A vortex ultrasonic transdermal drug delivery device and method

Abstract

The present invention provides a vortex ultrasonic transdermal drug delivery device and method, which are applied to the technical field of transdermal drug delivery. The device includes an annular transducer array and a multi-channel phase driving module. The multi-channel phase driving module is used to control each ultrasonic transducer in the annular transducer array to generate ultrasonic waves with different initial phases. The ultrasonic waves with multiple different initial phases are coherently superposed during the transmission process, and finally a vortex sound beam is formed in the area where transdermal drug delivery is required. The vortex sound beam has an axial acoustic radiation force for deeply promoting the drug in the main propagation direction, and a transverse acoustic radiation force for expanding the skin pore permeability in the plane perpendicular to the main propagation direction. Under the action of the axial acoustic radiation force and the transverse acoustic radiation force, the efficiency and effect of transdermal drug delivery are improved. The transverse acoustic radiation force and axial radiation force generated by the vortex sound beam promote the expansion of the gaps in the stratum corneum and push the drug to deeply penetrate, thereby improving the efficiency and effect of transdermal drug delivery.

Description

Technical Field

[0001] The invention belongs to the technical field of transdermal drug delivery, and in particular relates to a vortex ultrasonic transdermal drug delivery device and method. Background Art

[0002] Transdermal drug delivery refers to a treatment method that uses physical or chemical methods to allow drugs placed on the skin to penetrate the skin and enter the circulatory system to play a therapeutic role. Transdermal drug delivery has many advantages, and it can avoid the "first-pass effect" of the liver and the damage of the gastrointestinal tract.

[0003] Ultrasonic transdermal drug delivery is a method that uses the physical effects of ultrasound to promote the entry of drugs into the body through the skin barrier. Compared with chemical and pharmaceutical penetration enhancement methods, low-frequency ultrasound causes less irritation to patients when acting on the skin, avoids the phenomenon of human body allergic reactions to penetration enhancers and certain solvents in microbubbles, and has higher safety.

[0004] Among the existing ultrasound transdermal drug delivery schemes, the acoustic cavitation effect is mainly used to increase the permeability of the skin, while there are relatively few schemes based on the mechanical effect of ultrasound to promote drug penetration. As a direct manifestation of the mechanical effect of ultrasound, the acoustic radiation force is often only considered in existing schemes to promote drug delivery by using a focused acoustic beam and other methods to generate an axial radiation force perpendicular to the skin to push the drug to the targeted area. The efficiency and effect of transdermal drug delivery through this method are generally poor and need further improvement. Summary of the invention

[0005] In view of the above problems in the prior art, the purpose of the present invention is to provide a vortex ultrasonic transdermal drug delivery device, which promotes the expansion of the gaps in the stratum corneum through the lateral acoustic radiation force and axial radiation force generated by the vortex acoustic beam, promotes deep penetration of drugs, and thus improves the efficiency and effect of transdermal drug delivery.

[0006] A vortex ultrasonic transdermal drug delivery device comprises an annular transducer array and a multi-channel phase driving module. The multi-channel phase driving module is used to control each ultrasonic transducer in the annular transducer array to generate ultrasonic waves with different initial phases. Multiple ultrasonic waves with different initial phases are coherently superimposed during transmission, and finally form a vortex acoustic beam in an area where transdermal drug delivery is required. The vortex acoustic beam has an axial acoustic radiation force in the main propagation direction for deeply pushing drugs, and the vortex acoustic beam has a lateral acoustic radiation force in a plane perpendicular to the main propagation direction for expanding the permeability of skin pores. Under the action of the axial acoustic radiation force and the lateral acoustic radiation force, the efficiency and effect of transdermal drug delivery are improved.

[0007] Preferably, the annular transducer array includes N ultrasonic transducers and an annular connector, the center of the annular connector is set at the center of the transdermal drug delivery area, and the N connecting ends of the annular connector are respectively connected to the N ultrasonic transducers, so that the N ultrasonic transducers are distributed in a circular array.

[0008] Preferably, each ultrasonic transducer in the annular transducer array is arranged at the same height so that the annular transducer array is in close contact with the drug pool.

[0009] Preferably, the annular connector is made of resin and is manufactured by 3D printing.

[0010] Preferably, the calculation formula for the initial phase of the ultrasonic wave generated by the nth ultrasonic transducer in the annular transducer array is: , where m is the topological charge, N is the number of transducers, .

[0011] Preferably, the number of the ultrasonic transducers is set to eight, and the annular transducer array composed of eight ultrasonic transducers and an annular connector generates a vortex acoustic beam with a topological charge number m of 1 or 2.

[0012] Preferably, the multi-channel phase driving module includes an FPGA board, a signal generator and a power amplifier. The FPGA board controls the signal generator to generate an electrical signal. The electrical signal is processed by the power amplifier and reaches the annular transducer array to drive the ultrasonic transducer to emit an ultrasonic wave corresponding to the initial phase.

[0013] Another object of the present invention is to provide a vortex ultrasound transdermal drug delivery method, comprising the following steps:

[0014] The first step is to receive a drug administration instruction, wherein the drug administration instruction includes a drug administration time and a transdermal drug administration area, wherein the drug administration time is used to determine the start and end time of the drug administration device, and the transdermal drug administration area is used to determine the area size of the drug output range of the drug administration device;

[0015] The second step is to generate a corresponding vortex acoustic beam according to the determined transdermal drug delivery area: each ultrasonic transducer in the annular transducer array is controlled by a multi-channel phase driving module to generate ultrasonic waves with different initial phases, and multiple ultrasonic waves with different initial phases are coherently superimposed during the transmission process, and finally a vortex acoustic beam is formed in the transdermal drug delivery area;

[0016] The third step is drug release: the axial acoustic radiation force generated by the vortex acoustic beam is used to push the drug deeply, and the lateral acoustic radiation force is used to expand the permeability of skin pores to drive the drug to move.

[0017] Preferably, the annular transducer array includes N ultrasonic transducers and an annular connector, the center of the annular connector is set at the center of the transdermal drug delivery area, and the N connecting ends of the annular connector are respectively connected to the N ultrasonic transducers, so that the N ultrasonic transducers are distributed in a circular array, and each ultrasonic transducer in the annular transducer array is set at the same height, so that the annular transducer array is close to the drug pool; the multi-channel phase drive module includes an FPGA board, a signal generator and a power amplifier, the FPGA board controls the signal generator to generate an electrical signal, and the electrical signal is processed by the power amplifier and reaches the annular transducer array to drive the ultrasonic transducer to emit an ultrasonic wave corresponding to the initial phase.

[0018] Preferably, the axial acoustic radiation force direction of the vortex acoustic beam is the main propagation direction of the vortex acoustic beam, and the lateral acoustic radiation force direction of the vortex acoustic beam is perpendicular to the main propagation direction of the vortex acoustic beam.

[0019] The beneficial effects of the present invention are as follows: the vortex ultrasound transdermal drug delivery device and method controls the annular transducer array to generate a vortex acoustic beam through a multi-channel phase drive module, and relies on the characteristics of the spiral phase distribution of the vortex acoustic beam to enable it to generate a lateral acoustic radiation force on a plane perpendicular to the main propagation direction, thereby expanding the permeability of the pores on the stratum corneum of the skin through a mechanical effect; and the vortex acoustic beam can also generate a strong axial acoustic radiation force in the main propagation direction, thereby pushing the drug into the deep layer of the skin.

[0020] Compared with traditional ultrasonic transdermal drug delivery methods, the use of special vortex acoustic beams can also produce acoustic cavitation effects on the skin to increase drug permeability. In addition, vortex acoustic beams can generate strong lateral acoustic radiation forces, which provides new degrees of freedom in the design of ultrasonic transdermal drug delivery schemes and can achieve better drug delivery effects.

[0021] In addition, in the face of different situations in the transdermal drug delivery process, the annular transducer array can produce vortex acoustic beams with different topological charges by adjusting the number of ultrasonic transducers and the initial phase of the generated ultrasonic waves. Then, by changing the amplitude of the excitation signal, the magnitude of the generated acoustic radiation force can be controlled, thereby controlling the permeability of the drug. It has high flexibility in use and high adaptability. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0023] Figure 1 It is a schematic diagram of the principle of the present invention;

[0024] Figure 2 It is the normalized sound pressure distribution and phase distribution diagram of the vortex sound beam generated by the present invention;

[0025] Figure 3 It is a normalized sound pressure distribution diagram along the center of the vortex sound beam generated by the present invention;

[0026] Figure 4 It is a flow chart of the present invention. DETAILED DESCRIPTION

[0027] Embodiment 1

[0028] like Figure 1 As shown, a vortex ultrasonic transdermal drug delivery device includes an annular transducer array and a multi-channel phase driving module. The multi-channel phase driving module is used to control each ultrasonic transducer in the annular transducer array to generate ultrasonic waves with different initial phases. Multiple ultrasonic waves with different initial phases are coherently superimposed during the transmission process, and finally a vortex acoustic beam is formed in the area where transdermal drug delivery is required. The vortex acoustic beam opens the drug delivery channel to increase the permeability.

[0029] On the one hand, the annular transducer array includes N ultrasonic transducers and an annular connector, the center of the annular connector is set at the center of the transdermal drug delivery area, and the N connecting ends of the annular connector are respectively connected to the N ultrasonic transducers, so that the N ultrasonic transducers are distributed in a circular array. Specifically, each ultrasonic transducer in the annular transducer array is set at the same height, so that the annular transducer array is close to the drug pool, which is convenient for transmitting energy to the drug pool. Figure 1 As shown, in this embodiment, eight ultrasonic transducers are arranged in a ring-shaped distribution to form a ring-shaped transducer array, wherein the ring-shaped connecting member is made of resin and is made by 3D printing.

[0030] On the other hand, the multi-channel phase driving module includes an FPGA board, a signal generator and a power amplifier. The FPGA board controls the signal generator to generate an electrical signal. The electrical signal is processed by the power amplifier and reaches the annular transducer array to drive the ultrasonic transducer to emit an ultrasonic wave corresponding to the initial phase. According to actual needs, the corresponding FPGA board, signal generator and power amplifier in the prior art can be selected to generate an electrical signal capable of driving the ultrasonic transducer to emit the corresponding ultrasonic wave.

[0031] Among them, the vortex sound beam is a special sound beam with a central zero field intensity and a spiral phase. The mathematical expression of its spiral phase can be expressed by Said that among them It is the order of the vortex, indicating the topological charge of the vortex acoustic beam. It means the number of times the phase changes from 0 to 2π within a wavelength range, which is generally an integer. Relying on the acoustic radiation force of the vortex acoustic beam, it can penetrate biological tissues in a non-invasive and non-contact manner to manipulate drugs and cells.

[0032] Specifically, the calculation formula for the initial phase of the ultrasonic wave generated by the nth ultrasonic transducer in the annular transducer array is: , where m is the topological charge, N is the number of transducers, .like Figure 1 The annular transducer array formed by eight ultrasonic transducers shown is capable of generating vortex acoustic beams with topological charges of 1 and 2.

[0033] It should be noted that the number of ultrasonic transducers and the topological charge can be adjusted to cope with different situations in the transdermal drug delivery process, and then the magnitude of the acoustic radiation force generated can be controlled by changing the amplitude of the excitation electrical signal emitted by the multi-channel phase drive module, thereby adjusting the permeability of the drug.

[0034] Figure 2 The figure shows the normalized sound pressure diagram and phase distribution diagram of the vortex sound beam with a topological charge number m of 1 generated by the annular transducer array, where Figure 2 (a) shows the normalized sound pressure diagram of the vortex sound beam. Figure 2 (b) shows the phase distribution of the vortex acoustic beam.

[0035] Figure 3 Shown is the normalized pressure distribution diagram of the vortex acoustic beam along the center, which includes a central zero field intensity and a surrounding high sound pressure ring. The central zero field intensity area of ​​the vortex acoustic beam can be controlled by adjusting the topological charge number m of the vortex acoustic beam and the frequency of the ultrasonic wave that generates the vortex acoustic beam. The unique sound pressure distribution of the vortex acoustic beam can generate a strong acoustic radiation force near the center of the vortex, thereby promoting the permeability of the skin through the mechanical effect of ultrasound.

[0036] Please refer to Figure 1 , ultrasonic waves with different initial phases generated by multiple annular transducers are coherently superimposed during propagation to form a vortex acoustic beam with a central zero field intensity distribution and a spiral phase distribution. Because of the spiral phase distribution of the vortex acoustic beam, the velocity potential distribution on the plane perpendicular to the main propagation direction is also spiral. The strong lateral fluctuations can produce a strong lateral acoustic radiation force on the skin, expand the pore size on the skin and enhance the permeability, so that the therapeutic effect of transdermal drug delivery is enhanced. In addition, in the main propagation direction, the vortex acoustic beam can also generate a strong axial acoustic radiation force, thereby pushing the drug into the deep layer of the skin. Therefore, the lateral acoustic radiation force and the axial acoustic radiation force are simultaneously generated by the vortex acoustic beam, the skin permeability is expanded under the action of the lateral acoustic radiation force, and the drug is pushed deep under the action of the axial acoustic radiation force, so as to improve the efficiency and effect of transdermal drug delivery.

[0037] Embodiment 2

[0038] like Figure 4 As shown, a vortex ultrasound transdermal drug delivery method specifically comprises the following steps:

[0039] The first step is to receive a drug administration instruction, which includes a drug administration time and a transdermal drug administration area. The drug administration time is used to determine the start and end time of the drug administration device, and the transdermal drug administration area is used to determine the area of ​​the drug output range of the drug administration device. Combined with existing medical methods, the lesion area is observed through medical imaging equipment to determine the area that needs transdermal drug administration treatment.

[0040] The second step is to generate the required vortex acoustic beam corresponding to the determined transdermal drug delivery area: each ultrasonic transducer in the annular transducer array is controlled by a multi-channel phase drive module to generate ultrasonic waves with different initial phases. Multiple ultrasonic waves with different initial phases are coherently superimposed during the transmission process, and finally a vortex acoustic beam is formed in the area where transdermal drug delivery is required.

[0041] Specifically, the annular transducer array is composed of N ultrasonic transducers and an annular connector, the center of the annular connector is set at the center of the transdermal drug delivery area, and the N connecting ends of the annular connector are respectively connected to the N ultrasonic transducers, so that the N ultrasonic transducers are distributed in a circular array. Each ultrasonic transducer in the annular transducer array is at the same height, so that the annular transducer array is close to the drug pool, which is convenient for transmitting energy to the drug pool.

[0042] The multi-channel phase driving module includes an FPGA board, a signal generator and a power amplifier. The FPGA board controls the signal generator to generate an electrical signal. After being processed by the power amplifier, the electrical signal reaches the annular transducer array to drive the ultrasonic transducer to emit an ultrasonic wave corresponding to the initial phase.

[0043] The calculation formula for the initial phase of the ultrasonic wave generated by the nth ultrasonic transducer in the annular transducer array is: , where m is the topological charge, N is the number of transducers, By adjusting the number of ultrasonic transducers, topological charge and other parameters, the vortex acoustic beam can be accurately generated in the area where transdermal drug delivery is required.

[0044] The third step is to release the drug: ultrasonic waves with different initial phases generated by multiple annular transducers are coherently superimposed during propagation to form a vortex acoustic beam with a central zero field intensity distribution and a spiral phase distribution. The spiral phase distribution of the vortex acoustic beam makes the velocity potential distribution in the plane perpendicular to the main propagation direction also spiral. The strong lateral fluctuations produce a strong lateral acoustic radiation force on the skin, which can expand the pore size on the skin and enhance the permeability, thereby enhancing the therapeutic effect of transdermal drug delivery. In addition, in the main propagation direction, the vortex acoustic beam can also produce a strong axial acoustic radiation force to push the drug deeper into the skin. Use the vortex acoustic beam to continuously act on the treatment area to achieve the drug delivery function covering the entire treatment area to promote healing.

[0045] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention is described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A vortex ultrasonic transdermal drug delivery device, characterized in that: The invention comprises an annular transducer array and a multi-channel phase driving module, wherein the multi-channel phase driving module is used to control each ultrasonic transducer in the annular transducer array to generate ultrasonic waves with different initial phases, and multiple ultrasonic waves with different initial phases are coherently superimposed during the transmission process, and finally form a vortex acoustic beam in the area where transdermal drug delivery is required; The vortex acoustic beam has an axial acoustic radiation force in the main propagation direction for pushing the drug deeply, and a lateral acoustic radiation force in the plane perpendicular to the main propagation direction for expanding the permeability of skin pores. Under the action of the axial acoustic radiation force and the lateral acoustic radiation force, the efficiency and effect of transdermal drug delivery are improved.

2. The vortex ultrasonic transdermal drug delivery device according to claim 1, characterized in that: The annular transducer array includes N ultrasonic transducers and an annular connector, the center of the annular connector is set at the center of the transdermal drug delivery area, and the N connecting ends of the annular connector are respectively connected to the N ultrasonic transducers, so that the N ultrasonic transducers are distributed in a circular array.

3. The vortex ultrasonic transdermal drug delivery device according to claim 2, characterized in that: Each ultrasonic transducer in the annular transducer array is arranged at the same height so that the annular transducer array is closely attached to the drug pool.

4. The vortex ultrasonic transdermal drug delivery device according to claim 2, characterized in that: The annular connecting piece is made of resin.

5. The vortex ultrasonic transdermal drug delivery device according to claim 2, characterized in that: The calculation formula for the initial phase of the ultrasonic wave generated by the nth ultrasonic transducer in the annular transducer array is: Where m is the topological charge, N is the number of transducers, n=0, ..., (N-1).

6. The vortex ultrasonic transdermal drug delivery device according to claim 5, characterized in that: The number of the ultrasonic transducers is set to eight, and the annular transducer array composed of the eight ultrasonic transducers and the annular connector generates a vortex acoustic beam with a topological charge number m of 1 or 2.

7. The vortex ultrasonic transdermal drug delivery device according to claim 1, characterized in that: The multi-channel phase driving module includes an FPGA board, a signal generator and a power amplifier. The FPGA board controls the signal generator to generate an electrical signal. After being processed by the power amplifier, the electrical signal reaches the annular transducer array to drive the ultrasonic transducer to emit an ultrasonic wave corresponding to the initial phase.

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