CN103263727B - Metal micro-needle array, percutaneous dosing paster, micropin roller and microneedle electrodes array - Google Patents

Abstract

The present invention provides a metal microneedle array, comprising: a substrate; and a thin metal sheet fixed on the surface of the substrate; and/or a thin metal sheet whose side edge is embedded in the substrate; and/or at least Two metal sheets arranged at a certain interval and fixed on the surface of the substrate; and/or at least two metal sheets arranged at a certain interval and one edge embedded in the substrate; wherein, the metal sheets are at least There is an outwardly protruding microneedle array on the edge of one side, and the microneedle array includes at least two microneedles arranged at a certain interval, and the microneedles protrude from the surface of the substrate and are perpendicular or inclined to it. The angle is set, and the microneedle is perpendicular to or coplanar with the main plane where the central area of the metal sheet is located, and one end of the microneedle is a needle tip.

Description

Metal microneedle array, transdermal drug delivery patch, microneedle roller and microneedle electrode array

technical field

The invention relates to the fields of medical cosmetic devices and medical technology, in particular to a metal microneedle array, a transdermal drug delivery patch, a transdermal drug delivery stamp and a microneedle electrode array based on the array.

Background technique

In recent years, microneedle transdermal drug delivery has attracted widespread attention. By pressing the microneedle array, it can instantly generate a large number of micron-sized pores in the stratum corneum and epidermis of the skin, so it can significantly improve the permeability of drugs. Theoretically, it should be applicable to any drug including biomacromolecular drugs without being restricted by molecular weight, drug polarity, melting point, etc., thus laying a solid foundation for the transdermal administration of these drugs. Before piercing the skin, if the surface of the microneedle array, especially the needle tip, has been covered with drugs, it can be called a microneedle transdermal patch; in addition, the microneedle array can also be directly pierced into the skin and removed, and then The drug is then coated on the needle site and administered through self-diffusion. Because the microneedles are sharp and short, and the administration site does not touch the nerve tissue and blood vessels on the body surface, pain and bleeding will not occur, and the minimally invasive small holes can heal automatically in a short time; It does not require professionals to operate, 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.

In the same way as transdermal drug delivery, the use of microneedle arrays for beauty has become popular in recent years. Using them can form many tiny holes on the skin surface within a few minutes, and then apply beauty and skin care products, which will significantly improve the penetration of active nutrients through the stratum corneum. The ability to penetrate into the epidermis, thereby significantly improving the beauty and beauty effect.

In addition, using the microneedle array as an electrode to measure the biopotential by piercing the stratum corneum of the skin can effectively avoid the interference of the high impedance characteristics of the stratum corneum of the skin. Compared with ordinary potential electrodes, it does not require skin preparation and electrolytic gel, which is more conducive to For long-term measurement use. Therefore, it is more convenient and reliable to use microneedle array electrodes for measurement, with less impedance, and less electrochemical noise is expected to complete high-quality recordings of low biopotentials.

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. Currently, some metallic microneedle array structures have been reported. On the one hand, such as patents CN1562402A, US 20100130940-A1 and CN1415385A, which mainly manufacture microneedle arrays on the same metal substrate, but the manufacturing process is complicated, the cost is high, and the flexibility of structural design and application is low; on the other hand, For example, patents CN102727992A, CN102166387A, and CN101829396A mainly use single metal microneedles on substrates of other materials to form a microneedle array arranged at a certain distance, and there are also problems of complicated manufacturing process, high cost and poor consistency. question.

Contents of the invention

(1) Technical problems to be solved

The first technical problem to be solved by the present invention is not only to ensure good consistency between the microneedles in the metal microneedle array, but also to simplify the manufacturing process as much as possible, greatly reduce the cost, and improve the flexibility of structural design and application sex.

The second technical problem to be solved by the present invention is to increase the drug storage capacity of each microneedle in the metal microneedle array transdermal drug delivery patch. Time lasts longer.

The third technical problem to be solved by the present invention is that it is convenient to operate a metal microneedle array by hand to apply needles alternately in multiple drug administration areas. In order to facilitate its rapid diffusion and exert its drug effect.

The fourth technical problem to be solved by the present invention is to use the metal microneedle array to make a microneedle electrode array, which can not only effectively improve the signal-to-noise ratio of biopotential detection, but also apply various electrical signals to the skin.

(2) Technical solution

To solve the first technical problem, the present invention provides a metal microneedle array, comprising: a substrate; and a metal sheet fixed on the surface of the substrate; and/or a side edge embedded in the substrate and/or at least two metal sheets arranged at a certain interval and fixed on the surface of the substrate; and/or at least two metal sheets arranged at a certain interval and one side edge is embedded in the substrate ; wherein, at least one edge of the metal sheet has a microneedle array protruding outward, and the microneedle array at least includes two microneedles arranged at a certain interval, and the microneedles protrude from the lining The bottom surface is perpendicular or inclined to a set angle, and the microneedle is perpendicular or coplanar to the main plane where the central area of the metal sheet is located, and one end of the microneedle is a needle tip.

Preferably, the substrate consists of at least one planar or curved sheet or plate, or at least one hollow or solid polyhedral or curved body.

Preferably, the substrate is made of at least one of the following materials: polymer, rubber, wood, metal, ceramic, glass.

Preferably, the metal sheet is fixed on the surface of the substrate by a fixing structure and/or an adhesive.

Preferably, one edge of the metal foil is fixed in the substrate by a fixing structure and/or an adhesive, and the other side of the metal foil is protruding or concave or concave in the edge area between the microneedles Flatten the surface of the substrate.

Preferably, the substrate has an array of positioning grooves, and one side edge of the metal sheet is embedded in the positioning grooves.

Preferably, there are grooves or grooves and protrusions on the metal flake and/or the microneedle at the edge, and the groove means that one side surface of the microneedle or the microneedle and the metal flake is flat and the other side surface is smooth. Part of the area is concave, or the microneedle or the microneedle and the metal sheet are all or part of the surface on both sides of the concave structure formed by bending in a certain direction. The surface on one side of the needle is stamped to form a depression, and a corresponding protrusion is formed at the same location on the other side.

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

In order to solve the second technical problem, the present invention provides a microneedle transdermal drug delivery patch using the above-mentioned metal microneedle array, the microneedle transdermal drug delivery patch includes a metal microneedle array, A transdermal patch and a protective film or a protective bag, the transdermal patch contains one or more medicinal ingredients or cosmetic skin care products with therapeutic, health care or beauty care effects, and the protective film or protective bag has the functions of sealing and protecting The role of microneedles and the transdermal patches they cover.

In order to solve the third technical problem, the present invention provides a microneedle drug delivery stamp or a microneedle beauty stamp using the metal microneedle array, the microneedle drug delivery stamp or microneedle beauty stamp includes a metal microneedle array, a base seat and a protective cap, the metal microneedle array is permanently or detachably fixed on one end of the base, the other end of the base has a handle structure that is easy to operate by hand, and the protective cap can be set on the base Protect the microneedles from damage.

In order to solve the third technical problem, the present invention also provides a microneedle roller using the above-mentioned metal microneedle array, the microneedle roller includes a metal microneedle array of a cylindrical or drum-shaped substrate, a bracket and a protective cap, One end of the bracket is used as the axis of the roller to support the substrate and can make the metal microneedle array rotate freely around it, and the other end has a handle structure that is easy to operate by hand. damage.

To solve the fourth technical problem, the present invention provides a microneedle electrode array using the above metal microneedle array, the microneedle electrode array includes a metal microneedle array and an external wire connected to the metal sheet on it, the The side and/or back of the metal microneedle array are provided with interfaces connected with external wires. There are at least two external wires, and different metal sheets are set as short circuits or open circuits.

(3) Beneficial effects

The present invention can utilize very mature processing technologies in the industry such as laser, electric spark, electrochemical corrosion, and stamping to produce batches of metal sheets with microneedles on the edge. The structures and sizes of microneedles and metal sheets can be flexible and diverse, and computer control can Greatly improve the processing accuracy, repeatability and consistency; with other conventional medical materials as the substrate, metal microneedle arrays of various structural specifications can be assembled in batches very conveniently, which not only has beautiful appearance, firm structure, and good consistency. low cost.

The transdermal drug delivery device prepared by the present invention is safe, flexible and convenient to use, can not only carry more drugs, but also can effectively prevent the drugs from falling out of the body during the process of piercing the skin, and can not only significantly improve the percutaneous penetration of existing drugs High efficiency, so that drugs or skin care products quickly enter the epidermis and dermis through the stratum corneum, significantly improve the efficacy of drugs or beauty effects, and can also expand the types of applicable drugs, and develop more new transdermal dosage forms of drugs and cosmetics. The use of microneedle electrode arrays can effectively avoid the interference of the high impedance characteristics of the stratum corneum of the skin, and the measurement is more convenient and reliable, with a high signal-to-noise ratio.

Description of drawings

Fig. 1 is a structural sectional view of a metal microneedle array in an embodiment of the present invention;

Fig. 2 is the structural sectional view of another kind of metal microneedle array in the embodiment of the present invention;

Fig. 3 is the structural sectional view of another kind of metal microneedle array in the embodiment of the present invention;

Fig. 4 is the structural sectional view of another kind of metal microneedle array in the embodiment of the present invention;

Fig. 5 is the structural sectional view of another kind of metal microneedle array in the embodiment of the present invention;

6 is a cross-sectional view of another metal microneedle array in an embodiment of the present invention;

7 is a schematic structural view of a metal microneedle array in an embodiment of the present invention;

8 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

9 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

10 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

Fig. 11 is a structural sectional view of another metal microneedle array in an embodiment of the present invention;

12 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

Figure 13 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

Fig. 14 is a structural sectional view of another metal microneedle array in an embodiment of the present invention;

Fig. 15 is a structural sectional view of another metal microneedle array in an embodiment of the present invention;

16 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

17 is a schematic structural view of another metal microneedle array in an embodiment of the present invention;

Fig. 18 is a cross-sectional view of the structure of a medicine stamp or beauty stamp using a metal microneedle array in an embodiment of the present invention;

Fig. 19 is a structural sectional view of another medicine stamp or cosmetic stamp using a metal microneedle array in an embodiment of the present invention;

FIG. 20 is a schematic structural view of a microneedle roller using a metal microneedle array in an embodiment of the present invention.

Among them, 1: substrate; 2: metal foil; 3: microneedles protruding from the edge of metal foil; 4: needle tip; 5: positioning groove; 6: adhesive or fixed structure; 7: groove; 8: concave Pit or through hole; 9: base; 10: handle; 11: protective cap; 12: raised structure; 13: bracket; 14: edge area between microneedles on the metal foil.

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

Fig. 1-Fig. 17 shows the metal microneedle array provided by the present invention, and described metal microneedle array comprises substrate 1, and a metal foil 2 fixed on the surface of described substrate 1, and/or one side The edge of the metal sheet 2 embedded in the substrate 1, and/or at least two metal sheets 2 arranged at a certain distance and fixed on the surface of the substrate 1, and/or at least two metal sheets 2 arranged at a certain distance and one A metal sheet 2 whose side edge is embedded in the substrate 1, the metal sheet 2 has an array of microneedles 3 protruding outward at least on one edge thereof, and the array of microneedles 3 includes at least two The microneedles 3 arranged at intervals, the microneedles 3 protrude from the surface of the substrate and are perpendicular to it or at a set angle, and the microneedles 3 and the main plane where the central area of the metal sheet 2 is located are perpendicular or coplanar, the microneedles 3 One end of the needle tip 4.

The substrate 1 of the metal microneedle array can be composed of a flat or curved sheet or thin plate, and can adopt various shapes such as polygon, arc, circle or ring, as shown in Figures 1-4 and Figures 6-15; Or it can be composed of a plurality of flat or curved thin plates, which are fixed together by a plurality of metal sheets 2, as shown in Figure 5 and Figure 16; or it can be composed of at least one hollow or solid polyhedral or curved body, which can be presented as Various shapes such as cylinder or drum, as shown in Figure 17.

The substrate 1 is suitable to be made of a variety of materials, preferably polymer, wood, metal, ceramic, glass, and can be made of one of these materials or a combination of several. Polymers include resins, plastics, composite materials of plastics and resins, rubber, polyester and their composite materials, etc. For example, the substrate can be made of epoxy resin or polyester material, or plastic such as polyethylene and polypropylene can be used as the main body of the structure, and epoxy resin can be added to the fixed metal sheet 2 to achieve bonding of related materials.

The metal sheet 2 can be fixed on the surface of the substrate 1 by a fixing structure and/or an adhesive such as epoxy resin or silicon rubber 6 , as shown in FIGS. 1-3 . As a preference, one side edge of the metal foil 2 can also be fixed in the substrate through a fixed structure and/or adhesive 6, and the other side of the metal foil 2 is in the edge region 14 between the microneedles as shown in Figure 6 - As shown in FIG. 9, it may protrude from the surface of the substrate 1, or be recessed into the surface of the substrate 1 as shown in FIGS. 11-13, or be flat with the surface of the substrate 1 as shown in FIGS. 14 and 16. As another preference, the substrate 1 has an array of positioning grooves 5, and one side edge of the metal sheet is embedded in the positioning grooves 5, as shown in Fig. 4, Fig. 9, Fig. 10, Fig. 15 and Fig. 17 . Depending on the design and manufacturing process or equipment conditions, the shape of the edge region 14 between the microneedles of the metal sheet 2 may vary.

The shapes of the microneedles 3 can be varied, and holes can also be formed thereon. As a preference, there are grooves 7 or grooves and protrusions on the metal foil 2 and/or the microneedles 3 at the edge, and the grooves 7 mean that the microneedles or the microneedles and the metal foil are flat on one side. Part of the surface on the other side is concave, or the microneedle or all or part of the surface on both sides of the microneedle and the metal sheet are bent in a certain direction to form a concave structure as shown in Figure 13, the groove Concavity is formed by stamping the surface of the metal sheet and the microneedle on one side, and a protrusion is formed at the same position on the other side. The groove structure and/or holes on the microneedles are very beneficial to carry more medicines and can effectively prevent the medicines from being shed outside the body during skin penetration. As a preference, the tip 4 of the microneedle has a spear-like structure that prevents it from withdrawing automatically after being inserted, and the spear-like structure includes a protrusion protruding from the side wall of the microneedle.

The metal sheet 2 can be designed in various shapes such as straight strips, arcs, or rings according to needs, and the thickness can be 1 micron to 800 microns; the outwardly protruding microneedles 3 at the edge are used to penetrate the part. The length can be 10 microns-1500 microns, and the width of the microneedles 3 can be 10 microns-1000 microns. A variety of metal materials such as stainless steel and titanium alloy can be used to manufacture the metal sheet 2, and other metal films such as gold and platinum can be covered on its surface by mature processes such as evaporation, sputtering, and electroplating as required. The array of microneedles 3 protruding outward from the edge of the metal sheet 2 can be processed by mature techniques such as laser cutting, electric spark cutting, chemical or electrochemical corrosion, stamping and the like.

In a word, the metal microneedle array of the present invention can be manufactured in batches by using existing mature processing technology and assembly technology.

Example 2

An embodiment of the present invention provides a microneedle transdermal drug delivery patch based on the above-mentioned metal microneedle array, which consists of a metal microneedle array, a transdermal patch covering it, and a protective film or protective bag, wherein The transdermal patch contains one or more medicinal ingredients or cosmetic 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 in the metal microneedle array, which not only saves valuable pharmaceutical ingredients, but also easily controls the amount of medicine entering the skin. The grooves and holes on the microneedles can not only be used to store more drugs, and the administration time can be longer, but also can effectively avoid the problem of drugs falling out of the body during the process of piercing the skin. Various 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 substrate. The adopted protective film or protective bag has the function of sealing and protecting the microneedle and the transdermal patch covered thereon.

During use, first all the microneedle arrays on the microneedle transdermal drug delivery patch are pierced into the skin, and then the patch can be fixed on the surrounding skin surface with ordinary medical adhesive tape.

Example 3

Figure 18 and Figure 19 are cross-sectional views of the structure of the microneedle transdermal drug delivery stamp or microneedle beauty stamp using the metal microneedle array provided by the present invention, and the microneedle transdermal drug delivery stamp or microneedle beauty stamp includes metal microneedles array, a base 9 and a protective cap 12, the metal microneedle array is permanently or detachably fixed on one end of the base 9, and the other end of the base 9 has a handle structure 10 that is convenient to operate by hand, the The protective cap 12 can be covered on the base to protect the microneedle from damage.

In Fig. 18, the metal microneedle array is fixed in the middle of one end of the base 9, and the surrounding base is provided with a raised structure 11 to limit the maximum penetration depth of the microneedle, and the structure of the microneedle 3 is also different from the previous figures. same. The main difference between FIG. 19 and FIG. 18 lies in the shapes of the metal microneedle arrays, and the shapes of their handle structures 10 and protective caps 12 are also different.

The base 9 and the protective cap 12 can be made of commonly used soft and/or hard materials such as polymers, glass, wood, metal, ceramics, composite materials, etc., and are manufactured by mature processes 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 4

Figure 20 is a cross-sectional view of the structure of the microneedle roller applying the above-mentioned metal microneedle array provided by the present invention, the microneedle roller includes a metal microneedle array of a cylindrical or drum-shaped substrate, a bracket 13 and a protective cap (not shown) One end of the support 13 is used as the axis of the roller to support the substrate 1 and can make the metal microneedle array rotate freely around it. The microneedles are not damaged. Stents can be manufactured in batches using various materials such as polymers and metals and mature processes.

Example 5

An embodiment of the present invention provides a microneedle electrode array based on the above-mentioned metal microneedle array. The side and/or back are provided with an interface connected to the external wire, and the external lead can be connected to the interface by welding, conductive adhesive bonding, etc., and there are at least two external wires, but not more than the number of metal sheets, which can be determined according to It is necessary to set short circuit or open circuit between different metal sheets. During use, the microneedle array is first fully pierced into the skin, and then the back of its substrate can be fixed to the surrounding skin surface with ordinary medical tape. Using this microneedle electrode array can not only effectively improve the signal-to-noise ratio of biopotential detection, but also can apply various electrical signals to the skin and perform related measurements. In addition, the microneedle electrode array can also be coated with a transdermal patch, and the same or different electrical signals can be applied to each metal sheet while the microneedle is transdermally administered. Skin delivery to enhance efficacy.

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 (8)

1. A metal microneedle array, characterized in that, comprising: substrate; and A metal sheet with one side edge embedded in the substrate; or at least two metal sheets arranged at a certain interval and one side edge embedded in the substrate; wherein, At least one edge of the metal sheet has a microneedle array protruding outward, the microneedle array includes at least two microneedles arranged at a certain distance, the microneedles protrude from the surface of the substrate and It is perpendicular or inclined to a set angle, and the microneedle is perpendicular or coplanar to the main plane where the central area of the metal sheet is located, and one end of the microneedle is a needle tip; One edge of the metal foil is fixed in the substrate by a fixing structure and/or an adhesive, and the other side of the metal foil is recessed into the surface of the substrate in the edge area between the microneedles; The microneedles or all or part of the surfaces on both sides of the microneedles and the metal sheet are bent in a certain direction to form a concave structure. 2. The metal microneedle array according to claim 1, wherein the substrate is at least composed of a planar or curved sheet or thin plate, or at least composed of a hollow or solid polyface or curved body. 3. The metal microneedle array according to claim 1, wherein the substrate is made of at least one of the following materials: polymer, wood, metal, ceramics, glass. 4. A microneedle transdermal drug delivery patch using the metal microneedle array according to any one of claims 1-3, wherein the microneedle transdermal drug delivery patch comprises a metal microneedle array, A transdermal patch and a protective film or a protective bag covered thereon, the transdermal patch contains one or more medicinal ingredients or beauty and skin care products with therapeutic, health care or beauty care effects, the protective film or protective The pouch has the function of sealing and protecting the microneedles and the transdermal patch covered thereon. 5. A microneedle drug delivery stamp using the metal microneedle array according to any one of claims 1-3, wherein the microneedle drug delivery stamp comprises a metal microneedle array, a base and a protective cap, The metal microneedle array is permanently or detachably fixed on one end of the base, the other end of the base has a handle structure that is convenient for manual operation, and the protective cap can be placed on the base to protect the microneedles from damage. 6. A microneedle beauty stamp using the metal microneedle array according to any one of claims 1-3, wherein the microneedle beauty stamp comprises a metal microneedle array, a base and a protective cap, and the The metal microneedle array is permanently or detachably fixed on one end of the base, the other end of the base has a handle structure that is convenient for manual operation, and the protective cap can be covered on the base to protect the microneedles from damage. 7. A microneedle roller using the metal microneedle array according to any one of claims 1-3, characterized in that, the microneedle roller comprises a metal microneedle array of a cylindrical or drum-shaped substrate, a bracket With the protective cap, one end of the support is used as the axis of the roller to support the substrate and can make the metal microneedle array rotate freely around it, and the other end has a handle structure that is easy to operate by hand. The protective cap can be set on the support to protect The microneedles are not damaged. 8. A microneedle electrode array using the metal microneedle array according to any one of claims 1-3, characterized in that, the microneedle electrode array comprises a metal microneedle array and a metal sheet connected to it As for the external wire, the side and/or back of the metal microneedle array is provided with an interface connected with the external wire, and there are at least two external wires, and the different metal sheets are set as short circuit or open circuit.