WO2009030109A1 - Dispositif à induction pour thérapie et diagnostic photodynamiques - Google Patents

Dispositif à induction pour thérapie et diagnostic photodynamiques Download PDF

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Publication number
WO2009030109A1
WO2009030109A1 PCT/CN2008/001538 CN2008001538W WO2009030109A1 WO 2009030109 A1 WO2009030109 A1 WO 2009030109A1 CN 2008001538 W CN2008001538 W CN 2008001538W WO 2009030109 A1 WO2009030109 A1 WO 2009030109A1
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WO
WIPO (PCT)
Prior art keywords
light
electrically connected
treatment according
photodynamic diagnosis
sensing device
Prior art date
Application number
PCT/CN2008/001538
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English (en)
French (fr)
Inventor
Shyh Liang Lou
Tzong Rong Ger
Yih Chih Hsu
Original Assignee
Shyh Liang Lou
Tzong Rong Ger
Yih Chih Hsu
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Shyh Liang Lou, Tzong Rong Ger, Yih Chih Hsu filed Critical Shyh Liang Lou
Priority to US12/675,896 priority Critical patent/US20100305666A1/en
Publication of WO2009030109A1 publication Critical patent/WO2009030109A1/zh

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0601—Apparatus for use inside the body
    • A61N2005/0612—Apparatus for use inside the body using probes penetrating tissue; interstitial probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
    • A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
    • A61N2005/0645—Applicators worn by the patient
    • A61N2005/0647—Applicators worn by the patient the applicator adapted to be worn on the head

Definitions

  • the present invention relates to an inductive device, and more particularly to an inductive device for use in photodynamic diagnosis and treatment.
  • PDT photodynamic therapy
  • One of the most eye-catching medical technologies One of the most eye-catching medical technologies.
  • Photodynamic therapy firstly injects or smears a light-sensitive agent to a patient, and gives a light-sensitive agent to the tumor cell for a period of time, and then emits a specific wavelength of light through the light irradiation device to excite the light-sensitive agent to generate a photo-activated reaction. , causing tumor cell cytotoxicity, thereby eliminating tumor cells.
  • photodynamic therapy is limited by the lack of light source penetration of the photodynamic illumination device, so it is mostly used for the treatment of human surface organs, such as skin cancer, oral cancer, etc., and the illumination device directly irradiates the affected part of the human body to achieve Eliminate the therapeutic effect of tumor cells.
  • the light of the intracranial tissue is irradiated by the optical fiber exposed to the head, It is an invasive treatment method.
  • the long-term treatment process is a great burden on the patient's physical or psychological. It not only causes considerable inconvenience to the patient's normal life, but also has a cranial cavity that is susceptible to bacterial infection. Dangerous.
  • the light source of the photodynamic illumination device mostly uses a high-power light-emitting element, such as a high-energy light-emitting body such as a laser, to greatly shorten the time required for the light irradiation treatment.
  • a high-power light-emitting element such as a high-energy light-emitting body such as a laser
  • the present invention provides an inductive device for photodynamic diagnosis and treatment, which is used on a living body to excite a photo-sensitive agent in the living body to generate a photochemical reaction
  • the sensing device comprising an emitter And a light illuminator is disposed in the living body, the light illuminator has a first induction coil for receiving the wireless signal; a control circuit, electrical Connected to the first inductive coil and convert the wireless signal into a driving signal; and a light emitting element electrically connected to the control circuit, the light emitting element being driven by the driving signal to emit light to make the light sensitive agent Produces a photochemical reaction.
  • the invention further provides an inductive device applied to photodynamic diagnosis and treatment, thereby improving the prior art photodynamic illumination device capable of performing disease diagnosis in the human body, and it is known that the photodynamic illumination device must be installed outside the human body.
  • the fiber optic lead causes discomfort and inconvenience to the patient during the treatment period, and the well-known photodynamic therapy cannot simultaneously have the physical and mental burden of the patient, and the limitation of obtaining better therapeutic effects.
  • the invention further provides a light illuminator for photodynamic diagnosis and treatment, which is arranged in a living body, and the light illuminator emits a light through a wireless signal penetrating the biological surface layer to excite light in the living body.
  • Sensitive agent produces a photochemical reaction
  • the light illuminator The method includes: a first induction coil for receiving the wireless signal; a control circuit electrically connected to the first induction coil, and converting the wireless signal into a driving signal; and a light emitting component electrically connected The control circuit, the light-emitting element is driven by the driving signal to emit light to cause a photochemical reaction of the light-sensitive agent.
  • the sensing device for photodynamic diagnosis and treatment disclosed in the present invention is used for the treatment of a living body to stimulate a photochemical reaction of a light-sensitive agent injected into a living body.
  • the sensing device includes a transmitter and a light illuminator that can be implanted into the living body.
  • the light illuminator has a first induction coil, a control circuit electrically connected to the first induction coil, and an electrical connection to the control circuit. Light-emitting elements.
  • the transmitter is configured to emit a wireless signal that penetrates the surface of the biological body.
  • the first induction coil of the light illuminator converts the wireless signal into a driving signal through the control circuit, so that the illuminating element emits a wavelength matching the light sensitive agent. Light to cause a photochemical reaction of the light-sensitive agent.
  • the effect of the invention is that the emitter outside the body emits a light by means of wireless energy transmission, and the light illuminator disposed in the living body electromagnetically emits a light, and the light-sensitive agent is excited to generate a reaction for diagnosis or treatment of the living body. .
  • the invention not only improves the known photodynamic therapy device which is treated by wired transmission, but also has various side effects, discomfort, and inconvenience in daily life during the treatment, and also has the health and safety of the living body. And the efficacy of better therapeutic effects.
  • FIG. 1A is a schematic plan view of an inductive device of the present invention
  • 1B is a side view of the sensing device of the present invention applied to a human body
  • FIG. 2 is a circuit block diagram of a transmitter of the present invention
  • 3A is a perspective view of a light irradiator of the present invention.
  • 3B is a circuit block diagram of a light illuminator of the present invention
  • 3C is a circuit block diagram of a light illuminator having a secondary battery of the present invention
  • FIG. 4 is a measurement diagram of a penetration scatter rate of a light of different optical powers passing through a scattering element according to the present invention
  • FIG. 5 is a circuit block diagram of the image taking device of the present invention.
  • 6A is a view showing the application of the sensing device of the present invention to the diagnosis and treatment of human cranial tissue
  • 6B is a side view showing the application of the sensing device of the present invention to the diagnosis and treatment of human oral tissues
  • 6C is a view showing the application of the sensing device of the present invention to the diagnosis and treatment of a human thoracic organ
  • Figure 6D is a side view showing the application of the sensing device of the present invention to the diagnosis and treatment of a human abdominal cavity;
  • 6E is a diagnosis and treatment of an inductive device of the present invention applied to a human pelvic organ.
  • the reference numerals are as follows:
  • the sensing device for photodynamic diagnosis and treatment disclosed in the present invention performs operation by wirelessly transmitting energy, and the wireless transmission energy mode includes but is not limited to radio frequency (RF). Or wireless transmission technology such as microwave transmission.
  • RF radio frequency
  • RF radio frequency transmission
  • the drawings are provided for reference and description only, and are not intended to limit the invention.
  • the sensing device 100 for photodynamic diagnosis and treatment disclosed in the present invention is used on a living body 200 for stimulating a light-sensitive agent (not shown) injected into the body of the living body 200.
  • the photochemical reaction is generated, and the cell tissue of the organism 200 is treated, for example, a malignant tumor, a black spot, a skin whitening, a scar, a fundus macular lesion, or a development indicating a specific cell tissue or the like for treating a defective cell.
  • the sensing device described in the embodiment is used to treat tumor cells in the human body as an example of the embodiment, and those skilled in the art can apply to the actual needs of the technology.
  • the diagnosis and treatment of various biological species are not limited to the examples of the present invention.
  • the sensing device of the present invention includes a transmitter 1 10 and a light illuminator 120 (see figure
  • the transmitter 110 has a second inductive coil 1 124 for emitting a radio frequency signal, and the radio frequency signal can pass through the surface layer of the living body 200, such as skin, fat, muscle and other surface layers of the human body. Transfer to the body of the organism 200.
  • the light illuminator 120 disposed in the body of the living body 200 has a first induction coil 121, a control circuit 122 electrically connected to the first induction coil 121, and a light-emitting element 123 electrically connected to the control circuit 122.
  • the first induction coil 121 is configured to receive the radio frequency signal emitted by the transmitter 110, and convert the radio frequency signal into a driving signal having a voltage through the control circuit 122. Generate a current.
  • the light-emitting element 123 can be a light-emitting diode or a light source generating device such as a laser emitter. After receiving the current generated by the driving signal, the light-emitting element 123 emits a light of a specific wavelength matched to the light-sensitive agent to excite the light-sensitive agent. Photochemical reaction.
  • the present invention uses a 5-ALA aminolevulinic acid and a hematoprophine-based light-sensitive agent, for example, Photofrin as an example, and a technician skilled in the art of photodynamic therapy can be based on actual conditions.
  • the use requirements, corresponding to the use of different light-sensitive agents, coupled with light-matching light-activated excitation, are not limited by the embodiments of the present invention.
  • the preferred activation wavelength of 5-ALA and Photofrin is about 630 nm, and is matched with the red light source emitted by the light-emitting element 123 to stimulate the photochemical reaction of the 5-ALA and Photofrin agents to treat brain cancer and esophageal cancer in the biological body 200.
  • tumor cells such as gastrointestinal cancer, bladder cancer, or lung cancer. Since 5-ALA light-sensitive agents have the advantages of low toxicity, fast metabolism, and light-shielding time of only 1 to 2 days, they are widely used in medical clinical treatment.
  • the light-sensitive agent needs to receive a certain intensity of energy to be excited to react. Therefore, the present invention can accurately control the treatment time of the treatment process by controlling the light power of the light-emitting element 123 or the light irradiation time and the like, and avoid the biological activity. 200 discomfort and side effects caused by excessive optical power.
  • the transmitter 110 of the present invention includes a drive circuit 111 and an oscillating circuit 112.
  • the driving circuit 111 has a waveform generator 1111, a frequency divider 1112 electrically connected to the waveform generator 1111, an inverter 1 113 electrically connected to the frequency divider 1112, and two electrical connections to the inverter.
  • the modulators 1114 and 2 of the 1113 are electrically connected to the class D power amplifier 1 115 of the modulator 1114 and the transformer 1116 electrically connected to the class D power amplifier 1115, respectively.
  • the waveform generator 1111 is configured to generate a square wave, the square wave is adjusted to a specific range of carrier frequency by the frequency divider 1112, and the adjusted square wave is transmitted to the second modulator 1114 through the inverter 1113.
  • the square wave signal is transmitted to the transformer 1 116 via the gain of the power amplifier, and is converted by the second transformer 1 116 so that the positive wave signal is outputted as a control signal in the form of a sine wave and a negative sine wave, respectively.
  • the oscillating circuit 112 of the transmitter 110 includes a power source 1 121, two transistor switches 1 122 electrically connected to the power source 1 121, and a resonant circuit 1 123 electrically connected to the transistor switch 1 122.
  • the resonant circuit 1 123 has an electric
  • the second inductive coil 1 124 is connected to the transistor switch 1 122, and the capacitor 1 125 is electrically connected to the second inductive coil 1 124.
  • the two-transistor switch 1 122 is configured to receive the control signals of the transformers 1 1 16 and to perform the opening or closing operations of the other transistor switches 1 122, respectively.
  • the power source 1 121 continuously conducts current into the resonant circuit 1 123 according to one of the transistor switches 1 122 that is turned on, and the second induction coil 1124 generates and emits a wireless signal through the charging and discharging action of the capacitor 1 125.
  • An induction coil 121 forms a magnetic field inductive coupling.
  • the control circuit 122 of the illuminator 120 has a rectifier 1221 and a voltage regulator 1222 electrically connected to the rectifier 1221 and the illuminating element 123.
  • the control circuit 122 converts the magnetic wireless signal received by the first induction coil 121 into an electrical driving signal, and the driving signal passes through the function of the rectifier 1221 to convert the originally bidirectional oscillating driving signal into a one-way oscillating signal, and A certain range of output values is maintained by the regulator 1222 to prevent the light-emitting element 123 from being damaged due to the unstable voltage value of the drive signal.
  • the rectifier 1221 disclosed in the present invention may be a half-wave rectifier, a full-wave rectifier, or a rectifier of any form of a bridge rectifier.
  • the technology has been known to those skilled in the art, so the inventor This is not to be described separately.
  • the periphery of the light illuminator 120 further has a transparent light transmissive covering material 150 for completely covering the first induction coil 121, the control circuit 122, and the illuminating element 123.
  • the coating material 150 is made of a bio-silica material or a glass material, and has good biocompatibility, and also has excellent insulation and heat dissipation effects, and avoids the light illuminator 120 disposed in the body of the living body 200, which is generated by the operation. Excessive heat can cause discomfort to the creature 200.
  • the light illuminator 120 Since the light illuminator 120 has excellent biocompatibility, the light illuminator 120 can be taken out from the body of the living body 200 after the end of the treatment, or can be placed in the living body 200 for a long time, so as to avoid the inconvenience of re-surgery. And the risks that must be borne.
  • the present invention further includes a scattering element 130 coupled to the light-emitting element 123.
  • the scattering element 130 placed in the body of the living body 200 has good biocompatibility. Sex, does not cause immune rejection of the organism 200.
  • the scattering element 130 of the present invention is a spherical material having an accommodating space therein, and a fluid 140 is filled inside the scattering element 130, for example, a high-scattering fluid 140 such as air, physiological saline, or a mixture of oil and water, wherein The oil-water mixture can be selected from lipoftmdin or intralipid as a fluid 140 for light scattering.
  • Figure 4 of the present invention is an oil-water mixture - lipof mdin as an illustration of the present embodiment, light of different power levels emitted by the light-emitting element 123, passing through the fluid 140 in the scattering element 130 (to 0.12% of the lipoflmdin For example, when it penetrates and scatters outward, the penetration scatter rate of light increases linearly with increasing optical power.
  • the operator can select the appropriate amount of light power according to the actual treatment needs to uniformly irradiate the tissue cells in the body of the organism 200, thereby achieving a highly efficient and effective photodynamic treatment effect.
  • Fig. 4 simultaneously compares the difference in the scattering transmittance of the light-emitting element 123 in the scattering element 130 and the light-emitting element 123 to the surface of the scattering element 130. It is known from the measurement results that the transmittance of the light-emitting element 123 placed in the scattering element 130 is much lower than the scattering rate at which the light-emitting element 123 is attached to the surface of the scattering element 130. Therefore, the present invention is described in the form of a preferred embodiment in which the light-emitting element 123 is coupled to the surface of the scattering element 130.
  • the light sensor 170 may be mounted in the light-emitting element 123 for detecting.
  • the light refracted by the lens of the light-emitting element 123 is used to estimate the light intensity emitted by the light-emitting element 123.
  • the light sensor 170 is electrically connected to the control circuit 122 to detect the intensity of the light emitted by the light-emitting element 123, and transmits an analog signal of the optical power to the control circuit 122 for digital demodulation of the signal, and then by radio frequency (RF) or wireless transmission such as microwave transmission to an external demodulator (not shown) to know the current luminous intensity to assist the medical practitioner in translating the time required for the patient to illuminate.
  • RF radio frequency
  • wireless transmission such as microwave transmission to an external demodulator (not shown) to know the current luminous intensity to assist the medical practitioner in translating the time required for the patient to illuminate.
  • a light sensor (not shown) is disposed outside the living body 200 of the light illuminator 120 to receive the wireless illuminator 120 to feed back its current operating state, for example, whether the illuminating element 123 emits light, and The light power level of the light, etc., allows the medical practitioner to understand the treatment in the body of the living body 200.
  • An image capturing device 180 is mounted in the body. Wherein the image capturing device 180 having a processor 181, and is electrically connected to the processor 181 of the third sensing coil 182, the image capturing device 183, the wireless signal transmitter 184.
  • the third induction coil 182 starts to operate after receiving the wireless signal from the second induction coil 1 124.
  • the image finder 183 passes the light intensity generated by the light 200 through the light.
  • the processor 181 converts to an output signal and transmits it to an external receiver (not shown) via a wireless signal transmitter 184 in a wireless transmission manner such as radio frequency (RF) or microwave, thereby knowing the current internal treatment. situation.
  • RF radio frequency
  • two antennas may be added to the light illuminator 120 to respectively receive and transmit the output signals, so that the image signals are mainly output.
  • the signal is quickly passed to the external receiver.
  • the image capturing device 180 can also be incorporated into the light illuminator 120, without using the third induction coil 182, by sharing the current generated by the control circuit 122 to drive the image finder 183 to operate, so that the device disposed in the body of the living body 200 can be further For streamlining.
  • the light illuminator 120 of the present invention further includes a secondary battery 190 electrically connected to the control circuit 122 and the light-emitting element 123, and the secondary battery 190 has a charge and discharge circuit 191.
  • the driving signal of the control circuit 122 is converted by the rectifier 1221 and the voltage regulator 1222 to charge the secondary battery 190
  • the secondary battery 190 is activated or stopped to supply power to the light-emitting element 123 by external wireless triggering.
  • the light illuminator 120 does not need to be aligned with an external transmitter (not shown) at any time, and the user's action will be unrestricted, and the treatment can be continued.
  • the power output of the secondary battery 190 is started or stopped, and the driving method such as the coupling signal of different frequencies, the internal program code of the microprocessor, or the demodulation of the external signal by the carrier signal technology may be used to the secondary battery 190. Take control.
  • FIGS. 6A to 6E are schematic views showing the application of the sensing device of the present invention to the treatment and diagnosis of organ tissues in various parts of a living being.
  • the sensing device 100 disclosed by the invention can be applied to treat tumors of various parts of the human body 200 (biological body), such as cranial cavity, oral cavity, chest cavity, abdominal cavity, and various organ tissues in the pelvic cavity.
  • the transmitter 110 of the present invention can be fixed to the position of the light illuminator 120 disposed in the body of the human body 200 by a holding or wearing member 160 worn on the human body 200, so that the transmitter 1 10 can be combined with the light illuminator. Between 120 through the radio frequency The method of transmission is treated.
  • the holder 160 has a receiving portion 161 for the transmitter 110 to be fixed therein.
  • the retaining member 160 can be matched with the body 200 to be treated, and is designed in various forms such as a hat, a mask, or a strap to facilitate wearing the position of the human body 200 corresponding to the light irradiator 120.
  • the emitter located outside the body is electromagnetically induced by the light illuminator disposed in the living body through the transmission of the wireless signal, and the light illuminator can emit light of a specific wavelength by the magnetoelectric conversion effect.
  • the matched light-sensitive agent is excited to produce a photochemical reaction for diagnosis or treatment of the organism.
  • the present invention improves the inconvenience of the known photodynamic therapy device in wired transmission and reduces the risk of bacterial infection by the human body.
  • the transmitter of the present invention also enables the patient's action during the treatment process to be unrestricted by the transmitter through the arrangement of the holder, and can precisely control the light power of the light illuminator 120 or the light irradiation time to slow the body treatment. It produces discomfort and at the same time achieves better therapeutic effects.

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Description

应用于光动力诊断与治疗的感应装置 技术领域 本发明涉及一种感应装置， 特别涉及一种应用于光动力诊断与治 疗的感应装置。 背景技术 随着医疗科技及技术的快速发展， 光动力疗法 (photodynamic therapy, PDT)是一种突破传统癌肿瘤治疗方式的先进技术。 配合传统 外科手术切除肿瘤的技术， 光动力治疗是于大部分的癌肿瘤切除后， 再对剩余的肿瘤细胞加以消灭， 以达到最佳的治疗效果。 由于光动力 疗法具有对患者人体的侵害性小、 避免患者免疫功能的失调、 患者于 疗程过后恢复迅速、 可选择性杀死肿瘤细胞， 而不伤害到正常细胞等 优点， 已成为近年来备受瞩目的医疗技术之一。
光动力疗法先对患者注射或是涂抹光敏感药剂， 并给予一段时间 让光敏感药剂附着于肿瘤细胞上， 再通过光照射装置发出一特定波长 的光线， 以激发光敏感药剂产生一光活化反应， 引发肿瘤细胞毒性， 进而消灭肿瘤细胞。
公知的光动力疗法受限于光动力照射装置的光源穿透力不足， 因 此多半用于人体表层器官的治疗上， 例如皮肤癌、 口腔癌等病症， 照 射装置是直接照射于人体患部， 以达到消灭肿瘤细胞的治疗效果。
近年来， 光动力疗法也开始应用于人体较为深层的器官组织。 以 脑肿瘤治疗为例， 患者在进行外科手术的同时， 会将生物兼容材料一 并植入颅腔内， 并导入一光纤至生物兼容材料内， 以对颅腔内残留的 肿瘤细胞进行光照射治疗， 克服了传统光动力装置无法针对颅内肿瘤 进行治疗的限制。
但对于患者而言，通过外露于头部的光纤进行颅内组织的光照射， 是属于侵入式的治疗方式， 长期的治疗过程， 对于患者的生理或是心 理上都是极大的负担， 不仅对患者的平日生活造成相当多的不便外， 还存在有颅腔容易遭受细菌感染的危险性。
为了减少患者于长时间治疗的不便及所产生的副作用， 公知光动 力照射装置的光源多半会采用高光功率的发光元件， 如激光等高能量 的发光体， 而大幅缩短光照射疗程所需的时间， 以减缓患者的不适感 与细菌感染的风险。
然而， 于近年发表的相关研究报告显示， 以高光功率、 短时间的 光动力治疗方式， 所得到的疗效并不如以低光功率持续照射患部的治 疗效果。 就目前的光动力治疗技术而言， 是无法兼具患者于治疗过程 中的安全性及舒适性， 并且同时获得较佳的治疗成效。 发明内容 鉴于以上的问题， 本发明提供一种应用于光动力诊断与治疗的感 应装置， 使用于一生物上， 用以激发该生物体内的光敏感药剂产生光 化学反应， 该感应装置包括一发射器， 用以发出一穿透该生物表层的 无线信号； 以及一光照射器， 设置于该生物体内， 所述光照射器具有 一第一感应线圈， 用以接收该无线信号； 一控制电路， 电性连接于该 第一感应线圈，并将该无线信号转换为一驱动信号； 以及一发光元件， 电性连接于该控制电路， 该发光元件由该驱动信号驱动而发出光线， 以使该光敏感药剂产生光化学反应。
本发明又提供一种应用于光动力诊断与治疗的感应装置， 由此改 进先前技术的光动力照射装置无法进行人体体内的疾病诊断， 且公知 光动力照射装置必须装设一露出于人体外的光纤导线， 造成患者于治 疗期间内的不适与不便， 以及公知光动力治疗无法同时兼具患者身心 的负担， 与获得较佳治疗成效的限制。
本发明又提供一种应用于光动力诊断与治疗的光照射器， 设置于 一生物体内， 该光照射器通过一穿透该生物表层的无线信号而发出一 光线， 以激发该生物体内的光敏感药剂产生光化学反应， 该光照射器 包括有： 一第一感应线圈， 用以接收该无线信号； 一控制电路， 电性 连接于该第一感应线圈， 并将该无线信号转换为一驱动信号； 以及一 发光元件， 电性连接于该控制电路， 该发光元件由该驱动信号驱动而 发出光线， 以使该光敏感药剂产生光化学反应。
本发明所揭示的应用于光动力诊断与治疗的感应装置， 使用于生 物的治疗上， 以激发注射于生物体内的光敏感药剂产生光化学反应。 感应装置包括有一发射器， 及一可被植入生物体内的光照射器， 光照 射器具有一第一感应线圈、 一电性连接于第一感应线圈的控制电路、 及一电性连接于控制电路的发光元件。
发射器用以发出一穿透生物表层的无线信号， 光照射器的第一感 应线圈接收无线信号后,通过控制电路将无线信号转换为一驱动信号， 令发光元件发出一波长匹配于光敏感药剂的光线， 以使光敏感药剂产 生光化学反应。
本发明的功效在于， 位于生物体外的发射器通过无线能量传输方 式， 以电磁感应设置于生物体内的光照射器发出一光线， 而激发光敏 感药剂产生反应， 以进行生物体的诊断或是治疗。 本发明不仅改善了 以有线传输方式进行治疗的公知光动力治疗装置， 于治疗期间对生物 体所产生的各种副作用、 不适感、 以及平日生活不便的问题， 还同时 具备生物体的健康安全性与较佳治疗效果的功效。
以上的关于本发明内容的说明及以下的实施方式的说明是用以示 范与解释本发明的原理， 并且提供对本发明的权利要求更进一步的解 释。 附图说明 图 1A为本发明感应装置的平面示意图；
图 1B为本发明的感应装置应用于人体上的侧视图；
图 2为本发明发射器的电路方块图；
图 3A为本发明光照射器的立体示意图；
图 3B为本发明光照射器的电路方块图； 图 3C为本发明具有二次电池的光照射器的电路方块图； 图 4为本发明的不同光功率的光线经由散射元件的流体所产生的 穿透散射率的测量图；
图 5为本发明取像装置的电路方块图；
图 6A为本发明的感应装置应用于人体颅腔组织的诊断及治疗的
、 图 6B为本发明的感应装置应用于人体口腔组织的诊断及治疗的 侧视图；
图 6C为本发明的感应装置应用于人体胸腔器官的诊断及治疗的
、 图 6D为本发明的感应装置应用于人体腹腔器官的诊断及治疗的 侧视图； 以及
图 6E为本发明的感应装置应用于人体骨盆腔器官的诊断及治疗 其中: , 附图标记说明如下：
100 感应装置 110 发射器
111 驱动电路 1111波形产生器
1112 分频器 1113 反向器
1114 调变器 1115 功率放大器
1116 变压器 112 震荡电路
1121 电源 1122 晶体管幵关
1123 共振电路 1124 第二感应线圈
1125 电^" 120 光照射器
121 第一感应线圈 122控制电路
1221 整流器 1222 稳压器
123 发光元件 130 散射元件
140 流体 150 包覆材料
160 保持件 161 容设部
170 光传感器 180取像装置
181 处理器 182 第三感应线圈 183 取像器 184无线信号发射器
190 二次电池 191 充放电回路
200 生物 具体实施方式 根据本发明所揭示应用于光动力诊断与治疗的感应装置， 是通过 无线传输能量的方式执行运作， 而此无线传输能量方式包括但不局限 于无线射频 (radio frequency, RF)、 或是微波传输等无线传输技术。 以 下本发明的详细说明中， 将以使用 1MHz左右的无线射频传输 (RF)做 为本发明的最佳实施例。 然而附图仅提供参考与说明用， 并非用以限 制本发明。
如图 1A及图 1B所示，本发明所揭示应用于光动力诊断与治疗的 感应装置 100， 使用于一生物 200上， 用以激发注射于生物 200体内 的光敏感药剂 (图中未示)产生光化学反应， 而对生物 200的细胞组织 进行治疗， 例如恶性肿瘤、 黑斑、 皮肤美白、 伤疤、 眼底黄斑部病变、 或是显影标示特定细胞组织等用以针对不良细胞的治疗方式。
值得注意的是， 本发明于实施例中所述的感应装置， 以治疗人体 内的肿瘤细胞做为实施例的说明， 熟悉该项技术的技术人员， 可根据 实际的使 ^需求， 而应用于各类生物种的诊断与治疗上， 并不以本发 明的实施例为限。
本发明的感应装置包括有一发射器 1 10 及一光照射器 120(见图
1Β) ο 发射器 110具有一第二感应线圈 1 124， 用以发出一无线射频信 号， 且此无线射频信号可穿通过生物 200的表层， 例如人体的皮肤、 脂肪、 与肌肉等表层组织， 而传递至生物 200体内。
设置于生物 200体内的光照射器 120具有一第一感应线圈 121、 一电性连接第一感应线圈 121 的控制电路 122、 一电性连接控制电路 122的发光元件 123。
第一感应线圈 121用以接收发射器 1 10射出的无线射频信号， 并 通过控制电路 122将无线射频信号转换为一具有电压的驱动信号， 以 产生一电流。 发光元件 123可为一发光二极管或是激光发射器等光源 产生装置， 发光元件 123于接收驱动信号所产生的电流后， 发出一匹 配于光敏感药剂的特定波长的光线， 以激发光敏感药剂产生光化学反 应。
本发明以一 5-ALA 氨基乙酰丙酸（5-aminolevulinic acid)及 hematoprophine 类的光敏感药剂， 例如为 Photofrin 做为实施例的说 明，熟悉光动力治疗的该项技术的技术人员，可根据实际的使用需求， 而对应使用不同的光敏感药剂， 并搭配与光敏感药剂相匹配的光线进 行活化激发， 并不以本发明的实施例为限。 5-ALA及 Photofrin等药剂 的较佳活化波长约为 630nm，并搭配发光元件 123所发出的红色光源， 以激发 5-ALA及 Photofrin药剂产生光化学反应， 进而治疗生物 200 体内的脑癌、 食道癌、 胃肠道癌、 膀胱癌、 或是肺癌等肿瘤细胞。 由 于 5-ALA光敏感药剂具备有毒性低、 代谢快、 及避光时间只需 1至 2 天等优点， 而开始广泛应用于医疗临床的治疗上。
光敏感药剂需要接收一定强度的能量才可被激发反应， 因此本发 明可通过控制发光元件 123的光功率大小， 或是光照射时间等参数， 而可精确掌握治疗过程的疗时， 并且避免生物 200因光功率过强所产 生的不适感及副作用。
请参阅图 2的发射器的电路方块图。 如图所示， 本发明的发射器 110包含有一驱动电路 111及一震荡电路 112。驱动电路 111中具有一 波形产生器 1111、 一电性连接于波形产生器 1111的分频器 1112、 一 电性连接于分频器 1112的反向器 1 113、二电性连接于反向器 1113的 调变器 1114、二分别电性连接于调变器 1114的 D类功率放大器 1 115、 及二分别电性连结于 D类功率放大器 1115的变压器 1116。
其中，波形产生器 1111用以产生一方波，此方波通过分频器 1112 调整至一特定范围的载波频率，再通过反向器 1113将调整后的方波传 递至二调变器 1114中，以分别产生二反向的具有固定波宽与振幅的方 波信号。 方波信号经由功率放大器的增益作用， 而传递至变压器 1 116 内，并通过二变压器 1 116的转换，使得正波信号分别以一正弦波与一 负弦波形态的控制信号输出。 发射器 110的震荡电路 112包括有一电源 1 121、二电性连接于电 源 1 121的晶体管开关 1 122、以及一电性连接于晶体管开关 1 122的共 振电路 1 123，共振电路 1 123具有一电性连接于晶体管开关 1 122的第 二感应线圈 1 124， 及一电性连接于第二感应线圈 1 124的电容 1 125。
其中，二晶体管开关 1 122用以分别接收变压器 1 1 16的控制信号， 并相反于另一晶体管开关 1 122执行开启或是关闭的动作。 电源 1 121 根据其中一呈开启状态的晶体管开关 1 122，而持续导通电流至共振电 路 1 123中，第二感应线圈 1124通过电容 1 125的充放电作用， 以产生 并发出一无线信号至第一感应线圈 121， 而形成一磁力场感应耦合。
请参阅图 3A及图 3B的光照射器立体示意图与电路方块图。光照 射器 120的控制电路 122具有一整流器 1221，及一电性连接于整流器 1221与发光元件 123的稳压器 1222。 控制电路 122将第一感应线圈 121 所接收的磁性的无线信号转换为一电性的驱动信号， 驱动信号通 过整流器 1221的作用，以将原本双向震荡的驱动信号转换为单向震荡 的信号，并通过稳压器 1222维持一定的输出值范围， 以避免发光元件 123 因驱动信号的电压值不稳定而造成损坏。 本发明揭示的整流器 1221可为半波整流器、 全波整流器、或是桥式整流器的任一形态的整 流器， 然此一技术己为熟悉该项技术的通常人员所能知悉的设计， 故 发明人于此不另赘叙。
请继续参阅图 3A，光照射器 120外围还具有一透明可透光的包覆 材料 150， 以完全包覆住第一感应线圈 121、 控制电路 122、 及发光元 件 123。 包覆材料 150以生物用硅胶材料或是玻璃材料所制成， 不但 具有良好的生物兼容性， 还具备优良的绝缘与散热效果， 避免设置于 生物 200体内的光照射器 120，因运作所产生的过高热能造成生物 200 的不适感。
由于光照射器 120具备优良的生物兼容性， 因此可选择于疗程结 束后，将光照射器 120自生物 200体内取出；或是长期置放于生物 200 体内， 以免除再次进行外科手术的不便， 以及必须承担的风险性。
如图 1B所示， 本发明还包含有一衔接于发光元件 123的散射元 件 130， 放置于生物 200体内的散射元件 130具备有良好的生物兼容 性， 不致引起生物 200的免疫排斥反应。 本发明的散射元件 130为一 内部具有容置空间的球体材料， 且于散射元件 130内部填装有一流体 140， 例如为空气、 生理食盐水、 或是油水混合物等高散射性的流体 140， 其中油水混合物可选用力保肪宁 (lipoftmdin)或是因特立滋 (intralipid), 以做为光线散射的流体 140。
本发明的图 4以油水混合物-力保肪宁 (lipof mdin)做为本实施例的 说明， 发光元件 123发出的不同功率大小的光线， 通过散射元件 130 内的流体 140(以 0.12%的 lipoflmdin为例)而产生穿透并向外散射， 其 光线的穿透散射率随着光功率的提高而呈线性增加。 操作者可根据实 际治疗需求而选用适当的光功率大小， 以均匀照射生物 200体内的组 织细胞， 而达到高效率且效果良好的光动力治疗效果。
此外， 图 4同时比较将发光元件 123置于散射元件 130内， 以及 将发光元件 123衔接于散射元件 130表面的散射穿透率的差异。 由测 量结果得知， 发光元件 123置于散射元件 130内的穿透散射率， 远低 于发光元件 123衔接于散射元件 130表面的散射率。 因此， 本发明以 发光元件 123衔接于散射元件 130表面的形态作为最佳实施例的说明。
此外，为了确认设置于生物 200体内的光照射器 120确实地运作， 如图 3A及图 3B所示， 本发明在进行治疗时， 也可于发光元件 123 内安装有光传感器 170， 用以检测发光元件 123的透镜所折射回来的 光线， 以推算发光元件 123所发出的光强度。 光传感器 170电性连接 于控制电路 122， 以检测由发光元件 123射出的光线强度， 并将此光 功率的模拟信号传送至控制电路 122中， 以进行信号的数字解调， 再 以无线射频 (RF)或是微波等无线传输方式传送至外部的解调器 (图中 未示)， 从而得知目前的发光强度， 以辅助医疗者换算病患所需照射的 时间。
或是于接近光照射器 120的生物 200体外设置一光传感器 (图中未 示)， 以接收光照射器 120以无线信号回馈其目前的运作状态， 例如回 馈其发光元件 123是否发出光线、 及此光线的光功率大小等情况， 使 医疗者得以了解生物 200体内的治疗情况。
如图 1B及图 5所示， 为了观察内部的治疗状况，还可于生物 200 体内装设一取像装置 180。其中， 取像装置 180具有一处理器 181， 及 电性连接于处理器 181的第三感应线圈 182、取像器 183、与无线信号 发射器 184。第三感应线圈 182于接收第二感应线圈 1 124所发出的无 线信号后开始运作， 当光照射器 120照射生物 200的过程中， 取像器 183将生物 200通过光线而产生的光强度， 通过处理器 181转换为一 输出信号， 并经由无线信号发射器 184， 以无线射频 (RF)或是微波等 无线传输方式传送至外部的接收器 (图中未示)， 从而得知目前的内部 治疗状况。
另外， 为了快速处理取像装置 180所产生的输出信号， 还可于光 照射器 120 内加设二天线 (图中未示)， 以分别接收及传输输出信号， 使得以图像信号为主的输出信号， 得以快速地传递至外部的接收器。
取像装置 180也可结合于光照射器 120内， 无需使用第三感应线 圈 182， 通过共享控制电路 122所产生的电流， 以驱动取像器 183运 作， 使得设置于生物 200体内的装置可更为精简。
如图 3C所示， 本发明的光照射器 120还包括有一二次电池 190， 电性连接控制电路 122及发光元件 123， 且二次电池 190具有一充放 电回路 191。 当控制电路 122的驱动信号经由整流器 1221 及稳压器 1222的转换， 以对二次电池 190进行充电， 再通过外部无线触发的方 式， 启动二次电池 190执行或是停止提供电能至发光元件 123， 光照 射器 120无须随时与外部的发射器 (图中未示)对准， 使用者的行动将 不受限制， 而可持续地进行治疗。 其中， 启动或是停止二次电池 190 的电力输出，可通过不同频率的耦合信号、微处理器的内部程序代码、 或是利用载波信号技术解调外部信号等驱动方式， 以对二次电池 190 进行控制。
图 6A至图 6E为本发明的感应装置应用于治疗及诊断生物各部位 的器官组织的示意图。 本发明揭示的感应装置 100可应用于治疗人体 200(生物体)各个部位， 例如颅腔、 口腔、 胸腔、 腹腔、 骨盆腔内的各 器官组织的肿瘤治疗。 本发明的发射器 1 10可通过一绑持或是佩带于 人体 200上的保持件 160而固定设置于相对人体 200体内的光照射器 120的位置， 以使发射器 1 10得以与光照射器 120之间通过无线射频 传输的方式进行治疗。
保持件 160上具有一容设部 161， 以供发射器 110固设于其中。 且保持件 160可配合人体 200欲治疗的部位， 而设计为帽子、 口罩、 或是束带等各种形态，以方便佩带绑持于人体 200对应于光照射器 120 的位置。
与公知技术相比， 位于生物体外的发射器通过无线信号的传输， 而与设置于生物体内的光照射器相互电磁感应， 光照射器通过磁电转 换效应， 而可发出特定波长的光线， 以激发匹配的光敏感药剂产生光 化学反应， 以进行生物体的诊断或是治疗。 本发明改善了公知光动力 治疗装置以有线传输方式的不便，并降低人体遭受细菌感染的危险性。
本发明的发射器还通过保持件的设置， 使得患者于治疗过程中的 行动将不受发射器的限制， 并可精确控制光照射器 120的光功率或是 光照射时间， 以减缓人体因治疗时所产生不适感， 并同时获得较佳治 疗效果的功效。
虽然本发明的实施例揭示如上所述， 然而并非用以限定本发明， 任何熟悉相关技术的技术人员， 在不脱离本发明的精神和范围内， 凡 依本发明权利要求所述的形状、构造、特征及精神当可做些许的变动， 因此本发明的专利保护范围须视本说明书所附的权利要求书为准。

Claims

权 利 要 求
1.一种应用于光动力诊断与治疗的感应装置， 使用于一生物上， 用以激发该生物体内的光敏感药剂产生光化学反应，该感应装置包括: 一发射器， 用以发出一穿透该生物表层的无线信号； 以及 一光照射器， 设置于该生物体内， 其具有：
一第一感应线圈， 用以接收该无线信号；
一控制电路， 电性连接于该第一感应线圈， 并将该无线信号转换 为一驱动信号； 以及
一发光元件， 电性连接于该控制电路， 该发光元件由该驱动信号 驱动而发出光线， 以使该光敏感药剂产生光化学反应。
2.如权利要求 1所述的应用于光动力诊断与治疗的感应装置， 其 中该发射器包含一驱动电路及一震荡电路， 该驱动电路用以产生一控 制信号， 该震荡电路电性连接于该驱动电路， 以将该控制信号转换为 该无线信号并发出。
3.如权利要求 2所述的应用于光动力诊断与治疗的感应装置， 其 中该驱动电路还包含一波形产生器、 一电性连接于该波形产生器的分 频器、 一电性连接于该分频器的反向器、 至少一电性连接于该反向器 的调变器、 至少一电性连接于该调变器的功率放大器、 以及至少一电 性连接于该功率放大器的变压器， 以产生该控制信号。
4.如权利要求 2所述的应用于光动力诊断与治疗的感应装置， 其 中该震荡电路还包含一电源、至少一电性连接于该电源的晶体管开关、 及一电性连接于该晶体管开关的共振电路， 该晶体管开关接收该控制 信号， 以控制该共振电路发出该无线信号至该第一感应线圈。
5.如权利要求 4所述的应用于光动力诊断与治疗的感应装置， 其 中该共振电路具有一第二感应线圈及一电容， 该第二感应线圈电性连 接于该晶体管开关， 该电容电性连接于该第二感应线圈， 且该第二线 圈通过该电容的充放电作用， 以发出该无线信号至该第一感应线圈。
6.如权利要求 1所述的应用于光动力诊断与治疗的感应装置， 其 中还包含一衔接于该发光元件的散射元件， 且该散射元件内具有一容 置空间， 并填装有一流体， 以使该光线产生散射。
7.如权利要求 6所述的应用于光动力诊断与治疗的感应装置， 其 中该流体选自于由空气、 生理食盐水、 及油水混合物所构成的群组之
8.如权利要求 7所述的应用于光动力诊断与治疗的感应装置， 其 中该油水混合物为力保肪宁或是因特立滋。
9.如权利要求 1所述的应用于光动力诊断与治疗的感应装置， 其 中该控制电路具有一整流器及一稳压器， 该整流器用以接收该驱动信 号， 该稳压器电性连接该整流器及该发光元件， 以对该驱动信号整流 及稳压。
10.如权利要求 1所述的应用于光动力诊断与治疗的感应装置，其 中还包括一包覆于该光照射器外围并具有生物兼容性的包覆材料， 以 使该光照射器绝缘及散热。
1 1.如权利要求 10所述的应用于光动力诊断与治疗的感应装置， 其中该包覆材料为硅胶材料或是玻璃材料。
12.如权利要求 1所述的应用于光动力诊断与治疗的感应装置，其 中还包含一保持件， 且该保持件具有一容设部， 以固定该发射器于该 保持件上。
13.如权利要求 1所述的应用于光动力诊断与治疗的感应装置，其 中还包含一光传感器， 电性连接于该控制电路， 用以于该发光元件发 出该光线时， 检测该光线的强度， 并传送至该控制电路。
14.如权利要求 1所述的应用于光动力诊断与治疗的感应装置，其 中还包含有一取像装置， 其具有- 一处理器；
一第三感应线圈， 电性连接于该处理器， 用以接收该无线信号， 并驱动该处理器；
一取像器， 电性连接于该处理器， 用以检测该生物通过该光线所 产生的光强度， 并通过该处理器转换为一输出信号； 以及
一无线信号发射器， 电性连接于该处理器，用以发射该输出信号。
15.如权利要求 1所述的应用于光动力诊断与治疗的感应装置，其 中该光照射器还包括有一二次电池， 电性连接该控制电路及该发光元 件， 以提供一电能至该发光元件。
16.如权利要求 15所述的应用于光动力诊断与治疗的感应装置， 其中该二次电池还具有一充放电回路， 该充放电回路通过该控制电路 的驱动信号， 以对该二次、电池进行充电。
17.—种应用于光动力诊断与治疗的光照射器， 设置于一生物体 内， 该光照射器通过一穿透该生物表层的无线信号而发出一光线， 以 激发该生物体内的光敏感药剂产生光化学反应， 该光照射器包括有： 一第一感应线圈， 用以接收该无线信号；
一控制电路， 电性连接于该第一感应线圈， 并将该无线信号转换 为一驱动信号； 以及
一发光元件， 电性连接于该控制电路， 该发光元件由该驱动信号 驱动而发出光线， 以使该光敏感药剂产生光化学反应。
18.如权利要求 17所述的应用于光动力诊断与治疗的光照射器， 其中还包含有一衔接于该发光元件的散射元件， 且该散射元件内填装 有一流体， 以使该光线产生散射。
19.如权利要求 17所述的应用于光动力诊断与治疗的光照射器， 其中该控制电路具有一整流器及一稳压器， 该整流器电性连接该第一 感应线圈， 该稳压器电性连接该整流器及该发光元件， 以对该驱动信 号整流及稳压。
20.如权利要求 17所述的应用于光动力诊断与治疗的光照射器， 其中还包括有一包覆于该发光器外围并具有生物兼容性的包覆材料， 以使该发光器绝缘及散热。
21.如权利要求 20所述的应用于光动力诊断与治疗的光照射器， 其中该包覆材料为硅胶材料或是玻璃材料。
PCT/CN2008/001538 2007-08-28 2008-08-27 Dispositif à induction pour thérapie et diagnostic photodynamiques WO2009030109A1 (fr)

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