CN114305855B - Eye administration auxiliary device - Google Patents

Abstract

The application discloses an eye drug delivery auxiliary device, which comprises an ultrasonic transducer and an ultrasonic excitation source, wherein the ultrasonic transducer and the ultrasonic excitation source are separately or electrically connected, and the ultrasonic excitation source is used for driving the ultrasonic transducer to work; the ultrasonic transducer comprises a piezoelectric wafer array, an elastic membrane layer and a backing fixed layer, wherein the elastic membrane layer is in a spherical annular band shape and has curvature close to that of an eyeball; the piezoelectric wafer array is clamped between the elastic membrane layer and the backing fixed layer. When the application is applied to ocular administration, the drug is carried by adopting the sound sensitive agent and placed on the surface of ocular tissues, the sound sensitive agent is excited by utilizing the ultrasonic transducer, micron-sized perforation expansion is formed on the sclera, on the basis of avoiding tissue damage, the gap between tissue cells is obviously increased, the drug can quickly and efficiently permeate into the sclera and diffuse into the inside of the eye, the delivery breadth and depth of the drug in the tissues are improved, and the permeability and the utilization rate of the drug entering the eyes are greatly improved; the use of the medicine reduces the medicine waste, and ensures that the dosage control is more accurate and effective.

Description

Ocular drug delivery aids

Technical field

The present invention relates to the field of medical devices, and in particular to an eye drug delivery device.

Background technique

In recent years, biological macromolecule drugs have shown good application prospects in the treatment of eye diseases. For example, Ranibizumab (molecular weight 48kDa) inhibits choroidal neovascularization in macular degeneration, Adalimumab (molecular weight 148kDa) treats autoimmune factor attack in necrotizing scleritis, and ciliary medicine prevents retinal neurodegeneration. Therapeutic agents such as neurotrophic factor (Ciliary Neurotrophic Factor, molecular weight 24kDa) have been proven to be effective biological macromolecule drugs in the treatment of eye diseases. However, the efficiency of current diffusion and treatment of macromolecular drugs into the target area (such as the posterior segment of the eye) through eye tissue is limited by the ocular barrier. Taking ocular surface drug delivery as an example, the dense scleral and corneal barriers hinder the diffusion of biomacromolecule drugs into the inner tissues of the eye.

Existing ocular drug delivery methods include ocular surface drug delivery, systemic drug delivery, intraocular injection, microneedle drug delivery, etc. Specifically, ocular surface drug administration (such as direct application of eye drops, eye ointments, eye gels, etc.) is suitable for drugs with small molecular weights, but is not suitable for drugs with larger molecular weights, and ocular surface drugs are administered through the cornea/sclera, etc. While barrier diffusion and absorption are affected by blinking, tear dilution and nasolacrimal duct drainage, the bioavailability of drugs in the eye is only about 5% to 10%, and only 50% to 90% of the drugs enter the systemic circulation, that is In the end, only 2.5% to 9% of the drug enters the human body and plays a role. It can be seen that the utilization rate of ocular drug administration is very low, the drug waste is very large, and the dosage cannot be effectively controlled.

If systemic administration is used for ocular administration, such as oral administration, subcutaneous injection, intravenous injection, etc., it will be hindered by the blood-aqueous humor barrier and blood-retina barrier, resulting in low eye utilization and the difficulty of systemic administration. It requires a larger dose and may cause side effects on other tissues or organs.

If intraocular injection is used, although the drug utilization rate is improved, it will cause pain and fear to the patient. The risk of infection during the injection process will increase and may even cause permanent damage. It is not suitable for chronic eye diseases that require multiple administrations. .

Microneedle drug delivery uses needles with a diameter of tens to hundreds of microns to reduce damage to eye tissue and patient pain, and can improve the penetration rate of drugs through biological tissues and eye utilization, but this method is still invasive. , is also not suitable for chronic eye diseases that require multiple doses.

Contents of the invention

The main technical problem solved by the present invention is to improve the efficiency of drug delivery to the eye.

Accordingly, the present invention proposes an ocular drug delivery auxiliary device, which includes an ultrasonic transducer and an ultrasonic excitation source, both of which are separate or electrically connected, and the ultrasonic excitation source is used to drive the ultrasonic transducer to work; The ultrasonic transducer includes a piezoelectric chip array, an elastic film layer and a backing fixed layer. The elastic film layer is in the shape of a spherical ring, and its inner surface has a curvature approaching the curvature of the eyeball; the piezoelectric chip array is sandwiched between between the elastic film layer and the backing fixed layer.

In one embodiment, N=16, the 16 piezoelectric wafers form an annular distribution array, each of the piezoelectric wafers covers an annular 22.5° range; select to enable one or more of the Piezoelectric chip enables various combinations of scleral coverage.

In one embodiment, in the ocular drug administration auxiliary device, the ultrasonic excitation source includes a multi-channel transformation matcher, a multi-channel power output device, a multi-channel signal generator, a multi-channel voltage monitor and a microcontroller. device; the microcontroller sends output instructions to the multi-channel signal generator according to the set working parameters; the multi-channel signal generator outputs a low-voltage square wave signal to the multi-channel power output device; the multi-channel signal generator The channel power output device outputs a high-voltage square wave signal to the multi-channel conversion and matching device, and the multi-channel conversion and matching device outputs a high-voltage sine wave signal to drive the piezoelectric chip; the multi-channel voltage monitor monitors the multi-channel The multiple output voltages of the matching device are converted and fed back to the microcontroller. The period of the low-voltage square wave electrical signal of the ultrasonic excitation source is adjustable from 0.5 to 50 microseconds, and the time resolution is adjustable from 0.01 to 0.5 microseconds; the voltage of the high-voltage square wave signal is adjustable from 10 to 110 volts.

When the ocular drug delivery auxiliary device according to the above embodiment is used for ocular drug delivery, a sound sensitizer is used to carry the drug and is placed on the surface of the eye tissue. The mechanical effect of the ultrasonic transducer is used to stimulate the sound sensitizer. Micron-level perforations are formed on the sclera and expand, which significantly increases the gaps between tissue cells while avoiding tissue damage. Eye drugs can quickly and efficiently penetrate into the sclera and diffuse into the interior of the eye through the expansion of micron-level perforations. It improves the breadth and depth of drug delivery within tissues and greatly improves the penetration and utilization rate of drugs into the eye; its auxiliary use in eye drug administration reduces drug waste and makes dosage control more accurate and effective.

According to one of the above embodiments, the driving of the piezoelectric chip array elements of the present invention has different combination forms. Selecting and activating one or more of the piezoelectric chips can realize various combination forms of scleral coverage, which can continuously Or intermittently cover the multiple range of 22.5° in the scleral area, so that different scleral area perforation and penetration can be selected spatially, making the drug delivery site more accurate and controllable.

According to one of the above embodiments, since the period of the low-voltage square wave electrical signal of the ultrasonic excitation source is adjustable from 0.5 to 50 microseconds, the time resolution is adjustable from 0.01 to 0.5 microseconds; the voltage of the high voltage square wave signal is between 10 and 10 microseconds. 110 volts adjustable; therefore, the excitation power output by the ultrasonic excitation source can be adjusted according to different piezoelectric chips, different drugs or different sonosensitizers. The adjustable range is wide, and the adjustment is more accurate and reliable.

Description of the drawings

Figure 1 is a schematic diagram of ocular drug delivery according to an embodiment of the present invention;

Figure 2 is a schematic diagram of ocular drug delivery according to another embodiment of the present invention;

Figure 3 is a schematic diagram of ocular drug delivery according to another embodiment of the present invention;

Figure 4 is a schematic diagram of ocular drug administration according to another embodiment of the present invention;

Figure 5 is a schematic diagram of ocular drug administration according to another embodiment of the present invention;

Figure 6 is a schematic structural diagram of an ocular drug delivery device according to an embodiment of the present invention;

Figure 7 is a circuit structural block diagram of an ocular drug delivery device according to an embodiment of the present invention;

Figure 8 shows different combinations of piezoelectric chip arrays in an ocular drug delivery device according to an embodiment of the present invention;

Figure 9 is a schematic diagram of the penetration-promoting effect in a comparative test example of the present invention (this figure has a color display part);

Figure 10 is a schematic diagram of the depth of penetration promotion in another comparative test example of the present invention.

Detailed ways

The present invention will be further described in detail below through specific embodiments in conjunction with the accompanying drawings. Similar elements in different embodiments use associated similar element numbers. In the following embodiments, many details are described in order to make the present application better understood. However, those skilled in the art can readily recognize that some of the features may be omitted in different situations, or may be replaced by other elements, materials, and methods. In some cases, some operations related to the present application are not shown or described in the specification. This is to avoid the core part of the present application being overwhelmed by excessive descriptions. For those skilled in the art, it is difficult to describe these in detail. The relevant operations are not necessary, and they can fully understand the relevant operations based on the descriptions in the instructions and general technical knowledge in the field.

Additionally, the features, operations, or characteristics described in the specification may be combined in any suitable manner to form various embodiments. At the same time, each step or action in the method description can also be sequentially exchanged or adjusted in a manner that is obvious to those skilled in the art. Therefore, the various sequences in the description and drawings are only for clearly describing a certain embodiment, and do not imply a necessary sequence, unless otherwise stated that a certain sequence must be followed.

The serial numbers assigned to components in this article, such as "first", "second", etc., are only used to distinguish the described objects and do not have any sequential or technical meaning. The terms "connection" and "connection" mentioned in this application include direct and indirect connections (connections) unless otherwise specified.

In the description of the present invention, the symbol "-" between two numerical values indicates the value range of a certain parameter, and the value range includes two endpoint values; for example, the thickness of the piezoelectric wafer is 0.3-1.5 mm, indicating the thickness of The value range is any value greater than or equal to 0.3mm and less than or equal to 1.5mm. When referring to coverage, the value is an approximate number and does not need to be absolutely accurate, such as 22.5°, 45°, 90°, 180°, and 360° coverage.

A method of using an ultrasound device to assist drug delivery is used to place drug carrier sonosensitizers on the surface of the sclera of the eye, such as microbubbles, nanophase change droplets, hydrogels containing microbubbles or nanophase change droplets, etc. The sonosensitizer is used to locally amplify the ultrasound energy, thereby inducing micron-scale perforation expansion in the scleral surface area, and then using the sono-induced perforation effect to increase the permeability of the sclera; thus improving the permeability and utilization rate of ocular drug delivery.

In one embodiment of the present invention, please refer to Figures 1 and 2. In this example, microbubbles in the sonosensitizer are used as carriers for ocular administration. Microbubbles are micron-scale structures with an internal air core and an external coating. Microbubbles and ocular medications are instilled directly into the eye and adhere to the scleral and conjunctival surfaces. When the ultrasonic pulse is released, the air core in the middle of the microbubbles is driven by the periodic changes in positive and negative pressure of the ultrasonic energy to rapidly oscillate and explode. The mechanical effects produced by the oscillation and explosion are far greater than the mechanical effects of ultrasound alone. This sound The severe mechanical effect caused by the sensitizer can form micron-scale perforations and expand on the sclera, so that eye drugs can quickly and efficiently penetrate into the sclera and into the interior of the eye through the micron-scale perforation expansion, realizing transscleral drug delivery and eye drug treatment. Purpose.

As a micron-level sonosensitizer, the diameter of microbubbles is between 2-6 microns. The gas core of microbubbles includes perfluorocarbon, sulfur hexafluoride, nitrogen, etc., and its outer coating is lipid or polymer. Or protein, etc.

In one embodiment of the present invention, as shown in Figure 3, this example uses nano phase change droplets as carriers for ocular drug delivery. The diameter of nano phase change droplets is usually less than 600 nanometers, and its core has a lower boiling point. Liquid fluorocarbons, such as perfluoropentane with a boiling point of 29°C, are coated with lipids, polymers or proteins. When excited by ultrasonic pulses, the liquid fluorocarbon core of the nanophase-change droplets is excited by the acoustic energy and turns into a gas, causing the nanodroplets to phase-change into microbubbles. Subsequent ultrasonic pulses continue to excite the microbubbles generated by the phase change, and microbubbles occur. Oscillation and blasting achieve sound-induced perforation expansion of the sclera. Drugs penetrate into the interior of the eyeball through the perforation and are diffusely delivered to other tissues such as the choroid and retina.

In one embodiment of the present invention, please refer to Figure 4, microbubbles and drugs are prepared in a sound-sensitive hydrogel. When the ultrasonic pulse is excited, the sound-sensitive hydrogel is stimulated, which indirectly excites the microbubbles. The air core in the middle of the microbubbles is driven by the periodic changes of positive and negative pressure of the ultrasonic energy to rapidly oscillate and explode. This violent vibration caused by the sound-sensitive agent The mechanical effect can form micron-scale perforations and expand on the sclera, so that eye drugs can expand through the micron-scale perforations, quickly and efficiently penetrate into the sclera, diffuse and deliver to other tissues such as the choroid, retina, etc., and enter the interior of the eyeball.

In one embodiment of the present invention, please refer to Figure 5, nano phase change droplets and drugs are prepared in sound-sensitive hydrogel. When the ultrasonic pulse is excited, the sound-sensitive hydrogel is excited, which indirectly excites the liquid fluorocarbon core of the nano-phase-change droplets to turn into gas, causing the nano-droplets to phase-change into microbubbles. Subsequent ultrasonic pulses continue to excite the phase-change generated microbubbles. Microbubbles oscillate and explode to achieve sound-induced perforation expansion of the sclera. The drug penetrates into the eyeball through the perforation and is diffusely delivered to other tissues such as the choroid and retina.

The shape of the hydrogel is a spherical ring band, with an inner diameter ranging from 12 to 13 mm, an outer diameter ranging from 18 to 22 mm, and a radius of curvature of 10 to 15 mm, corresponding to the curvature of the scleral surface of the eye, and the thickness range is 0.04-1mm. The preparation method of the sound-sensitive hydrogel is as follows: take 4 ml of 3% (W/V) sodium alginate solution in beaker A, take 2920 μl of drug solution, 1048 μl of 40% acrylic acrylamide mixed solution, 40 μl of 10 % ammonium persulfate solution in beaker B, then mix the liquid in beaker B into beaker A, and add 15 μl of tetramethylethylenediamine and mix. Then take 2 ml of microbubble solution or 2 ml of phase change nanodroplet solution and mix it into beaker A. Pour the mixed solution into the mold and react at 4°C for 2 hours. Place the mold in 100 ml of 1M calcium chloride solution. Cross-link for 30 minutes, take out the mold and wash it twice with PBS before use.

In order to effectively adopt the ocular drug administration method of the embodiment of the present invention, in one embodiment of the present invention, an ocular drug administration device is proposed, which includes an ultrasonic transducer and an ultrasonic excitation source. The ultrasonic transducer is used to act on the eye. The ultrasonic excitation source is used to provide ultrasonic excitation to the ultrasonic transducer. As shown in Figure 6, the overall shape of the ultrasonic transducer in this example is a closed spherical ring belt, which is equivalent to a hollow sphere with a circle cut out of the middle ring. The diameter range of the inner transducer (the upper ring with a smaller circumference) is 12 -13 mm, the diameter range of the outer transverse (lower ring with longer circumference) is 18-22 mm, and the radius of curvature is 10-15 mm, adapting to the surface curvature of the human eyeball. Including backing fixed layer, piezoelectric chip array, piezoelectric chip leads and elastic film layer. The backing fixed layer is made of epoxy resin and tungsten powder, with a thickness of 0.3-3 mm; the elastic film layer is made of soft silicone or other elastic materials, in the shape of a ball ring belt, with an inner surface curvature adapted to the human eyeball. The thickness is 0.1-6 mm; the piezoelectric chip array and its leads are adhered between the backing fixed layer and the elastic film layer. In this example, the ultrasound used to drive the sonosensitizer belongs to the mid-frequency and high-frequency frequency range, that is, the operating frequency Any value between 0.5-5MHz (megahertz), the piezoelectric chip can adopt different thicknesses according to its different central operating frequency, and its thickness can be selected at any value between 0.3-1.5 mm; similarly, it can also According to the different operating frequencies required, make appropriate selections for the thickness of the piezoelectric wafer; in this way, through the combination of different working efficiencies and different piezoelectric wafer thicknesses, different excitation output efficiencies and effects can be achieved. When in use, the elastic film layer is located between the piezoelectric chip array and the human eye. It can also be used as a matching layer to transition the acoustic impedance difference between the eye tissue and the piezoelectric chip array, allowing more ultrasonic energy to enter the eye tissue.

In one embodiment of the present invention, the overall shape of the ultrasonic transducer is a spherical ring-shaped belt, with an inner transverse diameter range of 12 mm, an outer transverse diameter range of 18 mm, and a radius of curvature of 10 mm; adapted to a smaller eye surface area , the eyeball with higher curvature provides drug administration assistance.

In one embodiment of the present invention, the overall shape of the ultrasonic transducer is a spherical ring-shaped belt, with an inner transverse diameter range of 13 mm, an outer transverse diameter range of 22 mm, and a radius of curvature of 15 mm; adapted to larger eye surface areas , the lower curvature of the eyeball provides drug administration assistance.

In one embodiment of the present invention, the overall shape of the ultrasonic transducer is a spherical ring-shaped belt, with an inner diameter range of 12.5 mm, an outer diameter range of 20 mm, and a radius of curvature of 13 mm.

In one embodiment of the present invention, as shown in Figure 7, the excitation source of the ocular drug delivery device includes a multi-channel transformation matcher, a multi-channel power output, a multi-channel signal generator, a multi-channel voltage monitor and a microcontroller device; the microcontroller is electrically connected to the input end of the multi-channel signal generator, the output end of the multi-channel signal generator is electrically connected to the input end of the multi-channel power output, and the output end of the multi-channel power output is electrically connected to the input end of the multi-channel transformation matching device. Connection, the output end of the multi-channel transformation matching device is electrically connected to the piezoelectric chip array of the piezoelectric chip array layer, the signal sampling end of the multi-channel voltage monitor is electrically connected to the output end of the multi-channel conversion matching device; the multi-channel voltage monitor control end Electrically connected to the microcontroller, the multi-channel voltage monitor monitors multiple output voltages of the multi-channel conversion matcher in real time and feeds back to the microcontroller.

First, the microcontroller collects the working parameters set by the user through the human-computer interaction module (such as keyboard and display screen, etc., not shown in the figure). According to the working parameters set by the user (including the ultrasonic energy density and the number of working array elements) , ultrasonic energy duration, ultrasonic energy pulse interval, etc.) sends output instructions to the multi-channel signal generator; the multi-channel signal generator is mainly composed of a programmable logic gate array, and the multi-channel signal generator outputs multiple low-voltage square wave electrical signals. The period of the low-voltage square wave electrical signal is adjustable from 0.5 to 50 microseconds, and the time resolution is adjustable from 0.01 to 0.5 microseconds; the low-voltage square wave electrical signal is then sent to a multi-channel power output device, which mainly includes Composed of high-speed isolation optocoupler, adjustable voltage power supply, bipolar junction transistor and power field effect transistor, the multi-channel power output device can output a high-voltage square wave electric signal with the same parameters as the low-voltage square wave electric signal and an amplitude of 10-110 volts. signal; the high-voltage square wave electrical signal is then sent to the multi-channel transformation matching device. The multi-channel transformation matching device is mainly composed of a square wave sine wave transformation circuit and an LC impedance matching circuit. The square wave sine wave transformation circuit converts the high voltage square wave electrical signal into High-voltage sine wave electrical signal, LC impedance matching resistor matches the resistance of the transducer to close to 50 ohms, and the phase is close to 0 degrees. The electrical signal output by the multi-channel transformation matcher drives multiple piezoelectric wafers and corresponds one to one; There are two silver electrodes plated on one side of the electronic chip, which are the positive electrode and the negative electrode of the chip. The positive electrode is connected to the multi-channel transformation matcher through the piezoelectric chip signal line, and the negative electrode is connected to the ground through the piezoelectric chip ground wire. , the piezoelectric chip is a trapezoid, the upper base of the trapezoid does not exceed 3 mm, the lower base of the trapezoid does not exceed 5 mm, the height of the trapezoid does not exceed 6 mm, the maximum area does not exceed 24 square millimeters, multiple piezoelectric wafers form an annular distribution array; Driven by a high-voltage pulse electrical signal, the sound intensity output by the piezoelectric chip varies between 0.05-1 watt per square centimeter. In order to ensure the safety of the device when used on the human body, a multi-channel voltage monitor is designed to monitor the voltage on each piezoelectric chip signal line and feed back the data to the microcontroller. In the ultrasonic excitation source in this example, the period of the low-voltage square wave electrical signal is adjustable from 0.5 to 50 microseconds, and the time resolution is adjustable from 0.01 to 0.5 microseconds; the voltage of the high-voltage square wave signal is adjustable from 10 to 110 volts. Adjustment; therefore, the excitation power output by the ultrasonic excitation source can be adjusted according to different piezoelectric chips, different drugs, or/and different sonosensitizers. The adjustable range is wide, and the adjustment is more accurate and reliable.

In one embodiment of the present invention, please refer to Figure 8. 16 piezoelectric wafers form a closed-loop annular distribution array. One or more of the piezoelectric wafers can be selectively activated to achieve various combinations of scleral coverage. form. Figure 8 shows four combinations of piezoelectric chip arrays used to increase scleral drug penetration, covering the scleral area 45°, 90°, 180° and 360° respectively; taking increasing scleral drug penetration as an example, The piezoelectric chip array covering the 45°, 90°, 180° and 360° ranges of the scleral area can promote the penetration of ultrasound ocular surface drugs with different efficiencies through the sclera of 12.5%, 25%, 50% and 100% of the ocular surface area. In addition, each piezoelectric chip in the piezoelectric chip array can work independently to achieve 22.5° coverage of the sclera. Different piezoelectric chips can also be flexibly combined, in addition to 45°, 90°, 180° and Continuous coverage in the 360° range can also achieve continuous or interval coverage in multiples of 22.5° in the range of 22.5° to 360°. For example, 45° coverage of any two non-adjacent parts of the ocular surface, 45° coverage, 90° coverage of any two non-adjacent parts of the ocular surface, etc., thereby realizing a variety of ultrasound ocular surface drug penetration promotion solutions. The scope of action is more flexible and wider, promoting higher drug penetration efficiency on the ocular surface and more precise control of the administration site.

Figure 9 shows a schematic diagram of the penetration-promoting effect in a comparative test of an embodiment. In this comparative test, a microbubble solution with a concentration of 1×10 ⁶ per milliliter was first dropped on the surface of the isolated pig eyeball. The ocular drug delivery auxiliary device of the present invention was used to cover the sclera at 45° through the piezoelectric chip array. range, using an operating frequency of 3 MHz and an energy intensity of 0.25 watts per square centimeter, the porcine scleral structure was treated with sono-induced perforation to promote penetration, and then the surface of the porcine sclera was covered with fluorescein for 10 minutes to test the penetration-promoting effect of fluorescein . By quantifying the results of fluorescein penetration promotion through small animal fluorescence imaging, it can be verified that using the ocular drug administration auxiliary device of the present invention significantly increases the penetration of fluorescein in the sclera through sono-perforation treatment. The fluorescence intensity of the sono-perforation group is the control 16.4 times that of the group.

Please refer to the schematic diagram of the penetration depth effect in another comparative test shown in Figure 10. In this comparative test, a nanophase-change droplet solution with a concentration of 1×10 ⁸ per milliliter was first dropped on the surface of the isolated pig eyeball. The ocular drug delivery auxiliary device of the present invention was used to pass the sclera covering 180°. The piezoelectric chip array, operating at a frequency of 3 MHz and with an energy intensity of 0.65 watts per square centimeter, performed nano-droplet phase change and sono-induced permeation permeability treatment on the porcine scleral structure, and then covered the porcine scleral surface with fluorescein for 10 minutes. , to test the depth effect of fluorescein on promoting penetration. By imaging the results of fluorescein penetration promotion through frozen sections and microscopic imaging, it can be verified that using the ocular drug delivery auxiliary device of the present invention, ultrasonic treatment significantly increases the penetration of fluorescein in the sclera. Specifically, the fluorescein in the control group It is distributed on the surface of the sclera, while the distribution of fluorescein in the ultrasound group runs through the entire thickness of the sclera.

The above specific examples are used to illustrate the present invention, which are only used to help understand the present invention and are not intended to limit the present invention. For those skilled in the technical field to which the present invention belongs, several simple deductions, modifications or substitutions can be made based on the ideas of the present invention. For example, the piezoelectric chip can be a piezoelectric ceramic, a piezoelectric film, a piezoelectric single crystal, or other composite materials with electro-acoustic conversion functions.

Claims (10)

1. An eye auxiliary device that doses, its characterized in that: the ultrasonic transducer comprises an ultrasonic transducer and an ultrasonic excitation source which are separately or electrically connected, wherein the ultrasonic excitation source is used for driving the ultrasonic transducer to work; the ultrasonic transducer is in a spherical annular band shape and comprises a piezoelectric wafer array, an elastic membrane layer and a backing fixed layer, wherein the elastic membrane layer is in a spherical annular band shape, and the inner surface of the elastic membrane layer is provided with a curvature which is matched with the curvature of an eyeball; the piezoelectric wafer array is clamped between the elastic membrane layer and the back lining fixing layer, and one or more piezoelectric wafers are selectively started to realize various combination forms of sclera coverage.

2. The ocular drug delivery assist device of claim 1, wherein: the piezoelectric wafer array comprises N piezoelectric wafers, wherein N is more than or equal to 2; the thickness of the piezoelectric wafer is any value within 0.3-1.5 mm corresponding to any working frequency within 0.5-5 MHz.

3. The ocular drug delivery assist device of claim 2, wherein: the ultrasonic transducer has an inner transverse diameter ranging from 12 to 13 mm, an outer transverse diameter ranging from 18 to 22 mm and an inner surface with a radius of curvature ranging from 10 to 15 mm.

4. The ocular drug delivery assist device of claim 2, wherein: the piezoelectric wafers are trapezoid, and the N piezoelectric wafers form an annular distribution array.

5. An ocular drug delivery assist device as in claim 3, wherein: the thickness of the elastic film layer is 0.1-6 mm.

6. The ocular drug delivery assist device of claim 4, wherein: the N=16, the 16 piezoelectric wafers form an annular distribution array, and each piezoelectric wafer covers an annular shape 22.5 ^o Is not limited in terms of the range of (a).

7. The ocular drug delivery assist device of claim 4, wherein: the piezoelectric wafer is trapezoid, the upper bottom width of the trapezoid is less than or equal to 3mm, the lower bottom width of the trapezoid is less than or equal to 5mm, and the height of the trapezoid is less than or equal to 6 mm.

8. The ocular drug delivery assist device of any one of claims 1-7, wherein: the ultrasonic excitation source comprises a multichannel conversion matcher, a multichannel power output device, a multichannel signal generator, a multichannel voltage monitor and a microcontroller; the microcontroller sends an output instruction to the multichannel signal generator according to the set working parameters; the multi-channel signal generator outputs a low-voltage square wave signal to the multi-channel power output device; the multichannel power output device outputs a high-voltage square wave signal to the multichannel conversion matcher, and the multichannel conversion matcher outputs a high-voltage sine wave signal to drive the piezoelectric wafer; the multichannel voltage monitor monitors the multichannel output voltage of the multichannel conversion matcher and feeds back the multichannel output voltage to the microcontroller.

9. The ocular drug delivery assist device of claim 8, wherein: the period of the low-voltage square wave signal is an adjustable arbitrary value between 0.5 and 50 microseconds, and the time resolution is an adjustable arbitrary value between 0.01 and 0.5 microsecond; the voltage of the high-voltage square wave signal is any value which can be adjusted by 10-110 volts.

10. The ocular drug delivery assist device of claim 8, wherein: the composition also comprises a sound-sensitive agent, wherein the sound-sensitive agent comprises one or more of microbubbles, nano microphase liquid or sound-sensitive hydrogel.