channel 303 is made of a tubular polyimide film.
所述可更换注射执行器，用于存储药剂，以及接收红外控制信号后，通过热胀原理将存储的药剂推送入植入底座；The replaceable injection actuator is used to store medicine and, after receiving an infrared control signal, push the stored medicine into the implant base through the principle of thermal expansion;
所述可更换注射执行器包括与底座主体301相对设置的管状药仓主体201、相对第一磁铁302固定嵌入管状药仓主体201中的两个第二磁铁202和两个第三磁铁203、与药仓主体上端开口对应连接电路加热子模块；所述管状药仓主体201的一端与底座主体301通过两个第二磁铁202和两个第三磁铁203与四个第一磁铁302间的磁吸力连接。所述两个第二磁铁202的一端通过焊接与控制电路单元101连接。The replaceable injection actuator includes a tubular medicine chamber body 201 arranged opposite to the base body 301, two second magnets 202 and two third magnets 203 fixedly embedded in the tubular medicine chamber body 201 relative to the first magnet 302, and a circuit heating submodule connected to the upper opening of the medicine chamber body; one end of the tubular medicine chamber body 201 is connected to the base body 301 through the magnetic attraction between the two second magnets 202 and the 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.
所述控制电路单元101用于接收自供电模块的电能和红外控制信号，在自供电模块提供的电能供能的基础上，通过红外控制信号控制镍铬加热电极103发热，以及通过两个第二磁铁202、与两个第二磁铁202相对的两个第一磁铁302和银线304控制微米级LED305发射预设波长的光束。所述控制电路单元101采用型号为WL2815的低落差线性稳压器对自供电模块产生的电能进行稳压，WL2815线性稳压器在低陶瓷电容器成本的条件下保证了稳定输出电流，并提高效率以延长自供电模块的供电寿命；所述控制电路单元101采用型号为TSOP37438的红外接收器接收外部遥控的红外控制信号；所述控制电路单元101采用型号为ATtiny84的微控制器接收自供电模块经稳压后的电能，以及处理红外接收器接收的红外控制信号，以实现控制镍铬加热电极103发热推送药物和控制微米级LED305发射预设波长的光束。The control circuit unit 101 is used to receive the electric energy and infrared control signal from the self-powered module, and based on the electric energy provided by the self-powered module, controls the heating of the nickel-chromium heating electrode 103 through the infrared control signal, and controls the micron-sized LED 305 to emit a light beam of a preset wavelength through two second magnets 202, two first magnets 302 opposite to the two second magnets 202, and the silver wire 304. The control circuit unit 101 adopts a low-drop linear regulator of model WL2815 to stabilize the electric energy generated by the self-powered module. The WL2815 linear regulator ensures a stable output current under the condition of low ceramic capacitor cost, and improves efficiency to extend the power supply life of the self-powered module; the control circuit unit 101 adopts an infrared receiver of model TSOP37438 to receive infrared control signals from an external remote control; the control circuit unit 101 adopts a microcontroller of model ATtiny84 to receive the stabilized electric energy of the self-powered module, and processes the infrared control signal received by the infrared receiver, so as to control the nickel-chromium heating electrode 103 to generate heat and push the medicine and control the micron-level LED 305 to emit a light beam of a preset wavelength.
所述电路加热子模块包括电路板102、设置于电路板102上方的控制电路单元101，以及设置于电路板102下方的镍铬加热电极103；所述镍铬加热电极103包裹于热膨胀层104内，形成热驱动流体泵；所述热驱动流体泵与管状药仓主体201连接；所述热驱动流体泵用于将管状药仓主体201内的药物推送至底座主体301内。The circuit heating submodule 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 heat-driven fluid pump; the heat-driven fluid pump is connected to the tubular medicine chamber body 201; the heat-driven fluid pump is used to push the medicine in the tubular medicine chamber body 201 into the base body 301.
可更换注射执行器的结构尺寸为：The structural dimensions of the replaceable injection actuator are:
所述电路板102的厚度为0.6mm；所述管状药仓主体外部直径为10mm，厚度为3mm，容量约为30微升；所述两个第二磁铁202的直径为1mm，高度为2.6mm；所述两个第三磁铁203的直径为1mm高度为2mm。The thickness of the circuit board 102 is 0.6mm; the outer diameter of the tubular medicine chamber body is 10mm, the thickness is 3mm, and the capacity is about 30 microliters; the diameter of the two second magnets 202 is 1mm, and the height is 2.6mm; the diameter of the two third magnets 203 is 1mm and the height is 2mm.
实施例2Example 2
如图2所示，在实施例1的基础上，在本发明的另一个实施例中，本发明还提供一种自供电、无线、可拆卸的光药注射器的制备方法，包括如下步骤：As shown in FIG2 , based on Example 1, in another embodiment of the present invention, the present invention further provides a method for preparing a self-powered, wireless, detachable optical medicine injector, comprising the following steps:
S1、通过三维打印得到外径相同的底座主体301和管状药仓主体201，并利用环氧树脂胶将四个第一磁铁302均匀间隔、对称固定、贯穿嵌入底座主体301中；S1. Obtain a base body 301 and a tubular medicine chamber body 201 with the same outer diameter by 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;
S2、利用环氧树脂胶将管状聚酰亚胺薄膜一端穿设于底座主体301一侧中心作为管状流体通道303；S2, using epoxy resin glue to penetrate one end of the tubular polyimide film into the center of one side of the base body 301 as a tubular fluid channel 303;
S3、利用环氧树脂胶将聚酰亚胺作为基底的微米级LED305固定连接至管状聚酰亚胺薄膜的另一端外侧，并利用银线304将微米级LED305与两个第一磁铁302连接导通；S3, using epoxy resin glue to fix the micron-sized LED 305 with polyimide as the base to the outer side of the other end of the tubular polyimide film, and using silver wire 304 to connect the micron-sized LED 305 to the two first magnets 302;
S4、利用环氧树脂胶将相对四个第一磁铁302对称设置的两个第二磁铁202和两个第三磁铁203固定嵌入管状药仓主体201中；S4. Use epoxy resin glue to fix and embed two second magnets 202 and two third magnets 203 symmetrically arranged relative to the four first magnets 302 into the tubular medicine chamber body 201;
S5、将电路加热子模块中的控制电路单元101设置于电路板102的一侧，并将电路加热子模块中的镍铬加热电极103设置于电路板102的另一侧，其中，控制电路单元101与自供电模块连接；S5, disposing the control circuit unit 101 in the circuit heating submodule on one side of the circuit board 102, and disposing the nickel-chromium heating electrode 103 in the circuit heating submodule on the other side of the circuit board 102, wherein the control circuit unit 101 is connected to the self-power supply module;
S6、将膨胀微粒添加至聚二甲基硅氧烷与固化剂的混合物中，并搅拌均匀，形成热膨胀层104；S6, adding the expandable particles to the mixture of polydimethylsiloxane and the curing agent, and stirring evenly to form a thermal expansion layer 104;
作为优选方案，本实施例中添加的膨胀微粒的型号为：Expancel 031 DU 40,AkzoNobel；As a preferred solution, the model of the expanded particles added in this embodiment is: Expancel 031 DU 40, AkzoNobel;
所述热膨胀层104采用弹性体和固化剂比例为10:1的聚二甲基硅氧烷，以及膨胀微球，并按质量比2:1进行混合得到；The thermal expansion layer 104 is made of polydimethylsiloxane with an elastomer and a curing agent in a ratio of 10:1, and expandable microspheres, which are mixed in a mass ratio of 2:1;
S7、利用热膨胀层104包裹镍铬加热电极103，形成热驱动流体泵；S7, using the thermal expansion layer 104 to wrap the nickel-chromium heating electrode 103 to form a heat-driven fluid pump;
S8、将带有热驱动流体泵的电路加热子模块与管状药仓主体201的一端连接，并将两个第二磁铁202的一端与控制电路单元101焊接，并利用环氧树脂胶将热膨胀层104与管状药仓主体201的一端连接处密封；S8, connecting the circuit heating submodule with the heat-driven fluid pump to one end of the tubular medicine chamber body 201, welding one end of the two second magnets 202 to the control circuit unit 101, and sealing the connection between the heat expansion layer 104 and one end of the tubular medicine chamber body 201 with epoxy resin glue;
S9、利用第二磁铁202和第三磁铁203与第一磁铁302间的磁吸力，将管状药仓主体201的一端与底座主体301另一侧磁吸连接，使得两个第二磁铁202、与两个第二磁铁202相对的两个第一磁铁302和银线304将控制电路单元和微米级LED305导通，完成自供电、无线、可拆卸的光药注射器的制备。S9. Utilize the magnetic attraction between the second magnet 202 and the third magnet 203 and the first magnet 302 to magnetically connect one end of the tubular medicine chamber 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 turn on the control circuit unit and the micron-sized LED 305, thereby completing the preparation of a self-powered, wireless, and detachable optical medicine injector.
本实施例中所有元件均采用环氧树脂进行密封和连接，并在连接底座主体301与人体组织接触的部分采用聚二甲基硅氧烷封装，防止短路并满足生物相容性。In this embodiment, all components are sealed and connected with epoxy resin, and the portion where the base body 301 contacts human tissue is encapsulated with polydimethylsiloxane to prevent short circuit and meet biocompatibility.
实施例3Example 3
如图3所示，在实施例1和实施例2的基础上，在本发明的另一个实施例中，本发明提供一种自供电、无线、可拆卸的光药注射器的使用方法，包括如下步骤：As shown in FIG3 , based on Example 1 and Example 2, in another embodiment of the present invention, the present invention provides a method for using a self-powered, wireless, detachable optical medicine injector, comprising the following steps:
A1、将植入底座的管状流体通道303植入待进行节律光动力治疗部位；A1. Implant the tubular fluid channel 303 of the implant base into the site to be treated with rhythmic photodynamic therapy;
A2、添加药剂至管状药仓主体201，并利用两个第二磁铁202和两个第三磁铁203与四个第一磁铁302间的磁吸力，将管状药仓主体201与底座主体301磁吸连接，实现可更换注射执行器与植入底座的连接；A2. Add medicine to the tubular medicine chamber body 201, and use the magnetic attraction between the two second magnets 202 and the two third magnets 203 and the four first magnets 302 to magnetically connect the tubular medicine chamber body 201 with the base body 301, so as to achieve the connection between the replaceable injection actuator and the implant base;
A3、利用自供电模块获取人活动的机械能，并将机械能转换为电能，且将电能传输至电路加热子模块和微米级LED；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 submodule and the micron-level LED;
A4、利用红外信号发送器控制电路加热子模块中的控制电路单元101驱动镍铬加热电极103加热；A4, using the infrared signal transmitter to control the control circuit unit 101 in the circuit heating submodule to drive the nickel-chromium heating electrode 103 for heating;
A5、利用红外信号发送器控制电路加热子模块中的控制电路单元101通过两个第二磁铁202、与两个第二磁铁202相对的两个第一磁铁302和银线304控制微米级LED305发射预设波长的光束；A5. Using the infrared signal transmitter to control the control circuit unit 101 in the circuit heating submodule to control the micron-sized LED 305 to emit a light 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;
A6、利用镍铬加热电极103对热膨胀层104加热，通过热胀原理将药剂沿管状药仓主体201经底座主体301和管状流体通道303推送至待进行节律光动力治疗部位，进行节律光动力治疗。A6. Use the nickel-chromium heating electrode 103 to heat the thermal expansion layer 104, and push the medicine along the tubular medicine chamber body 201 through the base body 301 and the tubular fluid channel 303 to the site to be treated with rhythmic photodynamic therapy through the principle of thermal expansion, so as to perform rhythmic photodynamic therapy.
本实施例中发射的光束为波长为470nm的蓝光，药剂为型号为5,10,15,20-四(4-三甲氨基)苯基卟啉四甲苯磺酸盐；开启蓝光照射激活卟啉反应产生活性氧ROS从而杀死附近肿瘤细胞，实现了局部的光动力治疗；当可更换模块的药物和能量耗尽后，可简单快速更换新的执行器模块进行下次治疗。In this embodiment, the emitted light beam is blue light with a wavelength of 470nm, and the drug is 5,10,15,20-tetrakis(4-trimethylamino)phenylporphyrin tetratoluenesulfonate; turning on the blue light irradiation activates the porphyrin reaction to produce reactive oxygen species ROS, thereby killing nearby tumor cells, achieving local photodynamic therapy; when the drug and energy of the replaceable module are exhausted, the new actuator module can be simply and quickly replaced for the next treatment.
在无线控制局部给药和光刺激抗肿瘤实验中，采用本发明提供的自供电、无线、可拆卸的光药注射器进行小鼠乳腺癌移植瘤试验，试验包括如下步骤：In the wireless controlled local drug delivery and light stimulation anti-tumor experiment, the self-powered, wireless, detachable light drug injector provided by the present invention was used to carry out a mouse breast cancer transplant tumor experiment, and the experiment included the following steps:
B1、获取若干小鼠乳腺癌模型；B1. Obtain several mouse breast cancer models;
所述小鼠乳腺癌模型的构建方法包括如下步骤：The method for constructing the mouse breast cancer model comprises the following steps:
B11、采集6～8周龄雌性Balb/c小鼠（体重～20克）中对数生长的肿瘤细胞；B11, collect logarithmically growing tumor cells from 6- to 8-week-old female Balb/c mice (weight ∼20 g);
B12、将采集的肿瘤细胞置于无血清基质10毫升中，并在1500转/分下离心3分钟，离心结束后连续洗3次，且用无血清基质混匀，得到培养基；B12, placing the collected tumor cells in 10 ml of serum-free matrix, and centrifuging at 1500 rpm for 3 minutes. After the centrifugation, wash three times in succession, and mix with serum-free matrix to obtain culture medium;
B13、对培养基用计数器计算肿瘤细胞数量，并将培养基中4T1-luc乳腺癌细胞密度调至5×106个/毫升，得到待接种肿瘤细胞培养液；B13, counting the number of tumor cells in the culture medium with a counter, and adjusting the density of 4T1-luc breast cancer cells in the culture medium to 5×106 cells/ml to obtain the tumor cell culture fluid to be inoculated;
B14、将待接种肿瘤细胞培养液接种至若干只小鼠右侧大腿皮下，七日后得到扪及肿瘤小结节的若干小鼠乳腺癌模型；B14, inoculating the culture fluid of the tumor cells to be inoculated into the subcutaneous tissue of the right thigh of several mice, and obtaining several mouse breast cancer models with palpable tumor nodules after seven days;
B2、分别设置对照组CTRL、卟啉组POR、光照组LED和节律光动力治疗组mPDT对小鼠乳腺癌模型进行治疗；B2. The control group CTRL, the porphyrin group POR, the light group LED and the rhythmic photodynamic therapy group mPDT were set up to treat the mouse breast cancer model;
所述对照组CTRL不进行任何治疗；The control group CTRL did not receive any treatment;
所述卟啉组POR第7天开始在肿瘤附近注射卟啉25微升（2毫克/毫升），每天1次，共治疗2周；The porphyrin group POR was injected with 25 μl (2 mg/ml) of porphyrin near the tumor starting on day 7, once a day for a total of 2 weeks;
所述光照组LED第8天开始用植入的器件蓝光照射肿瘤2小时，每天一次，共治疗2周；The illumination group LED began 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;
所述光动力治疗组PDT第7天开始用本发明提供的自供电、无线、可拆卸的光药注射器注射卟啉25微升（2毫克/毫升），并在24小时后的第8天用470nm波长的蓝光照射肿瘤2小时，每天一次，共治疗2周；The photodynamic therapy group began to inject 25 μl (2 mg/ml) of porphyrin using the self-powered, wireless, detachable photomedicine injector provided by the present invention on the 7th day of PDT, and irradiated the tumor with 470 nm wavelength blue light for 2 hours on the 8th day after 24 hours, once a day, for a total of 2 weeks of treatment;
B3、在每天进行小鼠治疗实验之前测量各小鼠乳腺癌模型中每只小鼠的肿瘤大小并绘制肿瘤生长曲线，并观察小鼠存活周期；B3. Before conducting the mouse treatment experiment every day, measure the tumor size of each mouse in each mouse breast cancer model, draw a tumor growth curve, and observe the mouse survival cycle;
如图4所示，节律光动力治疗组mPDT的小鼠肿瘤增长速度明显低于对照组CTRL、卟啉组POR和光照组LED，明显存在统计学差异，且所有小鼠在实验过程中没有出现进食和饮水的异常，体重无异常变化。As shown in Figure 4, 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 group LED, with obvious statistical differences. All mice did not show abnormalities in eating and drinking during the experiment, and there was no abnormal change in body weight.
以上所述，仅为本发明的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本发明的保护范围之内。The above description is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311116180.5ACN118403256B (en) | 2023-08-31 | 2023-08-31 | Self-powered, wireless and detachable photo-drug injector and preparation method thereof |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311116180.5ACN118403256B (en) | 2023-08-31 | 2023-08-31 | Self-powered, wireless and detachable photo-drug injector and preparation method thereof |
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| CN202311116180.5AActiveCN118403256B (en) | 2023-08-31 | 2023-08-31 | Self-powered, wireless and detachable photo-drug injector and preparation method thereof |
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