CN103203072B - Metal micro-needle array flexible patch, transdermal applicator and transdermal application patch - Google Patents

Abstract

The invention discloses a metal micro-needle array flexible patch, a transdermal applicator and a transdermal application patch. The metal micro-needle array flexible patch comprises a flexible substrate and at least two metal micro-needle modules which are arranged at certain intervals and fixed on the bottom surface of the flexible substrate or partially inset in the flexible substrate. Each metal micro-needle module is a metal sheet with projecting micro-needles on the edge, or a metal sheet fixed on a needle holder and provided with projecting micro-needles on the edge, or composed of metal micro-needles separately erected and fixed on a needle holder. The micro-needles are perpendicular to the surface of the flexible substrate and are hollow or solid metal micro-needles with a tip pointing out. The micro-needle array is organically combined with the flexible substrate, so that medicine is allowed to directly pass corneum to quickly enter the human body. The metal micro-needle array flexible patch is comfortable to use and evident in efficacy.

Description

Metal microneedle array flexible patch, transdermal drug delivery device and transdermal drug delivery patch

technical field

The invention relates to the technical fields of medical beauty equipment and medicine, in particular to a metal microneedle array flexible patch, a transdermal drug delivery device and a transdermal drug delivery patch.

Background technique

Transdermal drug delivery system, also known as transdermal therapeutic system, refers to a class of preparations in which drugs are absorbed through the skin through capillaries and enter the systemic circulation at a certain rate to produce drug effects. Compared with traditional drug delivery methods, transdermal drug delivery has many advantages: it can produce persistent, constant and controllable blood drug concentration, significantly improve the activity of drugs with a short half-life due to rapid metabolism in the body, and avoid the liver's first It minimizes toxic and side effects; it is painless, non-invasive or minimally invasive, and patients can take their own medicine or interrupt the medicine at any time, which is convenient to use. Although transdermal drug delivery is very attractive, there are only more than 20 kinds of drugs that have entered the world's transdermal drug delivery market. This is mainly because the transdermal penetration rate of most drugs is too low to meet treatment needs. Drugs that can be administered transdermally are subject to many limitations, such as molecular weight less than 500D, high fat solubility, melting point less than 150°C, therapeutic dose less than 20 mg/day, etc. It is difficult to achieve passive transdermal administration of polymer and polar drugs.

In order to increase the permeability of the skin, various methods such as chemical penetration enhancers, iontophoresis and electroporation have been used. These methods all have different degrees of limitations on the drugs delivered, and some may also cause relatively large toxic and side effects. In 1998, the research group of Professor Prausnitz in the United States first used the miniature solid silicon needle array in the field of transdermal drug delivery, and found that it could increase the transdermal permeability of the biopolymer model drug calcein by 4 orders of magnitude, which has set off an international trend since then. The wave of microneedle transdermal drug delivery research. The method of pressing the microneedle array can instantly generate a large number of micron-sized pores in the stratum corneum and epidermis of the skin to significantly improve the permeability of the drug. In theory, it should be applicable to any drug including biomacromolecular drugs. Not limited by molecular weight, drug polarity, melting point, etc. Because the microneedles are sharp and short, and the administration site does not touch the nerve tissue and blood vessels on the body surface, there will be no pain and bleeding; the use of microneedles does not require professional operation, and it is flexible and convenient to use, and the administration can be interrupted at any time , so it is easier to be accepted by patients.

Similar to transdermal drug delivery, due to the blocking effect of the stratum corneum, most of the active nutrients are difficult to enter the active epidermis and dermis, so the cosmetic effect is not significant. If the microneedle array coated with beauty and skin care products is inserted into the skin, or the microneedle array is removed after being penetrated into the skin and then applied with beauty and skin care products, it will significantly improve the penetration of active nutrients into the epidermis and dermis cells through the stratum corneum. Penetration ability, thus significantly improving the beauty effect.

Materials for making microneedles include polymers, monocrystalline silicon, and metals. A prominent problem of existing polymer microneedles is that the material is not strong enough to pierce the dense stratum corneum of the skin; although monocrystalline silicon needles have been produced in batches, they are brittle and costly, and silicon is not yet a part of Conventional medical materials; for a long time, people have used metal to make acupuncture needles or injection needles, and its safety is beyond doubt. At present, some metal microneedle array structures have been reported, which mainly manufacture microneedle arrays on the same metal substrate, and the microneedles are perpendicular or coplanar with the substrate. Since the structure of the microneedle array using the metal substrate is hard and the human skin is soft, the two are not easy to be in close contact with the fitting parts of the body, which will inevitably lead to a considerable number of microneedles hanging in the air and unable to penetrate the skin. It is difficult to accurately control the actual dosage of transdermal administration, which has a serious impact on the curative effect. In addition, how to cover as much medicine as possible on the thin and short microneedles without falling off during skin penetration is undoubtedly a key problem that must be solved in practice.

Contents of the invention

(1) Technical problems to be solved

The purpose of the present invention is to realize that the metal microneedle array patch can change with the skin shape of the bonding part, ensure that all microneedles can penetrate the skin, and improve the comfort of use;

Another object of the present invention is to improve the convenience of the metal microneedle array patch for alternate needle application in multiple drug administration areas.

(2) Technical solution

In order to solve the above technical problems, the present invention provides a metal microneedle array flexible patch, the patch includes a flexible substrate, and at least two arrays arranged at a certain distance and fixed on the surface of the flexible substrate or partially embedded in the flexible substrate. The metal microneedle module in the flexible substrate; the metal microneedle module is a metal sheet with protruding microneedles on the edge, or a metal sheet fixed on the needle seat with protruding microneedles on the edge, or fixed on the Discrete metal microneedles on the needle seat; the microneedles are perpendicular to the surface of the flexible substrate, and the needle points of the microneedles protrude outward; the microneedles are solid or hollow metal microneedles.

Wherein, the length of the protruding part of the microneedle for piercing is 10 microns to 1500 microns, the outer diameter or width of the microneedle is 10 microns to 1000 microns, and the thickness of the metal sheet is 5 microns to 800 microns.

Wherein, the needle tip of the microneedle has a lancet-shaped structure that prevents it from withdrawing automatically after being inserted, and the lancet-shaped structure includes a protrusion protruding from the side wall of the microneedle.

Wherein, the needle seat is in the shape of a cuboid or a polyhedron, at least on one side of which the metal sheet or the discrete metal microneedles are fixed.

Wherein, the microneedles have perforations and/or grooves, and when the microneedles have grooves, the grooves are arranged along the length direction of the microneedles.

Wherein, the flexible substrate is a polygonal, or circular, or elliptical sheet or mesh structure, or consists of at least two strip structures, and the materials used include but are not limited to woven fabrics made of pure cotton fibers or Woven or non-woven fabric of elastic fibers, rubber, plastic, synthetic leather, paper, metal sheets, filaments or narrow strips, the flexible substrate can be composed of one of the above materials or a combination of several layers , each layer is connected by adhesive or fixed structure.

The present invention also provides a transdermal drug delivery device using any of the metal microneedle array flexible patches described above, the transdermal drug delivery device includes a metal microneedle array flexible patch and a base, and the base One end is a patch fixing surface, the other end is an operating handle, the patch fixing surface is a flat or arc-shaped curved surface, and the metal microneedle array flexible patch is permanently or detachably fixed on the patch fixing surface , or the metal microneedle array flexible patch is partially embedded in the patch fixing surface.

The present invention further provides a transdermal drug delivery patch using any one of the metal microneedle array flexible patches described above. The transdermal drug delivery patch includes a metal microneedle array flexible patch and a covering thereon. A transdermal patch, the transdermal patch contains one or more medicinal ingredients or beauty and skin care products that have therapeutic, health care or beauty-beautifying effects.

Wherein, the transdermal patch covers the protruding microneedles in the metal microneedle array flexible patch.

Wherein, the flexible substrate of the metal microneedle array flexible patch is covered with a medical adhesive material at least on the surface of its peripheral area, which is used to stick the transdermal drug delivery patch on the drug delivery site.

(3) Beneficial effects

The above technical solution uses conventional medical materials and mature processing technology to manufacture metal microneedle array flexible patches. Since the flexible substrate adopted is easy to conform to the skin surface, all the microneedles on it can be smoothly penetrated into the skin. , so as to significantly improve the consistency and controllability of the dosage, and feel more comfortable and convenient to use; the metal microneedles have a firm structure, sharp and short needle tips, and are easy to puncture; the microneedles in the array have good consistency, No pain, no blood, the minimally invasive skin will heal itself quickly after use, safe and reliable.

Using the transdermal drug delivery device with the above-mentioned metal microneedle array flexible patch as the core component, you can flexibly and conveniently operate in multiple drug delivery areas by yourself. Open it, and then coat the drug on the surface of the pierced area to facilitate its rapid diffusion and exert its drug effect. It is easy to use and has a good application effect.

The use of the above-mentioned metal microneedle array flexible patch as the core component of the transdermal drug delivery patch not only significantly increases the amount of drug stored on it, but also greatly reduces the possibility of the drug being dropped out of the body during the needle application process. Therefore, the range of drug selection, effective treatment time and cost performance of transdermal patches can be significantly improved. The patch prepared by the invention can not only significantly improve the transdermal penetration rate of existing drugs, but also make drugs or cosmetic skin care products quickly enter the epidermis and dermis through the stratum corneum, obviously improve the efficacy of drugs or beauty and beauty effects, and can also be extended and applied The types of drugs, and more new transdermal dosage forms of drugs and cosmetics have been developed.

Description of drawings

Fig. 1 is a schematic structural view of a metal microneedle array flexible patch in which a metal sheet with microneedles at the edge is fixed on a needle holder and a flexible substrate in Example 1 of the present invention;

2 is a schematic structural view of a metal microneedle array flexible patch in which discrete metal microneedles are fixed on needle holders and flexible substrates in Example 1 of the present invention;

3 is a schematic structural view of a metal microneedle array flexible patch that has grooves on both the microneedles and the metal sheet and is fixed on the surface of the flexible substrate in Example 1 of the present invention;

4 is a schematic structural view of a metal microneedle array flexible patch in which a metal sheet with microneedles at the edge is fixed on a strip-shaped flexible substrate in Example 1 of the present invention;

5 is a structural sectional view of a metal microneedle array flexible patch in which a metal sheet with microneedles at the edge is fixed on a flexible substrate in Example 1 of the present invention;

6 is a cross-sectional view of another metal microneedle array flexible patch in which a metal sheet with microneedles at the edge is fixed on a flexible substrate in Example 1 of the present invention;

7 is a structural sectional view of another metal microneedle array flexible patch in which a metal sheet with microneedles at the edge is fixed on a flexible substrate in Example 1 of the present invention;

8 is a cross-sectional view of another metal microneedle array flexible patch in which a metal sheet with microneedles at the edge is fixed on a flexible substrate in Example 1 of the present invention;

9 is a structural cross-sectional view of a metal microneedle array flexible patch in which the discrete metal microneedles are fixed on the needle base and the flexible substrate in Example 1 of the present invention;

10 is a cross-sectional view of a transdermal drug delivery device using a metal microneedle array flexible patch in Example 2 of the present invention;

11 is a cross-sectional view of another transdermal drug delivery device using a metal microneedle array flexible patch in Example 2 of the present invention;

12 is a cross-sectional view of another transdermal drug delivery device using a metal microneedle array flexible patch in Example 2 of the present invention.

Among them, 1: flexible substrate; 2: microneedle; 3: metal sheet; 4: needle seat; 5: needle tip; 6: fixed connection layer; 7: hole; 8: groove; 9: base; 10: handle ;11: Raised.

Detailed ways

The specific implementation manners of the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention.

Example 1

Figures 1-9 show the metal microneedle array flexible patch provided by the present invention, the patch includes a flexible substrate 1, and at least two are arranged at a certain distance and fixed on the surface of the flexible substrate 1 or A metal microneedle module partially embedded in the flexible substrate 1, the metal microneedle module is a metal sheet 3 with protruding microneedles 2 at the edge, or fixed on the needle base 4 with protruding microneedles at the edge The metal sheet 3 of the microneedle 2, or the discrete metal microneedle 2 fixed on the needle seat 4, the microneedle 2 is perpendicular to the surface of the flexible substrate 1, and the tip of the microneedle 2 protrudes outward. Through the metal microneedle array flexible patch, the patch can conform to the surface of the drug application site, ensuring that the microneedles 2 can penetrate the drug application skin at the same time, and improve the effect of drug application.

The metal foil 3 can be arranged parallel to the surface of the flexible substrate 1, and can also be arranged perpendicular to the surface of the flexible substrate 1. According to the arrangement of the metal foil 3, the microneedle 2 can be arranged vertically or vertically with respect to the surface of the metal foil 3. To be coplanar with the metal sheet 3, it is only necessary to realize that the microneedle 2 is perpendicular to the surface of the flexible substrate 1 and protrudes outward.

In this embodiment, the microneedles 2 are solid or hollow metal microneedles, both of which can achieve good drug application effects. The length of the protruding part of the microneedle 2 for piercing is 10 microns to 1500 microns, the outer diameter or width of the microneedle 2 is 10 microns to 1000 microns, and the thickness of the metal sheet 3 is 5 microns to 800 microns , to meet the needs of conventional transdermal drug application which can not only play a drug application effect but not damage the skin dermis.

In this embodiment, the metal microneedle module has at least one metal sheet 3 or one discrete metal microneedle 2 , and the metal sheet 3 has at least one protruding microneedle 2 on one side thereof. The metal microneedle module has a microneedle array composed of at least two protruding microneedles 2 arranged at a set interval.

Figure 1 is a schematic structural view of a metal microneedle array flexible patch in an embodiment of the present invention, nine metal microneedle modules are arranged and fixed at a certain distance on the flexible substrate 1, and each metal microneedle module includes a cuboid The needle holder 4 is fixed with a metal sheet 3 on its two opposite sides respectively, and each edge of the metal sheet 3 has two sides that are arranged according to the set interval and protrude outward and are perpendicular to the needle holder 4. A microneedle array composed of microneedles 2, the main plane of the microneedles 2 and the metal sheet 3 is coplanar, and the tip 5 of the microneedles 2 has a spear-like structure that prevents it from automatically withdrawing after piercing. The pointed structure includes a protrusion protruding from the sidewall of the microneedle.

Figure 2 is another metal microneedle array flexible patch, the main difference from Figure 1 is that discrete metal microneedles 2 are used instead of metal flakes 3 with protruding microneedles 2 on the side, and the tip of the microneedle 2 is No spear-like structures. The size and structure of adjacent metal microneedle modules in the patch can be different. The shapes and materials of the needle base 4 can be various, and it is only necessary to fix the metal on it easily. Preferably, the needle seat is in the shape of a cuboid or polyhedron, and can be made of polymer, such as epoxy resin, or metal, ceramics, etc. The metal can be various medical metal materials such as stainless steel and titanium alloy. The fixing of the microneedle 2 on the needle base 4 or the metal sheet 3 on the needle base 4 can be fixed by medical adhesives such as epoxy resin and silicon rubber or special structures.

The main difference between the metal microneedle array flexible patch in Figure 3 and Figures 1 and 2 is that three metal microneedle modules are arranged and fixed on the flexible substrate 1 at a certain distance, and each metal microneedle module has a It is composed of a metal sheet 3 with four protruding microneedles 2, the microneedle 2 is perpendicular to the main plane of the metal sheet 3, and the metal sheet 3 can be directly fixed on the metal sheet 3 according to a certain distance with a fixed connection layer 6 formed by epoxy resin adhesive. on the flexible substrate 1; on the other hand, both the microneedle 2 and the metal sheet 3 have a groove 8, and the groove 8 is arranged along the length direction of the microneedle 2, specifically the microneedle 2 or the microneedle 2 and the metal sheet A concave structure formed by bending all or part of the surfaces on both sides of the sheet 3 to one side, or a concave structure formed by grooves formed by microneedles 2 or microneedles 2 and a part of the surface of one side of the metal sheet 3, microneedles The groove structure on the 2 is very conducive to carrying more medicines and can effectively prevent the medicines from falling out of the body during the process of piercing the skin.

The main difference between the metal microneedle array flexible patch in Fig. 4 and Fig. 3 is that the shape of the needle point 5 is different on the one hand, and the shape of the flexible substrate 1 is different on the other hand, one is a quadrangular sheet structure, the other is composed of four strips. Composed of strip structure, the strip structure substrate has better flexibility and permeability. The shape and production material of the flexible substrate can be various, as preferred, it is a polygonal, or circular, or oval sheet-like or net-like structure, or consists of at least two strip-like structures, and the materials used include but Not limited to woven fabrics of pure cotton fibers or woven or non-woven fabrics of elastic fibers, rubber, plastics, synthetic leather, paper, metal sheets, filaments or narrow strips, may be composed of one or more of them The layers are combined, and the layers are connected by adhesives or fixed structures.

5 is a cross-sectional view of a metal microneedle array flexible patch in which a metal sheet 3 with protruding microneedles 2 is fixed on a flexible substrate 1 in an embodiment of the present invention. Wherein, the microneedle 2 is perpendicular to the main plane of the metal sheet 3, and the metal sheet 3 is fixed on the upper surface of the flexible substrate 1 by an adhesive.

The difference between the metal microneedle array flexible patch in FIG. 6 and that in FIG. 5 is that there are protruding microneedles 2 at two opposite sides of the metal sheet 3 .

The difference between the metal microneedle array flexible patch in FIG. 7 and that in FIG. 5 is that the microneedles 2 penetrate the upper surface of the flexible substrate 1, and the metal sheet 3 is fixed on the lower surface of the flexible substrate 1 with an adhesive.

The difference between the metal microneedle array flexible patch in Figure 8 and Figures 5-7 is that the flexible substrate is composed of two layers of materials, and the metal sheet 3 is embedded and fixed between the two to ensure that the entire patch structure is more firm and stable. For example, the upper layer of the flexible substrate is made of elastic materials such as silicon rubber, which will be attached to the skin during use, and the comfort will be stronger.

The main difference between the metal microneedle array flexible patch in Fig. 9 and Figs. 5-8 is that the discrete metal microneedles 2 are fixed on the flexible substrate 1 through the needle base 4, and the metal microneedles 2 have a function for storing more drugs. Through the hole 7, more drugs can be carried for transdermal administration without causing the drug to fall out of the body.

The metal microneedle array flexible patch of the present invention can be mass-produced by existing mature processing technology. For example, conventional methods such as laser cutting, electric spark cutting, stamping shearing, chemical or electrochemical corrosion can be used to process various microneedle structures at the edge of the metal sheet. If solid metal wires or hollow metal capillaries are used to make discrete metal microneedles, a variety of common needle tip structures can be processed by conventional grinding and polishing, and the through holes on the hollow needles can be used to carry more drugs into the skin. Finally, the metal microneedle array flexible patch can be prepared by using the existing mature assembly technology.

Example 2

Figure 10 and Figure 9 are cross-sectional views of the structure of the transdermal drug delivery device using the metal microneedle array flexible patch provided by the present invention, the transdermal drug delivery device includes a metal microneedle array flexible patch and a base 9, the One end of the base 9 is a patch fixing surface, and the other end is a handle 10 for operation. The patch fixing surface is a plane or an arc-shaped curved surface, and the metal microneedle array flexible patch is permanently or detachably fixed on the On the patch fixing surface, or the metal microneedle array flexible patch is partially embedded in the patch fixing surface.

In Fig. 10, the metal microneedle array flexible patch is fixed on the planar patch fixing surface at one end of the base 9, and the tip structure of the microneedle 2 is different from the previous figures, specifically the tip structure with a slope.

The main difference between the transdermal drug delivery device in Fig. 11 and Fig. 10 is that there are protrusions 11 on the base 9 around the flexible patch to limit the maximum penetration depth of the microneedle 2, which is also equivalent to the metal microneedle array flexible patch. The sheet part is embedded in the fixing surface of the patch, and there are protrusions around the flexible patch that can play a blocking role.

The main difference between the transdermal drug delivery device in Figure 12 and Figure 10 and Figure 11 is that the metal microneedle array flexible patch is fixed on the arc-shaped curved patch fixing surface at one end of the base 9, and their handles 10 are not Similarly, the handle 10 can be set in a columnar shape, or an ellipsoidal shape, or a combination of columnar and ellipsoidal shapes, as long as it is comfortable to hold.

The base 9 can be commonly used soft and/or hard materials such as rubber, plastic, glass, ceramics, wood, metal, composite materials, etc., and is manufactured by mature techniques such as injection molding and machining. Assembling and fixing methods can adopt various mature methods such as bonding and movable structure fastening. For transdermal drug delivery, the microneedles in the above-mentioned transdermal drug delivery device can be pierced into the skin surface and then removed, and then the medicament or cosmetic and skin care products can be coated on the skin surface.

Example 3

An embodiment of the present invention provides a transdermal drug delivery patch based on the metal microneedle array flexible patch, which consists of a metal microneedle array flexible patch and a transdermal patch covering it, wherein the transdermal The patches contain one or more medicinal ingredients or beauty and skin care products with therapeutic, health care or beauty care effects. Preferably, the transdermal patch is only covered on the protruding microneedles or needle tips of the metal microneedle array flexible patch, which can not only save precious medicine, but also easily control the amount of medicine entering the skin. The grooves and holes on the microneedles can not only be used to store more drugs, but also can effectively prevent the drug from falling out of the body during the skin penetration process. A variety of common physical or chemical methods such as dipping, coating, fumigation and deposition can be used to cover the transdermal drug delivery patch or cosmetic patch on the microneedle array or even the flexible substrate.

During use, first all the microneedle arrays on the transdermal drug delivery patch are pierced into the skin, and then the patch can be fixed with ordinary medical adhesive tape. Preferably, the surface of the peripheral edge area of the flexible substrate of the patch can be covered with a medical adhesive material, and the transdermal drug delivery patch can be pasted on the administration site, which is more convenient to use.

The present invention uses conventional medical materials to manufacture transdermal drug delivery patches and beauty patches based on metal microneedle array flexible patches, and the organic combination of microneedle arrays and flexible substrates can make drugs or cosmetic skin care products quickly pass through the cutin The layer enters the epidermis and dermis, thereby significantly improving the efficacy or beauty and beauty effects, and using mature processing technology to achieve its low-cost, high-yield, high-repeatability mass production; because the flexible substrate used is easy to share with the skin shape, it feels more comfortable and convenient to use; the microneedle structure is firm, the needle tip is sharp, and it is easy to puncture; the microneedles in the array have good consistency, and there is no pain and no blood when used, and the minimally invasive skin will heal itself quickly after use. Safe and reliable; more drugs carried in the grooves or holes on the microneedles ensure that the patch can act for a longer time; this patch can completely avoid or greatly reduce the use of chemical penetration enhancers, not only can significantly improve The transdermal penetration rate of existing drugs can also expand the types of applicable drugs, and develop more transdermal delivery products for drugs and cosmetics.

The above is only a preferred embodiment of the present invention, it should be pointed out that for those of ordinary skill in the art, without departing from the technical principle of the present invention, some improvements and replacements can also be made, these improvements and replacements It should also be regarded as the protection scope of the present invention.

Claims (10)

1. A metal microneedle array flexible patch, characterized in that the patch comprises a flexible substrate, and at least two are arranged at a certain interval and fixed on the surface of the flexible substrate or partially embedded in the flexible substrate. The metal microneedle module in the bottom; the metal microneedle module is a metal sheet with a protruding microneedle array on the edge, or a metal sheet that is fixed on the needle seat and has a protruding microneedle array at the edge; the microneedle array It consists of at least two microneedles arranged at a set interval, the microneedles are perpendicular to the surface of the flexible substrate, and the tips of the microneedles protrude outward; the microneedles are solid or hollow metal microneedles ; The microneedles are made by cutting at the edge of a metal sheet. 2. metal microneedle array flexible patch as claimed in claim 1, is characterized in that, the length of the protruding part that described microneedle is used for piercing is 10 micron～1500 micron, and the external diameter or width of microneedle is 10 microns to 1000 microns, the thickness of the metal flake is 5 microns to 800 microns. 3. metal microneedle array flexible patch as claimed in claim 1, is characterized in that, the needle point portion of described microneedle has the spear point structure that prevents it from withdrawing automatically after piercing, and described spear point structure comprises A tab protruding from the sidewall of the microneedle. 4. The metal microneedle array flexible patch according to claim 1, wherein the needle base is in the shape of a cuboid or polyhedron, and the metal sheet is fixed at least on one side thereof. 5. metal microneedle array flexible patch as claimed in claim 1, is characterized in that, has perforation and/or groove on the described microneedle, when groove is arranged on the described microneedle, described groove along The length direction of the microneedles is arranged. 6. metal microneedle array flexible patch as claimed in claim 1, is characterized in that, described flexible substrate is polygonal, or circular, or elliptic sheet-like or net-like structure, or is made of at least two strips. The materials used include but are not limited to woven fabrics of pure cotton fibers or woven or non-woven fabrics of elastic fibers, rubber, plastic, synthetic leather, paper, metal sheets, filaments or narrow strips. The flexible substrate can be composed of one of the above materials or a combination of several layers, and the layers are connected by adhesives or fixed structures. 7. A transdermal drug delivery device that adopts a metal microneedle array flexible patch as described in any one of claims 1-6, wherein the transdermal drug delivery device includes a metal microneedle array flexible patch and a base One end of the base is a patch fixing surface, and the other end is an operating handle. The patch fixing surface is a flat or arc-shaped curved surface. The metal microneedle array flexible patch is permanently or detachably fixed on the The fixed surface of the patch, or the flexible metal microneedle array patch is partially embedded in the fixed surface of the patch. 8. A transdermal drug delivery patch adopting the metal microneedle array flexible patch as described in any one of claims 1-6, wherein the transdermal drug delivery patch comprises a metal microneedle array flexible patch And a transdermal patch covered thereon, the transdermal patch contains one or more medicinal ingredients or cosmetic skin care products with therapeutic, health care or beauty care effects. 9. The transdermal drug delivery patch according to claim 8, characterized in that, the transdermal patch covers the protruding microneedles in the metal microneedle array flexible patch. 10. The transdermal drug delivery patch as claimed in claim 9, characterized in that, on the flexible substrate of the metal microneedle array flexible patch, at least the surface of its peripheral edge area is covered with a medical adhesive material, with The transdermal patch is pasted on the administration site.