无针注射器技术研究
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摘要
无针注射是利用药液的高速射流进入被注射体内,从而完成注射的技术过程。随着临床需要的推动和科学技术的发展,无针注射器技术呈现出蓬勃发展的态势,美国和欧洲已经有不同类型的商品面世,我国对无针注射的研究刚刚起步,目前还没有针对国内需求的产品上市。
本文主要研究的内容如下：
1.介绍了国内外已有的无针注射器技术,总结了现有无针注射器的技术指标及研究开发路线；
2.进行无针注射器总体方案的设计,根据功能,将无针注射器分为机械结构部分、液压回路部分和电气控制部分,对各部分分析并确定最终采用的方案；
3.根据分析及要求细化结构,对关键参数进行理论计算,设计得到产品三维模型,并且简化设计原理样机,验证无针注射器原理的可行性；
4.基于前人设计的小孔喷射模型和液体撞击模型,对设计的机器进行仿真,得到对于各个高压空气弹簧的喷射特性分布；
5.进行稳定性实验、高速摄像实验、注射仿生材料实验以及离体猪肉注射实验,四个实验层层递进,逐步证实了无针注射器原理样机的稳定性、模型仿真数据与实验数据的吻合度以及注射形态稳定性,并且验证了随着注射动力的增加,注射深度随之增加的结论。
本文设计了机械机构、电气控制,对喷射过程进行理论分析,加工调试样机,并开展了多种实验,验证了样机的可行性和可靠性,完成了新产品开发的前期工作,为后续的新产品开发的完善奠定了坚实的基础。
Needle-free injection makes use of high-speed liquid jet to inject liquid pharmaceutical into the body, thus completing the process of injection. Along with the clinical needs and the development of science and technology, needle-free injector technology presents a booming trend. United States and Europe have different types of products available. As the research of needle-free injection has just started, there is no product can meet the demand for the domestic market now.
The main contents of this paper are as follows:
Section 1 describes the existing needle-free injector technology home and abroad, and then summarizes the technical specifications along with the research and development route of the existing needle-free injector;
The overall scheme design of the needle-free injector is introduced in section 2, which is divided into three parts---mechanical structure, hydraulic circuit and electrical control system according to the function. Followed by analyzing each part, the eventual adopted scheme is determined.
Section 3 refines the structure according to the analysis and requirements, makes theoretical calculations of key parameters, gets the three-dimensional model for the product and then simply designs the prototype to test the possibility of the principle of needle-free injector.
Based on the previous design of hole injection model and liquid hit model, Section 4 simulations the designed machine and then gets the distribution of injection characteristics for each high-pressure air spring.
In section 5, four experiments of stability, high-speed camera, injection of biomimetic materials and pork injection is conducted, which gradually confirmed the stability of the prototype and Injection form, the goodness of fit of model simulation data and experimental data. In addition, the conclusion that injection depth will increase along with the increase of injection power is verified.
This paper not only designs mechanical structure and electrical control, analysis the jet process theoretical, but also conducts a series of experiments after designing the prototype. Thanks to the above work, the feasibility and reliability of the prototype is verified and preliminary work to develop the new product is completed, laying a solid foundation for the followed-up improvement of the new product.
本文主要研究的内容如下：
1.介绍了国内外已有的无针注射器技术,总结了现有无针注射器的技术指标及研究开发路线；
2.进行无针注射器总体方案的设计,根据功能,将无针注射器分为机械结构部分、液压回路部分和电气控制部分,对各部分分析并确定最终采用的方案；
3.根据分析及要求细化结构,对关键参数进行理论计算,设计得到产品三维模型,并且简化设计原理样机,验证无针注射器原理的可行性；
4.基于前人设计的小孔喷射模型和液体撞击模型,对设计的机器进行仿真,得到对于各个高压空气弹簧的喷射特性分布；
5.进行稳定性实验、高速摄像实验、注射仿生材料实验以及离体猪肉注射实验,四个实验层层递进,逐步证实了无针注射器原理样机的稳定性、模型仿真数据与实验数据的吻合度以及注射形态稳定性,并且验证了随着注射动力的增加,注射深度随之增加的结论。
本文设计了机械机构、电气控制,对喷射过程进行理论分析,加工调试样机,并开展了多种实验,验证了样机的可行性和可靠性,完成了新产品开发的前期工作,为后续的新产品开发的完善奠定了坚实的基础。
Needle-free injection makes use of high-speed liquid jet to inject liquid pharmaceutical into the body, thus completing the process of injection. Along with the clinical needs and the development of science and technology, needle-free injector technology presents a booming trend. United States and Europe have different types of products available. As the research of needle-free injection has just started, there is no product can meet the demand for the domestic market now.
The main contents of this paper are as follows:
Section 1 describes the existing needle-free injector technology home and abroad, and then summarizes the technical specifications along with the research and development route of the existing needle-free injector;
The overall scheme design of the needle-free injector is introduced in section 2, which is divided into three parts---mechanical structure, hydraulic circuit and electrical control system according to the function. Followed by analyzing each part, the eventual adopted scheme is determined.
Section 3 refines the structure according to the analysis and requirements, makes theoretical calculations of key parameters, gets the three-dimensional model for the product and then simply designs the prototype to test the possibility of the principle of needle-free injector.
Based on the previous design of hole injection model and liquid hit model, Section 4 simulations the designed machine and then gets the distribution of injection characteristics for each high-pressure air spring.
In section 5, four experiments of stability, high-speed camera, injection of biomimetic materials and pork injection is conducted, which gradually confirmed the stability of the prototype and Injection form, the goodness of fit of model simulation data and experimental data. In addition, the conclusion that injection depth will increase along with the increase of injection power is verified.
This paper not only designs mechanical structure and electrical control, analysis the jet process theoretical, but also conducts a series of experiments after designing the prototype. Thanks to the above work, the feasibility and reliability of the prototype is verified and preliminary work to develop the new product is completed, laying a solid foundation for the followed-up improvement of the new product.
引文
[1]王伽伯等.无针粉末注射给药技术研究进展[J].解放军药学学报.2006,22(04)：292-295
[2]周旭,王伽伯,肖小河.无针注射给药系统及应用[J].解放军药学学报,2005,21(6)：439-443
[3]S. Mitragotri. Immunization without needles[J]. NatRevImmunol,2005.5:905-916
[4]铮奎.无针注射器新品迭出将对我国一次性注射器出口产生影响[N].中国医药报,2008.7.23
[5]金京.无针安全注射器的设计[J]. Journal of Biomedical Engineering Research,2007,26:297-298
[6]James S. Parsons, Laguna Niguel. Needless hypodermic jet injector [P]. United States Patent.5704911,1998.1
[7]陈凯,吕永桂.一种新型液体喷射注射器的研制[J].中国医疗器械杂志,2009(6)：410-412
[8]Toles, Warren L, etc. Charging mechanism for a needle-free injector [P]. International patent. PCT/CA2007/001007,2007.6
[9]Victor T. Rogatchev, etc. Jet injector with hand piece [P]. United States Patent. US 7029457B2,2006.4.18
[10]Pat McCalmon, etc. Hand piece for jet injector [P]. United States atent. US D488862S,2004.4.20
[11]Oliver A. Shergold, Norman A. Fleck, Toby S. King, The penetration of a soft solid by a liquid jet, with application to the administration of a needle-free injection[J], Journal of Biomechanics,2006 (39):2593-2602
[12]帕特里克·亚历山大等.具有两级注射速度的无针注射器[P].中国专利.01805865.5,2003.3.26
[13]艾米·B·安吉尔等,无针注射器[P].中国专利,02824660.8,2005.3.30
[14]Mark W. Rice, etc.. Medical injector and medicament loading system for use therewith [P]. United States Patent. US7341575B2,2008.3.11
[15]帕特里克·亚历山大等.具有嵌合件式注射头的无针注射器[P].中国专利.00810388.7,2002.7.31
[16]鲍里斯·V·斯莫列洛夫等.无针注射器用的通用防感染保护器[P].中国专利.200610121202.7,2007.4.25
[17]韩惠霖.喷射理论及其应用[M].杭州：浙江大学出版社,1990.
[18]陈凯周华.弹簧式液体喷射注射系统的喷射模型及实验研究[J].中国生物医 学工程学报,2010,29(1)：140-144
[19]张玉荣等.高速液体射流流动特性的实验测试方法[J].力学与实践.1999.5：57-58
[20]应人龙.基于喷射理论的无针注射系统建模及实验研究[D].硕士论文.杭州：浙江大学,2008
[21]O.A. Shergold, etc. The uniaxial stress versus strain response of pig skin and silicone rubber at low and high strain rates International Journal Impact Engineering, 2006 (32):1384-1402
[22]曾立群.无针注射器研发[D].硕士论文.杭州：浙江大学,2008
[23]Linn L, Boyd B, Iontchev H, King T, Farr SJ. The effects of system parameters on in vivo administration performance of a needle-free injector in humans. Pharm Res. 2007(24):1501-1507
[24]Joy Baxter, Samir Mitragotri, Jet-induced skin puncture and its impact on needle-free jet injections:Experimental studies and a predictive model, Journal of Controlled Release 2005 (106) 361-373
[25]Samir Mitragotri, Current status and future prospects of needle-free liquid jet injectors, Nature Reviews Drug Discovery,2006 (5) 543-548
[26]Gursoy A, Ertugrul DT, Sahin M, Tutuncu NB, Demirer AN,Demirag NG 2007 Needle-free delivery of lidocaine for reducing the pain associated with the fine-needle aspiration biopsy of thyroid nodules:time-saving and efficacious procedure. Thyroid 17:317-321
[27]焦坤.无针注射器测试评价系统的研究[D].硕士论文.武汉：华中科技大学,2007
[28]Aaron B. Baker, Joan E. Sander. Fluid Mechanics Analysis of a Spring-Loaded Jet Injector, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL.46, NO.2,1999.2
[29]沈星,刘永刚,裘进浩RAINBOW压电陶瓷与形状记忆合金的集成(M).金属热处理.2006.31(8)：15-17
[30]Brian D. Hemond, etc. Development and Performance of a Controllable Auto loading Needle-Free Jet Injector [J]. Journal of Medical Devices,2011.3, Vol.5: 015001
[31]帕特里克·亚历山大等.带有模块化储液器的无针注射器(P).中国专利,01811507.1,2003.8.20
[32]Jeanne C. Stachowiak, etc. Dynamic control of needle-free jet injection [J]. J Control Release,2009,135(2):104-112
[33]赵万生等.应用线电极磨削法的电火花微孔加工[J].电加工.1997.3：13-16
[34]成大先.机械设计手册(第五版)第三卷[S].螺旋传动、摩擦轮传动.北京：化学工业出版社.2007：12-45表12-1-40,47
[35]范洁川.近代流动显示技术[M].国防工业出版社.2002.
[36]Schramm-Baxter, J., Katrencik, J., and Mitragotri, S., Jet Injection Into Polyacrylamide Gels:Investigation of Jet Injection Mechanics," J. Biomech., 2004,37(8):1181-1188
[37]张志涌.精通MATLAB 6.5版[M].北京：北京航空航天大学出版社,2003
[38]王沫然MATLAB 6.0与科学计算[M].北京：电子工业出版社,2001
[39]王积伟等.液压传动[M].北京：机械工业出版社,2006.12
[40]夏廷栋,胥德孝,彭拾义等.实用密封技术手册[M].哈尔滨：黑龙江科学技术出版社,1985
[41]陈秀宁,顾大强.机械设计[M].杭州：机械设计出版社,2010.1
[42]刘君华,申忠如,郭福田.现代测试技术与系统集成[M].北京：电子工业出版,2005.1
[43]张忠占.概率论与数理统计[M].北京：机械工业出版社,2008.9
[44]International standard. Needle-free injector for medical use:Requirements and test methods [S](ISO21649:2006)
[2]周旭,王伽伯,肖小河.无针注射给药系统及应用[J].解放军药学学报,2005,21(6)：439-443
[3]S. Mitragotri. Immunization without needles[J]. NatRevImmunol,2005.5:905-916
[4]铮奎.无针注射器新品迭出将对我国一次性注射器出口产生影响[N].中国医药报,2008.7.23
[5]金京.无针安全注射器的设计[J]. Journal of Biomedical Engineering Research,2007,26:297-298
[6]James S. Parsons, Laguna Niguel. Needless hypodermic jet injector [P]. United States Patent.5704911,1998.1
[7]陈凯,吕永桂.一种新型液体喷射注射器的研制[J].中国医疗器械杂志,2009(6)：410-412
[8]Toles, Warren L, etc. Charging mechanism for a needle-free injector [P]. International patent. PCT/CA2007/001007,2007.6
[9]Victor T. Rogatchev, etc. Jet injector with hand piece [P]. United States Patent. US 7029457B2,2006.4.18
[10]Pat McCalmon, etc. Hand piece for jet injector [P]. United States atent. US D488862S,2004.4.20
[11]Oliver A. Shergold, Norman A. Fleck, Toby S. King, The penetration of a soft solid by a liquid jet, with application to the administration of a needle-free injection[J], Journal of Biomechanics,2006 (39):2593-2602
[12]帕特里克·亚历山大等.具有两级注射速度的无针注射器[P].中国专利.01805865.5,2003.3.26
[13]艾米·B·安吉尔等,无针注射器[P].中国专利,02824660.8,2005.3.30
[14]Mark W. Rice, etc.. Medical injector and medicament loading system for use therewith [P]. United States Patent. US7341575B2,2008.3.11
[15]帕特里克·亚历山大等.具有嵌合件式注射头的无针注射器[P].中国专利.00810388.7,2002.7.31
[16]鲍里斯·V·斯莫列洛夫等.无针注射器用的通用防感染保护器[P].中国专利.200610121202.7,2007.4.25
[17]韩惠霖.喷射理论及其应用[M].杭州：浙江大学出版社,1990.
[18]陈凯周华.弹簧式液体喷射注射系统的喷射模型及实验研究[J].中国生物医 学工程学报,2010,29(1)：140-144
[19]张玉荣等.高速液体射流流动特性的实验测试方法[J].力学与实践.1999.5：57-58
[20]应人龙.基于喷射理论的无针注射系统建模及实验研究[D].硕士论文.杭州：浙江大学,2008
[21]O.A. Shergold, etc. The uniaxial stress versus strain response of pig skin and silicone rubber at low and high strain rates International Journal Impact Engineering, 2006 (32):1384-1402
[22]曾立群.无针注射器研发[D].硕士论文.杭州：浙江大学,2008
[23]Linn L, Boyd B, Iontchev H, King T, Farr SJ. The effects of system parameters on in vivo administration performance of a needle-free injector in humans. Pharm Res. 2007(24):1501-1507
[24]Joy Baxter, Samir Mitragotri, Jet-induced skin puncture and its impact on needle-free jet injections:Experimental studies and a predictive model, Journal of Controlled Release 2005 (106) 361-373
[25]Samir Mitragotri, Current status and future prospects of needle-free liquid jet injectors, Nature Reviews Drug Discovery,2006 (5) 543-548
[26]Gursoy A, Ertugrul DT, Sahin M, Tutuncu NB, Demirer AN,Demirag NG 2007 Needle-free delivery of lidocaine for reducing the pain associated with the fine-needle aspiration biopsy of thyroid nodules:time-saving and efficacious procedure. Thyroid 17:317-321
[27]焦坤.无针注射器测试评价系统的研究[D].硕士论文.武汉：华中科技大学,2007
[28]Aaron B. Baker, Joan E. Sander. Fluid Mechanics Analysis of a Spring-Loaded Jet Injector, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL.46, NO.2,1999.2
[29]沈星,刘永刚,裘进浩RAINBOW压电陶瓷与形状记忆合金的集成(M).金属热处理.2006.31(8)：15-17
[30]Brian D. Hemond, etc. Development and Performance of a Controllable Auto loading Needle-Free Jet Injector [J]. Journal of Medical Devices,2011.3, Vol.5: 015001
[31]帕特里克·亚历山大等.带有模块化储液器的无针注射器(P).中国专利,01811507.1,2003.8.20
[32]Jeanne C. Stachowiak, etc. Dynamic control of needle-free jet injection [J]. J Control Release,2009,135(2):104-112
[33]赵万生等.应用线电极磨削法的电火花微孔加工[J].电加工.1997.3：13-16
[34]成大先.机械设计手册(第五版)第三卷[S].螺旋传动、摩擦轮传动.北京：化学工业出版社.2007：12-45表12-1-40,47
[35]范洁川.近代流动显示技术[M].国防工业出版社.2002.
[36]Schramm-Baxter, J., Katrencik, J., and Mitragotri, S., Jet Injection Into Polyacrylamide Gels:Investigation of Jet Injection Mechanics," J. Biomech., 2004,37(8):1181-1188
[37]张志涌.精通MATLAB 6.5版[M].北京：北京航空航天大学出版社,2003
[38]王沫然MATLAB 6.0与科学计算[M].北京：电子工业出版社,2001
[39]王积伟等.液压传动[M].北京：机械工业出版社,2006.12
[40]夏廷栋,胥德孝,彭拾义等.实用密封技术手册[M].哈尔滨：黑龙江科学技术出版社,1985
[41]陈秀宁,顾大强.机械设计[M].杭州：机械设计出版社,2010.1
[42]刘君华,申忠如,郭福田.现代测试技术与系统集成[M].北京：电子工业出版,2005.1
[43]张忠占.概率论与数理统计[M].北京：机械工业出版社,2008.9
[44]International standard. Needle-free injector for medical use:Requirements and test methods [S](ISO21649:2006)