Transdermal delivery system

Abstract

The present application relates to a transdermal drug delivery technology, in particular, to a transdermal delivery system. The transdermal delivery system comprises a delivery device and a delivery unit, the delivery unit comprises a base and a micro-protrusion formed on the base, the micro-protrusion is coated with a dissolvable coating; the delivery unit is assembled on the delivery device, the delivery device can drive the delivery unit to reciprocate and repeatedly pierce the skin; each time the dissolvable coating can partially dissolve when the delivery unit pierces into the skin, and the dissolvable coating completely dissolves when the delivery unit pierces into the skin for a certain number of times. The transdermal delivery system can effectively enhance the reduction of the problem of traditional dissolvable microneedle body fracture, and has the technical progress of simple and convenient operation, balanced skin care, precise and controllable dose, safe and efficient, painless and non-invasive.

Description

Technical Field

[0001] The present invention relates to a transdermal drug delivery technology, in particular to a transdermal delivery system. Background Art

[0002] In the field of transdermal drug delivery, chemical delivery methods, such as plasters, are the most common. To ensure efficient transdermal absorption of drugs, these plasters often incorporate chemical penetration enhancers. However, these chemical penetration enhancers can easily cause skin discomfort, resulting in adverse reactions such as itching, redness, swelling, and allergies. Consequently, physical transdermal delivery technologies have emerged.

[0003] Among physical transdermal delivery technologies, microneedle transdermal delivery offers numerous advantages. Microneedle transdermal products are made of metal, single-crystal silicon, polymers, or other suitable materials and comprise a substrate and a microneedle array formed on the substrate. Microneedle transdermal products act on the skin surface through the microneedle array, overcoming the skin's surface barrier and forming a channel for rapid and efficient transdermal absorption of active ingredients. In physical transdermal drug delivery technology, the microneedle array on the nanochip achieves nanometer-level precision, offering advantages such as non-invasiveness, painlessness, safety, and high efficiency, earning it the favor of experts both domestically and internationally.

[0004] Current microneedle transdermal drug delivery technology primarily involves two steps: first, using a massage device to control microneedles or nanochips to repeatedly puncture specific areas of the skin at high frequency, thereby clearing the skin's surface; second, applying the active ingredient to the specific skin surface. The puncture and clearing step enhances transdermal absorption, while the application step enables targeted, precise drug delivery.

[0005] However, this operation procedure has the following aspects to be improved. First, it is impossible to determine whether the active ingredients applied to the skin surface can be completely absorbed. The active ingredients may remain on the skin surface or on the microneedles or massage instruments. These situations make it impossible to determine the absorbed dose of the active ingredients. Second, the puncture and dredging area will not change significantly. It is easy for the application area and the puncture and dredging area to not overlap, resulting in some active ingredients not being effectively absorbed, and there is a certain degree of difficulty in getting started. Third, the entire care process is divided into two steps, which require preparing the active ingredients and controlling the massage instrument to care for the skin separately, and the operation is relatively cumbersome.

[0006] In addition, a type of soluble microneedle product has emerged in the field of microneedle transdermal delivery technology. This soluble microneedle product includes a substrate and a microneedle array, wherein the microneedle array is made of soluble materials. Since the microneedle array is made of soluble materials, the strength of its needle structure is limited. Its conventional method of use is to pierce the skin once, the needle body breaks, and the soluble material remains in the skin. This type of soluble microneedle product can only be used once, and it is easy for the needle body to break prematurely during use, and the active ingredients cannot enter the skin. In addition, when caring for the entire face, it is necessary to Figure 1 In this way, applying the product to different areas of the face one by one is cumbersome and inconvenient. At the same time, it is easy for some skin to be left untreated or to be treated repeatedly, resulting in unbalanced skin care.

[0007] In summary, there are many areas for improvement in the existing microneedle transdermal delivery methods. Summary of the Invention

[0008] To address the shortcomings of existing transdermal delivery methods, such as cumbersome operation, uncontrollable dosage, uneven care, and the susceptibility to skin allergies, the present invention provides a transdermal delivery system. The transdermal delivery system comprises a delivery device and a delivery unit, wherein the delivery unit comprises a base and micro-protrusions formed on the base, the micro-protrusions being coated with a soluble coating. The delivery unit is mounted on the delivery device and is capable of driving the delivery unit in reciprocating motion and repeatedly puncturing the skin. The soluble coating partially dissolves with each puncture, and completely dissolves after the delivery unit has punctured the skin a specified number of times.

[0009] The above technical solution is further explained.

[0010] Delivery device: Delivery devices can take many forms, such as mechanical transmission devices driven by electric motors or electromagnetically driven mechanical transmission devices. The mechanical transmission structure converts the driving force into reciprocating motion, driving the delivery unit to reciprocate within a certain range.

[0011] Delivery unit: The delivery unit consists of a base, micro-protrusions, and may also include fixing components, support components, and connectors. The connectors allow the delivery unit to be assembled onto the delivery equipment, while the fixing components and support components make the delivery unit more secure and more stable during reciprocating motion.

[0012] Soluble coating: This coating contains an active ingredient and is applied as a solid to the micro-protrusions. The coating is soluble in water, tissue fluid, or blood. Each time the micro-protrusions penetrate the skin, the coating comes into contact with the water, tissue fluid, or blood in the skin and partially dissolves. After a specific number of contacts, the coating completely dissolves into the skin.

[0013] Beneficial Effects of the Present Invention: Conventional soluble microneedles are made of soluble materials. In conventional application methods, effective active ingredients often remain in the skin after a single puncture. It should be noted that when conventional soluble microneedles are used for multiple skin punctures, they only have good puncture ability during the first or first few punctures. As the number of punctures increases, the needle body melts, causing the needle tip to become blunt and unable to continue effectively puncturing the skin. Therefore, conventional soluble microneedles are only capable of single punctures or a small number of punctures, and accordingly, the active ingredient can only be delivered to a localized area of ​​the skin. When users need to care for their entire face or head, they need to frequently replace soluble microneedles. This makes it difficult to ensure uniform and even delivery of active ingredients to different areas, which can easily lead to uneven skin care. In contrast, in this technical solution, a soluble coating containing the effective active ingredient is disposed on the microprotrusions. The microprotrusions consistently provide sufficient strength to efficiently and stably puncture the skin. After the microprotrusions penetrate the skin, the soluble coating is partially absorbed by the skin. This design improves the defects of traditional soluble microneedles, such as low needle strength, easy blunting of the tip, and inability to deliver active ingredients through multiple punctures, allowing effective active ingredients to enter the skin efficiently.

[0014] In this transdermal delivery system, the delivery unit can drive the soluble coating to puncture the skin back and forth multiple times. During the high-frequency reciprocating motion, the time for the micro-protrusions to puncture the skin each time is relatively fixed, so the amount of the soluble coating dissolved into the skin each time is fixed. By moving the delivery device, different positions of the skin are cared for, and the soluble coating will be evenly dissolved into different positions of the skin, thereby nourishing the skin in a balanced manner. In this technical solution, by controlling the dissolution rate of the soluble coating, the soluble coating is slowly dissolved and released, and the time for the soluble coating to be completely dissolved is matched with the care process. During the high-frequency, long-term reciprocating puncture process, the effective active ingredients can be evenly dissolved into various areas of the skin, so that the skin can be cared for in a balanced manner. In addition, this technical solution can also enable users to have a longer care operation time, which is convenient for users to care for their skin more calmly.

[0015] In this technical solution, the soluble coating is only applied to the micro-protrusions. During the treatment process, the micro-protrusions can fully penetrate the skin, allowing the soluble coating to be fully absorbed by the skin. This design can reduce the waste of effective active ingredients and make the dosage more precise and controllable.

[0016] When using this technical solution, users only need to move the handheld delivery device across the skin surface to complete the skin care operation, without having to worry about applying the active ingredients. The entire operation is simpler and more convenient, and the difficulty of getting started is reduced.

[0017] In a preferred embodiment, the soluble coating is applied only to the tips of the microprotrusions. When skin only requires superficial or light care, the microprotrusions do not fully penetrate the skin; only the tips do. In this preferred embodiment, the soluble coating is applied only to the tips of the microprotrusions, enabling precise, light or superficial skin care while effectively reducing waste of active ingredients.

[0018] In a preferred technical solution, the soluble coating includes at least one of finasteride, minoxidil, GLP-1, insulin, semaglutide, conopeptide, tranexamic acid, hexapeptide, salicylic acid, L-ascorbic acid, tretinoin, and botulinum toxin. In this preferred technical solution, the transdermal delivery system can provide scalp care, improve the absorption efficiency of effective active ingredients, stimulate hair follicles and hair regeneration, and provide a more convenient and comfortable treatment experience for patients with hair loss.

[0019] In a preferred technical solution, the content of finasteride in the soluble coating is not less than 0.01% and not more than 3%.

[0020] In a preferred technical solution, in the soluble coating, the content of minoxidil is not less than 0.01% and not more than 5%.

[0021] In the preferred technical solution, the specific number of times is not less than 100 times and not more than 50,000 times. This preferred technical solution can accurately and quantitatively adjust the dissolution rate of the soluble coating by adjusting the number of punctures required for the soluble coating to completely dissolve. For example, skin care around the eyes usually takes less than 30 seconds, so that the soluble coating is completely dissolved when the skin is punctured 1,000 times. The vibration frequency of the delivery device is selected to be 2,000 times / minute, and the user can complete eye care within half a minute. At the same time, the effective active ingredients in the soluble coating can be evenly absorbed by the skin around the eyes. The vibration frequency of the delivery device is usually 1,000-5,000 times / minute. Depending on the specific number of times, the delivery device can be used for tens of seconds to tens of minutes to complete the care of the skin in different positions such as the eye area, face, and scalp.

[0022] In a preferred technical solution, the diameter of the end of the micro-protrusion is no more than 200 nanometers. In this technical solution, the end of the micro-protrusion reaches the nanometer level, which can achieve painless and non-invasive high-efficiency penetration promotion.

[0023] In a preferred technical solution, the length of the micro-protrusion is no more than 3000 microns.

[0024] In a preferred embodiment, each microprotrusion comprises multiple tips, which are clustered together. The soluble coating is applied to the tips and the spaces between them. In this embodiment, the microprotrusions have multiple tips at their ends, and their structure multiplies the coating's adhesion area. Furthermore, these tips are clustered together to form drug storage spaces. This structure significantly increases the drug storage capacity at the microprotrusion ends, facilitating large-dose drug delivery.

[0025] In a preferred technical solution, the end of the micro-protrusion is conical, pyramidal or blade-shaped.

[0026] In a preferred technical solution, the micro-protrusions are made of at least one of single crystal silicon, ceramics, and polymer materials.

[0027] In a preferred technical solution, the micro-protrusions are arranged on the base in a rectangular array, a circular array, or a honeycomb array. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 Schematic diagram of the structure of the delivery device and the delivery unit in one embodiment of the transdermal delivery system.

[0029] Figure 2 Schematic diagram of the structure of the delivery unit in Example 1 of the transdermal delivery system.

[0030] Figure 3 yes Figure 2 Schematic diagram of the enlarged structure at point A in the middle.

[0031] Figure 4 It is a schematic structural diagram of the delivery unit in Example 2 of the transdermal delivery system.

[0032] Figure 5 yes Figure 4 Schematic diagram of the enlarged structure at point B in the middle.

[0033] Figure 6 Schematic diagram of the structure of the delivery unit in Example 3 of the transdermal delivery system.

[0034] List of reference numerals:

[0035] 1. Delivery device, 11. Transmission rod, 2. Delivery unit, 20. Connector, 201. Support member, 21. Base, 22. Micro-protrusion, 23. End of micro-protrusion, 231. Tip, 24. Soluble coating. DETAILED DESCRIPTION

[0036] The present technical solution is further explained and illustrated below through some embodiments. It should be noted that the following embodiments are only used to make the inventive concept and design ideas of the present technical solution clearer and are not used to limit the scope of protection of the present invention. It is easy to understand that all other embodiments completed under the guidance of the inventive concept of the present technical solution should also fall within the scope of protection of the present invention.

[0037] To address the shortcomings of existing transdermal delivery methods, such as cumbersome operation, uncontrollable dosage, uneven care, and the susceptibility to skin allergies, the present invention provides a transdermal delivery system. The transdermal delivery system comprises a delivery device 1 and a delivery unit 2. The delivery unit 2 comprises a base 21 and micro-protrusions 22 formed on the base, each coated with a soluble coating 24. The delivery unit 2 is mounted on the delivery device 1, which drives the delivery unit 2 in reciprocating motion and repeatedly punctures the skin. The soluble coating 24 partially dissolves with each puncture, and completely dissolves after the delivery unit 2 has punctured the skin a specified number of times.

[0038] In some embodiments, the delivery device 1 includes a drive motor, a power supply, a switch, a reciprocating transmission mechanism, and a transmission rod 11, wherein the transmission rod 11 is assembled and connected to the delivery unit 2. The power supply is used to provide electrical energy to the drive motor. The power supply can be a rechargeable battery, a disposable battery, or a power cord connected to an outlet. The drive motor can be an electric motor, whose output shaft is mechanically connected to the reciprocating transmission mechanism. The reciprocating transmission mechanism converts the rotation of the output shaft into reciprocating linear motion, thereby driving the transmission rod 11 and the delivery unit 2 to reciprocate. Alternatively, the drive motor can be an electromagnetic drive, which controls the transmission rod 11 through the reciprocating transmission mechanism to drive the delivery unit 2 to reciprocate.

[0039] In some embodiments, delivery unit 2 is directly mounted on the end of transmission rod 11. It will be readily understood that to facilitate assembly and replacement of delivery unit 2, the delivery unit may further include fixing components, support components 201, connectors 20, and the like. Delivery unit 2 can be mounted on transmission rod 11 using connectors 20 such as threads or snaps. The fixing components and support components 201 contact the housing of delivery device 1, ensuring a more secure assembly and more stable reciprocating motion of the delivery unit.

[0040] The present technical solution is further described below through several specific embodiments. Example 1

[0041] Figure 1 Schematic diagram of the structure of the delivery device and the delivery unit in one embodiment of the transdermal delivery system. Figure 2 Schematic diagram of the structure of the delivery unit in Example 1 of the transdermal delivery system. Figure 3 yes Figure 2 Schematic diagram of the enlarged structure at point A in the middle.

[0042] like Figure 1 In the illustrated embodiment 1, the delivery device 1 includes a transmission rod 11, which is powered by a drive motor and capable of reciprocating along its own axis. The delivery unit 2 includes a connector 20 and a support member 201. The delivery unit 2 is detachably mounted to the end of the transmission rod 11 via the connector 20, and the support member 201 is detachably mounted to the housing of the delivery device 1. When the delivery unit 2 is driven by the transmission rod 11 to reciprocate along a straight line, it has an upper position and a lower position. The upper position refers to the position where the delivery unit 2 has moved to the outside of the housing to its maximum extent, while the lower position refers to the position where the delivery unit 2 has moved to the inside of the housing to its maximum extent. In some embodiments, when the delivery unit 2 is in the lower position, it is completely retracted within the end of the support member 201, i.e., the delivery unit 2 does not extend beyond the end of the support member 201. This design facilitates the user's sliding operation of the delivery device 1 when caring for the skin.

[0043] like Figure 2 and Figure 3 As shown, in this first embodiment, the delivery unit 2 includes a base 21 and micro-protrusions 22. The base 21 is made of materials such as single crystal silicon, metal, ceramic, and polymer. In some processing scenarios, the surface of the base 21 is processed by 3D etching, laser engraving, or wet etching to form the micro-protrusions 22. In this case, the micro-protrusions 22 are made of single crystal silicon, metal, ceramic, or polymer.

[0044] like Figure 3 As shown in the first embodiment, the micro protrusion 22 is generally conical. Alternatively, the micro protrusion 22 can also be generally prism-shaped, cylindrical, pyramid-shaped, etc., and the end portion thereof can be processed to form an end portion that is convenient for puncturing the skin. Figure 3 As shown, the end 23 of the micro-protrusion 22 is conical. Alternatively, the end of the micro-protrusion 22 can also be pyramidal or blade-shaped. In the first embodiment of the present invention, the diameter of the end 23 of the micro-protrusion is not greater than 200 nanometers, and the fineness reaches the nanometer level. Optionally, the size of the end 23 is 80 nanometers, which is one thousandth of the diameter of a hair, and can perform painless and non-invasive high-efficiency penetration-promoting treatment on the skin. In the first embodiment of the present invention, the length of the micro-protrusion 22 is not greater than 3000 microns. In some products, the micro-protrusions 22 are arranged in a rectangular array, a circular array or a honeycomb array on the base 21. Optionally, the micro-protrusions 22 are arranged in a square array on the base 21 in the form of 8*8, 7*7, 6*6, 5*5, 4*4, and 3*3.

[0045] In some usage scenarios, such as daily beauty projects, when superficial skin care or slight neglect is required, the micro-protrusions 22 do not need to penetrate the skin completely, but only the ends 23 of the micro-protrusions 22 enter the skin. Figure 3 In the first embodiment shown, a soluble coating 24 is applied only to the end 23 of the micro-protrusion 22. The soluble coating 24 does not contact the base 21. The soluble coating 24 of a specific thickness or a specific dose can be applied to the end 23 of the micro-protrusion 22 by spraying, immersion, dripping, dispensing, etc., and the soluble coating 24 is solidified by a specific process. In the first embodiment, the soluble coating contains an effective active ingredient, which includes at least one of finasteride, minoxidil, GLP-1, insulin, semaglutide, conoside, tranexamic acid, hexapeptide, salicylic acid, levorotatory vitamin C, retinoic acid, and botulinum toxin. It is easy to imagine that in some embodiments, the soluble coating contains at least one of water, ethanol, hyaluronic acid, isopropanolamine, and isopropyl alcohol. The soluble coating is soluble in water, tissue fluid, or blood. When the ends 23 of the microprotrusions 22 penetrate the skin, the soluble coating 24 comes into contact with the water, tissue fluid, or blood in the skin and partially dissolves, thereby retaining the active ingredient in the skin. In some embodiments, when using this technology for scalp hair loss treatment, the active ingredient content of finasteride is no less than 0.01% and no more than 3%. The content of minoxidil is no less than 0.01% and no more than 5%.

[0046] In this embodiment, a soluble coating 24 containing an effective active ingredient is disposed on the micro-protrusions 22 and punctures the skin with high frequency reciprocating motions of the micro-protrusions 22. The delivery device 1 typically has a vibration frequency of 1000-5000 times / minute, so the contact time between the soluble coating 24 and the water, tissue fluid, or blood in the skin is very short. Thus, each time the soluble coating 24 punctures the skin, it can temporarily partially dissolve until the micro-protrusions 22 have punctured the skin a sufficient number of times, at which point the soluble coating 24 can completely dissolve. In this first embodiment, the specific number of times is not less than 100 times and not more than 50,000 times. Furthermore, the specific number of times is not less than 1,000 times and not more than 50,000 times, such as 1,000 times, 2,000 times, 3,000 times, 10,000 times, 30,000 times, 35,000 times, 40,000 times, 45,000 times, and the like.

[0047] By controlling the number of punctures required for the soluble coating 24 to completely dissolve, the dissolution rate of the soluble coating 24 can be precisely and quantitatively adjusted to suit different usage scenarios, medication application rates, and dosages. For example, in the case of periocular skin care, the specific number of punctures is set to 1000, and the delivery device's vibration frequency is selected to be 2000 times / minute. This allows the user to perform a uniform, repeated massage treatment of the periocular skin within half a minute. During the high-frequency reciprocating motion, the micro-protrusions 22 penetrate the skin for a relatively fixed amount of time each time, resulting in a fixed amount of soluble coating 24 dissolving into the skin each time. Therefore, within this timeframe, the soluble coating 24 is evenly released into the periocular skin. Users can tailor treatments to specific eye wrinkle areas for extended periods of time. In this embodiment, users can perform targeted, quantitative, and targeted skin care, similar to applying a swipe. The operation is simple, intuitive, and controllable. Furthermore, when the user needs to pause treatment, the soluble coating 24 remains stably stored at the ends 23 of the micro-protrusions 22, preventing waste or loss and enhancing ease of use. It is easy to understand that this technical solution has a wide range of application scenarios and can be used to care for skin in different locations such as around the eyes, face, and scalp.

[0048] It is worth noting that the number of punctures required for the complete dissolution of the soluble coating 24 can be adjusted by adjusting parameters such as the thickness and dissolution difficulty of the soluble coating 24 . Example 2

[0049] Figure 4 It is a schematic structural diagram of the delivery unit in Example 2 of the transdermal delivery system. Figure 5 yes Figure 4 Schematic diagram of the enlarged structure at B in the figure. Figure 4 and Figure 5 As shown, different from the first embodiment, in the second embodiment, a plurality of tips 231 are formed on the end 23 of each micro protrusion 22. The plurality of tips 231 are combined into a cluster, as shown in FIG. Figure 5 As shown, in this second embodiment, four tips 231 are clustered together, with the gaps between the tips 231 forming a drug storage space. A soluble coating 24 is applied to the tips 231 and the drug storage space. In this second embodiment, the tips 231 increase the surface area of ​​the end portion 23, multiplying the adhesion area of ​​the soluble coating 24 and thereby strengthening the bonding force between the soluble coating 24 and the microprotrusions 22. This structure also increases the drug loading capacity of the microprotrusions, enabling high-dose drug delivery. Example 3

[0050] Figure 6 FIG. 1 is a schematic diagram of the structure of the delivery unit in Example 3 of the transdermal delivery system. Figure 6As shown, unlike the first embodiment, in the third embodiment, the soluble coating 24 is coated on the entire micro-protrusion 22, and the soluble coating 24 does not contact the base 21. The soluble coating 24 of a specific thickness or a specific dose can be coated on the micro-protrusion 22 by spraying, immersion, dripping, dispensing, etc., and the soluble coating 24 is solidified by a specific process. In the third embodiment, the soluble coating contains an effective active ingredient, which includes at least one of finasteride, minoxidil, GLP-1, insulin, semaglutide, conoside, tranexamic acid, hexapeptide, salicylic acid, levovitamin C, retinoic acid, and botulinum toxin. It is easy to imagine that in some embodiments, the soluble coating contains at least one of water, ethanol, hyaluronic acid, isopropylamine, and isopropyl alcohol, and the soluble coating can be soluble in water, tissue fluid, or blood.

[0051] In some use cases, such as medical care and hair loss treatment, where deep skin care is required, the micro-protrusions 22 need to fully penetrate the skin. In these use cases, when the micro-protrusions 22 fully penetrate the skin, the soluble coating 24 covering the entire micro-protrusions 22 can come into contact with more water, tissue fluid, or blood in the skin and partially dissolve, thereby retaining more effective active ingredients in the skin per unit time. Therefore, in some use cases, the transdermal delivery system of Example 3 has higher transdermal delivery efficiency than that of Example 1.

Claims

1. A transdermal delivery system comprising a delivery device and a delivery unit, characterized in that: The delivery unit includes a base and micro-protrusions formed on the base, wherein the micro-protrusions are coated with a soluble coating; The delivery unit is assembled on the delivery device, and the delivery device can drive the delivery unit to reciprocate and repeatedly puncture the skin; each time the skin is punctured, the soluble coating can be partially dissolved, and when the delivery unit punctures the skin a specific number of times, the soluble coating is completely dissolved. By controlling the number of punctures required for the soluble coating to completely dissolve, the dissolution rate of the soluble coating can be accurately and quantitatively adjusted to adapt to different usage scenarios or drug application speeds and dosages.

2. The transdermal delivery system according to claim 1, wherein The soluble coating is applied only to the ends of the microprotrusions.

3. The transdermal delivery system according to claim 1, wherein The soluble coating comprises at least one of finasteride, minoxidil, GLP-1, insulin, semaglutide, conopeptide, tranexamic acid, hexapeptide, salicylic acid, L-ascorbic acid, tretinoin, and botulinum toxin.

4. The transdermal delivery system according to claim 3, wherein In the soluble coating, the content of finasteride is not less than 0.01% and not more than 3%.

5. The transdermal delivery system according to claim 3, wherein In the soluble coating, the content of minoxidil is not less than 0.01% and not more than 5%.

6. The transdermal delivery system according to claim 1, wherein The specific number of times is not less than 100 times and not more than 50,000 times.

7. The transdermal delivery system according to claim 1, wherein The diameter of the end of the micro protrusion is no greater than 200 nanometers.

8. The transdermal delivery system according to claim 1, wherein The length of the micro protrusion is no more than 3000 microns.

9. The transdermal delivery system according to claim 1, wherein Each of the micro-protrusions includes a plurality of tips, the plurality of tips are combined into a cluster, and the soluble coating is coated on the plurality of tips and in the gaps between the tips.

10. The transdermal delivery system according to claim 1, wherein The end of the micro protrusion is in a cone shape, a pyramid shape or a knife edge shape.

11. The transdermal delivery system according to claim 1, wherein The micro protrusions are made of at least one of single crystal silicon, ceramics, and polymer materials.

12. The transdermal delivery system according to claim 1, wherein The micro protrusions are arranged on the base in a rectangular array, a circular array or a honeycomb array.

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