Transdermal delivery system

Abstract

The invention 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 micro protrusions formed on the base, and the micro protrusions are coated with soluble coatings; the delivery unit is assembled on the delivery equipment, and the delivery equipment can drive the delivery unit to reciprocate and repeatedly puncture the skin; each time the delivery unit is punctured into the skin, the soluble coating can be partially dissolved, and when the delivery unit is punctured into the skin for a specific number of times, the soluble coating can be completely dissolved. The transdermal delivery system can effectively enhance and reduce the problem that a traditional soluble micro-needle body is broken, and has the technical advantages of being easy and convenient to operate, balanced in skin care, accurate and controllable in dosage, safe, efficient, painless, noninvasive and the like.

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 delivery technology, it is more common to deliver drugs through chemical means, such as plasters. In order to ensure the transdermal absorption efficiency of drugs, chemical penetration enhancers are added to plaster transdermal products. Such chemical penetration enhancers are prone to cause skin discomfort, resulting in adverse reactions such as itching, redness, swelling, and allergies. Therefore, physical transdermal delivery technology came into being.

[0003] Among physical transdermal delivery technologies, microneedle transdermal delivery technology has many advantages. Microneedle transdermal products are made of metal, single crystal silicon, polymer or other suitable materials, and have a substrate and a microneedle array formed on the substrate. Microneedle transdermal products act on the skin surface through the microneedle array, overcome the skin surface barrier layer and form a dredging channel, so that the active ingredients can be quickly and efficiently absorbed through the skin. In physical transdermal drug delivery technology, the microneedle array on the nanochip has achieved nanometer-level precision, and has the advantages of being non-invasive, painless, safe, and efficient, and has won the favor of domestic and foreign experts.

[0004] The current microneedle transdermal drug delivery technology mainly includes two operating steps: the first is to control the microneedles or nanochips to puncture the skin of a specific area at high frequency and repeatedly through a massage instrument to dredge the skin surface; the second is to apply the active ingredients on the skin surface of a specific area. The puncture and dredging step can improve the transdermal absorption effect of the skin, and the application step can achieve targeted and precise drug delivery.

[0005] However, this operation procedure has room for improvement in the following aspects. 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, and it is easy for the application area to not overlap with the puncture and dredging area, 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 the needle structure is limited. Its conventional method of use is to pierce the skin once, the needle 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 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] In order to solve the defects of the existing transdermal delivery methods, such as cumbersome operation, uncontrollable dosage, unbalanced care, and easy skin allergies, the present invention provides a transdermal delivery system. The transdermal delivery system includes a delivery device and a delivery unit, wherein the delivery unit includes a base and micro-protrusions formed on the base, and the micro-protrusions are coated with a soluble coating; the delivery unit is mounted 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 for a specific number of times, the soluble coating is completely dissolved.

[0009] The above technical solution is further explained.

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

[0011] Delivery unit: The delivery unit includes a base, micro-protrusions, and may also include fixing components, supporting components, connectors, etc. Through the connectors, the delivery unit can be assembled to the delivery device, and the fixing components and supporting components can make the delivery unit more secure and more stable during reciprocating motion.

[0012] Soluble coating: The soluble coating contains effective active ingredients and is solid and formed on the micro-protrusions. The soluble coating can be dissolved in water, tissue fluid or blood. Each time the micro-protrusions pierce the skin, the soluble coating contacts the water, tissue fluid or blood in the skin and partially dissolves. When the contact reaches a certain number of times, the soluble coating completely dissolves into the skin.

[0013] Beneficial effects of the present invention: The needle body of the traditional soluble microneedle is made of soluble material. In the traditional application method, the effective active ingredient is often retained in the skin after a single puncture. It should be noted that when the traditional soluble microneedle is used to puncture the skin multiple times, the traditional soluble microneedle only has good puncture ability when the skin is punctured for the first time or the first few times. As the number of punctures increases, the needle body will melt, resulting in the passivation of the end of the needle body, and it is impossible to continue to effectively puncture the skin. Therefore, the traditional soluble microneedle can only achieve a single puncture or a small number of punctures of the skin, and accordingly, the active ingredient can only be delivered to the skin locally. When the user needs to care for the entire face or head, the soluble microneedle needs to be replaced frequently. At this time, the amount of active ingredient delivered to different areas will be difficult to ensure uniformity and averageness, which easily leads to uneven skin care. In the present technical solution, the soluble coating containing the effective active ingredient is arranged on the micro-protrusions, and the micro-protrusions can always provide sufficient strength, and can efficiently and stably puncture the skin. After the micro-protrusions puncture the skin, the soluble coating can be 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 completely dissolve 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 arranged on the micro-protrusions. During the care process, the micro-protrusions can fully enter the skin, so that the soluble coating can be fully absorbed by the skin. This design can reduce the waste of effective active ingredients and make the dosage more accurate and controllable.

[0016] When using this technical solution, the user only needs to hold the delivery device and move it on the skin surface to complete the skin care operation without having to pay attention to the application of active ingredients. The entire operation is simpler and more convenient, and the difficulty of getting started is reduced.

[0017] In a preferred technical solution, the soluble coating is only coated on the ends of the micro-protrusions. When the skin only needs shallow or light care, the micro-protrusions will not completely enter the skin, and only the ends will enter the skin. In this preferred technical solution, the soluble coating is only coated on the ends of the micro-protrusions, which can not only meet the requirements of light or shallow care with precise dosage for the skin, but also effectively reduce the 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, levovitamin C, retinoic acid, and botulinum toxin. In this preferred technical solution, the transdermal delivery system can care for the scalp, improve the absorption efficiency of effective active ingredients, stimulate hair follicles and hair regeneration, and bring a more convenient and comfortable treatment experience to patients with hair loss.

[0019] In a preferred technical solution, in the soluble coating, the content of finasteride 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, periocular skin care is usually within 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 periocular care within half a minute. At the same time, the effective active ingredients in the soluble coating can be evenly absorbed by the periocular skin. 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 periocular 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-protrusions is no more than 3000 microns.

[0024] In a preferred technical solution, 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. In this technical solution, the end of the micro-protrusion has a plurality of tips, and the structure of these tips increases the adhesion area of ​​the coating exponentially; at the same time, these tips are combined into a cluster to form a drug storage space, and this structure can greatly increase the amount of drug stored at the end of the micro-protrusion, thereby facilitating the delivery of large doses of drugs.

[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 It is a schematic diagram of the structure of a delivery device and a delivery unit in one embodiment of the transdermal delivery system.

[0029] Figure 2 It is a schematic diagram of the structure of the delivery unit in the first embodiment 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 diagram of the structure of the delivery unit in the second embodiment 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 It is a schematic diagram of the structure of the delivery unit in the third embodiment of the transdermal delivery system.

[0034] List of reference numerals: 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

[0035] The present technical solution is further explained and elaborated by some embodiments below. 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 protection scope 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 belong to the protection scope of the present invention.

[0036] In order to solve the defects of the existing transdermal delivery methods, such as cumbersome operation, uncontrollable dosage, unbalanced care, and easy skin allergy, the present invention provides a transdermal delivery system. The transdermal delivery system includes a delivery device 1 and a delivery unit 2, wherein the delivery unit 2 includes a base 21 and micro-protrusions 22 formed on the base, and a soluble coating 24 is coated on the micro-protrusions 22; the delivery unit 2 is assembled on the delivery device 1, and the delivery device 1 can drive the delivery unit 2 to reciprocate and repeatedly puncture the skin; each time the skin is punctured, the soluble coating 24 can be partially dissolved, and when the delivery unit 2 punctures the skin for a specific number of times, the soluble coating 24 is completely dissolved.

[0037] 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 used to be assembled and connected with the delivery unit 2. The power supply is used to provide electrical energy to the drive motor, and the power supply can be a rechargeable battery, a disposable battery, etc., or it can be powered by a wire connected to a socket. The drive motor can be an electric motor, and the output shaft of the electric motor is mechanically connected to the reciprocating transmission mechanism. The reciprocating transmission mechanism converts the rotation of the output shaft into reciprocating linear motion and drives the transmission rod 11 and the delivery unit 2 to reciprocate. Alternatively, the drive motor can also be an electromagnetic driver, which controls the transmission rod 11 through the reciprocating transmission mechanism to drive the delivery unit 2 to reciprocate.

[0038] In some embodiments, the delivery unit 2 is directly assembled on the end of the transmission rod 11. It is easy to understand that in order to facilitate the assembly and replacement of the delivery unit 2, the delivery unit may also have a fixing component, a supporting component 201, a connecting member 20, etc. The delivery unit 2 can be assembled on the transmission rod 11 by a connecting member 20 such as a thread or a buckle, and the fixing component and the supporting component 201 are in contact with the housing of the delivery device 1, so that the delivery unit is assembled more securely and the reciprocating motion is more stable.

[0039] The present technical solution is further described below through several specific embodiments. Embodiment 1

[0040] Figure 1 It is a schematic diagram of the structure of a delivery device and a delivery unit in one embodiment of the transdermal delivery system. Figure 2 It is a schematic diagram of the structure of the delivery unit in the first embodiment of the transdermal delivery system. Figure 3 yes Figure 2 Schematic diagram of the enlarged structure at point A in the middle.

[0041] like Figure 1 In the embodiment 1 shown, the delivery device 1 has a transmission rod 11, which is powered by a driving motor and can reciprocate along its own axis. The delivery unit 2 has a connecting member 20 and a supporting member 201, and the delivery unit 2 is detachably assembled at the end of the transmission rod 11 through the connecting member 20, and the supporting member 201 is detachably assembled with 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 moves to the limit outside the housing, and the lower position refers to the position where the delivery unit 2 moves to the limit inside the housing. In some embodiments, when the delivery unit 2 is in the lower position, the delivery unit 2 is completely retracted in the port of the supporting member 201, that is, the delivery unit 2 does not exceed the port of the supporting member 201. This design can facilitate the user to slide and operate the delivery device 1 when caring for the skin.

[0042] like Figure 2 and Figure 3 As shown, in the 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, polymer, etc. In some processing scenarios, the surface of the base 21 is processed by a 3D etching process, a laser engraving process, or a wet etching process, so that the micro protrusions 22 are formed on the surface of the base 21. At this time, the material of the micro protrusions 22 is single crystal silicon, metal, ceramic, or polymer material.

[0043] like Figure 3 As shown, in the first embodiment, the micro protrusion 22 is generally conical. Alternatively, the micro protrusion 22 may be generally prism-shaped, cylindrical-shaped, pyramid-shaped, etc., and the end portion thereof may 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 more 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 effectively promote the penetration of the skin painlessly and non-invasively. In the first embodiment of the present invention, the length of the micro-protrusion 22 is not more 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 manner of 8*8, 7*7, 6*6, 5*5, 4*4, and 3*3.

[0044] In some usage scenarios, such as daily beauty projects, when the skin needs to be superficially cared for or slightly neglected, the micro-protrusions 22 do not need to pierce the skin completely, and 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 on 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 cured 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, cono peptide, tranexamic acid, hexapeptide, salicylic acid, L-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 isopropanol. The soluble coating can be dissolved in water, tissue fluid or blood. When the end 23 of the micro-protrusion 22 pierces the skin, the soluble coating 24 contacts the water, tissue fluid or blood in the skin and partially dissolves, so that the effective active ingredient remains in the skin. In some embodiments, when the present technical solution is used for scalp hair loss care, the content of finasteride in the active ingredient is not less than 0.01% and not more than 3%. The content of minoxidil is not less than 0.01% and not more than 5%.

[0045] In this embodiment, a soluble coating 24 containing an effective active ingredient is arranged on the micro-protrusion 22, and punctures the skin reciprocatingly with the micro-protrusion 22 at a high frequency. The common vibration frequency of the delivery device 1 is 1000-5000 times / minute, so the contact time of the soluble coating 24 with the water, tissue fluid or blood in the skin is very short each time. Therefore, each time the soluble coating 24 punctures into the skin, it can be temporarily partially dissolved until the micro-protrusion 22 punctures the skin a sufficient number of times, and the soluble coating 24 can be completely dissolved. In the first embodiment, the specific number of times is not less than 100 times and not more than 50,000 times. Further, the specific number of times is not less than 1000 times and not more than 50,000 times, such as 1000 times, 2000 times, 3000 times, 10,000 times, 30,000 times, 35,000 times, 40,000 times, 45,000 times, etc.

[0046] 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 accurately and quantitatively adjusted to adapt to different usage scenarios or application speeds and dosages. For example, when performing periorbital skin care, the specific number of times is designed to be 1000 times, and the vibration frequency of the delivery device is selected to be 2000 times / minute. That is, the user can perform uniform and repeated massage care on the periorbital skin within half a minute. During the high-frequency reciprocating motion, the time for the micro-protrusion 22 to puncture the skin each time is relatively fixed, so the dosage of the soluble coating 24 dissolved into the skin each time is fixed. Therefore, the soluble coating 24 is uniformly released to the skin around the eye during this time period. Users can perform longer care for eye wrinkles in specific areas according to their own needs. In this embodiment, the user can perform fixed-point, quantitative, and positioned precise care on the skin like a smearing operation, which is simple, intuitive, and controllable. In addition, when the user needs to suspend care, the soluble coating 24 can remain stably stored at the end 23 of the micro-protrusion 22, without waste or loss, and is more convenient to use. It is easy to understand that the technical solution has a wide range of application scenarios and can be used to care for the skin in different parts of the body, such as around the eyes, face, scalp, etc.

[0047] It is worth noting that the number of punctures required for complete dissolution of the soluble coating 24 can be adjusted by adjusting parameters such as the thickness of the soluble coating 24 and the difficulty of dissolution. Embodiment 2

[0048] Figure 4 It is a schematic diagram of the structure of the delivery unit in the second embodiment of the transdermal delivery system. Figure 5 yes Figure 4 The enlarged structural diagram of point 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, such as Figure 5 As shown, in the second embodiment, four tips 231 are surrounded in a cluster, and the gaps between the tips 231 form a drug storage space. The soluble coating 24 is coated on the tips 231 and the drug storage space. In the second embodiment, the tips 231 can increase the surface area of ​​the end 23, so that the attachment area of ​​the soluble coating 24 is multiplied, thereby enhancing the bonding force between the soluble coating 24 and the micro-protrusions 22. At the same time, this structure can increase the drug loading capacity of the micro-protrusions and achieve large-dose drug delivery. Embodiment 3

[0049] Figure 6 FIG. 1 is a schematic diagram of the structure of the delivery unit in the third embodiment 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, cono peptide, tranexamic acid, hexapeptide, salicylic acid, L-vitamin C, retinoic acid, and botulinum toxin. It is easy to think that in some embodiments, the soluble coating contains at least one of water, ethanol, hyaluronic acid, isopropanolamine, and isopropanol, and the soluble coating can be dissolved in water, tissue fluid or blood.

[0050] In some use scenarios, such as medical care, hair loss treatment, and other scenarios that require deep skin care, the micro-protrusions 22 need to completely penetrate the skin. In these use scenarios, when the micro-protrusions 22 fully enter the skin, the soluble coating 24 covering the entire micro-protrusions 22 can be more in contact with the water, tissue fluid, or blood of the skin and partially dissolved, so that more effective active ingredients remain in the skin per unit time. Therefore, in some use scenarios, compared with the first embodiment, the transdermal delivery system in the third embodiment has a higher transdermal delivery efficiency.

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 mounted 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.

2. The transdermal delivery system according to claim 1, characterized in that The soluble coating is applied only to the ends of the micro-protrusions.

3. The transdermal delivery system according to claim 1, characterized in that The soluble coating comprises at least one of finasteride, minoxidil, GLP-1, insulin, semaglutide, conopeptide, tranexamic acid, hexapeptide, salicylic acid, L-vitamin C, retinoic acid, and botulinum toxin.

4. The transdermal delivery system according to claim 3, characterized in that 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, characterized in that 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, characterized in that 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, characterized in that The diameter of the end of the micro protrusion is no greater than 200 nanometers.

8. The transdermal delivery system according to claim 1, characterized in that The length of the micro protrusion is no greater than 3000 microns.

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

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