Transdermal drug delivery device
The transdermal drug delivery device uses a transducer to convert electrical energy into ultrasonic waves, forming bubble clouds and shock waves to accelerate the passage of drugs through the skin. This solves the problems of poor absorption and uncontrollable medication process of traditional transdermal drug delivery methods, and achieves accurate drug delivery and efficient absorption.
Patent Information
- Application Number
- CN202510731996.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-03
- Publication Date
- 2025-09-19
AI Technical Summary
Traditional transdermal drug delivery methods have poor absorption effects and uncontrollable medication processes. Nanocarriers also have complex preparation processes and unverified long-term safety.
A transdermal drug delivery device is used, which uses a transducer to convert electrical energy into ultrasonic waves, forming capillary waves to spray droplets on a metal sheet. The droplets form a bubble cloud on the skin and generate shock waves. The longitudinal and lateral driving forces of the bubble cloud are used to accelerate the drug through the stratum corneum of the skin, and precise drug delivery is achieved by controlling the input voltage.
It improves the transdermal absorption effect of drugs, reduces skin damage, achieves precise control of drug release efficiency and dosage, and significantly promotes the skin absorption of large and small molecule drugs.
Smart Images
Figure CN120661828A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of transdermal drug delivery, and in particular to a transdermal drug delivery device. Background Art
[0002] Transdermal drug delivery technology is a method of delivering drugs directly into the body through the skin. Compared to traditional oral and injection methods, transdermal drug delivery offers advantages such as avoiding the "first-pass effect" in the liver, being non-invasive, providing sustained drug release, and improving patient compliance.
[0003] Common transdermal drug delivery systems include drug patches, gels, emulsions, and nanocarriers. While these are easy to use, they are affected by the drug's physical and chemical properties, the skin's barrier function, and skin permeability, leading to poor skin absorption through poor drug penetration rates, uncontrollable medication processes, and a limited range of drug applications. While nanocarriers can increase drug penetration and efficiency, their preparation is complex, their long-term safety remains unverified, and they pose risks of nanoparticle accumulation and toxicity. Summary of the Invention
[0004] The present application provides a transdermal drug delivery device, which aims to solve the problems of poor absorption effect and uncontrollable medication process in traditional transdermal drug delivery methods.
[0005] The present application provides a transdermal drug delivery device, comprising: a drug container, wherein the drug container is used to store a drug solution; a metal sheet, wherein the metal sheet is provided with micropores, and the micropores are connected to the drug container; A piezoelectric substrate having a hollow ring structure, the metal sheet being disposed on the piezoelectric substrate, the metal sheet and the piezoelectric substrate forming a transducer; The ultrasonic waves generated by the transducer form capillary waves of the drug solution on the metal sheet, so that the drug is squeezed and sprayed out as droplets through the micropores. When the droplets are sprayed onto the stratum corneum of the skin, they will wrap gas to form bubble clouds. The bubble clouds have a longitudinal driving force in the vertical direction of the skin to accelerate the movement of the drug to the deep layer of the skin. The shock waves generated by the bubble clouds have a lateral driving force at the level of the skin to enlarge the cell gap, so that the drug can pass through the stratum corneum of the skin.
[0006] The present application provides a transdermal drug delivery device, which converts electrical energy into ultrasonic waves through a transducer, forms capillary waves on a metal sheet, and causes the drug solution to be squeezed and sprayed out through micropores. The droplets are sprayed onto the stratum corneum of the skin to form a bubble cloud and generate shock waves. The shock waves generate a lateral driving force in the horizontal direction of the skin, enlarging the intercellular gaps to form instantaneous microchannels. At the same time, the bubble cloud also generates a longitudinal driving force in the vertical direction of the skin, accelerating the flow of the drug liquid and allowing the drug to pass through the stratum corneum of the skin, thereby achieving drug delivery to the deep layers of the skin. At the same time, by controlling the input voltage of the transducer, while retaining the non-invasiveness of traditional transdermal drug delivery methods, the transdermal absorption effect of the drug is improved, skin damage is reduced, and precise control of drug release efficiency and dosage is achieved. BRIEF DESCRIPTION OF THE DRAWINGS
[0007] In order to more clearly illustrate the technical solution of the present application, the following is a brief introduction to the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.
[0008] Figure 1 This is a schematic diagram of an exploded view of the structure of a transdermal drug delivery device provided by the present application; Figure 2a This application provides a schematic structural diagram of a transdermal drug delivery device; Figure 2b This is a schematic structural diagram of a transducer provided by the present application; Figure 3 A schematic cross-sectional view of a micropore provided in this application; Figure 4 This is a schematic diagram of the working principle of a transdermal drug delivery device provided in an embodiment of the present application; Figure 5a is a schematic diagram of three regions formed during the droplet ejection process in an embodiment of the present application; Figure 5b The droplet falling process of the embodiment of the present application and the droplet diameter, spraying speed, and droplet number under different voltages are shown; Figure 5c This is the process of spraying droplets to form bubbles in the embodiment of the present application; Figure 5d It is a quantitative schematic diagram of region II during the droplet ejection process of an embodiment of the present application; Figure 5e It is a quantitative schematic diagram of region III during the droplet ejection process in an embodiment of the present application.
[0009] Figure 6 is a schematic diagram of the dorsal skin of a BALB / c nude mouse; Figure 7Schematic diagram of relative fluorescence intensity of cross-sections of the back skin of BALB / c nude mice after treatment at different input voltages for 5 minutes in the control group and the embodiment of the present application; Figure 8 Schematic diagram of relative fluorescence intensity of longitudinal sections of the back skin of BALB / c nude mice after 5 minutes of treatment with the control group and the example of the present application; Figure 9 Schematic diagram of the relative fluorescence intensity of 10 kDa fluorescein isothiocyanate-dextran and 70 kDa fluorescein isothiocyanate-dextran in longitudinal sections of the dorsal skin of BALB / c nude mice after treatment for 5 minutes in a control group and in an example of the present application; Figure 10a This is a schematic diagram of HE staining of the back skin of BALB / c nude mice after 5 minutes of treatment in the control group; Figure 10b This is a schematic diagram of HE staining of the longitudinal skin section of a BALB / c nude mouse back after treatment with a 250 Vpp input voltage for 5 minutes in an embodiment of the present application.
[0010] Description of reference numerals: 10. Fixing seat; 20. Support rod; 30. Fixing member; 40. Clamping assembly; 41. First clamping member; 42. Second clamping member; 50. Transducer; 51. Metal sheet; 511. Micropore; 52. Piezoelectric substrate; 521. Cavity; 60. Seal; 70. Drug container; 80. Drug solution; 90. Bubble cloud; 100. Skin stratum corneum; 110. Epidermis; 120. Dermis; 130. Cross section; 140. Longitudinal section. DETAILED DESCRIPTION
[0011] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.
[0012] It will be understood that when used in this specification and the appended claims, the terms “comprises” and “comprising” indicate the presence of described features, integers, steps, operations, elements and / or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or groups thereof.
[0013] It should also be understood that the terms used in this specification are for the purpose of describing specific embodiments only and are not intended to limit the present application. As used in this specification and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms unless the context clearly indicates otherwise.
[0014] It should be further understood that the term "and / or" used in this specification and the appended claims refers to and includes any and all possible combinations of one or more of the associated listed items.
[0015] The following describes some embodiments of the present application in detail with reference to the accompanying drawings. In the absence of conflict, the following embodiments and features therein may be combined with each other.
[0016] Transdermal drug delivery technology is a method of delivering drugs directly into the body through the skin. Compared to traditional oral and injection methods, transdermal drug delivery offers advantages such as avoiding the "first-pass effect" in the liver, being non-invasive, providing sustained drug release, and improving patient compliance.
[0017] Common transdermal drug delivery systems include drug patches, gels, emulsions, and nanocarriers. While these are easy to use, they are affected by the drug's physical and chemical properties, the skin's barrier function, and skin permeability, leading to poor skin absorption through poor drug penetration rates, uncontrollable medication processes, and a limited range of drug applications. While nanocarriers can increase drug penetration and efficiency, their preparation is complex, their long-term safety remains unverified, and they pose risks of nanoparticle accumulation and toxicity.
[0018] Ultrasonic drug delivery technology uses ultrasound to generate tiny bubbles in liquids. These bubbles rapidly grow and collapse under the action of ultrasound, producing intense local energy release and microjets, known as the cavitation effect. The cavitation effect can temporarily damage the skin's stratum corneum and epidermis, forming microchannels that allow drugs to penetrate the skin and enter the body. Ultrasonic drug delivery technology can enhance drug penetration and control the drug delivery process. It can not only be used for drug delivery, but also promote blood circulation and metabolism in local tissues. However, ultrasonic drug delivery technology still has the following shortcomings: 1. Skin damage: High-intensity or long-term ultrasound may cause skin damage, resulting in redness, swelling, pain and other discomfort symptoms.
[0019] 2. Local inflammation: The cavitation effect may trigger a local inflammatory response, affecting the absorption and efficacy of the drug.
[0020] 3. Equipment complexity: Specialized ultrasound equipment is required, and the operation is complicated, which increases the difficulty and cost of clinical application.
[0021] 4. Drug stability: The high temperature and high pressure environment generated during ultrasonic cavitation may affect the stability and activity of some drugs.
[0022] To solve the above problem, please refer to Figure 1 , Figure 1 This is a schematic exploded view of a transdermal drug delivery device provided in this application.
[0023] like Figure 1 As shown, the present application provides a transdermal drug delivery device comprising: a fixed base 10, a support rod 20, a fixing member 30, a clamping assembly 40, a transducer 50, a sealing member 60, and a drug container 70. The support rod 20 is mounted on the fixed base 10; the fixing member 30 is adjustably mounted on the support rod 20 and connected to the clamping assembly 40, and is used to fix the transducer 50 to the support rod 20, and the distance between the transducer 50 and the fixed base 10 is adjustable; the drug container 70 is used to store a drug solution 80; the transducer 50 includes a metal sheet 51 and a piezoelectric substrate 52, which is used to convert electrical energy into acoustic energy. The metal sheet 51 is provided with a micropore 511, which is connected to the drug container 70. The piezoelectric substrate 52 includes a cavity 521, making the piezoelectric substrate 52 an annular hollow structure, and the metal sheet 51 is mounted on the piezoelectric substrate 52.
[0024] Specifically, the holder 10 may be provided with a slot adapted to fit the clamping assembly 40, allowing the clamping assembly 40 to be partially or completely embedded in the holder 10, thereby preventing displacement caused by vibration when the transducer 50 converts electrical energy into acoustic energy. The holder 10 is provided with an outlet, which communicates with the micropore 511, allowing the drug solution 80 to pass through the holder 10 outlet.
[0025] In some embodiments, the metal sheet 51 and the piezoelectric substrate 52 are fixedly connected by a clamping assembly 40 .
[0026] Illustratively, the clamping assembly 40 includes a first clamping member 41 disposed under the piezoelectric substrate 52 and a second clamping member 42 disposed on the metal sheet 51 . The first clamping member 41 and the second clamping member 42 securely connect the metal sheet 51 and the piezoelectric substrate 52 together.
[0027] In some embodiments, the first clamping member 41 is provided with a groove for placing the transducer 50; the second clamping member 42 is used to clamp the transducer 50 on the first clamping member 41, and the second clamping member 42 has a solution hole. The second clamping member 42 clamps the transducer 50, and the solution hole and the metal sheet 51 form a drug container 70.
[0028] It should be noted that the drug container 70 can be a accommodating space formed by the solution hole on the second clamping member 42 and the metal sheet 51, or it can be directly set on the metal sheet 51, or it can be set separately from the metal sheet 51 and connected to the micropore 511 through a pipe. It only needs to ensure that the drug solution 80 in the drug container 70 can spray drug droplets through the micropore 511. Therefore, this embodiment does not limit the specific shape and specific position of the drug container 70.
[0029] In some embodiments, a seal 60 is disposed between the drug container 70 and the metal sheet 51 .
[0030] Exemplarily, the transducer 50 is disposed between the first clamping member 41 and the second clamping member 42, and the first clamping member 41 and the second clamping member 42 are fixedly connected so that the metal sheet 51 and the piezoelectric substrate 52 are fixedly connected, and the transducer 50 is fixed on the first clamping member 41. The accommodating space formed between the solution hole on the second clamping member 42 and the metal sheet 51 is the drug container 70; the sealing member 60 is disposed between the second clamping member 42 and the metal sheet 51 to prevent liquid leakage.
[0031] It should be noted that if Figure 2a As shown, the transdermal drug delivery device provided by the present application may include a transducer 50 and a drug container 70. The drug container 70 is used to store a drug solution 80, and the transducer 50 is used to convert electrical energy into acoustic energy. Figure 2b , Figure 2b : This is a schematic diagram of the structure of a transducer 50 provided in the present application. The transducer 50 includes a metal sheet 51 and a piezoelectric substrate 52. The metal sheet 51 is provided with a micropore 511, which is connected to the drug container 70. The piezoelectric substrate 52 includes a cavity 521, and the metal sheet 51 covers the cavity 521. The metal sheet 51 is arranged on the piezoelectric substrate 52. The metal sheet 51 and the piezoelectric substrate 52 constitute the transducer 50. The ultrasonic wave generated by the transducer 50 forms capillary waves on the metal sheet 51 and sprays droplets through the micropores 511. When the droplets are sprayed onto the stratum corneum 100 of the skin, they will encapsulate gas to form a bubble cloud 90. The bubble cloud 90 has a longitudinal driving force in the vertical direction of the skin to accelerate the movement of the drug into the deep layer of the skin. The shock wave generated by the bubble cloud 90 has a lateral driving force at the level of the skin to widen the intercellular space, so that the drug can pass through the stratum corneum 100 of the skin.
[0032] Among them, the piezoelectric substrate 52 can be a piezoelectric ceramic sheet, the metal sheet 51 and the piezoelectric substrate 52 can be any shape such as rectangular or circular, and the drug container 70 can be a storage space formed by other components and the metal sheet 51, or it can be directly set on the metal sheet 51, or it can be set separately from the metal sheet 51 and connect the drug container 70 to the micropore 511 through a pipe.
[0033] In some embodiments, the side of the metal sheet 51 close to the drug container 70 is the first side, and the side close to the piezoelectric substrate 52 is the second side. The aperture of the micropores 511 on the first side is greater than or equal to the aperture of the micropores 511 on the second side.
[0034] The micropores 511 on the first surface and the micropores 511 on the second surface may be in any shape, such as a rectangle, a circle, or a triangle.
[0035] Exemplarily, the metal sheet 51 is a circular metal sheet, the piezoelectric substrate 52 is an annular piezoelectric ceramic sheet, and the micropores 511 on the first surface and the micropores 511 on the second surface of the circular metal sheet are both circular in shape.
[0036] In some embodiments, the pore diameter of the micropores 511 gradually decreases from the first surface to the second surface.
[0037] In particular, from the cross-section of the micropore 511 , the cross-section of the micropore 511 can be in a rectangular, trapezoidal, peak-shaped or other shapes.
[0038] For example, see Figure 3 , Figure 3 This is a schematic cross-sectional view of a micropore 511 provided in this application. Figure 3 As shown, the aperture of the micropore 511 gradually decreases from the first surface to the second surface, and the cross section of the micropore 511 is trapezoidal.
[0039] In some embodiments, the micropores 511 on the second surface have a pore diameter of 20-130 μm.
[0040] For example, the diameter of the circular micropores 511 located on the first side of the circular metal sheet is 130 μm, and the diameter of the circular micropores 511 located on the second side of the circular metal sheet is 100 μm.
[0041] It should be noted that the pore size of the micropores on the first surface must be greater than or equal to the pore size of the micropores on the second surface. No specific limitation is imposed on the pore size of the micropores on the first surface.
[0042] In some embodiments, the thickness of the metal sheet 51 is smaller than the thickness of the piezoelectric substrate 52 .
[0043] It should be noted that the thickness of the piezoelectric substrate 52 is determined according to the frequency required by the transducer 50 to ensure the output frequency of the transducer 50. In some embodiments, the thickness of the piezoelectric substrate 52 is 500-700 μm, and the thickness of the metal sheet 51 is 30-70 μm.
[0044] For example, the thickness of the piezoelectric ceramic ring is 600 μm, and the thickness of the circular metal sheet is 50 μm.
[0045] In some embodiments, the piezoelectric substrate 52 is a piezoelectric ceramic ring, the metal sheet 51 is a circular metal sheet, and the microhole 511 is located at the center of the circular metal sheet.
[0046] In some embodiments, the outer ring radius of the piezoelectric ceramic ring is 8 mm, the radius of the cavity 521 is 6 mm, and the radius of the circular metal sheet is 8 mm, so that the circular metal sheet can completely cover the cavity 521 of the piezoelectric ceramic ring.
[0047] It should be noted that the metal sheet 51 includes at least one micropore 511, that is, the metal sheet 51 may include one or more micropores 511, and the projections of all micropores 511 need to fall within the cavity 521 of the piezoelectric substrate 52 to ensure that the drug solution 80 sprayed from the micropore 511 can smoothly pass through the cavity 521 and be sprayed out to form droplets.
[0048] See also Figure 4 , Figure 4 This is a schematic diagram of the working principle of a transdermal drug delivery device provided in an embodiment of the present application. The transducer 50 converts electrical energy into ultrasonic waves, forming capillary waves on the metal sheet 51, squeezing and spraying droplets through the micropores 511. The droplets are sprayed onto the bubble cloud 90 formed on the skin stratum corneum 100 and generate shock waves. The shock waves generate a lateral driving force in the horizontal direction of the skin, enlarging the cell gap to form an instantaneous microchannel. At the same time, the bubble cloud 90 also generates a longitudinal driving force in the vertical direction of the skin, accelerating the flow of the drug liquid, allowing the drug to pass through the skin stratum corneum 100, thereby achieving drug delivery to the deep layer of the skin.
[0049] Next, the performance of a transdermal drug delivery device provided in the present application was measured, wherein the transducer 50 uses a circular metal sheet with a radius of 8 mm and a thickness of 50 μm and a piezoelectric ceramic ring sheet with an outer ring radius of 8 mm, a hollow inner diameter of 6 mm, and a thickness of 600 μm. The micropore 511 is arranged in the center of the metal sheet 51, the diameter of the micropore 511 on the first surface is 130 μm, the diameter of the micropore 511 on the second surface is 100 μm, and the cross-section of the micropore 511 on the metal sheet 51 is trapezoidal.
[0050] See also Figure 5a , Figure 5a Schematic diagram of the three regions formed during the droplet ejection process in the embodiment of the present application. Figure 5a This diagram illustrates three quantitative regions. First, quantitative analysis of the sprayed droplets from the present embodiment (Region I); second, monitoring the dynamic process of droplets introducing bubbles when they splash into the liquid container (Region II); and finally, monitoring the liquid flow acceleration process caused by the bubble droplets generated by the present embodiment (Region III).
[0051] See also Figure 5b , where I is a frame during the falling process of the droplet in the embodiment of the present application; Among them, II, III, and IV are schematic diagrams of droplet diameter, spraying speed, and number of droplets generated by the embodiments of the present application under different input voltages.
[0052] NS indicates no significant difference, * indicates p < 0.05, ** indicates p < 0.01, *** indicates p < 0.001, and **** indicates p < 0.0001.
[0053] As shown in Ⅱ, at input voltages of 150Vpp, 200Vpp and 250Vpp, the droplet sizes generated in the embodiments of the present application all obey the normal distribution, among which, the difference in droplet sizes generated at input voltages of 150Vpp and 200Vpp is not significant. Compared with the droplet sizes generated at input voltages of 150Vpp and 200Vpp, the droplet size generated at an input voltage of 250Vpp is significantly increased.
[0054] As shown in Ⅲ, under the input voltages of 150Vpp, 200Vpp and 250Vpp, the droplet injection speed generated by the embodiment of the present application obeys the normal distribution, and as the voltage increases, the droplet injection speed generated by the embodiment of the present application increases significantly.
[0055] The unit time used for measuring the number of droplets in the embodiment of the present application is 0.72 milliseconds. As shown in IV, within the unit time, the number of droplets generated at input voltages of 150 Vpp, 200 Vpp, and 250 Vpp all obey a normal distribution, and as the voltage increases, the number of droplets generated increases significantly.
[0056] Combining II-IV, it can be seen that the droplet diameter, droplet injection speed and droplet number generated in the embodiment of the present application can be controlled by controlling the magnitude of the input voltage, thereby achieving precise drug delivery.
[0057] See also Figure 5c , Figure 5c The diagram shows the process of droplet formation during the embodiment of the present application. Part I is a schematic diagram of the formation of bubbles by the sprayed droplet contacting the underlying liquid, creating an air cavity. Part II is a high-speed camera capture of the dynamic process of droplet transformation into bubbles, showing the droplet states generated by the embodiment of the present application at 0 milliseconds, 2.19 milliseconds, 4.01 milliseconds, and 4.47 milliseconds after reaching the surface of the liquid container.
[0058] See also Figure 5d , Figure 5d Figure 1 is a quantitative diagram of region II during the droplet ejection process of an embodiment of the present application. The framed area in Figure 1 shows a bubble cloud 90 in one frame of the embodiment of the present application; Figure 2 is a quantitative diagram of the average size of the bubble clusters generated by the impact of the droplet ejection of the embodiment of the present application at different voltages.
[0059] See also Figure 5e , Figure 5e This is a quantitative schematic diagram of region III during the droplet ejection process of the embodiment of the present application. I shows the liquid flow velocity in one frame of the embodiment of the present application; II is the quantitative average regional velocity of the liquid flow at three voltages.
[0060] See also Figure 6 , Figure 6Schematic diagram of the dorsal skin of a BALB / c nude mouse.
[0061] like Figure 6 As shown, the back skin of a BALB / c nude mouse is divided into an epidermis 110 and a dermis 120 from outside to inside, wherein the cross section 130 only includes the surface of the skin stratum corneum 100 , and the longitudinal section 140 includes the epidermis 110 and the dermis 120 .
[0062] See also Figure 7 , Figure 7 1 is a schematic diagram of relative fluorescence intensity of a cross section 130 of the back skin of BALB / c nude mice after being treated at different input voltages for 5 minutes in a control group and in an embodiment of the present application.
[0063] like Figure 7 As shown, compared with the control group, the relative fluorescence intensity of the cross-section 130 of the back skin of the BALB / c nude mouse treated with the embodiment of the present application for 5 minutes increased with the increase of the input voltage.
[0064] See also Figure 8 , Figure 8 140 is a schematic diagram of the relative fluorescence intensity of the longitudinal section 140 of the back skin of BALB / c nude mice after 5 minutes of treatment in the control group and the example of the present application.
[0065] like Figure 8 As shown, compared with the control group, the relative fluorescence intensity of sodium fluorescein on the longitudinal section 140 of the back skin of BALB / c nude mice treated with the example of the present application for 5 minutes was significantly increased.
[0066] Combine Figure 7 and Figure 8 It can be seen that compared with the control group, the embodiment of the present application can promote the small molecule drug sodium fluorescein to pass through the skin stratum corneum 100, achieve uniform delivery to the dermis 120, and significantly increase the skin's absorption of small molecule drugs.
[0067] See also Figure 9 , Figure 9 Schematic diagram of the relative fluorescence intensity of fluorescein isothiocyanate-dextran (10 kDa) and fluorescein isothiocyanate-dextran (70 kDa) in the longitudinal section 140 of the dorsal skin of BALB / c nude mice after treatment for 5 minutes in the control group and the example of the present application.
[0068] like Figure 9 As shown, the relative fluorescence intensity on the longitudinal section 140 of the dorsal skin of BALB / c nude mice significantly increased after 5 minutes of treatment with the Example of the present application compared to the control group. This result demonstrates that the Example of the present application can significantly promote the delivery of macromolecular drugs to the epidermis 110 and dermis 120, and significantly increase the absorption of macromolecular drugs by the skin.
[0069] See also Figure 10a and Figure 10b , Figure 10a This is a schematic diagram of HE staining of the back skin of BALB / c nude mice after 5 minutes of treatment in the control group. Figure 10b This is a schematic diagram of HE staining of the longitudinal skin section of a BALB / c nude mouse back after treatment with a 250 Vpp input voltage for 5 minutes in an embodiment of the present application.
[0070] Will Figure 10a and Figure 10b By comparison, it was found that under an input voltage of 250 Vpp, the integrity of the back skin of BALB / c nude mice treated with the embodiment of the present application for 5 minutes was basically the same as that of the control group, indicating that the embodiment of the present application would not damage the skin even under high input voltage.
[0071] Combined with the above results, it can be seen that by controlling the magnitude of the input voltage, the droplet size, droplet injection speed and number of droplets ejected from the micropores 511 of the embodiment of the present application can be controlled, thereby achieving precise control of drug release efficiency and dosage, and can significantly promote the delivery of drugs to the deep layers of the skin, and significantly increase the skin's absorption of large molecule drugs and small molecule drugs, while maintaining the integrity of the skin under high input voltage.
[0072] The above description is merely a specific embodiment of the present application, but the scope of protection of the present application is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the technical scope disclosed in the present application, and such modifications or substitutions should be included in the scope of protection of the present application. Therefore, the scope of protection of the present application should be based on the scope of protection of the claims.
Claims
1. A transdermal drug delivery device, characterized in that: include: a drug container, wherein the drug container is used to store a drug solution; a metal sheet, wherein the metal sheet is provided with micropores, and the micropores are connected to the drug container; A piezoelectric substrate having a ring-shaped hollow structure, the metal sheet being disposed on the piezoelectric substrate, the metal sheet and the piezoelectric substrate forming a transducer; The piezoelectric substrate vibrates to form capillary waves on the metal sheet, causing the drug solution in the drug container to spray droplets through the micropores. When the droplets are sprayed onto the stratum corneum of the skin, they will wrap gas to form bubble clouds. The bubble clouds have a longitudinal driving force in the vertical direction of the skin to accelerate the movement of the drug into the deep layer of the skin. The shock waves generated by the bubble clouds have a lateral driving force at the level of the skin to enlarge the cell gap, so that the drug can pass through the stratum corneum of the skin.
2. The transdermal drug delivery device according to claim 1, wherein The side of the metal sheet close to the drug container is the first side, and the side close to the piezoelectric substrate is the second side. The aperture of the micropores on the first side is greater than or equal to the aperture of the micropores on the second side.
3. The transdermal drug delivery device according to claim 2, wherein The diameter of the micropores on the second surface is 20-130 μm.
4. The transdermal drug delivery device according to claim 1, wherein The thickness of the metal sheet is smaller than the thickness of the piezoelectric substrate.
5. The transdermal drug delivery device according to claim 4, characterized in that: The thickness of the piezoelectric substrate is 500-700 μm, and the thickness of the metal sheet is 30-70 μm.
6. The transdermal drug delivery device according to claim 5, wherein The piezoelectric substrate includes a piezoelectric ceramic ring sheet, the metal sheet is a circular metal sheet, and the microhole is located at the center of the metal sheet.
7. The transdermal drug delivery device according to claim 6, wherein The outer ring radius of the piezoelectric ceramic ring piece is 8 mm, the hollow inner diameter is 6 mm, and the radius of the circular metal piece is 8 mm.
8. The transdermal drug delivery device according to claim 1, wherein Also includes: A clamping assembly, wherein the metal sheet and the piezoelectric substrate are fixedly connected via the clamping assembly.
9. The transdermal drug delivery device according to claim 8, wherein The clamping assembly comprises: a first clamping member, wherein the first clamping member is provided with a groove, and the groove is used for placing the transducer; The second clamping member is used to clamp the transducer on the first clamping member. The second clamping member is provided with a solution hole. The second clamping member clamps the transducer. The solution hole and the metal sheet form a medicine container.
10. The transdermal drug delivery device according to claim 8, wherein Also includes: Fixed seat; A support rod, the support rod being arranged on the fixing seat; A fixing member is adjustably arranged on the support rod, the fixing member is connected to the clamping assembly, and is used to fix the transducer on the support rod, and the distance between the transducer and the fixing seat is adjustable.