靶向磁场发生器的研究
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摘要
磁靶向给药系统是靶向给药系统的一种,近几年来成为研究热点之一。磁靶向给药系统的目的是使磁性药物微粒在引导磁场的作用下,到达靶区并振荡释放。引导磁场要求有一定的磁场强度和磁场陡度,而且在空间上分布,以利于磁性药物的振荡吸收。现在研究的靶向磁场发生装置中磁场陡度不是很高,而且只是在靶向两极产生磁场,没有在空间上分布,为此本文提出了磁场陡度性好,在空间分布的靶向磁场发生器的研究方案。本文做的主要内容如下:
①阐述了旋转磁场的各种产生方式,通过对比分析确定电磁线圈产生旋转磁场的方式比较适合旋转磁场靶向研究。
②通过对磁性材料特性的了解以及对磁性材料要求的分析,提出了用软磁性材料硅钢片作为磁极材料,工业纯铁作为磁轭材料。
③根据磁场强度陡度高的要求,提出了利用电容对电磁线圈实行前沿和后沿箝位的方法。由于要求快速关断,采用关断速度比较快的功率场效应晶体管MOSFET作为开关器件。蓄电池供电体积大,不方便移动,为此设计了输出电流为10安培左右的电压源电路。利用PSIM仿真软件对主电路进行了仿真分析,验证主电路的可行性。
④对驱动电路进行了设计。主电路上桥臂开关管由于是浮地,需要独立的电源。为了减少供电电源的数目,提出自举供电的驱动电路解决方案。自举供电中自举电容的确定至关重要,为此分析并计算自举电容值。对设计的驱动电路进行实验,测得的波形完全符合功率场效应晶体管MOSFET的驱动要求。
⑤对控制电路进行了设计。为了使单片机输出的脉冲信号占空比为50%,使用D触发器设计了二分频电路来实现相应的驱动控制信号。设计了相应的程序流程图,实现了拨动开关控制频率档位、线圈控制口依次导通的功能。
⑥对各种电流波形进行了对比分析,确定了双极性延时方波更适合靶向治疗。对磁性微粒在双极性延时方波中的运动及受力做了定性分析,知道了双极性延时方波有利于药物振荡释药的原因。Protel软件绘制了PCB板,并对实验板进行了调试。调试结果表明本文所设计的靶向磁场发生器解决了现有的靶向磁场发生器磁场陡度不高的问题,为下一步的产品开发奠定了良好的基础。
⑦最后对研究工作进行了总结和展望,并指出了进一步的研究方向和内容。
Magnetic targeted drug delivery system is one of targeted drug delivery systems,and is becoming a hotspot in recent years. Magnetic targeted drug delivery system is designed to make the magnetic particles arrive at the target area and oscillate release.Guide magnetic is requested to has a certain magnetic field intensity and magnetic field gradient as well as distribute in space ,so that it is in favour of the magnetic drug oscillation absorption. The magnetic field gradient is not very hight in the current targeted magnetic field generator research,and it only exists in both targeted poles,not in spatial distribution. For this reason,the paper proposes a research plan of magnetic field generator which has good magnetic field gradient and spatial distribution.The work of this paper are mainly as follows:
①The paper expounds various ways of producing magnetic field ,and finds that the electromagnetic coils is more suitable for targeting researches by comparative analysis.
②By the understand of the characteristics of magnetic materials and analysis of the requirements for the soft magnetic materials , the paper proposes to use industrial silicon steel sheet as magnetic pole materials and pure iron as magnetic yoke materials.
③Based on the requirement of magnetic field gradient , the paper proposes to use capacitance to clamp the front edge and trailing edge of transmitting coils.Because of the requirment of fast shutoff,the paper use the faster shutoff speed power field effect transistors MOSFET as switch. The volume of storage battery is big and not convenient for moving,so we design a voltage source circuit which has a output current about 5 amp. The paper uses PSIM simulation software to analysis the main circuit,verifies the feasibility of the main circuit.
④The paper designs the drive circuit.Because the top bridge arm in main circuit is floating ground,so the circuit requires independent power supply.For the purpose of reducing number of supply power sources, the paper proposes the solution of bootstrap drive circuit. The bootstrap capacitance is very important in bootstrap circuit,so we analyse and calculate the value of bootstrap capacitance.The experiments were performed for the designed drive circuit,and the waveform of measurement complies with the driver requirements of power field effect transistors MOSFET.
⑤The paper designs the contorl circuit.In order to make the output pulse signal duty cycle arrive at fifty percent,the paper uses D flip-flop to design half frequency circuit and realizes the corresponding drive control signals. The paper also designs the corresponding program flowchart to realize that switches control frequence tap position and the coil controlled ports conduct successively.
⑥The paper gives a comparison analysis for different sorts of current waveform,and determines the dual polarity delay square-wave to be more suitable for targeted therapy. The paper gives a qualitative analysis to the magnetic particles movement and force analysis in dual polarity delay sqare-wave,and knows why the dual polarity delay sqare-wave is in favour of the drug oscillation release. The paper applys Protel software to design PCB board ,and debugs the experimental board. The test results prove that the designed magnetic field generator in this paper solves the problem of low magnetic field gradient, which provides a better base for the product ulterior exploitation.
⑦Finally, the summarization and prospect of this study are proposed.
①阐述了旋转磁场的各种产生方式,通过对比分析确定电磁线圈产生旋转磁场的方式比较适合旋转磁场靶向研究。
②通过对磁性材料特性的了解以及对磁性材料要求的分析,提出了用软磁性材料硅钢片作为磁极材料,工业纯铁作为磁轭材料。
③根据磁场强度陡度高的要求,提出了利用电容对电磁线圈实行前沿和后沿箝位的方法。由于要求快速关断,采用关断速度比较快的功率场效应晶体管MOSFET作为开关器件。蓄电池供电体积大,不方便移动,为此设计了输出电流为10安培左右的电压源电路。利用PSIM仿真软件对主电路进行了仿真分析,验证主电路的可行性。
④对驱动电路进行了设计。主电路上桥臂开关管由于是浮地,需要独立的电源。为了减少供电电源的数目,提出自举供电的驱动电路解决方案。自举供电中自举电容的确定至关重要,为此分析并计算自举电容值。对设计的驱动电路进行实验,测得的波形完全符合功率场效应晶体管MOSFET的驱动要求。
⑤对控制电路进行了设计。为了使单片机输出的脉冲信号占空比为50%,使用D触发器设计了二分频电路来实现相应的驱动控制信号。设计了相应的程序流程图,实现了拨动开关控制频率档位、线圈控制口依次导通的功能。
⑥对各种电流波形进行了对比分析,确定了双极性延时方波更适合靶向治疗。对磁性微粒在双极性延时方波中的运动及受力做了定性分析,知道了双极性延时方波有利于药物振荡释药的原因。Protel软件绘制了PCB板,并对实验板进行了调试。调试结果表明本文所设计的靶向磁场发生器解决了现有的靶向磁场发生器磁场陡度不高的问题,为下一步的产品开发奠定了良好的基础。
⑦最后对研究工作进行了总结和展望,并指出了进一步的研究方向和内容。
Magnetic targeted drug delivery system is one of targeted drug delivery systems,and is becoming a hotspot in recent years. Magnetic targeted drug delivery system is designed to make the magnetic particles arrive at the target area and oscillate release.Guide magnetic is requested to has a certain magnetic field intensity and magnetic field gradient as well as distribute in space ,so that it is in favour of the magnetic drug oscillation absorption. The magnetic field gradient is not very hight in the current targeted magnetic field generator research,and it only exists in both targeted poles,not in spatial distribution. For this reason,the paper proposes a research plan of magnetic field generator which has good magnetic field gradient and spatial distribution.The work of this paper are mainly as follows:
①The paper expounds various ways of producing magnetic field ,and finds that the electromagnetic coils is more suitable for targeting researches by comparative analysis.
②By the understand of the characteristics of magnetic materials and analysis of the requirements for the soft magnetic materials , the paper proposes to use industrial silicon steel sheet as magnetic pole materials and pure iron as magnetic yoke materials.
③Based on the requirement of magnetic field gradient , the paper proposes to use capacitance to clamp the front edge and trailing edge of transmitting coils.Because of the requirment of fast shutoff,the paper use the faster shutoff speed power field effect transistors MOSFET as switch. The volume of storage battery is big and not convenient for moving,so we design a voltage source circuit which has a output current about 5 amp. The paper uses PSIM simulation software to analysis the main circuit,verifies the feasibility of the main circuit.
④The paper designs the drive circuit.Because the top bridge arm in main circuit is floating ground,so the circuit requires independent power supply.For the purpose of reducing number of supply power sources, the paper proposes the solution of bootstrap drive circuit. The bootstrap capacitance is very important in bootstrap circuit,so we analyse and calculate the value of bootstrap capacitance.The experiments were performed for the designed drive circuit,and the waveform of measurement complies with the driver requirements of power field effect transistors MOSFET.
⑤The paper designs the contorl circuit.In order to make the output pulse signal duty cycle arrive at fifty percent,the paper uses D flip-flop to design half frequency circuit and realizes the corresponding drive control signals. The paper also designs the corresponding program flowchart to realize that switches control frequence tap position and the coil controlled ports conduct successively.
⑥The paper gives a comparison analysis for different sorts of current waveform,and determines the dual polarity delay square-wave to be more suitable for targeted therapy. The paper gives a qualitative analysis to the magnetic particles movement and force analysis in dual polarity delay sqare-wave,and knows why the dual polarity delay sqare-wave is in favour of the drug oscillation release. The paper applys Protel software to design PCB board ,and debugs the experimental board. The test results prove that the designed magnetic field generator in this paper solves the problem of low magnetic field gradient, which provides a better base for the product ulterior exploitation.
⑦Finally, the summarization and prospect of this study are proposed.
引文
[1]李凌冰,魏培,刘君义.靶向给药系统的体内药动学模型研究[J].中国药学杂志,2008,43(10):798-799.
[2]张强.靶向给药系统的研究进展[J].北京生物医药发展论坛,230-231.
[3]张景勃,张志荣,谭群友.磁靶向给药系统的研究进展[J].中国医药工业杂志,2001,32(12):564-566.
[4]李树杰,综述,毕宏生,崔彦.靶向给药系统及其在眼科的应用[J].山东大学耳鼻喉眼学报,2007,26(3).
[5]辛胜昌,李忠彦,吴新荣.磁性靶向药物的研究进展[J].医药导报,2006,7(25):680-681.
[6] RITTER J A ,EBNER A D,DANIEL K D,et al.Application of high gradient magnetic separation principles to magnetic drug targeting [J]. Journal of Magnetism and Magnetic Materials,2004,,280 (9):184-189.
[7]熊平,郭萍,向东等.引导磁场下磁性药物靶向治疗的理论分析[J].物理学报,2006,55(8):4383-4387.
[8] DAVEY K,EPSTEIN C M..Magnetic stimulation coil and circuit design[J].IEEE Trans Biomed Eng,2000,47(11):1493-1499.
[9] NOVAC B M,SMITH I R,YOUNG A J,et al.A powerful magnetic stimulator for medical applications[J].IEEE Transctions on Plasma Science,2002,30(5).
[10] ASMATUL U R, ZALICH M A,CLAUS R O,et al.Synthesis characterization and targeting of biodegrada-ble magnetic nanocomposite particles by external magnetic fields [J]. Journal of Magnetism and Magnetic Materials,2005,292(4):108-112.
[11]郭明霞,王明时,王学民,等.脉冲磁场对大鼠记忆能力和海马神经递质的影响[J].中国生物医学工程学报,2002,21(2):179-181.
[12]康宏向,钱焕文,杨在富,等.磁靶向药物的磁场定位分析[J].中国生物医工程学报,2006,25(1):10-13.
[13]岳鹏飞,袁海龙.磁靶向微粒给药系统的研究进展[J].2007年中华中医药学会中成药学术研讨会论文集,2007,64-69.
[14]成登苗,翟学良,徐洋.磁性靶向药物粒子的研究进展[J].河北师范大学学报/自然科学版.2009,35(5):649-654.
[15] Asmatulu R.,Zalich M.A.,Claus R.O.,et al .Synthesis, characterization and targeting of biodegradable magnetic nanocomposite particles by external magnetic fields [J].Journal of Magnetism and Magnetic Materials,2005,292(4):108-112.
[16] Babincova M,Machova E. Magnetoliposomes maybe useful for elimination of HIV from infected individuals[J].Z Naturforsch,1998,53(9-10):935-936.
[17] Yanase M,Shinkai M, Honda H,et al.Antitumor immunity induction by intracellular hyperthermia using magnetite cationic liposomes[J].Jpn J Cancer Res,1998,89(7):775-782.
[18] Vironchatapan E,Sato H,Ueno M,et al.Microdialysis assessment of 5-fluorouracil release from thermosensitive magnetoliposomes induced by anelectromagnetic field in tumor-bearing mice [J].JDrug Target,1998,5(5):379-390.
[19] Pulfer SK,Ciccotto SL,Gallo JM.Distribution of small magnetic particles in brain tumor-bearing rats[J].J Neurooncol,1999,41(2):99-105.
[20]许剑,马净植,陈卫民.磁控纳米载药系统在肿瘤治疗领域中的应用[J].临床口腔医学杂志.2004,20(10)
[21] Alexion C,Amold W,Klein RJ,et al.Loooregional cencer treat-ment with magneitic drug targeting [J].Cancer Res,2000,6(23):6641-8.
[22]吴伟斌,魏树礼,卢炜,等.磁性微球的磁响应性及狗肾动脉栓塞实验研究[J].药学学报,1994,29(4):311-315.
[23]梁可道.用于肿瘤治疗的陡脉冲磁场发生器的研制[D].重庆大学硕士学位论文.2008:8-9页
[24]唐甫南.脉冲磁疗法的进展[J].第二届海峡两岸医疗仪器学术会议.1995:54-57.
[25] Walker JL,Kryscio R,Smith J,et al.Electromagnetic field treatment of nerve crush injury in a rat model:effect of signal configuration on functional recovery[J].Bioelectromagnetics,2007,28(4):256-263.
[26] De Seze R,Tuffet S,Moreau JM,Veyret B.Effects of 100 mT time varying magnetic fields on the growth of tumors in mice[J].Bioelectromagnetics,2000,21(2):107-111.
[27] Carlo Ventura,argherita Maioli,ianfranco Pintus,t al.lf-pulsed magnetic fields modulate opioid peptide gene expression in myocardial cells[J].Cardiovascular Research,2000,45(4):1054-1064.
[28] Hong xiang Liu et al.Pulsed electromagnetic fields preserve proteoglycan composition of extracellular matrix in embryonic chick sternal cartilage [J]. Biochimica et Biophysica Acta (BBA)General Subjects,1997,1336(2):303-314.
[29] Pericles Diniz,Kazuhisa Soejima,Gakuji Ito.Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation [J].Nitric Oxide,2002,7(1):18-23.
[30]文峻,屈学民,杨继庆,王斯刚,龙开平.脉冲磁场刺激仪的研制[J].医疗卫生装备.2006,27(1):5-6.
[31]付志红,赵俊丽,罗聪,谢品芳.靶向振荡磁场发生器的研制[J].重庆大学学报.2008,31(7):749-752.
[32]赵俊丽.宽频恒幅交流方波电流源的研究[D].重庆大学硕士学位论文,2008:47-56.
[33]电感量计算公式[EB/OL]. http://wenku.baidu.com/view/b256c9659b6648d7c1c74682.html
[34] 1998.LM338.pdf [EB/OL]. http://pdf.dzsc.com/search.asp?keyword=lm338
[35] 1997.at89c51.pdf [EB/OL]. http://pdf.dzsc.com/search.asp?keyword=at89c51&Submit= %26nbsp%3B
[36]陈光东.单片微型计算机原理及其C语言程序设计[M].华中科技大学出版社.2003:25-30
[37]华中工学院等编.电工学[M].人民教育出版社.1977:42
[38] 2001. psim使用说明pdf. [EB/OL]. http://www.docin.com/p-11914054.html.
[39]王兆安,黄俊.电力电子技术(第4版) [M].机械工业出版社,2001:8-37.
[40]顾建平,夏春燕.自举电路在MOSFET驱动电路中的应用[J].常州工学院学报,38-40.
[41]王志强,王莉.一种新颖的MOSFET驱动电路[J].电力电子技术.2005,39(1):92-94.
[42]王春仁.基于单片机的旋转磁场磁力研磨加工的计算机仿真与系统设计[D].大连理工大学硕士学位论文.2002:28-30.
[43]刘桂英,成叶琴,周琴.驱动高压浮动MOSFET的自举电容设计[J]. 2009,12(3):190-193.
[2]张强.靶向给药系统的研究进展[J].北京生物医药发展论坛,230-231.
[3]张景勃,张志荣,谭群友.磁靶向给药系统的研究进展[J].中国医药工业杂志,2001,32(12):564-566.
[4]李树杰,综述,毕宏生,崔彦.靶向给药系统及其在眼科的应用[J].山东大学耳鼻喉眼学报,2007,26(3).
[5]辛胜昌,李忠彦,吴新荣.磁性靶向药物的研究进展[J].医药导报,2006,7(25):680-681.
[6] RITTER J A ,EBNER A D,DANIEL K D,et al.Application of high gradient magnetic separation principles to magnetic drug targeting [J]. Journal of Magnetism and Magnetic Materials,2004,,280 (9):184-189.
[7]熊平,郭萍,向东等.引导磁场下磁性药物靶向治疗的理论分析[J].物理学报,2006,55(8):4383-4387.
[8] DAVEY K,EPSTEIN C M..Magnetic stimulation coil and circuit design[J].IEEE Trans Biomed Eng,2000,47(11):1493-1499.
[9] NOVAC B M,SMITH I R,YOUNG A J,et al.A powerful magnetic stimulator for medical applications[J].IEEE Transctions on Plasma Science,2002,30(5).
[10] ASMATUL U R, ZALICH M A,CLAUS R O,et al.Synthesis characterization and targeting of biodegrada-ble magnetic nanocomposite particles by external magnetic fields [J]. Journal of Magnetism and Magnetic Materials,2005,292(4):108-112.
[11]郭明霞,王明时,王学民,等.脉冲磁场对大鼠记忆能力和海马神经递质的影响[J].中国生物医学工程学报,2002,21(2):179-181.
[12]康宏向,钱焕文,杨在富,等.磁靶向药物的磁场定位分析[J].中国生物医工程学报,2006,25(1):10-13.
[13]岳鹏飞,袁海龙.磁靶向微粒给药系统的研究进展[J].2007年中华中医药学会中成药学术研讨会论文集,2007,64-69.
[14]成登苗,翟学良,徐洋.磁性靶向药物粒子的研究进展[J].河北师范大学学报/自然科学版.2009,35(5):649-654.
[15] Asmatulu R.,Zalich M.A.,Claus R.O.,et al .Synthesis, characterization and targeting of biodegradable magnetic nanocomposite particles by external magnetic fields [J].Journal of Magnetism and Magnetic Materials,2005,292(4):108-112.
[16] Babincova M,Machova E. Magnetoliposomes maybe useful for elimination of HIV from infected individuals[J].Z Naturforsch,1998,53(9-10):935-936.
[17] Yanase M,Shinkai M, Honda H,et al.Antitumor immunity induction by intracellular hyperthermia using magnetite cationic liposomes[J].Jpn J Cancer Res,1998,89(7):775-782.
[18] Vironchatapan E,Sato H,Ueno M,et al.Microdialysis assessment of 5-fluorouracil release from thermosensitive magnetoliposomes induced by anelectromagnetic field in tumor-bearing mice [J].JDrug Target,1998,5(5):379-390.
[19] Pulfer SK,Ciccotto SL,Gallo JM.Distribution of small magnetic particles in brain tumor-bearing rats[J].J Neurooncol,1999,41(2):99-105.
[20]许剑,马净植,陈卫民.磁控纳米载药系统在肿瘤治疗领域中的应用[J].临床口腔医学杂志.2004,20(10)
[21] Alexion C,Amold W,Klein RJ,et al.Loooregional cencer treat-ment with magneitic drug targeting [J].Cancer Res,2000,6(23):6641-8.
[22]吴伟斌,魏树礼,卢炜,等.磁性微球的磁响应性及狗肾动脉栓塞实验研究[J].药学学报,1994,29(4):311-315.
[23]梁可道.用于肿瘤治疗的陡脉冲磁场发生器的研制[D].重庆大学硕士学位论文.2008:8-9页
[24]唐甫南.脉冲磁疗法的进展[J].第二届海峡两岸医疗仪器学术会议.1995:54-57.
[25] Walker JL,Kryscio R,Smith J,et al.Electromagnetic field treatment of nerve crush injury in a rat model:effect of signal configuration on functional recovery[J].Bioelectromagnetics,2007,28(4):256-263.
[26] De Seze R,Tuffet S,Moreau JM,Veyret B.Effects of 100 mT time varying magnetic fields on the growth of tumors in mice[J].Bioelectromagnetics,2000,21(2):107-111.
[27] Carlo Ventura,argherita Maioli,ianfranco Pintus,t al.lf-pulsed magnetic fields modulate opioid peptide gene expression in myocardial cells[J].Cardiovascular Research,2000,45(4):1054-1064.
[28] Hong xiang Liu et al.Pulsed electromagnetic fields preserve proteoglycan composition of extracellular matrix in embryonic chick sternal cartilage [J]. Biochimica et Biophysica Acta (BBA)General Subjects,1997,1336(2):303-314.
[29] Pericles Diniz,Kazuhisa Soejima,Gakuji Ito.Nitric oxide mediates the effects of pulsed electromagnetic field stimulation on the osteoblast proliferation and differentiation [J].Nitric Oxide,2002,7(1):18-23.
[30]文峻,屈学民,杨继庆,王斯刚,龙开平.脉冲磁场刺激仪的研制[J].医疗卫生装备.2006,27(1):5-6.
[31]付志红,赵俊丽,罗聪,谢品芳.靶向振荡磁场发生器的研制[J].重庆大学学报.2008,31(7):749-752.
[32]赵俊丽.宽频恒幅交流方波电流源的研究[D].重庆大学硕士学位论文,2008:47-56.
[33]电感量计算公式[EB/OL]. http://wenku.baidu.com/view/b256c9659b6648d7c1c74682.html
[34] 1998.LM338.pdf [EB/OL]. http://pdf.dzsc.com/search.asp?keyword=lm338
[35] 1997.at89c51.pdf [EB/OL]. http://pdf.dzsc.com/search.asp?keyword=at89c51&Submit= %26nbsp%3B
[36]陈光东.单片微型计算机原理及其C语言程序设计[M].华中科技大学出版社.2003:25-30
[37]华中工学院等编.电工学[M].人民教育出版社.1977:42
[38] 2001. psim使用说明pdf. [EB/OL]. http://www.docin.com/p-11914054.html.
[39]王兆安,黄俊.电力电子技术(第4版) [M].机械工业出版社,2001:8-37.
[40]顾建平,夏春燕.自举电路在MOSFET驱动电路中的应用[J].常州工学院学报,38-40.
[41]王志强,王莉.一种新颖的MOSFET驱动电路[J].电力电子技术.2005,39(1):92-94.
[42]王春仁.基于单片机的旋转磁场磁力研磨加工的计算机仿真与系统设计[D].大连理工大学硕士学位论文.2002:28-30.
[43]刘桂英,成叶琴,周琴.驱动高压浮动MOSFET的自举电容设计[J]. 2009,12(3):190-193.