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Publication numberCN103861204 A
Publication typeApplication
Application numberCN 201410112423
Publication date18 Jun 2014
Filing date25 Mar 2014
Priority date25 Mar 2014
Also published asCN103861204B
Publication number201410112423.2, CN 103861204 A, CN 103861204A, CN 201410112423, CN-A-103861204, CN103861204 A, CN103861204A, CN201410112423, CN201410112423.2
Inventors王安
Applicant王安
Export CitationBiBTeX, EndNote, RefMan
External Links: SIPO, Espacenet
Modulation ultrasonic wave device and percutaneous administration permeation facilitating method thereof
CN 103861204 A
Abstract
The invention discloses a modulation ultrasonic wave device and application thereof in the percutaneous administration aspect. The modulation ultrasonic wave device comprises a modulation ultrasonic wave generator and a single-channel multi-frequency ultrasonic wave transducer, wherein the modulation ultrasonic wave generator is used for generating modulation ultrasonic wave stimulation electric signals, and the single-channel multi-frequency ultrasonic wave transducer is used for emitting modulation ultrasonic waves. The modulation ultrasonic waves have a synergistic effect on the permeation facilitating effect of percutaneous administration, and the technical problem that ultrasonic waves are insufficient in permeation facilitating of percutaneous administration. An efficient modulation ultrasonic wave permeation facilitating percutaneous administration method is provided for the pharmaceutical industry.
Claims(9)  translated from Chinese
1.一种调制超声波装置,其特征在于:该调制超声波装置包括产生调制超声波激励电信号的调制超声波发生器和发射调制超声波的单通道多频率超声波换能器。 An ultrasonic modulating means, wherein: the modulation means includes an ultrasonic generating an ultrasonic excitation electrical signal modulator modulating the ultrasonic generator and the ultrasonic wave emitting modulated single-channel multi-frequency ultrasonic transducer.
2.根据权利要求1所述的调制超声波装置,其特征在于:所述的调制超声波发生器包括中央控制器,与中央控制器连接的开关电路控制单元、参数设定单元、显示单元以及功率放大控制单元,与开关电路控制单元连接的调制器,与开关电路控制单元和中央控制器连接的高频分量单元、中频分量单元以及低频分量单元,还包括与功率放大控制单元连接的高频分量功率放大器、中频分量功率放大器以及低频分量功率放大器;高频分量单元与高频分量功率放大器连接,中频分量单元与中频分量功率放大器连接,低频分量单元与低频分量功率放大器连接,调制器又分别与高频分量功率放大器、中频分量功率放大器和低频分量功率放大器连接;高频分量单元、中频分量单元以及低频分量单元内部分别设置有连续波发生器和脉冲波发生器。 The modulated ultrasonic apparatus according to claim 1, wherein: said modulation ultrasonic generator comprises a switching circuit control unit central controller, the central controller is connected, the parameter setting unit, a display unit and a power amplification control unit, and a switching circuit connected to the modulator control unit, high-frequency component of the switching circuit unit and the central control unit connected to the controller, the IF component units and low-frequency component unit, further comprising a power amplification control unit is connected with the high-frequency component power amplifier, the intermediate frequency component of the power amplifier and the low frequency component power amplifier; high-frequency component and high frequency component power amplifier unit connected to the intermediate frequency component of the power amplifier unit is connected with an intermediate frequency component, low-frequency component and low frequency component of the power amplifier unit connected to the modulator and high, respectively, and frequency component of the power amplifier, the power amplifier and the intermediate frequency component of a low frequency component power amplifier is connected; high-frequency component unit, the intermediate frequency component and a low-frequency component unit cells are provided with a continuous internal wave generator and the pulse wave generator.
3.根据权利要求2所述的调制超声波装置,其特征在于:调制超声波发生器产生调制超声波激励电信号既含有调频调制成分也包含调幅调制成分,是对三个频率不同和振幅不同的脉冲波、或连续波或脉冲波与连续波组合成的混合波电信号加以合成,生成具有关联性调制超声波激励电信号。 3. modulating the ultrasonic apparatus according to claim 2, wherein: the modulation ultrasonic generator generates ultrasonic excitation electrical signal containing both modulation FM modulation component also includes AM modulated component is of three different frequencies with different amplitudes and pulse , or continuous wave or pulsed wave and continuous wave mixing wave electrical signal to be combined into the synthesis, to generate relevance modulated ultrasonic excitation electrical signal.
4.根据权利要求3所述的调制超声波装置,其特征在于:调制超声波发生器所产生的激励电信号有脉冲波、或连续波或脉冲波与连续波组合成的混合波多种波形激励电信号;激励电信号的频率和幅度(或脉冲幅度与脉冲宽度)可以调节;激励电信号的高频分量频率范围为I~5MHz,中频分量频率范围为200~1000KHz,低频分量频率范围为20~200KHz ;脉冲波的占空比范围为1%~99% ;调制超声波激励电信号周期为调制超声波包含的高频分量、中频分量和低频分量各自的持续时间与三个分量相互之间时间间歇的加和,三个分量各自的持续时间范围为调制超声波周期2~98%。 The modulation of the ultrasonic apparatus according to claim 3, characterized in that: an ultrasonic excitation electrical signal generated by modulating the modulation pulse wave or continuous wave or pulsed wave and continuous wave combined into a variety of mixed wave excitation electrical signal waveform ; excitation frequency and amplitude of the electrical signal (or pulse amplitude and pulse width) can be adjusted; high-frequency component of the frequency range of the excitation electrical signal I ~ 5MHz, the IF component of the frequency range 200 ~ 1000KHz, low frequency components in the frequency range 20 ~ 200KHz ; pulse duty ratio range is 1% to 99%; modulated ultrasonic excitation electrical cycles of the high frequency component modulated ultrasonic waves, the intermediate frequency component and low-frequency components of each of the three components and the duration of the time interval between each other plus and, three components of the duration of each cycle of the ultrasonic modulation range 2 - 98%.
5.根据权利要求1所述的调制超声波装置,其特征在于:所述的单通道多频率超声波换能器包括圆柱形和圆柱梯形单通道多频率超声波换能器,其中,圆柱形单通道多频率超声波换能器,包括外部的支架`和内部的填料,三个圆形压电陶瓷平行分布于填料中,分别通过各自的压电陶瓷电极引线与调制器和开关电路控制单元连接;圆柱梯形单通道多频率超声波换能器,包括外部的支架和内部的填料,填料中央的腔体一端形成梯形,三个圆环状压电陶瓷分布于腔体一端的梯形阶梯上,分别通过各自的压电陶瓷电极引线与调制器和开关电路控制单元连接;单通道多频率超声波换能器把调制超声波激励电信号转换调制超声波。 The modulated ultrasonic apparatus according to claim 1, wherein: said multi-channel frequency of the ultrasonic transducer comprises a cylindrical and a cylindrical single-channel multi-frequency ladder ultrasonic transducer, wherein the cylindrical multi-channel frequency of the ultrasonic transducer, including external and internal brackets `filler, three circular piezoelectric ceramic filler distributed in parallel, respectively, each of the piezoelectric ceramic and the electrode lead with the modulator control unit is connected via a switch circuit; cylindrical trapezoid single-channel multi-frequency ultrasonic transducer, including external and internal stent filler, one end of the cavity forming a trapezoidal central filler, three annular piezoelectric ceramic distributed in the cavity at one end of the step ladder, through their respective pressure ceramics and the modulator electrode leads and the switch circuit connected to the control unit; single-channel multi-frequency ultrasonic transducer converting electrical signals modulated ultrasonic excitation modulated ultrasound.
6.根据权利要求5所述的调制超声波装置,其特征在于:单通道多频率超声波换能器内三个压电陶瓷各自谐振频率取值分别处在高频分量(I~5MHz)、中频分量(200~ΙΟΟΟΚΗζ)、低频分量(20~200KHz)的频率范围内,具体取值取决于所用药物,药物不同,取值不同;所发射调制超声波强度范围为0.05~lOW/cm2 ;单通道系指调制超声波幅射方向和路径相同。 6. Modulation ultrasonic apparatus according to claim 5, characterized in that: a single-channel multi-frequency ultrasonic transducer within three piezoelectric ceramic transducer resonance frequency of the respective frequency component values are respectively in (I ~ 5MHz), middle band component inner (200 ~ ΙΟΟΟΚΗζ), low frequency components (20 ~ 200KHz) frequency range, the specific value depending on the drug, the different drugs used, different values; intensity of the transmitted ultrasonic wave modulated in the range of 0.05 ~ lOW / cm2; single channel means modulated ultrasonic horn same direction and path.
7.权利要求1所述调制超声波装置所产生的调制超声波在经皮给药方面的应用。 The modulated ultrasonic wave generated by the modulation device used in the ultrasonic transdermal administration aspect of claim.
8.根据权利要求7所述的应用,其特征在于:调制超声波参数设定,包括激励电信号波形,是脉冲波、还是连续波或者是脉冲波与连续波组合成的混合波,高频分量(I~5MHz)、中频分量(200~ΙΟΟΟΚΗζ)、低频分量(20~200ΚΗζ)三个分量的频率具体取值,三个分量的振幅或脉冲幅度和脉冲波占空比取值,调制超声波三个分量的强度取值(强度范围`0.05~10 ff/cm2),闻频分量、中频分量、低频分量三个分量相互之间的时间间歇取值(时间间歇范围为高频分量周期时间的I倍至低频分量周期时间的1000倍);调制超声波的高频分量、中频分量和低频分量各自的持续时间,三个分量各自的持续时间范围为调制超声波周期2~98%,调制超声波幅射时间取值(幅射时间范围0.5分钟至24小时)。 8. The use according to claim 7, characterized in that: the ultrasonic modulation parameter setting, including stimulating electrical signal waveform, pulse wave, or a continuous wave or pulsed wave and continuous wave combined into a mixed wave, high frequency components (I ~ 5MHz), an intermediate frequency component (200 ~ ΙΟΟΟΚΗζ), low frequency components (20 ~ 200ΚΗζ) frequency of the specific values of the three components, the three components of the amplitude or pulse amplitude and duty cycle of the pulse wave value, modulation ultrasonic three a component of the intensity values (intensity range `0.05 ~ 10 ff / cm2), Wen-frequency component, IF component, the low-frequency component of the three components of the time interval between each other values (time interval in the range of high-frequency components of the cycle time I 1000-fold to the low frequency components of the cycle time); ultrasonic wave modulated high-frequency component, the intermediate frequency component and low-frequency components of the respective duration of the three components of the duration of each cycle of the ultrasonic modulation range 2 to 98%, the time modulation of the ultrasonic horn value (radiation time ranges from 0.5 to 24 minutes).
9.根据权利要求7所述的应用,其特征在于:调制超声波的高频分量(I~5MHz)、中频分量(200~ΙΟΟΟΚΗ`ζ)、低频分量(20~200KHz)对经皮给药促渗透效应产生协同作用。 9. Application according to claim 7, characterized in that: the ultrasonic wave modulated high-frequency component (I ~ 5MHz), an intermediate frequency component (200 ~ ΙΟΟΟΚΗ`ζ), low frequency components (20 ~ 200KHz) to promote percutaneous administration osmotic effect synergies.
Description  translated from Chinese

一种调制超声波装置及其经皮给药的促渗透方法 An ultrasonic apparatus and the penetration-facilitating transdermal administration prepared by the method

技术领域 FIELD

[0001] 本发明属于超声波经皮治疗、诊断和经皮给药医药领域,调制超声波可进一步提高其穿透生物活体皮肤和组织的能力。 [0001] The present invention belongs to an ultrasonic transdermal therapeutic, diagnostic percutaneous administration and the field of medicine, ultrasound modulation can be further improved its ability to penetrate the skin and in vivo biological tissue. 本发明包括一种调制超声波装置及调制超声波对经皮给药的促渗透方法。 The present invention comprises an ultrasonic modulating means and modulated ultrasound on the percutaneous administration of the penetration method.

背景技术 BACKGROUND

[0002] 经皮给药(也称为透皮给药)是药物通过皮肤吸收的一种给药方式,药物作用于皮肤,穿过角质层,通过皮肤扩散,由毛细血管吸收进入人体循环。 [0002] percutaneous administration (also known as transdermal administration) is a mode of administration of drugs through skin absorption, the drug acting on the skin, through the stratum corneum, diffusion through the skin into the body by capillary absorption cycle. 与传统给药方式相比,具有避免肝脏首过效应及肠胃灭活、维持恒定的血药浓度或药理效应、提高生物利用度、降低药物的不良反应、尽可能地保持药物的持续释放、患者可以自主用药等特点。 Compared with the traditional mode of administration, having to avoid hepatic first-pass effect and gastrointestinal inactivated, maintaining a constant plasma concentration or pharmacological effect, improve the bioavailability, reduce adverse drug reactions, sustained release of the drug as much as possible, the patient You can self-medication and so on. 但是,由于皮肤角质层的屏障作用,大多数药物的透皮性能很差,经皮给药达不到药物的有效治疗血药浓度要求,以至不能实现临床应用。 However, due to the barrier function of the stratum corneum, transdermal poor performance of most drugs, the transdermal administration of drugs reach effective therapeutic blood concentration requirements, as well as clinical application can not be achieved. 所以使用辅助方法提高药物透过皮肤的量,就成了经皮给药的关键。 Therefore, the use of auxiliary methods to improve the amount of drug through the skin, it becomes critical after transdermal administration. 超声波照射皮肤能够明显促进药物的经皮吸收,这种物理方法称之为超声波促渗透,其使用相对安全,皮肤屏障能够很快恢复,药物不会被降解破坏,具有很好的发展前景。 Ultrasonic irradiation of the skin can significantly promote the percutaneous absorption of the drug, which is called the ultrasound penetration-physical methods, the use of relatively safe, can quickly restore the skin barrier, the drug will not be degraded destroyed, with good prospects for development. 现有的超声波促渗透技术对药物的经皮吸收的促渗透作用较为有限,以致大多数透皮性能差的药物还无法实现临床应用。 Existing technology ultrasonic penetration-promoting permeation of drugs for percutaneous absorption is more limited, resulting in poor performance of most transdermal drug can not achieve clinical application. 本发明公开了调制超声波对经皮给药促渗透效应具有协同作用,为医药行业提供了一种高效促渗透经皮给药方法。 The present invention discloses a modulated ultrasonic transdermal drug delivery synergistic effect of the penetration for the pharmaceutical industry to provide an efficient method for the penetration of percutaneous administration.

发明内容 SUMMARY

[0003] 本发明公开了一种调制超声波装置及其经皮给药的促渗透方法。 [0003] The present invention discloses an ultrasonic apparatus and modulating transdermal delivery of the penetration method.

[0004] 1.一种调制超声波装置,本发明所采用的技术方案是: [0004] An ultrasonic modulating apparatus aspect of the present invention is used:

本发明的调制超声波装置`包括产生调制超声波激励电信号的调制超声波发生器和发射调制超声波的超声波换能器,所述的超声波换能器为单通道多频率超声波换能器。 Ultrasonic modulator means `present invention comprises generating an ultrasonic excitation electrical signal modulated ultrasonic generator and modulating modulated ultrasonic transmitter ultrasonic transducer, the ultrasonic transducer is a single-channel multi-frequency ultrasonic transducer.

[0005] 所述的调制超声波发生器包括中央控制器,与中央控制器连接的开关电路控制单元、参数设定单元、显示单元以及功率放大控制单元,与开关电路控制单元连接的调制器,与开关电路控制单元和中央控制器连接的高频分量单元、中频分量单元以及低频分量单元,还包括与功率放大控制单元连接的高频分量功率放大器、中频分量功率放大器以及低频分量功率放大器;高频分量单元与高频分量功率放大器连接,中频分量单元与中频分量功率放大器连接,低频分量单元与低频分量功率放大器连接,调制器又分别与高频分量功率放大器、中频分量功率放大器和低频分量功率放大器连接。 Modulated ultrasonic generator [0005] comprises a central controller, the switching circuit control unit connected with the central controller, the parameter setting unit, a display unit and a power amplification control unit, and a switching circuit connected to the modulator control unit, and high-frequency component unit switching circuit connected to the control unit and the central controller, and the intermediate frequency component of the unit and a low-frequency component unit, further comprising a power amplification control unit is connected with the high frequency component power amplifier, the power amplifier and the intermediate frequency component of the low frequency component power amplifier; High Frequency component units and a power amplifier connected to the high frequency component, the intermediate frequency component of the power amplifier unit is connected with an intermediate frequency component, low-frequency component and low frequency component of the power amplifier unit is connected, the modulator and the power amplifier, respectively, the high frequency component, the intermediate frequency component of the power amplifier and a low frequency component power amplifier connection.

[0006] 其中,高频分量单元、中频分量单元以及低频分量单元内部分别设置有连续波发生器和脉冲波发生器。 [0006] wherein the high-frequency component unit, the intermediate frequency component and a low-frequency component unit cells are provided with a continuous internal wave generator and the pulse wave generator. 高频分量频率范围为I~5MHz,中频分量频率范围为200~1000KHz,低频分量频率范围为20~200KHz。 High-frequency component in the frequency range I ~ 5MHz, the frequency range of the intermediate frequency component is 200 ~ 1000KHz, low frequency components in the frequency range 20 ~ 200KHz.

[0007] 本发明调制超声波装置既含有调频调制成分也包含调幅调制成分,是对三个频率不同和振幅不同电信号加以合成,生成具有一定的关联性调制超声波。 Modulating an ultrasonic apparatus of the invention [0007] The present both an FM modulation component also includes AM modulated component, is to be synthesized on three different frequencies and amplitudes of different electrical signals, generate a modulated ultrasound certain relevance.

[0008] 所述的单通道多频率超声波换能器采用圆柱形单通道多频率超声波换能器或圆柱梯形单通道多频率超声波换能器。 [0008] The single-channel multi-frequency of the ultrasonic transducer using a cylindrical single-channel multi-frequency ultrasonic transducer or cylindrical trapezoidal single-channel multi-frequency ultrasonic transducer. 单通道系指调制超声波幅射方向和路径相同。 Single-channel modulation means the same direction and path of the ultrasonic horn. 圆柱形单通道多频率超声波换能器包括外部的支架和内部的填料,三个圆形压电陶瓷平行分布于填料中,分别通过各自的压电陶瓷电极引线与调制器和开关电路控制单元连接。 Cylindrical multi-channel frequency of the ultrasonic transducer includes an outer stent and an internal filler, three parallel distributed in a circular piezoelectric ceramic filler, respectively, through the respective piezoelectric ceramic electrode lead and the modulator and a switching circuit connected to the control unit . 圆柱梯形单通道多频率超声波换能器包括外部的支架和内部的填料,填料中央的腔体一端形成梯形,三个圆环状压电陶瓷分布于腔体一端的梯形阶梯上,分别通过各自的压电陶瓷电极引线与调制器和开关电路控制单元连接。 Cylindrical trapezoidal single-channel multi-frequency ultrasound transducer includes an outer stent and an internal filler, the filler end of the central cavity formed trapezoid, three annular piezoelectric ceramic distributed on an end of the trapezoidal stepped cavity, through their respective piezoelectric ceramic electrode lead and the modulator and the switch circuit connected to the control unit. 最后,通过单通道多频率超声波换能器把调制激励电信号转化成调制超声波。 Finally, by single-channel multi-frequency ultrasonic transducers is converted to an electric signal modulated excitation modulated ultrasound.

[0009] 2.本发明进一步公开了调制超声波装置在经皮给药促渗透方面的应用,公开了调制超声波对经皮给药的促渗透方法 [0009] 2. The present invention further discloses an ultrasonic modulating means in terms of the penetration-facilitating percutaneous administration application, discloses the modulation of ultrasound on the percutaneous administration method of the penetration-

设置适当调制超声波参数,包括激励电信号波形,是脉冲波、还是连续波或者是脉冲波与连续波组合成的混合波,高频分量(I~5MHz)、中频分量(200~ΙΟΟΟΚΗζ)、低频分量(20~200ΚΗζ)三个分量的频率具体取值,三个分量的振幅或脉冲幅度和脉冲波占空比取值,调制超声波三个分量的强度取值(强度范围0.05~10 W/cm2)及照射时间取值(照射时间范围0.5分钟至24小时),闻频分量、中频分量、低频分量三个分量相互之间的时间间歇取值(时间间歇范围为高频分量周期时间的I倍至低频分量周期时间的1000倍)。 Set the appropriate modulation of ultrasonic parameters, including electrical excitation waveforms, pulse wave, or continuous wave or pulsed wave and continuous wave combined into hybrid wave, high frequency components (I ~ 5MHz), intermediate frequency component (200 ~ ΙΟΟΟΚΗζ), low frequency the specific values of the frequency components (20 ~ 200ΚΗζ) of the three components, the three components of the amplitude or pulse amplitude and duty cycle of the pulse wave value, the three components of the ultrasonic intensity modulation value (intensity range 0.05 ~ 10 W / cm2 ) and the irradiation time value (exposure time range from 0.5 to 24 minutes), Wen frequency component, the intermediate frequency component, low frequency components of the three component values of the time interval between each other (time interval in the range of high frequency components of the cycle time of I-fold to 1000 times the low frequency components of the cycle time). 调制超声波的高频分量、中频分量和低频分量各自的持续时间,三个分量各自的持续时间范围为调制超声波周期2~98%。 Ultrasonic wave modulated high-frequency component, the intermediate frequency component and low-frequency components of the respective duration of each of the three components of duration in the range of 2 to 98 period modulated ultrasonic%. 使用单通道多频率超声波换能器发射调制超声波照射涂抹过药物的皮肤,能够非常显著地提高药物透过皮肤的渗透作用。 Single-channel multi-frequency ultrasonic transducer emitting ultrasonic waves modulated drug applicator through the skin, can be very significantly improve penetration of the drug through the skin.

[0010] 本发明公开了调制超声波中的高频(I~5MHz)分量、中频(20(T1000KHz)和低频(20-200ΚΗζ)分量超声波对经皮给药促渗透效应具有协同作用,调制超声波中的高频分量对经皮给药的促渗透主要作用是打开浅层皮肤(角质层和表皮)的给药传输通道,中频分量和低频分量的超声波促渗透主要作用是在高频分量超声波作用的基础上,进一步突破深层皮肤(真皮和皮下组织)的屏障,进行深度渗透。为医药行业提供了一种高效调制超声波促渗透经皮给药方法。 [0010] The present invention discloses an ultrasonic high frequency modulation (I ~ 5MHz) component, the intermediate frequency (20 (T1000KHz) and low frequency (20-200ΚΗζ) component for percutaneous administration ultrasonic penetration-facilitating synergistic effects, modulation ultrasonic waves The high-frequency component of the penetration-facilitating percutaneous administration role is primarily open shallow skin (stratum corneum and epidermis) administration transmission channel, the intermediate frequency component and the low-frequency component ultrasonic waves of the penetration-major role in the high-frequency component ultrasonic on the basis of a further breakthrough deep skin (dermis and subcutaneous tissue) barrier penetration depth. for the pharmaceutical industry to provide an efficient penetration-modulated ultrasonic transdermal drug delivery methods.

[0011] 3.附图说明 [0011] 3. Brief Description

图1是本发明的调制超声波装置的结构框图; Figure 1 is a block diagram showing the modulation of an ultrasonic apparatus of the present invention;

图2是本发明的调制超声波(脉冲波)的激励电信号图; Figure 2 is a modulator of the present invention, an ultrasonic (pulse wave) of FIG excitation electrical signal;

图3是本发明的调制超声波(连续波)的激励电信号图; Figure 3 is a modulated ultrasonic present invention (continuous wave) excitation electrical diagram;

图4是本发明的调制超声波(混合波)的激励电信号图; Figure 4 is a modulator of the present invention, an ultrasonic (wave mixing) the stimulating electrical signal diagram;

图5是本发明的圆柱形单通道多频率超声波换能器的结构图; Figure 5 is a single channel of the present invention is a cylindrical multiple frequency ultrasonic transducer configuration diagram;

图6是本发明的圆柱梯形单通道多频率超声波换能器的结构图; Figure 6 is a cylindrical trapezoid present invention a single channel multi-frequency ultrasonic transducer configuration diagram;

图中主要部件符号说明: Figure Symbol Description main components:

1.参数设定单元 2.显示单元 1. The parameter setting unit 2. The display unit

3.开关电路控制单元 4.中央控制器 3. The switching circuit control unit 4. The central controller

5.高频分量单元 6.中频分量单元 5. 6. IF frequency component unit component unit

7.低频分量单元 8.高频分量功率放大器 7. 8. The low-frequency component unit frequency component power amplifier

9.中频分量功率放大器 10.低频分量功率放大器 9. IF amplifier 10. The low frequency component power amplifier components

11.单通道多频率超声波换能器 11. The single-channel multi-frequency ultrasound transducer

12.调制器 13.功率放大控制单兀14.调制超声波高频分量的脉冲幅度与脉冲宽度 12. The modulator 13. Wu power amplification control unit 14. The high-frequency component of the modulated ultrasonic pulse amplitude and pulse width

15.调制超声波高频分量的脉冲频率 15. The ultrasonic wave pulse frequency modulation of the high frequency component

16.调制超声波高频分量与中频分量之间间歇时间 16. The interval time between the ultrasound modulation frequency component and intermediate frequency components

17.调制超声波中频分量的脉冲幅度与脉冲宽度 17. The ultrasonic pulse amplitude modulation and pulse width of the intermediate frequency component

18.调制超声波中频分量的脉冲频率 18. IF ultrasonic pulse frequency modulation components

19.调制超声波中频分量与低频分量之间间歇时间 19. The interval time between the ultrasonic IF modulation component and a low frequency component

20.调制超声波低频分量的脉冲幅度与脉冲宽度 20. The ultrasonic pulse amplitude modulated with a low frequency component of the pulse width

21.调制超声波低频分量的脉冲频率 21. The ultrasonic wave pulse frequency modulated low frequency component

22.调制超声波低频分量与高频分量之间间歇时间 22. The time interval between the modulation frequency component and high frequency component ultrasonic

23.调制超声波高频分量的频率 23. The ultrasonic frequency modulation frequency components

24.调制超声波闻频分量的振幅 24. The ultrasound modulation frequency component amplitudes smell

25.调制超声波高频分量与中频分量之间间歇时间 25. The interval time between the high-frequency component and intermediate frequency modulated ultrasonic components

26.调制超声波中频分量的频率 26. IF frequency modulated ultrasonic components

27.调制超声波中频分量的振幅 27. IF amplitude modulated ultrasonic components

28.调制超声波中频分量与低频分量之间间歇时间 28. The time interval between the intermediate frequency modulated ultrasonic component and a low frequency component

29.调制超声波低频分量的频率 29. The modulation frequency of the ultrasonic frequency component

30.调制超声波低频分量的振幅 30. The low frequency ultrasonic wave amplitude modulation component

31.调制超声波低频分量与高频分量之间间歇时间 31. intermittent time between the ultrasonic modulation frequency component and high frequency component

32.调制超声波高频分量的脉冲幅度与脉冲宽度 32. The ultrasonic pulse amplitude modulation and pulse width of the high-frequency component

33.调制超声波高频分量的脉冲频率 33. The ultrasonic wave pulse frequency modulation of the high frequency component

34.调制超声波高频分量与中频分量之间间歇时间 34. The time interval between the intermediate frequency modulated ultrasonic high frequency components and component

35.调制超声波中频分量的频率 35. IF frequency modulated ultrasonic components

36.调制超声波中频分量的振幅 36. IF amplitude modulated ultrasonic components

37.调制超声波中频分量与低频分量之间间歇时间 37. The time interval between the intermediate frequency modulated ultrasonic component and a low frequency component

38.调制超声波低频分量的脉冲幅度与脉冲宽度 38. The ultrasonic pulse amplitude modulated with a low frequency component of the pulse width

39.调制超声波低频分量的脉冲频率 39. The ultrasonic wave pulse frequency modulated low frequency component

40.调制超声波低频分量与高频分量之间间歇时间 40. The time interval between the modulation frequency component and high frequency component ultrasonic

41.谐振频率I压电陶瓷 42.谐振频率2压电陶瓷43.谐振频率3压电陶瓷44.填料 41. The resonant frequency of the piezoelectric ceramic 42. I resonance frequency of two piezoelectric ceramic 43. 44. The resonant frequency of the piezoelectric ceramic filler 3

45.背衬吸收块 45. The backing absorber block

46.谐振频率I压电陶瓷电极引线 46. I resonance frequency of the piezoelectric ceramic electrode lead

47.谐振频率2压电陶瓷电极引线 47. The resonant frequency of the two piezoelectric ceramic electrode lead

48.谐振频率3压电陶瓷电极引线 48. The resonant frequency of the piezoelectric ceramic electrode leads 3

49.支架 50.谐振频率I压电陶瓷51.谐振频率2压电陶瓷52.谐振频率3压电陶瓷 49. I stand resonant frequency of the piezoelectric ceramic 50. 51. 52. The resonant frequency of the resonant frequency of the piezoelectric ceramic 2 3 piezoelectric ceramics

53.腔体 53. Cavity

54.谐振频率I压电陶瓷电极引线 54. I resonance frequency of the piezoelectric ceramic electrode lead

55.谐振频率2压电陶瓷电极引线 55. The resonant frequency of the two piezoelectric ceramic electrode lead

56.谐振频率3压电陶瓷电极引线57.填料 58.支架。 56. The resonant frequency of the piezoelectric ceramic electrode lead 3 57. 58. filler bracket.

[0012] [0012]

具体实施方式 DETAILED DESCRIPTION

[0013] 下面结合附图和具体实施例对本发明调制超声波装置及其经皮给药的促渗透方法做进一步说明,附图中与现有技术相同的部件采用了相同的标号。 [0013] further described below in conjunction with the accompanying drawings and specific embodiments of the present invention, the modulation device and the ultrasonic transdermal delivery of the penetration method to do, the drawings and the prior art like parts are designated with the same reference numerals. 下述各实施例仅用于说明本发明而并非对本发明的限制。 The following examples are for illustration only and not to limit the present invention, the present invention.

[0014] 1.调制超声波装置具体实施方式 [0014] 1. modulating ultrasonic apparatus DETAILED DESCRIPTION

调制是各种通信系统的重要基础,广泛用于广播、电视、雷达、测量仪等电子设备。 Modulation is an important foundation of various communication systems, widely used in radio, television, radar, measuring instruments and other electronic equipment. 调制是一种将信号注入载波,以此信号对载波加以调制的技术,以便将原始信号转变成适合处理和传送的电波信号。 A modulation signal is injected into the carrier, the carrier signal is modulated in this technique, in order to convert the raw signal into a radio signal for processing and transmission. 所谓调幅调制是用调制信号控制载波的振荡振幅,使载波的振幅随着调制信号变化;调频调制是用调制信号控制载波的振荡频率,使载波的频率随着调制信号变化。 The so-called amplitude modulation is used to control the oscillation amplitude modulated carrier signal, the amplitude of the carrier wave with the modulating signal changes; FM modulator is controlled by the oscillation frequency-modulated carrier signal, the frequency carrier with modulation signal changes. 这些不同的调制,是以不同的方法,将信号和载波合成的技术。 These different modulation, different methods based on the signal and the carrier synthesis techniques.

[0015] 本发明的调制超声波装置既含有调频调制成分也包含调幅调制成分,是对三个频率不同和振幅不同电信号加以合成,生成具有一定的关联性调制超声波。 [0015] modulating the ultrasonic apparatus of the present invention contains both FM modulation component also includes AM modulated component, is to be synthesized on the different frequencies and amplitudes of three different electrical signals, generate a modulated ultrasound certain relevance.

[0016] 图1是本发明的调制超声波装置的结构框图。 [0016] FIG. 1 is a block diagram showing the modulation of an ultrasonic apparatus of the present invention. 如图1所示,本发明的调制超声波装置包括产生调制超声波激励电信号的调制超声波发生器和发射调制超声波的超声波换能器,所述的超声波换能器为单通道多频率超声波换能器11。 , The modulation of the ultrasonic apparatus shown in Figure 1 of the present invention includes generating an ultrasonic excitation electrical signal modulated ultrasonic generator and modulating modulated ultrasonic transmitter ultrasonic transducer, the ultrasonic transducer is a single-channel multi-frequency ultrasound transducer 11.

[0017] 调制超声波发生器包括中央控制器4,与中央控制器4连接的开关电路控制单元 [0017] The modulated ultrasonic generator comprises a central controller 4, and the switching circuit control unit connected to the central controller 4

3、参数设定单元1、显示单元2以及功率放大控制单元13,与开关电路控制单元3连接的调制器12,与开关电路控制单元3和中央控制器4连接的高频分量单元5、中频分量单元6以及低频分量单元7,还包括与功率放大控制单元13连接的高频分量功率放大器8、中频分量功率放大器9以及低频分量功率放大器10。 3, the parameter setting unit 1, a display unit 2 and a power amplification control unit 13, a high-frequency component unit and the control unit 3 is connected a switch circuit modulator 12, and the switching circuit control unit 3 and 5 connected to the central controller 4, IF component and a low-frequency component unit 6 unit 7, further comprising a power amplification control unit 13 is connected to the high-frequency component power amplifier 8, 9 and the intermediate frequency component of the low frequency component power amplifier power amplifier 10. 高频分量单元5与高频分量功率放大器8连接,中频分量单元6与中频分量功率放大器9连接,低频分量单元7与低频分量功率放大器10连接。 High-frequency component unit 5 is connected to the high frequency component power amplifier 8, the intermediate frequency component unit 6 is connected to the intermediate frequency component of the power amplifier 9, 7 low-frequency component unit 10 is connected with the low frequency component power amplifier. 调制器12又分别与高频分量功率放大器8、中频分量功率放大器9和低频分量功率放大器10连接。 Modulator 12 and 8, 9 and the intermediate frequency component of the power amplifier 10 is connected with the low frequency components of the power amplifier power amplifier high frequency components, respectively.

[0018] 其中,高频分量单元5、中频分量单元6以及低频分量单元7内部分别设置有连续波发生器和脉冲波发生器,可以产生频率和幅度不同的脉冲波、连续波。 [0018] wherein the internal high-frequency component unit 5, the intermediate frequency component of low-frequency component unit 6 and unit 7 are respectively provided with a continuous-wave generator and a pulse generator, can produce different frequency and amplitude of the pulse wave, continuous wave.

[0019] 调制器按照参数设定的要求,输出调制超声波(脉冲波)的激励电信号,如图2 ;或输出调制超声波(连续波)的激励波电信号,如图3 ;或输出调制超声波(混合波)的激励波电信号,如图4。 [0019] The modulator according to the parameter setting request, the output of the ultrasonic modulation (pulse wave) of the stimulating electrical signal, as shown in Figure 2; excitation wave modulated electrical signal or an ultrasonic output (continuous wave), and FIG. 3; or modulated ultrasound output (mixed wave) excitation wave electrical signal, as shown in Figure 4.

[0020] 单通道多频率超声波换能器系指共用同一腔体副射多个不同频率的超声波,副射方向和路径相同。 [0020] Single-channel multi-frequency ultrasonic transducer ultrasonic means sharing the same cavity deputy shot a number of different frequencies, the same deputy shot direction and path. 单通道多频率超声波换能器11可以采用圆柱形单通道多频率超声波换能器,或者圆柱梯形单通道多频率超声波换能器。 Multi-channel frequency of the ultrasonic transducer 11 may employ a cylindrical single-channel multi-frequency ultrasonic transducer, trapezoidal or cylindrical-channel multi-frequency ultrasonic transducer.

[0021] 图5是本发明的圆柱形单通道多频率超声波换能器的结构图。 [0021] FIG. 5 is a single channel of the present invention, the cylindrical multi-frequency ultrasonic transducer structure. 如图5所示,圆柱形单通道多频率超声波换能器包括外部的支架49,填充在支架49内部的填料44和背衬吸收块45。 As shown in Figure 5, the cylindrical multi-channel frequency of the ultrasonic transducer includes an outer bracket 49, the bracket 49 is filled in the interior of the filler 44 and backing absorber block 45. 背衬吸收块45位于左半部分,填料44位于右半部分。 The backing block 45 is located in the left part of the absorption, the packing 44 in the right half portion. 超声波换能器内部设置有分别对应于三个不同频率的谐振频率I压电陶瓷41、谐振频率2压电陶瓷42和谐振频率3压电陶瓷43。 Ultrasonic transducer is provided with an internal resonance frequency corresponding to the three different frequencies I piezoelectric ceramic 41, the resonant frequency of the piezoelectric ceramic 2 3 42 and the resonance frequency of the piezoelectric ceramic 43. 谐振频率I压电陶瓷41两侧设置有谐振频率I压电陶瓷电极引线46,谐振频率2压电陶瓷42两侧设置有谐振频率2压电陶瓷电极引线47,谐振频率3压电陶瓷43两侧设置有谐振频率3压电陶瓷电极引线48。 I the resonant frequency of the piezoelectric ceramic 41 are provided on both sides of the resonance frequency of the piezoelectric ceramic I electrode leads 46, 42 on both sides of the resonance frequency of the piezoelectric ceramic 2 is provided with a resonant frequency of the second piezoelectric ceramic electrode lead 47, the resonant frequency of the piezoelectric ceramic 43 two 3 3 side is provided with a resonant frequency of the piezoelectric ceramic electrode lead 48. 三个圆形压电陶瓷平行分布于填料中,分别通过各自的压电陶瓷电极弓丨线与调制器和开关电路控制单元连接。 Three circular piezoelectric ceramic filler distributed in parallel, are connected via respective piezoelectric ceramic electrodes bow 丨 line modulator and the switching circuit control unit.

[0022] 图6是本发明的圆柱梯形单通道多频率超声波换能器的结构图。 [0022] FIG. 6 is a cylindrical trapezoid present invention multi-channel frequency of the ultrasonic transducer structure. 如图6所示,圆柱梯形单通道多频率超声波换能器包括外部的支架58和内部的填料57,填料57中央的腔体53 —端形成梯形。 As shown in Figure 6, the cylindrical single-channel multi-frequency ladder ultrasonic transducer holder 58 comprises an external and internal packing 57, the packing 53 of the central cavity 57 - terminal formed trapezoidal. 超声波换能器内部设置有分别对应于三个不同频率的谐振频率I压电陶瓷50、谐振频率2压电陶瓷51和谐振频率3压电陶瓷52。 Ultrasonic transducer is provided with an internal resonance frequency corresponding to the three different frequencies I piezoelectric ceramic 50, the resonant frequency of the piezoelectric ceramic 2 3 51 and the resonance frequency of the piezoelectric ceramic 52. 谐振频率I压电陶瓷50两侧设置有谐振频率I压电陶瓷电极引线54,谐振频率2压电陶瓷51两侧设置有谐振频率2压电陶瓷电极引线55,谐振频率3压电陶瓷52两侧设置有谐振频率3压电陶瓷电极引线 50 I the resonant frequency of the piezoelectric ceramic is provided on both sides of the resonance frequency of the piezoelectric ceramic I electrode lead 54, the resonant frequency of the second piezoelectric ceramic 51 are provided on both sides of the resonance frequency of the second piezoelectric ceramic electrode lead 55, the resonant frequency of the piezoelectric ceramic 52 two 3 side is provided with a resonant frequency of the piezoelectric ceramic electrode lead 3

56。 56. 三个圆环状压电陶瓷分布于腔体一端的梯形阶梯上,分别通过各自的压电陶瓷电极引线与调制器和开关电路控制单元连接。 Three annular piezoelectric ceramic distributed in the cavity at one end of the step ladder, are connected via respective piezoelectric ceramic electrode lead and the modulator and a switching circuit control unit. 压电陶瓷用于将调制电信号转化为调制超声波,并向外发射。 Piezoelectric ceramic used to modulate electrical signals into a modulated ultrasound, and fired out.

[0023] 本发明的调制超声波装置的工作过程如下: [0023] processes and modulating the ultrasonic apparatus of the present invention as follows:

中央控制器根据设定的参数同时向开关电路控制单元、功率放大控制单元和高频分量单元、中频分量单元、低频分量单元发出指令,高频分量单元、中频分量单元和低频分量单元按照指令要求生产连续波或脉冲波高频分量、中频分量和低频分量电信号,这三个分量电信号分别由高频分量功率放大器、中频分量功率放大器和低频分量功率放大器加以适当的放大,放大倍数服从功率放大控制单元的指令要求,调制器将放大后的高频分量、中频分量和低频分量电信号按照参数设定要求进行合成,完成调制。 Central controller according to the set parameters at the same to the switching circuit control means, power amplification control unit and the high-frequency component unit, the intermediate frequency component unit, a low-frequency component unit issues the instruction, the high-frequency component unit, the intermediate frequency component and the low-frequency component unit in accordance with the instruction unit request producing a continuous wave or pulsed wave high frequency component, the intermediate frequency component and low frequency component signals, respectively, the three components of the electrical signal to the high frequency component by the power amplifier, the power amplifier and the intermediate frequency component of a low frequency component power amplifier appropriate amplification, obey power magnification amplification control unit an instruction request, the high-frequency component of the modulator the amplified, intermediate frequency electrical signal component and low-frequency components are synthesized in accordance with the set requirements the parameters, for modulation. 开关电路控制单元按照中央控制器的指令要求对高频分量单元、中频分量单元和低频分量单元是生产连续波还是脉冲波电信号进行切换,还负责单通道多频率超声波换能器的工作频率与调制器输出的调制高频分量、中频分量和低频分量电信号的步调一致的切换。 Switching circuit control means in accordance with the instruction of the central controller unit requires high-frequency component, the intermediate frequency component and low-frequency component unit is a unit for producing a continuous wave or pulsed wave electrical switch, also responsible for single-channel multi-frequency ultrasonic transducer operating frequency modulator output modulation frequency component, the intermediate frequency component and a low-frequency component of the electrical signal in step switching. 最后,通过单通道多频率超声波换能器把调制电信号转化成调制超声波。 Finally, by single-channel multi-frequency ultrasonic transducer to modulate the modulated electrical signal into ultrasonic waves.

[0024] 2.调制超声波对经皮给药的促渗透方法具体实施方式: [0024] 2. Ultrasonic modulation of percutaneous administration of the penetration DETAILED DESCRIPTION:

调制超声波发生器的输出终端需用电缆与单通道多频率超声波换能器连接,使用单通道多频率超声波换能器照射涂过药物的皮肤。 Modulated ultrasonic generator output terminal cable required single-channel multi-frequency ultrasonic transducer is connected, using a single-channel multi-frequency ultrasonic transducer irradiating the coated skin medicines.

[0025] 实施例1 [0025] Example 1

生物活体经皮给药试验:选用约200克昆明种雄性大鼠一只,剃除约4cm2皮肤表面的体毛,表皮处理干净后,涂抹药物2%盐酸利多卡因胶浆(具体配方:盐酸利多卡因10g,壳聚糖4 g, 二甲硅油10 ml,轻苯乙脂0.2 g,5ml聚山梨脂80,加蒸懼水至500ml) 2克。 Transdermal drug delivery in vivo biological tests: selection of about 200 species of male rats 克昆明 one, about 4cm2 shave body hair skin surface after treatment clean skin, apply glue drug lidocaine hydrochloride 2% (specific formula: hydrochloric bullish Cain 10g, chitosan 4 g, simethicone 10 ml, light-phenethyl fat 0.2 g, 5ml polysorbate 80 fat, add distilled water to fear 500ml) 2 grams. 根据实际需求,设置调制超声波的所有参数,高频分量1000kHz、强度0.20W/cm2、脉冲序列占空比10%,中频分量220 kHz、强度0.18W/cm2、脉冲序列占空比16%,低频分量20 kHz、强度 According to actual demand, all the parameters set modulated ultrasonic, high-frequency component 1000kHz, intensity 0.20W / cm2, 10% duty cycle pulse train, the intermediate frequency component of 220 kHz, intensity 0.18W / cm2, 16% duty cycle pulse train, the low-frequency component of 20 kHz, the intensity

0.14 W/cm2、脉冲序列占空比18%,闻频分量与中频分量间歇为5 us,中频分量与低频分量间歇为15us,低频分量与高频分量间歇为50us,调制超声波的高频分量、中频分量和低频分量各自的持续时间分别为20 us,45 us、150 us。 0.14 W / cm2, 18% duty cycle pulse train, the frequency component and the intermediate frequency component of the smell intermission 5 us, the intermediate frequency component and the low-frequency components intermittently for 15us, low-frequency components and high frequency components to high-frequency components intermittently 50us, modulated ultrasonic waves, middle band component and low-frequency components of the respective durations were 20 us, 45 us, 150 us. 用单通道多频率超声波换能器照射涂过药物2%盐酸利多卡因胶浆的皮肤,换能器幅射直径为20mm。 With a single-channel multi-frequency ultrasonic transducer irradiating the coated drug lidocaine hydrochloride 2% mucilage skin, radiation transducer having a diameter of 20mm. 第60分钟抽取老鼠的血液 The first 60 minutes to extract the blood of mice

1.5ml,立刻加1.5ml枸櫞酸,离心分离后取上清液20ul,进行液相色谱分析。 1.5ml, immediately add 1.5ml citrate, after centrifugation the supernatant 20ul, analyzed by liquid chromatography. 色谱条件为:C18柱、4.6X250mm、5um,以醋酸溶液(取冰醋酸50ml,加蒸懼水930ml,用lmol/L氢氧化钠溶液调节PH值至3.40)—甲醇(40:60 )为流动相,检测波长254nm,柱温30C。 Chromatographic conditions: C18 column, 4.6X250mm, 5um, with acetic acid solution (glacial acetic acid taken 50ml, add distilled water fear 930ml, adjusting the PH value to 3.40 with lmol L sodium hydroxide solution /) - methanol (40:60) as the mobile detection wavelength 254nm, the column temperature was 30 C. 测得盐酸利多卡因血药浓度为19.7ug/ml。 Measured plasma concentration of lidocaine hydrochloride 19.7ug / ml. 用同样的方法,同样的实验参数,分别用高频分量对应的超声波1000kHz、强度0.20W/cm2、脉冲序列占空比10%,中频分量对应的超声波220 kHz、强度 The same way, the same experimental parameters, respectively corresponding to high-frequency component ultrasonic 1000kHz, intensity 0.20W / cm2, 10% duty cycle pulse train, the intermediate frequency component corresponding ultrasonic 220 kHz, intensity

0.18 W/cm2、脉冲序列占空比16%,和低频分量对应的超声波20 kHz、强度0.14 W/cm2、脉冲序列占空比18%,使用对应频率超声波换能器(幅射直径为20mm)照射涂过2克药物2%盐酸利多卡因胶浆的皮肤。 0.18 W / cm2, 16% duty cycle pulse train, and the low-frequency component corresponding to the ultrasound 20 kHz, intensity 0.14 W / cm2, 18% duty cycle pulse sequence, using the corresponding frequency of the ultrasonic transducer (radiation having a diameter of 20mm) 2 g of drug coated irradiation of 2% lidocaine hydrochloride skin glue. 在第20分钟抽取老鼠的血液1.5ml,经处理后,测得盐酸利多卡因血药浓度分别为3.lug/ml、3.7ug/ml、3.8ug/ml。 Extracting the first 20 minutes the rat blood 1.5ml, after treatment, the measured plasma concentration of lidocaine hydrochloride were 3.lug / ml, 3.7ug / ml, 3.8ug / ml. 实验结果是,使用调制超声波方法测得盐酸利多卡因血药浓度大于高频分量、中频分量和低频分量对应的超声波方法3次测得盐酸利多卡因血药浓度的加和。 The experimental results, the use of modulation of ultrasonic waves measured lidocaine hydrochloride plasma concentration is greater than the high frequency component, the intermediate frequency component and a low frequency component corresponding to the ultrasonically measured 3 times the plasma concentration of lidocaine hydrochloride additive.

[0026] 使用与调制超声波相同参数的高频分量对应的超声波照射20分钟后,切换用中频分量对应的超声波照射20分钟后,切换用低频分量对应的超声波照射20分钟,分别使用对应频率超声波换能器(换能器幅射直径为20mm)照射涂过2克药物2%盐酸利多卡因胶浆的老鼠的皮肤。 [0026] The high-frequency component ultrasonic waves using the same modulation parameters corresponding to the ultrasonic irradiation for 20 minutes after switching the intermediate frequency component corresponding to ultrasonic irradiation for 20 minutes, switching the low frequency component corresponding to ultrasonic irradiation for 20 minutes, respectively, using the corresponding frequency of the ultrasonic transducer transducer (transducer radiation diameter 20mm) irradiated coated 2 g 2% lidocaine hydrochloride drug mortar mouse skin. 第60分钟(三段超声波照射的合计时间为60分钟)抽取老鼠的血液1.5ml,经处理后,测得盐酸利多卡血药浓度为11.8ug/ml。 60 minutes (total time of three sections for 60 minutes ultrasonic irradiation) rat blood drawn 1.5ml, after treatment, the measured plasma concentration of lidocaine hydrochloride 11.8ug / ml. 实验结果是,使用调制超声波方法测得盐酸利多卡因血药浓度大于高频分量、中频分量和低频分量对应的超声波三段照射测得盐酸利多卡因血药浓度的总和。 The experimental results, the use of modulation of ultrasonic waves measured lidocaine hydrochloride plasma concentration is greater than the high frequency component, the irradiation measure three sections corresponding to the intermediate frequency component and a low-frequency component ultrasonic waves was the sum of the plasma concentration of lidocaine hydrochloride.

[0027] 本底实验:没有超声波照射,用同样的方法检测,在第60分钟测得药物盐酸利多卡因血药浓度是9.8ug/ml。 [0027] Background experiments: no ultrasonic irradiation, detected by the same method, in the first 60 minutes of drug measured plasma concentration of lidocaine hydrochloride is 9.8ug / ml.

[0028] 实验证明,调制超声波中的高频分量、中频分量和低频分量对经皮给药的促渗透效应具有协同作用。 [0028] The experiments show that, in the ultrasound modulated high-frequency components and low frequency components of the intermediate frequency component percutaneous administration of the penetration-facilitating effect of a synergistic effect.

[0029] 完成以上实验所用的大鼠为同一只,每次实验时间相隔叁天。 [0029] After the above experiment used only for the same rats, each experimental time intervals Santian.

[0030] 实施例2` [0030] EXAMPLE 2`

离体经皮给药试验:离体鼠皮的制备,取约200克昆明种雄性大鼠一只,处死后剃除鼠毛,确保皮肤角质层完好无损,除去皮下组织和脂肪,用生理盐水漂洗干净。 In vitro percutaneous administration test: Preparation Rat skin off, take about 200 克昆明 a kind of male rats, mice were sacrificed after shave the hair to ensure the cuticle intact skin, subcutaneous tissue and fat is removed with saline rinse clean. 取适当面积漂洗干净的离体鼠皮,角质层面朝向供给池,固定于Franz扩散池(Franz扩散池由供给池和接收池两部分组成)中间。 Take appropriate area rinse vitro rat skin, the stratum corneum side facing the supply tank, fixed on Franz diffusion cells (Franz diffusion cell pool by the supply tank and the reception of two parts) in the middle. Franz扩散池直径22mm,其中供给池容积30ml,接收池容积60ml,接收池注满25%乙醇一生理盐水,确保与鼠皮之间无气泡,接收池内需放入一枚磁力搅拌子,在供给池内加入药物5%咖啡因(配制方法:取5g咖啡因、25ml乙醇、IOml丙二醇,加 Franz diffusion cell diameter of 22mm, wherein the supply tank volume 30ml, receiving tank volume 60ml, receiving tank filled with 25% ethanol and a physiological saline, to ensure that no air bubbles between the rat skin, the reception tanks into 一枚 need a magnetic stirrer, the supply join the pool of drug 5% caffeine (Preparation method: Take 5g caffeine, 25ml ethanol, IOml propylene glycol, plus

0.1M醋酸钠缓冲溶液(PH=7.1)至100ml,搅拌至咖啡因完全溶解后,再加Ig卡波940,搅匀)2g。 0.1M sodium acetate buffer solution (PH = 7.1) to 100ml, stir until completely dissolved caffeine, plus Ig Kaposi 940, stir) 2g. Franz扩散池需保持32C恒温,将Franz扩散池放在磁力搅拌器上,搅拌速度200转/分钟。 Franz diffusion cells required to maintain constant temperature 32 C, the Franz diffusion cell on a magnetic stirrer, a stirring speed of 200 rev / min. 把单通道多频率超声波换能器插入供给池,换能器幅射直径为20_,设置调制超声波的所有参数,高频分量3000kHz连续波、强度0.40ff/cm2,中频分量为无,低频分量20kHz连续波、强度0.30 W/cm2,高频分量与低频分量之间无间歇,调制超声波的高频分量和低频分量各自的持续时间相同,均为300 us,开启调制超声波发生器。 The single-channel multi-frequency ultrasonic transducer inserted into the feeder tank, the transducer diameter 20_ radiation, ultrasonic setting modulation parameters of all, the high frequency component 3000kHz continuous wave, the intensity 0.40ff / cm2, the intermediate frequency component is no low-frequency component 20kHz continuous wave, the intensity of 0.30 W / cm2, no high-frequency component and low frequency component between the intermittent, high-frequency components and low frequency components of the modulated ultrasound same respective durations, are 300 us, open modulated ultrasonic generator. 分别在第15、30、45、60分钟,吸取5ml接收液,同时回补等量的25%乙醇一生理盐水。 15,30,45,60 respectively, in the first minute, draw 5ml receiving liquid, while covering the same amount of 25% ethanol and a saline. 吸取的接收液经离心分离过滤处理后,使用紫外分光光度法检测其药物咖啡因浓度,检测波长273nm。 After receiving the liquid drawn by centrifugation filtration treatment using ultraviolet spectrophotometry to detect the drug caffeine concentration, detection wavelength 273nm. 测得药物咖啡因浓度分别为17.6ug/ml、17.2ug/ml、16.7ug/ml、16.7ug/ml。 Measured drug concentrations of caffeine were 17.6ug / ml, 17.2ug / ml, 16.7ug / ml, 16.7ug / ml.

[0031] 用同样的方法,同样的实验参数,使用高频分量对应的超声波3000kHz连续波、强度0.40W/cm2,和对应频率3000kHz超声波换能器,分别在第15、30、45、60分钟,吸取5ml接收液,同时回补等量的25%乙醇一生理盐水。 [0031] the same way, the same experimental parameters, the use of high-frequency component corresponding to 3000kHz ultrasonic continuous wave, the intensity of 0.40W / cm2, and the corresponding frequency 3000kHz ultrasonic transducers, respectively, in the first 15,30,45,60 minutes absorb 5ml receiving liquid, while covering the same amount of 25% ethanol and a saline. 吸取的接收液经离心分离过滤处理后,使用紫外分光光度法测得药物咖啡因浓度分别是3.3ug/ml、7.2ug/ml、7.3ug/ml、7.4ug/ml ;使用低频分量对应的超声波20kHz连续波、强度0.40 W/cm2,和对应频率20 kHz超声波换能器,分别在第15、30、45、60分钟,测得药物咖啡因浓度分别是4.8ug/ml、9.0ug/ml、8.8ug/ml、8.6ug/ml。 After receiving the liquid drawn by centrifugation filtration treatment using ultraviolet spectrophotometry drug caffeine concentrations measured were 3.3ug / ml, 7.2ug / ml, 7.3ug / ml, 7.4ug / ml; the use of low-frequency component corresponding ultrasound 20kHz continuous wave, the intensity of 0.40 W / cm2, and the corresponding frequency of 20 kHz ultrasonic transducers, respectively, in the first 15,30,45,60 minutes, measured drug concentrations of caffeine is 4.8ug / ml, 9.0ug / ml, 8.8ug / ml, 8.6ug / ml.

[0032] 实验结果也是,使用调制超声波方法测得接收液的药物咖啡因浓度大于高频分量3000kHz和低频分量20kHz对应的超声波方法测得接收液的药物咖啡因浓度。 [0032] The results also, the drug caffeine concentrations measured using the modulation method of ultrasonic receiver solution is greater than the high-frequency components and low frequency components 3000kHz 20kHz ultrasonic method corresponding drug caffeine concentration measured receiving fluid.

[0033] 本底实验:没有超声波照射,用同样的方法检测,在第15、30、45、60分钟测得接收液的药物咖啡因浓度分别是3.2ug/ml、4.9ug/ml、5.4ug/ml、5.5ug/ml。 [0033] The end of the experiment: no ultrasonic irradiation, detected by the same method, the caffeine concentration of the drug in the first receiving liquid 15,30,45,60 minute measured were 3.2ug / ml, 4.9ug / ml, 5.4ug /ml,5.5ug/ml.

[0034] 实验证明,调制超声波对经皮给药的促渗透效应具有协同作用。 [0034] Experimental results show that modulation of ultrasound on the percutaneous administration of the synergistic effect of the penetration.

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