Micronode and method for producing a micronode

Description

[0001] The present invention relates to a method for manufacturing a microneedle, in particular for transdermal and / or intradermal drug delivery. The present invention also relates to a method for manufacturing a microneedle device.

[0002] Transdermal therapeutic systems or transdermal patches can deliver active ingredients systemically after permeation of the skin. However, some active ingredients cannot be absorbed by the body simply through application to the skin. In particular, certain drugs cannot cross the skin's main diffusion barrier, the stratum corneum, or layer of dead cells. For this reason, microneedle patches or microarray patches have been developed. These microneedle patches or microarray patches feature a multitude of very small needles that penetrate the upper layers of the skin, thereby enabling improved drug delivery.

[0003] Microneedles can be manufactured using methods such as micromolding, lithography (soft lithography or drawing lithography), droplet-born airblowing, and electrospun pillar array. These methods are only suitable for producing large quantities to a limited extent. Furthermore, there is a risk of material stress due to high processing temperatures. Casting processes can also lead to high material consumption and thus waste of active ingredient due to sprue structures. Finally, there are limitations regarding the choice of substrate material.

[0004] The prior art described in publication CN 109125912 A relates to a 3D-printed microneedle patch for regulating blood glucose levels, made from a biocompatible, photosensitive material. The microneedle patch essentially comprises two parts: a substrate and a microneedle array, the microneedle array containing a plurality of conical microneedles.

[0005] Publication WO 2019 / 136133 A1 concerns a microneedle comprising an elongated body with a detachable section, the detachable section comprising a therapeutic agent.

[0006] Document WO 2016 / 149152 A1 relates to a microneedling device comprising a substrate and a plurality of biocompatible microneedles projecting from the substrate. The microneedles have: (i) a curved, discontinuous, undercut and / or perforated sidewall; (ii) a sidewall comprising a fragile support; and / or (iii) a cross-section that is neither circular nor polygonal, and / or wherein the microneedles are stepped and wherein the microneedles have a cross-sectional width that varies in both dimensions along at least part of their length.

[0007] Document US 2018 / 177990 A1 relates to a microneedle array comprising a film with first and second outward-facing principal surfaces, wherein the first outward-facing principal surface has a plurality of microneedles penetrating the stratum corneum, and wherein the plurality of microneedles comprises a plurality of first microneedles with a first active ingredient and a plurality of second microneedles with a second active ingredient.

[0008] The state of the art described in publication CN 109 747 149 A relates to a method for producing microneedles in which a conical tip structure is exposed in a layer of printed material by controlling the exposure time of a printing jet using a DPD-based 3D printer.

[0009] Against the background outlined above, the object of the present invention was to provide a method for manufacturing a microneedle that allows for high-volume production with limited effort and greater flexibility or broader application possibilities. The object was also to provide a method for manufacturing a microneedle device.

[0010] With regard to a method for manufacturing a microneedle, this problem has been solved by the subject matter of claim 1. A method according to the invention for manufacturing a microneedle device is the subject matter of claim 14. Advantageous embodiments are specified in the dependent claims.

[0011] A first aspect of the present invention relates to a method for producing a microneedle, in particular for transdermal and / or intradermal drug delivery, in which a support structure is provided and in which at least one needle structure arranged on the support structure for penetrating the stratum corneum of human and / or animal skin is produced layer by layer by 3D screen printing, wherein drying steps are carried out between individual steps for the layer-by-layer production of the needle structure, by which drying of the respective pre-printed layer is ensured.

[0012] A microneedle produced according to the invention is particularly suitable for transdermal and / or intradermal drug delivery. Such a microneedle thus allows drug delivery through and / or into the skin. This enables greater flexibility in drug delivery.

[0013] A microneedle manufactured according to the invention comprises a support structure and at least one needle structure arranged on the support structure for penetrating the stratum corneum of human and / or animal skin. According to the invention, at least the needle structure is produced by 3D screen printing.

[0014] The needle structure can be permanently attached to the support structure. The support structure can therefore be designed to hold the needle structure, thus simplifying its handling for drug delivery.

[0015] The production of the needle structure using 3D screen printing allows for greater flexibility regarding material composition and the shape of the needle structure. At the same time, 3D screen printing enables the production of a large number of microneedles or needle structures with minimal effort. Furthermore, the creation of a needle structure with minimal material and temperature stress is achieved through 3D screen printing. This reduces limitations regarding material selection and / or the active ingredients to be processed.

[0016] In the present context, three-dimensional screen printing can be understood, in a particularly preferred manner, as an additive manufacturing process in which a powder-based suspension is transferred to a substrate through a solid printing mask, in particular a printing screen and / or a printing stencil, using a squeegee and then dried. This process can be repeated several times until the desired component height or shape is achieved. This results in a screen-printed workpiece.

[0017] In the present context, the term "screen-printed workpiece" can preferably be understood to mean workpieces that are to be subjected to, or have been subjected to, a drying and / or sintering step. This applies in particular to workpieces made of metal, ceramic, glass, and / or polymer material. Printed products made of polymer materials and / or materials containing or consisting of cellulose can also be included under the term "three-dimensional screen-printed workpiece." In particular, it is also possible to subject printed workpiece layers made of polymer material to a sintering step. In the present context, the term "screen-printed workpiece" can also be understood to include workpieces that are made of non-sinterable materials or that are produced without a sintering step.

[0018] For the purposes of the present invention, a screen-printed workpiece is in particular a workpiece that is produced at least partially by means of three-dimensional screen printing.

[0019] According to a preferred embodiment, the support structure can also be produced by additive manufacturing, in particular 3D screen printing. This further increases manufacturing flexibility. The entire microneedle can thus be produced in large quantities with less effort. Furthermore, the needle structure and the support structure can be manufactured from the same material or base material, thereby further reducing manufacturing effort. Accordingly, the entire microneedle can be produced by additive manufacturing, in particular 3D screen printing.

[0020] According to a further preferred embodiment, the needle structure and the support structure can be formed in one piece. Forming the needle structure and the support structure in one piece ensures, in particular, that the needle structure is attached to the support structure with sufficiently high strength, thus preventing unwanted detachment. It is also possible to produce the needle structure and the support structure in a continuous process sequence. This continuous process sequence can be achieved, in particular, by using three-dimensional screen printing. For this purpose, for example, the support structure can be created in one or more layers, and the needle structure can then be applied to the support structure through further printing sequences. The printed material is dried between each printing step.Following the printing sequences, thermal solidification can be carried out, for example by using UV light.

[0021] According to a further preferred embodiment, the support structure can be produced separately from the needle structure. It is possible to arrange and / or attach the needle structure to the support structure using 3D screen printing. The needle structure can thus be applied layer by layer to the separately produced support structure, namely through layer-by-layer construction using the 3D screen printing process.

[0022] It is particularly possible for the supporting structure to be produced differently than the needle structure, namely without the use of additive manufacturing or 3D screen printing. A needle structure can then be applied to such an alternatively produced supporting structure using 3D screen printing and thus bonded to it. Depending on the method used to produce the supporting structure, the manufacturing effort can be further reduced in this way.

[0023] According to a further preferred embodiment, the needle structure can be cylindrical at least in sections and / or have a cross-section that is uniform and / or circular along its longitudinal extent. Furthermore, it is possible for the entire needle structure to be cylindrical and / or have a cross-section that is uniform and / or circular along its longitudinal extent. Such a geometric configuration can be produced using additive manufacturing with minimal effort, thereby reducing manufacturing costs, especially for large production runs.

[0024] A circular cross-section can be produced, in particular, through manufacturing steps of limited complexity. The cross-sectional shape, which remains at least partially uniform along its length, allows, for example, the maintenance of manufacturing parameters along the longitudinal axis or in the production of multiple superimposed layers.

[0025] Instead of a round or circular cross-section, other cross-sectional shapes can also be implemented. For example, the needle structure can be formed, at least in sections, with an oval, rectangular, especially square, or triangular, pentagonal, or hexagonal cross-section. Such cross-sectional shapes can also be uniform, at least in sections, meaning they can be consistent along the longitudinal direction or length of the needle structure.

[0026] It can be further advantageous if the needle structure is designed with a cross-section that changes along its longitudinal extent and / or with different cross-sectional sizes and / or constant or changing cross-sectional shapes. The flexibility of the design can be further improved in this way. Different sections of the needle structure along its longitudinal extent can be specifically designed with regard to external dimensions and shape, depending on functional requirements, for example, with regard to penetrating the stratum corneum of human or animal skin or administering or delivering the desired active ingredient into or through the skin.

[0027] In a particularly preferred manner, the needle structure can be formed in steps along its longitudinal extent and / or with a cross-section that remains constant between at least two steps, in particular with a constant cross-sectional shape and / or cross-sectional size. Such a design of the needle structure allows for changes in the needle structure along its longitudinal extent while simultaneously limiting the effort required to produce these changes. For example, a relatively small tip area of ​​the needle structure can be created in this way, through which the respective corneal layer can be easily penetrated.Simultaneously, the area of ​​the needle structure adjacent to the supporting structure can be produced with greater thickness or larger outer dimensions, thus enabling a better connection with the supporting structure and also a greater delivery of the active ingredient. This can improve the effectiveness of the respective microneedle's use.

[0028] According to a further preferred embodiment, the needle structure can be formed along its longitudinal extent, at least in sections, with a cross-sectional diameter of at least 30 µm, preferably at least 50 µm, preferably at least 70 µm, more preferably at least 80 µm or more than 90 µm, in particular more than 100 µm, even more preferably more than 150 µm, even more preferably more than 200 µm, even more preferably more than 250 µm, or even more preferably more than 300 µm. Such dimensioning of the needle structure ensures sufficient mechanical stiffness, thus guaranteeing a high degree of reliability in penetrating the stratum corneum of human and / or animal skin. Simultaneously, such dimensioning ensures a sufficiently high concentration of the active ingredient within or on the needle structure.

[0029] According to a further preferred embodiment, the needle structure can be designed along its longitudinal extent, at least in sections, with a cross-sectional diameter of less than 300 µm, preferably less than 250 µm, preferably less than 200 µm, more preferably less than 150 µm, less than 100 µm, less than 90 µm, or less than 80 µm. Such a geometric design of the needle structure ensures safe and virtually painless penetration of the needle structure through the stratum corneum of human and / or animal skin. Small cross-sectional diameters can be particularly advantageous in the region of the tip of the needle structure, which is located at an end of the needle structure facing away from the supporting structure. Penetration of the stratum corneum can be easily achieved with relatively small cross-sectional diameters.

[0030] In the case of a square or rectangular cross-section, the preceding dimensions may refer to the length of a diagonal. More generally, the preceding dimensions may refer to the greatest possible distance between two points on the outer circumference of a cross-sectional plane. This could, for example, be the length of a diagonal of a rectangular cross-section.

[0031] It can be advantageous if the needle structure has a total length of at least 200 µm, 300 µm, 400 µm, 500 µm, 600 µm, or 700 µm. Such a length dimension ensures reliable penetration of the stratum corneum of human and / or animal skin. It is also possible for the needle structure to have a total length of less than 1000 µm, 900 µm, 800 µm, 700 µm, 600 µm, 500 µm, or 400 µm. This prevents the needle structure from penetrating too deeply into the tissue and also avoids undesirable deformation.By appropriately limiting the length of the needle structure, mechanical stability can be particularly improved, thereby ensuring the desired penetration of the stratum corneum with a high degree of safety.

[0032] According to a further preferred embodiment, the needle structure can be formed with at least one needle structure segment extending longitudinally between two stages, with a length of less than 200 µm, less than 150 µm, less than 100 µm, or less than 50 µm. By limiting the length of such a needle structure segment, desired variations in the cross-sectional dimensions or cross-sectional shape can be implemented on further needle structure segments or along further needle structure segments.

[0033] According to a further preferred embodiment, the needle structure can be formed with at least one needle structure segment extending longitudinally between two stages, with a length of at least 20 µm, at least 50 µm, at least 100 µm, at least 150 µm, at least 200 µm, or at least 250 µm. Such dimensioning of the needle structure between two adjacent stages enables the manufacturing of the needle structure with relatively little effort. In particular, the cross-sectional shape or dimensions can be maintained between two adjacent stages, so that the manufacturing parameters can be retained for the production of the respective needle structure segment. For example, when using three-dimensional screen printing, the same printing screens or printing stencils can be used for the production of the respective needle structure segment.Therefore, multiple printing layers can be produced using the same printing screen or printing stencil, thus reducing the handling effort in the production of the respective needle structure section to a minimum.

[0034] According to a further preferred embodiment of the method according to the invention, the needle structure can be designed with at least one active ingredient or with several active ingredients. An active ingredient provided in the needle structure can be released with a high degree of certainty after penetration of the stratum corneum of human and / or animal skin and thus made systemically available in the respective organism. It is also possible for the needle structure to be designed without active ingredients and to be suitable only for perforating the stratum corneum of human and animal skin. After the respective perforation, the active ingredient can be administered through the perforated areas via a patch.

[0035] In a further preferred configuration, the needle structure for drug delivery can be formed by material dissolution. Material dissolution ensures particularly precise drug delivery and dosage. If the respective needle structure is designed for complete material dissolution, subsequent removal of the needle structure from the tissue is unnecessary. This improves user-friendliness.

[0036] According to a further preferred embodiment, the needle structure can be designed with different active ingredient densities along its longitudinal length. It is also possible for the needle structure to be designed with different active ingredients along its longitudinal length, or for the respective active ingredients to be provided in different densities or quantities along its longitudinal length. The delivery of the active ingredients to different layers of the skin can thus be precisely adjusted or controlled. Different active ingredients can therefore be administered to different levels or layers of the skin, thereby further improving the functionality of the microneedle.

[0037] Furthermore, varying drug densities along the longitudinal axis of the needle structure allow for the appropriate control and regulation of drug delivery profiles. Depending on the tissue depth at which the drug is released, the systemic availability of the respective drug can vary.

[0038] A variation in active ingredient or active ingredient density along the longitudinal axis of the needle structure can be achieved with minimal effort using three-dimensional screen printing. Different layers of the needle structure can be created using different printing pastes or pastes with different compositions. In this way, an active ingredient gradient or variation along the longitudinal axis of the needle structure can be achieved with minimal effort.

[0039] It can be further advantageous if the needle structure is designed with a dissolving coating containing at least one active ingredient. Accordingly, a needle structure with a needle core and a coating applied to it can be provided. The coating can be designed to dissolve in living tissue, and the core of the needle structure can remain after the coating dissolves. The core of the needle structure can be produced together with the coating using additive manufacturing, particularly 3D screen printing. It is also possible for the core of the needle structure to be designed to dissolve in living tissue, especially in a defined sequence after the coating.

[0040] In a further preferred embodiment, the needle structure can be designed with a cavity containing at least one active ingredient. After penetrating a stratum corneum of human and / or animal skin, the respective active ingredient can be released from the cavity of the needle structure and thus made systemically available within the respective organism. Accordingly, the needle structure can be designed to deliver the active ingredient from a cavity within the needle structure. The drug delivery can therefore occur independently of the dissolution or complete dissolution of the needle structure or any coating, and can thus be achieved in a relatively short time.

[0041] It can be further advantageous if the needle structure and / or the supporting structure is made of polyvinylpyrrolidone (PVP) or a material containing polyvinylpyrrolidone (PVP). Generally, the needle structure and / or the supporting structure can consist of a polymer and / or be made of a polymer-containing material. It is also possible for the needle structure and / or the supporting structure to be made of a plurality of material components, for example, glycerin, polysorbate 80, trehalose, disodium hydrogen phosphate dodecahydrate, disodium hydrogen phosphate monohydrate, and / or distilled water (or generally "purified water") or solvents.In a further preferred manner, the material used to produce the needle structure and / or the supporting structure may contain viscosity-enhancing components, in particular to improve the processability of the material by means of additive manufacturing, especially 3D screen printing.

[0042] In a further preferred embodiment, a material containing at least one of the following components, particularly as a matrix material, can be used for the production of the needle structure and / or the supporting structure: hyaluronic acid, carboxymethylcellulose, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVO), PVM / MA copolymer, poly(lactide-co-glycolide) (PLGA), polylactides (PLA), and / or polyglycolic acid (PGA). The use of such components can further improve the manufacturing flexibility and the application flexibility of the respective microneedle.

[0043] A further aspect of the present invention relates to a method for manufacturing a pure microneedle device, particularly for transdermal and / or intradermal drug delivery, in which a plurality of microneedles are produced according to the method described above. The microneedles can preferably be configured as a so-called needle array. In this context, a needle array is defined as a regular or irregular arrangement of microneedles along a spatially defined area. A needle array can, for example, be circular or rectangular and / or contain a defined number of microneedles.

[0044] According to a further preferred embodiment, the support sections of the microneedles can be formed integrally or joined to form a complete support structure. The microneedles can thus have and maintain a defined arrangement relative to one another, thereby improving the handling and user-friendliness of the microneedle device.

[0045] In a further preferred embodiment, at least two adjacent microneedles of a microneedle device can have a distance of at least 100 µm, at least 200 µm, at least 300 µm, at least 350 µm, at least 400 µm, at least 500 µm, at least 600 µm, at least 700 µm, at least 800 µm, or at least 1000 µm from each other. Likewise, it is possible for at least two adjacent needle structures to have a distance of less than 1000 µm, less than 900 µm, less than 800 µm, less than 700 µm, less than 600 µm, at least less than 500 µm, or less than 400 µm.

[0046] The aforementioned dimensions refer in particular to a longitudinal axis or longitudinal center axis of the respective needle structure. Such a geometric arrangement of multiple microneedles ensures a dense needle density and thus a relatively high drug delivery rate over a relatively small skin area. The user-friendliness of such a microneedling device can be further improved in this way.

[0047] Another independent aspect of the present teaching concerns a medical patch, particularly for transdermal and / or intradermal drug delivery. Such a patch is equipped with a plurality of microneedles and / or a single microneedle as described above. Furthermore, such a patch can be equipped with an adhesive device, such as an adhesive strip, which allows the respective microneedles or the microneedle device to be firmly adhered to the skin, thus ensuring safe drug delivery.

[0048] The present invention is explained in more detail below by way of example with reference to the attached figures.

[0049] They each show schematically: Fig. 1 a perspective view of a microneedle according to a first embodiment of the present invention, Fig. 2 a perspective view of a microneedle according to a further embodiment of the present invention, Fig. 3 a perspective view of a microneedle according to a yet further embodiment of the present invention, Fig. 3 longitudinal section of the microneedle according to Fig. 3A Fig. 4A a perspective view of a microneedle according to a further embodiment of the present invention, Fig. 4A longitudinal section of the microneedle according to Fig. 4A , Fig. 5 a perspective view of a microneedle device according to an embodiment of the present invention and Fig. 6 a perspective view of a medical plaster according to an embodiment of the present invention.

[0050] The Fig. 1 Figure 1 shows a microneedle 10 according to an embodiment of the present invention. The microneedle 10 has a support structure 12 and at least one needle structure 14 arranged on the support structure 12 for penetrating the stratum corneum of human and / or animal skin. The needle structure 14 can be dimensioned, in particular, for penetrating the stratum corneum of human and / or animal skin, or have a suitable geometric shape for this purpose.

[0051] The needle structure 14 is produced according to the invention by 3D screen printing. For this purpose, the needle structure 14 is built up layer by layer. Between individual steps of layer-by-layer production, drying steps are carried out to ensure that each pre-printed layer is dried.

[0052] It is also possible that the support structure 12 is produced by additive manufacturing, in particular 3D screen printing. Furthermore, the needle structure 14 and the support structure 12 can be formed in one piece and / or manufactured by a continuous process sequence. In particular, it is possible that both the support structure 12 and the needle structure 14 are produced by means of 3D screen printing, using a continuous layer-by-layer process sequence.

[0053] Furthermore, it is possible that the support structure 12 is produced separately from the needle structure 14 and that the needle structure 14 is arranged and / or attached to the support structure 12 by means of additive manufacturing, in particular 3D screen printing.

[0054] Again Fig. 1 As can be seen, the needle structure 14 can be cylindrical at least in sections or have a cross-section that is at least partially uniform and / or circular along its longitudinal extent. In particular, the entire needle structure 14 can be cylindrical or have a cross-section that is uniform and / or circular along its longitudinal extent.

[0055] The needle structure 14 can have a cross-sectional diameter of at least 30 µm, preferably at least 50 µm, preferably at least 70 µm, more preferably at least 80 µm, or more than 90 µm, at least in sections along its longitudinal extent. Likewise, it is possible that the needle structure 14 has a cross-sectional diameter of more than 100 µm, more preferably more than 150 µm, more preferably more than 200 µm, more preferably more than 250 µm, or more preferably more than 300 µm, at least in sections along its longitudinal extent.

[0056] Furthermore, the needle structure 14 can have a cross-sectional diameter of less than 300 µm, preferably less than 250 µm, preferably less than 200 µm, more preferably less than 150 µm or less than 100 µm or less than 90 µm or less than 80 µm along its longitudinal extent, at least in sections.

[0057] The needle structure 14 can furthermore have a total length of at least 200 µm, at least 300 µm, at least 400 µm, at least 500 µm, at least 600 µm, at least 700 µm or less than 1000 µm, less than 900 µm, less than 800 µm, less than 700 µm, less than 600 µm, less than 500 µm or less than 400 µm. The length of the needle structure 14 can, in particular, extend between the support structure 12 and a free end 16 facing away from the support structure 12.

[0058] In the embodiment according to Fig. 1 The needle structure 14 can have a cross-sectional shape and size that remain constant along its longitudinal extent. The outer circumference 15 of the needle structure 14 therefore remains unchanged along its longitudinal extent. Such a geometric design can be produced with minimal effort using additive manufacturing, in particular by means of 3D screen printing.

[0059] The Fig. 2 Figure 1 shows a further embodiment of a microneedle 10 according to the present invention. The microneedle 10 according to Fig. 2 differs from the embodiment in Fig. 1 with regard to the geometric design of the needle structure 14. Thus, the needle structure 14 exhibits in Fig. 2 along its longitudinal extent, it exhibits a changing cross-section. In particular, the needle structure 14 in Fig. 2 Different cross-sectional sizes are observed along its longitudinal extent. For this purpose, the needle structure 14 can, for example, be stepped along its longitudinal extent.

[0060] In the embodiment according to Fig. 2 Four stages 18a, 18b, 18c, and 18d are provided as examples. Between stages 18a and 18b, 18b and 18c, and 18c and 18d, the needle structure 14 can have a constant cross-section or a continuous cross-sectional shape along its longitudinal extent. Likewise, the cross-sectional size can be constant between any two stages 18a and 18b, 18b and 18c, or 18c and 18d. Finally, the cross-sectional size and / or shape can be constant between the supporting structure 12 and stage 18a and / or between stage 18d and the free end 16.

[0061] Stages 18a, 18b, 18c, and 18d can subdivide the needle structure 14 into a total of five needle structure sections 20a, 20b, 20c, 20d, and 20e. Needle structure section 20a borders the supporting structure 12, and needle structure section 20e forms the free end 16. Needle structure sections 20a to 20e can each have the same cross-sectional shape but different cross-sectional sizes. With increasing distance from the supporting structure 12, the respective cross-sectional diameter of the individual needle structure sections 20a to 20e can decrease. Accordingly, the cross-sectional size of the needle structure sections 20a to 20e can decrease stepwise from the supporting structure 12.

[0062] The foregoing regarding the embodiment in Fig. 1 The dimensions mentioned can also apply to the individual needle structure sections 20a to 20e. Furthermore, the specifications regarding the overall length of the needle structure 14 may vary. Fig. 2 refer to the sum of the individual lengths of the needle structure sections 20a to 20e.

[0063] The length of a needle structure section 20b, 20c, and 20d extending between two stages 18a and 18b, 18b and 18c, and 18c and 18d can be less than 200 µm, less than 150 µm, less than 100 µm, or less than 50 µm. Such a needle structure section can also have a length of at least 20 µm, at least 50 µm, at least 100 µm, at least 150 µm, at least 200 µm, or at least 250 µm. The aforementioned dimensions can also apply to the needle structure section 20a extending between the supporting structure 12 and the stage 18a. Likewise, the preceding dimensions can apply to the needle structure section 20e, which extends between stage 18d and the free end 16.

[0064] The needle structure 14 according to the Fig. 1 and 2The needle structure can contain at least one active ingredient. Likewise, the needle structure can contain 14 different active ingredients. The active ingredients or active ingredient densities of the needle structure 14 can differ along its longitudinal extent or vary along its longitudinal extent.

[0065] Furthermore, the needle structure 14 can be described according to the Fig. 1 and 2 The device is designed for drug delivery by material dissolution. In particular, the needle structure 14 may dissolve completely for drug delivery. Therefore, removing the needle structure 14 after drug delivery is unnecessary.

[0066] The Fig. 3A and 3B show a further embodiment of a microneedle 10 according to the present invention. The embodiment of Fig. 3 differs from the embodiment in Fig. 1 by the fact that the needle structure 14 has a dissolving coating containing at least one active ingredient. The coating 22 can be formed on a core structure 24 or arranged on or around it. It is also possible that the core structure 24 is not dissolving or is made of a dissolving-resistant material that differs from the material of the coating 22.

[0067] Furthermore, it is possible that both the coating 22 and the core structure 24 are designed for drug delivery by dissolution, wherein the coating 22 contains a different drug or drugs than the core structure 24, so that a desired drug delivery profile can be achieved. The aforementioned dimensions regarding the cross-sectional diameter may vary in the embodiment. Fig. 3 refer to the total cross-sectional diameter formed by the core structure 24 and the coating 22.

[0068] The Fig. 4A and 4B show a further embodiment of a microneedle 10 according to the present invention. The embodiment in the Fig. 4A and 4B differs from the embodiment in Fig. 1 by the fact that the needle structure 14 has a cavity 26 with at least one active ingredient arranged therein. Accordingly, the needle structure 12 can be designed according to Fig. 4A and 4B for the administration of the active ingredient from the cavity 26 of the needle structure 14.

[0069] The cavity 26 can be a channel extending along the longitudinal axis, opening into the free end 16 of the needle structure 14. The cavity 26 can also extend into an active ingredient reservoir 28, which is at least partially formed by or embedded in the supporting structure 12. It is also possible that the active ingredient reservoir 28 is formed solely within the needle structure 14, which is not shown in detail here.

[0070] After penetrating the stratum corneum of human and / or animal skin, the active ingredient can be administered from the cavity 26 into the respective organism, whereby emptying or partial emptying of the active ingredient reservoir 28 can also occur. Furthermore, the needle structure 14 can be resistant to dissolution in a living organism. It is also possible that the needle structure 14 is designed according to Fig. 4 It is also designed for drug delivery by dissolution. In this case, the dissolution of the needle structure 14 can occur after the drug delivery from the cavity 26, so that, for example, different drugs can be released into the respective organism in sequential succession.

[0071] The Fig. 5 Figure 1 shows a microneedle device 30 according to an embodiment of the present invention. The microneedle device 30 comprises a plurality of microneedles 10 according to Fig. 1 on. Likewise, it is possible that the microneedle device 30 consists of microneedles 10 according to one of the further embodiments in the Fig. 2 bis 4 is educated, which is not described in detail here.

[0072] According to Fig. 5 The individual microneedles 10 within the microneedle device 30 are arranged in a specific configuration relative to one another, forming a predefined or random arrangement pattern. The support structures 12 of the microneedles 10 can be interconnected or formed as a single piece. The support structures 12 of the microneedles 10 can thus form an overall support structure 32 to which the individual needle structures 12 are arranged or attached.

[0073] The needle structures 12 of the individual microneedles 10 can be spaced at a defined distance from each other. For example, the needle structures 12 of two immediately adjacent microneedles 10 can be spaced more than 300 µm or less than 500 µm, for example, approximately 350 µm. The number of individual microneedles 10 of a microneedle device 30 can be varied or selected as desired, depending on the specific application. The microneedles 10 of the microneedle device 30 thus form a needle array 34.

[0074] The Fig. 6 Figure 36 shows a medical patch 36. Such a medical patch 36 can have a microneedle device 30 or a plurality of microneedles 10. The microneedle device 30 or the microneedles 10 can be arranged or attached to an adhesive tape 38 or medical tape material. The adhesive tape 38 is particularly suitable for adhesive attachment to human or animal skin, thereby ensuring a high degree of safety in the administration of active ingredients over a period of time via the microneedles 10. Bezugszeichenliste

[0075] 10 Microneedle 12 Support structure 14 Needle structure 15 Outer circumference 16 Free end 18a-18d Steps 20a-20e Needle structure sections 22 Coating 24 Core structure 26 Cavity 28 Drug reservoir 30 Microneedle device 32 Overall support structure 34 Needle array 36 Medical patch 38 Adhesive tape

Claims

1. Method for producing a microneedle (10), in particular for transdermal and / or intradermal administration of active substances, in which a support structure (12) is provided and in which at least one needle structure (14), arranged on the support structure (12), for penetrating the horny layer of human and / or animal skin is produced layer by layer by means of 3D screen printing, wherein drying steps are carried out between individual steps for the layer-by-layer production of the needle structure (14), thereby ensuring that the respective pre-printed layer is dried.

2. Method (10) according to claim 1, characterized in that the support structure (12) is produced by additive manufacturing, in particular 3D screen printing, and / or that the needle structure (14) and the support structure (12) are formed in one piece and / or are produced by an uninterrupted sequence of processes.

3. Method (10) according to claim 1, characterized in that the support structure (12) is produced separately from the needle structure (14) and / or that the needle structure (14) is arranged and / or attached to the support structure (12) by means of 3D screen printing.

4. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed cylindrically at least in sections and / or is formed with a cross-section that is at least sectionally uniform and / or circular along its longitudinal extension and / or that the entire needle structure (14) is designed to be cylindrical and / or has a cross-section that is uniform and / or circular along its longitudinal extension.

5. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed with a cross-section that varies along its longitudinal extension and / or with different cross-sectional sizes and / or uniform cross-sectional shapes.

6. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed in steps along its longitudinal extension and / or with a cross-section that remains constant between at least two steps (18), in particular with a constant cross-sectional shape and / or cross-sectional size.

7. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed along its longitudinal extension at least in sections with a cross-sectional diameter of at least 30 µm, preferably at least 50 µm, preferably at least 70 µm, more preferably of at least 80 µm or of more than 90 µm, in particular more than 100 µm, even more preferably of more than 150 µm, even more preferably of more than 200 µm, even more preferably of more than 250 µm, even more preferably of more than 300 µm.

8. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed along its longitudinal extension at least in sections with a cross-sectional diameter of less than 300 µm, preferably less than 250 µm, preferably less than 200 µm, more preferably less than 150 µm or less than 100 µm or less than 90 µm or less than 80 µm.

9. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed with a total length of at least 200 µm, at least 300 µm, at least 400 µm, at least 500 µm, at least 600 µm, at least 700 µm or less than 1000 µm, less than 900 µm, less than 800 µm, less than 700 µm, less than 600 µm, less than 500 µm or less than 400 µm, and / or that the length of the needle structure (14) extends between the support structure (12) and a free end (16) facing away from the support structure (12).

10. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed with at least one needle structure section (20) extending longitudinally between two steps (18) with a length of less than 200 µm, less than 150 µm, less than 100 µm or less than 50 µm.

11. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed with at least one needle structure section (20) extending longitudinally between two steps (18) with a length of at least 20 µm, at least 50 µm, at least 100 µm, at least 150 µm, at least 200 µm or at least 250 µm.

12. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed with at least one active substance and / or that the needle structure (14) is formed with several active substances and / or that the needle structure (14) is formed with different active substance densities and / or active substances along its longitudinal extension and / or that the needle structure (14) is formed for active substance administration by material dissolution.

13. Method (10) according to one of the preceding claims, characterized in that the needle structure (14) is formed with a coating (22) designed to dissolve, with at least one active ingredient, and / or that the needle structure (14) is formed with a cavity (26) with at least one active substance arranged therein and / or that the needle structure (14) is formed for administering active substances from a cavity (26) of the needle structure (14).

14. Method for manufacturing a microneedle device (30), in particular for transdermal and / or intradermal active substance administration, in which a plurality of microneedles (10) are produced according to a method according to one of the preceding claims, wherein the microneedles (10) are preferably formed as a needle array (34).

15. Method according to claim 14, characterized in that the support sections (12) of the microneedles (14) are formed integrally with one another or are connected to form an overall support structure (32).