Metallic microneedle array flexible patch and transdermal patch

Abstract

The application discloses a metal microneedle array flexible patch and a transdermal patch, wherein the metal microneedle array flexible patch comprises a flexible substrate and metal sheets, the metal sheet is composed of a base sheet and at least one microneedle connected to one side of the base sheet and in the same plane with the base sheet; a plurality of the metal sheets and the microneedles are perpendicular to the flexible substrate, a plurality of the metal sheets are arranged into multiple rows according to a set interval, and are embedded in the flexible substrate through the base sheet and the microneedle, only the needle tip of the microneedle protrudes from one side of the flexible substrate by a set length. The needle tip is short, sharp and firm, when closely attached to the skin, the microneedle can move freely in three dimensions and ensure that all microneedles can penetrate the skin, the pain is relieved, the comfort is high, the transdermal penetration rate of the drug can be significantly improved, and the mass production is suitable.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of medical cosmetology apparatus and medicine, and particularly relates to a metal microneedle array flexible patch and a transdermal drug delivery patch. BACKGROUND

[0002] Because of the blocking effect of the stratum corneum on the skin surface, the transdermal penetration rate of most drugs is too low to meet the needs of treatment. Similarly, using general traditional methods to use cosmetic skin care products, most of the active nutrients therein are difficult to enter the active epidermis and dermis, so the cosmetic effect is not significant. In order to increase the permeability of the skin, people have adopted various methods such as chemical penetration enhancers, iontophoresis and electroporation. These methods have different degrees of limitations on the drugs transported, and some may also cause greater toxic side effects.

[0003] In recent years, the use of microneedle array to promote penetration for transdermal drug delivery has received increasing attention. The pressing method of microneedle array can instantly generate a large number of micron-sized pores in the stratum corneum and epidermis to significantly improve the permeability of drugs. In theory, it is suitable for any drug including biological macromolecular drugs without limitation on molecular weight, drug polarity, melting point, etc., and can greatly improve the drug efficacy. Because the microneedle is sharp and small, the drug delivery site does not touch the nerve tissue and blood vessels on the body surface, so it does not cause pain and bleeding. The use of microneedles does not require professional operation, is flexible and convenient to use, and can be interrupted at any time, so it is more easily accepted by patients.

[0004] According to the material for manufacturing the microneedle, there are soluble microneedles, polymer microneedles, single crystal silicon microneedles and metal microneedles prepared by different effective components. The soluble microneedles and polymer microneedles prepared by polymer materials and carbohydrates have a prominent problem of insufficient material strength, and may be bent or broken when penetrating the skin. At the same time, the polymer for preparing the soluble microneedle may be partially deposited in the skin after dissolving in the body, which may form granulation, local erythema or accumulate in the organs in the body, and the long-term effects are not completely clear at present. Although single crystal silicon needles can be mass-produced, they are brittle, high in cost, and silicon is not a conventional medical material. For a long time, people have been using metal to manufacture acupuncture needles or injection needles, and the safety of the use is not in doubt. At present, some metal microneedle array structures have been reported, which are mainly to manufacture microneedle arrays on the same metal substrate. However, due to the hard texture of the metal substrate microneedle array structure, the skin of human body is very soft, and the two are not easy to tightly contact in the body attachment part. Even if the array area is reduced to 3x3 square millimeters, a considerable number of microneedles may be suspended in the air and cannot penetrate the skin, and the comfort of the user is not good. In the practical application of transdermal drug delivery patches, cosmetic masks and the like, the patch area required is usually at least several square centimeters. SUMMARY

[0005] The present application aims to at least solve one of the technical problems existing in the prior art. To this end, one object of the present application is to provide a metal microneedle array flexible patch, which has short and sharp needle tips and is firm. When closely attached to the skin, the microneedles can move freely in three dimensions and ensure that all microneedles can penetrate the skin, with no pain, high comfort, significantly improved drug transdermal penetration rate, and suitable for mass production.

[0006] The metal microneedle array flexible patch according to the first aspect of the present application comprises:

[0007] a flexible substrate;

[0008] a metal sheet, which is a one-piece member composed of a base sheet and at least one microneedle connected to one side of the base sheet and in the same plane as the base sheet; the metal sheet has a plurality of metal sheets and microneedles, and the metal sheet and the microneedle are perpendicular to the flexible substrate, and the plurality of metal sheets are arranged into multiple rows according to the set spacing, and are embedded in the flexible substrate through the base sheet and the microneedle, and only the needle tip of the microneedle protrudes from one side of the flexible substrate by a set length.

[0009] According to the metal microneedle array flexible patch of the first aspect of the present application, since the base sheet of each metal sheet in each row is coplanar with the microneedle and both the base sheet and the microneedle are perpendicular to the flexible substrate, the contact area of the end of the base sheet away from the microneedle with the flexible substrate is very small, which does not affect the conformal application of the flexible substrate to the body surface part, and the single metal sheet and the microneedle thereof can realize three-dimensional free movement on the flexible substrate. At the same time, since the material of the microneedle is metal, the needle tip is short and has good rigidity, and the solid and sharp microneedle can pierce the skin without breaking, and will not reach the nerves and blood vessels to cause pain or bleeding infection. Therefore, the metal microneedle array flexible patch of the first aspect of the present application is more easily applied to the body surface part and conforms to the body surface part, and ensures that all microneedles can smoothly pierce the skin, thereby significantly improving the uniformity, consistency and controllability of piercing and drug amount, and the use is more comfortable and convenient. The minimally invasive skin after use can quickly self-heal, and is safe and reliable. In addition, the metal microneedle can be mass-produced by using existing conventional medical materials and mature processing technology.

[0010] In some embodiments, the flexible substrate is made of the same material or different materials.

[0011] In some embodiments, the flexible substrate comprises a first layer of substrate and a second layer of substrate; the other side edge of the base sheet away from the microneedle is connected to one side of the first layer of substrate, the base sheet and the microneedle are embedded in the second layer of substrate, the second layer of substrate is fixed on one side of the first layer of substrate in a stacked manner, and the needle tip extends out of one side of the second layer of substrate; the materials of the first layer of substrate and the second layer of substrate are the same or different.

[0012] In some embodiments, the thickness of the flexible substrate is 0.2-4.0 mm.

[0013] In some embodiments, the thickness of the metal sheet is 0.03-0.3 mm, and the extension length of the needle tip extending out of one side of the flexible substrate is 0.1-2.0 mm.

[0014] In some embodiments, the distance between adjacent needle tips is 0.3-5 mm.

[0015] In some embodiments, in the normal direction of the metal sheet, the two side edges of the root of the microneedle connected to the base sheet are arc-shaped transition edges, the needle tip is triangular, and the microneedle is connected between the needle tip and the root through at least one of a strip-shaped segment and a trapezoidal segment.

[0016] In some embodiments, one side edge of the base sheet is connected to only one microneedle, and the projection of the microneedle in the normal direction of the metal sheet is triangular or nail-shaped with a nail head.

[0017] In some embodiments, the base sheet is strip-shaped, and a plurality of the microneedles are connected to one side edge of the base sheet at a set interval, and the size of the base sheet in the length direction of the microneedles is 0.02-0.5 mm.

[0018] The second aspect of the present application further provides a transdermal patch.

[0019] The transdermal patch according to the second aspect of the present application comprises a transdermal patch layer and the metal microneedle array flexible patch according to any one of the embodiments of the first aspect of the present application, the transdermal patch layer is covered on one side of the flexible substrate, and the needle tip can protrude, be flush or be embedded in the transdermal patch layer.

[0020] The transdermal patch according to the second aspect of the present application can be manufactured by using the metal microneedle array flexible patch according to the first aspect of the present application as the base and covering a transdermal patch layer such as a therapeutic patch layer or a cosmetic patch layer. The organic combination of the microneedle array and the flexible substrate can make the drug or the cosmetic skin care product quickly pass through the stratum corneum into the epidermis and the dermis, thereby significantly improving the drug efficacy or the cosmetic effect, and the mature processing technology is used to realize the batch manufacturing with low cost, high yield and high repeatability. Since the flexible substrate is easy to conform to the skin, the use is more comfortable and convenient. The microneedle structure is firm, the needle tip is sharp and easy to pierce. The microneedles in the array are consistent, and the use is painless and bloodless. The slightly injured skin will quickly heal after use, and the transdermal patch is safe and reliable. Therefore, the use amount of the chemical penetration enhancer can be completely avoided or greatly reduced, the transdermal penetration rate of the existing drugs can be significantly improved, the types of applicable drugs can be expanded, and more transdermal delivery products of drugs and cosmetics can be developed.

[0021] Additional aspects and advantages of the present application will be in part apparent and in part pointed out hereinafter. BRIEF DESCRIPTION OF DRAWINGS

[0022] The above and / or additional aspects and advantages of the present application will become apparent and be readily appreciated from the following description, including the appended drawings.

[0023] Figure 1 Fig. 1 is a structural schematic diagram of a metal microneedle array flexible patch according to an embodiment of the first aspect of the present application;

[0024] Figure 2 Fig. 2 is a cross-sectional schematic diagram of a first metal microneedle array flexible patch according to an embodiment of the first aspect of the present application;

[0025] Figure 3is a cross-sectional view of a second metal microneedle array flexible patch in the first aspect of the present application;

[0026] Figure 4 is a cross-sectional view of a third metal microneedle array flexible patch in the first aspect of the present application;

[0027] Figure 5 is a cross-sectional view of a fourth metal microneedle array flexible patch in the first aspect of the present application;

[0028] Figure 6 is a cross-sectional view of a fifth metal microneedle array flexible patch in the first aspect of the present application;

[0029] Figure 7 is a cross-sectional view of a sixth metal microneedle array flexible patch in the first aspect of the present application;

[0030] Figure 8 is a cross-sectional view of a seventh metal microneedle array flexible patch in the first aspect of the present application;

[0031] Figure 9 is a cross-sectional view of an eighth metal microneedle array flexible patch in the first aspect of the present application;

[0032] Figure 10 is a cross-sectional view of a ninth metal microneedle array flexible patch in the first aspect of the present application;

[0033] Figure 11 is a schematic view of a first transdermal administration patch in the second aspect of the present application;

[0034] Figure 12 is a schematic view of a second transdermal administration patch in the second aspect of the present application.

[0035] Reference Signs:

[0036] Metal microneedle array flexible patch 1000; flexible substrate 1; metal sheet 2; base sheet 201; microneedle 202; needle tip 2021; strip segment 2022, trapezoidal segment 2023; first layer of substrate 101; second layer of substrate 102; transdermal administration patch 2000; transdermal patch layer 3. DETAILED DESCRIPTION

[0037] Embodiments of the present application are described in detail below, examples of which are shown in the accompanying drawings, wherein the same or similar reference numerals are used throughout to designate the same or similar elements or elements having the same or similar functions. The embodiments described below, which are illustrated in the accompanying drawings, are exemplary only, and are not intended to limit the present application.

[0038] The following is combined Figures 1 to 12 The present invention describes a flexible metal microneedle array patch 1000 and a transdermal drug delivery patch 2000 according to embodiments of the present invention.

[0039] like Figures 1 to 10 As shown, the flexible patch 1000 of the metal microneedle array according to the first aspect of the present invention includes a flexible substrate 1 and a metal sheet 2. The metal sheet 2 is an integrally formed part, consisting of a base sheet 201 and at least one microneedle 202 connected to one side of the base sheet 201 and on the same plane as the base sheet 201; there are multiple metal sheets 2, and the multiple metal sheets 2 and microneedles 202 are all perpendicular to the flexible substrate 1, and the multiple metal sheets 2 are arranged in multiple rows according to a set interval, and are embedded in the flexible substrate 1 by their respective base sheets 201 and microneedles 202, with only the tips 2021 of the microneedles 202 extending out of one side of the flexible substrate 1 by a set length.

[0040] Specifically, the flexible substrate 1 is used to conform to the shape of the body surface, making it comfortable to use, and is also used to fix the metal sheet 2.

[0041] The metal sheet 2 is a single-piece molded component, consisting of a base sheet 201 and at least one microneedle 202 connected to one side of the base sheet 201 and lying on the same plane as the base sheet 201. That is, the microneedle 202 and the base sheet 201 are a single, independent metal sheet 2. For this single metal sheet 2, the length of one side of the base sheet 201 is greater than the width of the microneedle 202. One, two, three, or more microneedles can be connected to one side of the base sheet 201. The metal sheet 2 can be mass-produced using existing conventional medical materials such as stainless steel, titanium, or titanium alloys, and employing mature processing technologies, such as laser cutting, electrical discharge machining, and chemical or electrochemical etching.

[0042] Multiple metal sheets 2 are present, and all metal sheets 2 and microneedles 202 are perpendicular to the flexible substrate 1. The metal sheets 2 are arranged in multiple rows at predetermined intervals. Each metal sheet 2 is embedded in the flexible substrate 1 via its respective base sheet 201 and microneedles 202. Only the tips 2021 of the microneedles 202 extend out of one side of the flexible substrate 1 at a predetermined length, thus forming an array of microneedles 202. It can be understood that the flexible substrate 1 has at least two rows of metal sheets 2, such as... Figure 1 The diagram illustrates four rows of metal sheets 2, with at least one metal sheet 2 in each row, and each metal sheet 2 having at least one microneedle 202; for example, Figure 2The single row of metal foils 2 shown has four metal foils 2, two of which each have one microneedle 202, and two of which each have two microneedles 202; Figure 3 The single row of metal foils 2 shown has three metal foils 2, one of which has one microneedle 202, one of which has two microneedles 202, and one of which has three microneedles 202; Figures 4 to 8 Each of the metal foils 2 in the single row of metal foils 2 shown in FIG. 1 has only one microneedle 202; Figure 9 Three of the metal foils 2 in the single row of metal foils 2 shown in FIG. 2 each have two microneedles 202; Figure 10 The single row of metal foils 2 shown in FIG. 3 has only one metal foil 2, which has six microneedles 202, that is, the microneedles 202 are arranged in multiple rows at a set interval by multiple metal foils 2 to form an array of microneedles 202. Since the microneedles 202 are connected to the base foils 201, the length dimension of one side of the base foils 201 is generally significantly greater than the width dimension of the microneedles 202, and the base foils 201 and the microneedles 202 are embedded in the flexible substrate 1 and thus are not easy to fall off. Since the base foils 201 and the microneedles 202 of each metal foil 2 in each row are coplanar and both are perpendicular to the flexible substrate 1, the end of the base foil 201 opposite the microneedle 202 has a very small contact area with the flexible substrate 1, which does not affect the conformal adhesion of the flexible substrate 1 to the body surface, and allows the individual metal foils 2 and their own microneedles 202 to move freely in three dimensions on the flexible substrate 1. At the same time, since the microneedles 202 are made of metal, the needle tip 2021 is short and has good rigidity, and is firm and sharp, and will not break when piercing the skin, so when the flexible substrate 1 is conformally adhered to the body surface, the needle tip 2021 can all pierce the skin.

[0043] The metal microneedle array flexible patch 1000 according to the first aspect of the present application is characterized in that the base sheet 201 of each metal sheet 2 in each row is coplanar with the microneedle 202, and both the base sheet 201 and the microneedle 202 are perpendicular to the flexible substrate 1. The end of the base sheet 201 opposite to the microneedle 202 has a very small contact area with the flexible substrate 1, which does not affect the conformal application of the flexible substrate 1 to the body surface, and allows the individual metal sheet 2 and its microneedle 202 to move freely in three dimensions on the flexible substrate 1. Since the microneedle 202 is made of metal, the needle tip 2021 is short and has good rigidity, and it can firmly and sharply penetrate the skin without breaking, and it will not reach the nerves and blood vessels to cause pain or bleeding and infection. Therefore, the metal microneedle array flexible patch 1000 according to the first aspect of the present application is more easily applied to the body surface and conforms to it, ensuring that all microneedles 202 can smoothly penetrate the skin, thereby significantly improving the uniformity, consistency and controllability of penetration and drug delivery, and providing a more comfortable and convenient experience. The minimally invasive skin will heal quickly after use, and it is safe and reliable. In addition, the metal microneedle 202 can be made of existing conventional medical materials and manufactured in large quantities using mature processing technology.

[0044] In some embodiments, the flexible substrate 1 is made of the same flexible material or different flexible materials to meet the use requirements as needed. The flexible material of the flexible substrate 1 includes but is not limited to woven or non-woven fabric made of pure cotton fibers or synthetic fibers, polymers, leather or synthetic leather, paper or composite materials, etc. The polymer can be made of silicone rubber, flexible thin plastic film such as polypropylene, polyethylene film, etc.

[0045] In some embodiments, the flexible substrate 1 includes a first layer of substrate 101 and a second layer of substrate 102; the other side of the base sheet 201 opposite to the microneedle 202 is connected to one side of the first layer of substrate 101, and the base sheet 201 and the microneedle 202 are embedded in the second layer of substrate 102, which is fixed on one side of the first layer of substrate 101 in a stacked manner, for example, the second layer of substrate 102 and the first layer of substrate 101 can be fixed by flexible adhesive, and the needle tip 2021 protrudes from one side of the second layer of substrate 102; thereby, the metal sheet 2 can be fixed conveniently and reliably. The materials of the first layer of substrate 101 and the second layer of substrate 102 are the same or different, for example, both the first layer of substrate 101 and the second layer of substrate 102 are made of silicone rubber, composite material, etc., or in order to improve comfort and flexibility, the second layer of substrate 102 is made of silicone rubber, in order to better fix the metal sheet 2 so as not to withdraw from the back of the first layer of substrate 101 during the operation of penetrating the skin, and to effectively reduce the overall thickness of the required flexible substrate 1, the first layer of substrate 101 can be made of paper, non-woven fabric or polypropylene, polyethylene plastic film which is relatively thin and flexible and has strong tensile resistance.

[0046] In some embodiments, the thickness of the flexible substrate 1 is 0.2-4.0 mm; preferably, the thickness of the flexible substrate 1 is 0.2-2.0 mm; most preferably, the thickness of the flexible substrate 1 is 0.2-1.0 mm. It can be understood that the thinner the flexible substrate 1 is, the softer, lighter and more comfortable the flexible substrate 1 is, and the volume, weight and cost can be reduced.

[0047] In some embodiments, the thickness of the metal sheet 2 is 0.03-0.3 mm; preferably, the thickness of the metal sheet 2 is 0.04-0.2 mm; most preferably, the thickness of the metal sheet 2 is 0.05-0.15 mm; the protruding length of the needle tip 2021 from the side of the flexible substrate 1 is 0.1-2.0 mm; preferably, the protruding length is 0.1-1.5 mm, and most preferably, the protruding length is 0.1-1.0 mm. It can be understood that the thinner the metal sheet 2 is, the smaller and sharper the needle tip 2021 can be, and the smaller the wound is. The protruding length of the needle tip 2021 can correspond to different applications and be suitable for different drugs. For most drug treatments and cosmetic and health care products, 0.1-1 mm can meet the requirements, and it is easy to realize painless, bloodless and greatly reduce the risk of infection, and the use is safer. Therefore, the thickness of the metal sheet 2 and the protruding length of the needle tip 2021 are selected in the above ranges, the needle tip 2021 prepared is thin, small and firm, and will not be broken during the process of piercing the skin, so as to meet the needs of regular transdermal drug administration which can achieve the effect of drug administration without damaging the dermis of the skin. The material for preparing the metal sheet 2 can be various, and as a preferred, it can be stainless steel, titanium or titanium alloy, which are all common medical materials.

[0048] In some embodiments, the distance between adjacent needle tips 2021 is 0.3-5 mm; preferably, the distance is 0.4-3 mm, and most preferably, the distance is 0.5-1.5 mm. It can be understood that the distance between the needle tips 2021 reflects the density of the microneedle array. The greater the density is, the more the number of the needle tips 2021 per unit area is, and the easier the uniform drug administration is. However, if the density is too great, the pin bed effect is easy to occur, which is not easy to pierce the skin, but will damage the skin. Therefore, the above distance range of the needle tips 2021 can ensure uniform drug administration without obvious damage to the skin.

[0049] In some embodiments, in the normal direction of the metal sheet 2, the two side edges of the root of the microneedle 202 connected to the base sheet 201 are arc-shaped transition edges, the needle tip 2021 is triangular, and the microneedle 202 is connected between the needle tip 2021 and the root through at least one of a strip-shaped section 2022 and a trapezoidal section 2023. In this way, the microneedle 202 is firm, the needle tip 2021 is sharp, it is easier to pierce the skin and difficult to exit from the back of the flexible substrate 1, and it is not easy to be broken.

[0050] In some embodiments, only one microneedle 202 is connected to one side edge of the base sheet 201, and the projection of the microneedle 202 in the normal direction of the metal sheet 2 is a triangle or a nail with a nail head, wherein the thickness of the nail head can be different according to needs. In this way, the metal sheet 2 is more likely to realize the three-dimensional free movement of the microneedle 202, and the needle tip 2021 is firm and sharp, more easily penetrates the skin and is difficult to exit from the back of the flexible substrate 1, and is not easy to break.

[0051] In some embodiments, the base sheet 201 is strip-shaped, and a plurality of microneedles 202 are connected to one side edge of the base sheet 201 at a set interval, and the size of the base sheet 201 in the length direction of the microneedle 202 is 0.02-0.5 mm; preferably, the size of the base sheet 201 in the length direction of the microneedle 202 is 0.03-0.3 mm; most preferably, the size of the base sheet 201 in the length direction of the microneedle 202 is 0.04-0.2 mm. It can be understood that as long as the metal sheet 2 is thin enough and the base sheet 2021 is narrow enough, it is easy to realize three-dimensional movement and not easy to break due to its excellent elasticity and ductility. In summary, within a certain range, the number of microneedles 202 arranged on the metal sheet 2 is sufficient and the size of the above-mentioned base sheet 201 in the length direction of the microneedle 202 is sufficient, so as to realize the goal of relatively fast assembly with a certain array density and good three-dimensional movement of the microneedle 202. Accordingly, the cost of preparing the flexible patch can be reduced and the comfort of use can be improved.

[0052] The structure of the metal microneedle array flexible patch 1000 of the first aspect of the present application will be described in detail below. Figures 1 to 10

[0053] Figure 1 The structure of the metal microneedle array flexible patch 1000 of the first aspect of the present application will be described in detail below.

[0054] Figure 2 ​The cross-sectional view of the first metal microneedle array flexible patch 1000 in the first embodiment of the first aspect of the present application is shown in Figure 1. It is prepared by embedding and fixing four independent metal sheets 2 with one and two microneedles 202 in a row on the flexible substrate 1. The microneedles 202 are perpendicular to the surface of the flexible substrate 1, and the tips 2021 of the microneedles 202 protrude from one side of the flexible substrate 1 by a set length. The base sheet 201 and the microneedles 202 are embedded and fixed in the flexible substrate 1. The flexible substrate 1 is made of an elastic material such as silicone rubber, with a thickness of 1 mm. The metal sheet 2 is made of stainless steel, with a thickness of 0.1 mm. The tips 2021 of the microneedles 202 protrude from one side of the flexible substrate 1 by a length of 1 mm.

[0055] Figure 3 The cross-sectional view of the second metal microneedle array flexible patch 1000 in the first embodiment of the first aspect of the present application is shown in Figure 2. It is prepared by embedding and fixing three independent metal sheets 2 with one, two, and three microneedles 202 in a row on the flexible substrate 1 composed of the first layer substrate 101 and the second layer substrate 102. The first layer substrate 101 is made of non-woven fabric, and the second layer substrate 102 is made of silicone rubber.

[0056] In the first embodiment of the first aspect of the present application, the metal microneedle array flexible patch 1000 is prepared by embedding and fixing independent titanium alloy metal sheets 2 with only one microneedle 202 in a set interval on the flexible substrate 1. Figures 4 to 8 In the first embodiment of the first aspect of the present application, the metal microneedle array flexible patch 1000 is prepared by embedding and fixing independent titanium alloy metal sheets 2 with only one microneedle 202 in a set interval on the flexible substrate 1.

[0057] In the first embodiment of the first aspect of the present application, the metal microneedle array flexible patch 1000 is prepared by embedding and fixing independent titanium alloy metal sheets 2 with only one microneedle 202 in a set interval on the flexible substrate 1. Figure 9In the embodiment of the present application, each row of metal sheet 2 is arranged by three separate stainless steel metal sheets 2 with a set interval and embedded and fixed on the flexible substrate 1. The material of the first layer of substrate 101 is paper, and the material of the second layer of substrate 102 is non-woven fabric. Each stainless steel metal sheet 2 has two micro-needles 202 protruding with a set interval. Although the size of the base sheet 201 of the micro-needle 202 in the length direction of the micro-needle 202 is relatively wide, the relative movement between the two micro-needles 202 on the same stainless steel metal sheet 2 is difficult, but this patch structure is sufficient to ensure that all micro-needles 202 can penetrate the skin on the flexible patch and can move three-dimensionally with it, and the user still has a good comfort feeling.

[0058] In Figure 10 In the first aspect of the embodiment of the present application, although only one stainless steel metal sheet 2 with a thickness of 0.1 mm is arranged in each row of metal sheet 2, a large number of micro-needles 202 are arranged on the stainless steel metal sheet 2 with a set interval, and the size of the base sheet 201 of the micro-needle 202 in the length direction of the micro-needle 202 is very narrow, such as only 0.15 mm. Therefore, by virtue of the excellent elasticity and ductility of stainless steel, it is sufficient to ensure that all micro-needles 202 can smoothly penetrate the skin on the flexible patch and can move three-dimensionally with it, and the user has a good comfort feeling. The use of Figure 10 The structure of the metal sheet 2 given above can significantly improve the positioning and assembly efficiency of the metal sheet 2, and is more suitable for mass production of the metal micro-needle array flexible patch 1000 of the present application, even if two or more independent metal sheets 2 are used in each row.

[0059] The metal micro-needle array flexible patch 1000 of the present application can be mass-produced by using existing mature processing technology. For example, various micro-needle 202 structures can be processed at the edge of the metal sheet 2 by using conventional methods such as laser cutting, electric spark cutting, stamping and shearing, chemical or electrochemical corrosion, etc. Finally, the metal micro-needle array flexible patch 1000 can be prepared by using existing mature assembly technology.

[0060] As Figure 11 and Figure 12 It is shown that the second aspect of the present application further provides a transdermal drug delivery patch 2000.

[0061] As Figure 11 and Figure 12As shown, the transdermal drug delivery patch 2000 according to the second aspect of the present application comprises a transdermal patch layer 3 and the flexible patch with metal microneedle array 1000 according to any one of the embodiments of the first aspect of the present application, the transdermal patch layer 3 is covered on one side of the flexible substrate 1, and the needle tips 2021 can protrude, be flush with or be embedded in the transdermal patch layer 3. The transdermal patch layer 3 contains one or more drug components or cosmetic skin care products with therapeutic, health care or beauty care effects, and can be covered on the array of microneedles 202 and one side of the flexible substrate 1 by using various common physical or chemical methods such as dipping, coating, fumigation and deposition.

[0062] In use, the array of microneedles 202 on the transdermal drug delivery patch 2000 is first inserted into the skin, and then the patch can be fixed by using a common medical tape. As a preferred embodiment, the surface of the back of the flexible substrate 1 and the edge area around it can be covered with a medical adhesive material, so that the transdermal drug delivery patch 2000 can be pasted on the drug delivery site, and the use is more convenient.

[0063] The transdermal drug delivery patch 2000 according to the second aspect of the present application can be manufactured by using common medical materials, and a transdermal patch layer 3 such as a therapeutic drug delivery patch layer or a cosmetic drug delivery patch layer is covered on one side of the flexible patch with metal microneedle array 1000 according to the first aspect of the present application. The organic combination of the array of microneedles 202 and the flexible substrate 1 can make the drug or cosmetic skin care product quickly pass through the stratum corneum into the epidermis and dermis, thereby significantly improving the drug efficacy or beauty care effect, and the low cost, high yield and high repeatability of batch manufacturing can be realized by using mature processing technology. Since the flexible substrate 1 is easy to conform to the skin, the use is more comfortable and convenient. The microneedle 202 has a strong structure and a sharp needle tip 2021, and is easy to pierce. The uniformity and consistency of the microneedles 202 in the array are good, and there is no pain and no blood during use. The slightly injured skin will quickly heal after use, and is safe and reliable. Therefore, the use amount of chemical penetration enhancer can be completely avoided or greatly reduced in the transdermal drug delivery patch 2000 according to the second aspect of the present application. Not only can the transdermal penetration rate of existing drugs be significantly improved, but also the types of applicable drugs can be expanded, and more transdermal delivery products of drugs and cosmetics can be developed.

[0064] In the description of the present specification, the description of the terms "one embodiment", "some embodiments", "exemplary embodiment", "example", "specific example", or "some examples" means that the specific features, structures, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the exemplary description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0065] While embodiments of the application have been shown and described, it is to be understood that the embodiments described are merely divergences of the principles and application of the present application. Numerous modifications, changes, variations, substitutions, and equivalents will occur to those skilled in the art without departing from the spirit and scope of the present application as defined by the following claims and their equivalents.

Claims

1. A metal microneedle array flexible patch, characterized by, The application relates to a flexible patch of metal microneedle array, which comprises the following components: a flexible substrate; a plurality of metal foils, which are integrally formed and consist of a base foil and at least one microneedle connected to one side edge of the base foil and in the same plane with the base foil; the metal foils and the microneedles are perpendicular to the flexible substrate, and the metal foils are arranged in multiple rows at a set interval and embedded in the flexible substrate through the base foils and the microneedles, and only the tips of the microneedles protrude from one side of the flexible substrate at a set length; the flexible substrate comprises a first layer of substrate and a second layer of substrate; the other side edge of the base foil away from the microneedle is connected to one side of the first layer of substrate, the base foil and the microneedle are embedded in the second layer of substrate, the second layer of substrate is fixed on one side of the first layer of substrate in a laminated manner, and the tips of the microneedles protrude from one side of the second layer of substrate; the first layer of substrate and the second layer of substrate are made of the same material or different materials; and the tips of the microneedles are arranged at equal intervals; in the normal direction of the metal foil, the two side edges of the root of the microneedle connected to the base foil are arc-shaped transition edges, the tip of the microneedle is triangular, and the microneedle is connected to the tip and the root through at least one of a strip-shaped section and a trapezoidal section.

2. The metal microneedle array flexible patch of claim 1, wherein, The thickness of the flexible substrate is 0.2-4.0 mm.

3. The metal microneedle array flexible patch of claim 1, wherein, The thickness of the metal foil is 0.03-0.3 mm; and the protruding length of the tip of the microneedle protruding from one side of the flexible substrate is 0.1-2.0 mm.

4. The metal microneedle array flexible patch of claim 3, wherein, The interval between adjacent tips of the microneedle is 0.3-5 mm.

5. The metal microneedle array flexible patch of claim 1, wherein, Only one microneedle is connected to one side edge of the base foil, and the projection of the microneedle in the normal direction of the metal foil is triangular or nail-shaped with a nail head.

6. The metal microneedle array flexible patch of claim 1, wherein, The base foil is strip-shaped, a plurality of microneedles are connected to one side edge of the base foil at a set interval, and the size of the base foil in the length direction of the microneedle is 0.02-0.5 mm.

7. A transdermal patch for the administration of a drug, characterized in that, The application further relates to a transdermal patch layer and the flexible patch of metal microneedle array, the transdermal patch layer is covered on one side of the flexible substrate, and the tips of the microneedles can protrude, be flush or be embedded in the transdermal patch layer. ​

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