HK1244657B - Microneedle system for delivering liquid formulations and method for producing a microneedle system - Google Patents

Description

Microneedle system for delivering liquid formulations and method for manufacturing the microneedle system

Technical Field

The present invention relates to a microneedle system (MNS) for intradermal delivery of solutions or preparations. The present invention relates to a microneedle system comprising a cover element, an active substance container, a frame, a microneedle array (MNA), and a substrate. The microneedle array (MNA) is connected to the frame, and the substrate has an opening for accommodating the microneedle array. The cover element and the substrate are movably connected to each other, the substrate is connected to a fixing tape, and the frame and the substrate are linearly movable relative to each other. The present invention also relates to a method for manufacturing the microneedle system.

The MNS according to the invention is suitable for the intradermal administration of medicaments, active substances, pharmaceutical or cosmetic ingredients or other substances to individuals, preferably patients, over a longer period of time.

Background Art

Microneedle systems and devices are known in the prior art in which microneedle arrays are used for painless intradermal drug delivery.

The skin consists of several layers. The outermost skin layer, the stratum corneum, has known barrier properties to prevent the entry of foreign substances into the body and the excretion of internal substances from the body. The stratum corneum forms a waterproof membrane to protect the body. It is a complex structure consisting of flat, cornified cell remnants with a thickness of approximately 10-30 micrometers. The natural impermeability of the stratum corneum prevents the transdermal administration of most pharmaceutical preparations and other substances within the context of intradermal delivery.

Thus, for example, by making micropores or incisions in the stratum corneum and by delivering or delivering the agent into or below the stratum corneum, administration of different substances can be achieved. In this way, for example, a large number of agents can also be administered subcutaneously or intradermally.

For use, a microneedle system (MNS), which includes a microneedle array (MNA) and optionally other components, requires elements that press the microneedles of the array (MNA) (also called skin-penetrating elements) onto a delivery site on the skin, thereby penetrating the stratum corneum and establishing a fluid channel between an external drug reservoir (e.g., a container) and the skin via the MNA. If a liquid preparation is selected as the drug, the MNS requires elements that open the active substance container and, depending on the design, also extrude the drug from the active substance container. Various embodiments are known to implement the aforementioned elements, which typically utilize a mechanical energy reservoir to open the active substance container. For example, a syringe or a small pump integrated into the MNS is responsible for the expulsion of the active substance container.

WO 02/05889 A1 describes a relatively simple microneedle system. The device comprises a housing with an active substance container in the form of a flexible bladder within. The flexible bladder is placed in a cavity within the housing. This cavity is covered by a cover member that can be pressed downward to press the flexible bladder toward the microneedle array at the bottom of the housing. This opens the active substance container, and the liquid contained in the flexible bladder flows to the plurality of microneedles.

DE60305901T2 discloses a device comprising a housing and a cartridge. The cartridge contains a container for a solution containing an active substance and, in addition to a bottom wall, has a lower outer wall spaced apart from the bottom wall and integrated with a needle array. The housing comprises a base member, surrounding side walls, and a cover member that can be pivoted between an open and closed position and is connected to the base member by a hinge, snap fit, press fit, or friction fit. The microneedle system is assembled by placing the cartridge in the housing, where it is positioned in a defined position by means of a groove. The microneedle system is placed on the patient's skin surface so that the needle array pierces the skin surface, and the housing cover member is then pivoted into the closed position. When the cover member is closed, the active substance container is pierced. The housing cover member has a spring for applying pressure to the cartridge, and the cover member causes the solution containing the active substance to be dispensed when the cover member is closed. Furthermore, an armband is required for securement.

The devices and methods known in the prior art for the intradermal delivery of active substances are successful only to a limited extent.

Known microneedle systems have the disadvantage that they exert force on the MNA only for a short period of use (seconds or less), and the MNA easily loosens from the skin again during subsequent use (minutes to days). However, for many applications, it is necessary to ensure a permanent force lock with the skin during delivery or over a longer period of time.

Furthermore, many known microneedle systems have the disadvantage of requiring delivery devices that are not part of the microneedle system but must be provided as an additional, separate unit. For intradermal delivery, a design that combines the MNS and delivery system in a single unit is desirable, where the overall system configuration—particularly the overall height and diameter—does not affect the comfort of use or portability of the MNS.

Furthermore, all known devices with liquid active substance containers consist of a combination of a microneedle array and a syringe, pump, or spring for dispensing the active substance-containing solution. Due to their design, these devices are uncomfortable to use and complex to manufacture. There is a need for devices that are simple to manufacture and use.

Summary of the Invention

According to the invention, this object is achieved by a microneedle system (MNS) comprising a cover element, an active substance container, a frame, a microneedle array, a substrate, and a fixing adhesive tape.

The microneedle system for intradermal delivery of the present invention comprises:

i.) a cover element above the active substance container, wherein the active substance container is accommodated in a frame having the microneedle array; and

ii.) a substrate, wherein the substrate has an opening for accommodating the microneedle array, the substrate has a circumferential protrusion offset inwardly relative to an edge of the substrate together with the opening, and the substrate has a thread on the outer side of the circumferential protrusion that is complementary to the thread of the cover element, and the cover element and the substrate are movably connected to each other via the thread;

iii.) the substrate is fully or partially connected to the fixing tape; and

iv.) The frame and the base plate are movably connected to one another, wherein the frame with the microneedle array is linearly movable in the direction of the opening of the base plate and the base plate has at least one opening element for opening the active substance container.

In the MNS according to the invention, the microneedle array is connected to the frame, preferably on the underside of the frame, and the base plate has an opening for accommodating the microneedle array.

The frame can also be regarded as a support for the microneedle array, which serves to fix the microneedle array and also to accommodate the active substance container.

Covering element and substrate are movably connected to each other, preferably are connected to each other by screw thread.In addition, substrate is connected with fixing adhesive tape wholly or in part or this substrate is provided with adhesive tape and framework and substrate can move linearly mutually.

The MNS is preferably protected before use by a protective film, in particular a fixing tape.

Therefore, unlike microneedle systems known in the prior art, the MNS according to the present invention primarily comprises an active substance container that can be connected to the skin in a single unit via a fixing patch. The MNS according to the present invention does not require additional applicators, pumps, syringes, or springs. The microneedle system can be manufactured simply and cost-effectively. The MNS can, but does not necessarily, be supplemented with other components. The microneedle system is suitable for administering medicaments, active substances, pharmaceutical or cosmetic ingredients, or other substances intradermally to individuals, preferably patients, over an extended period of time. The MNS according to the present invention is simple to operate and can be performed by patients themselves at home or at a point of care, for example, within the context of self-medication, or for cosmetic applications. In particular, inserting the microneedles into the skin is a routine procedure and does not require medical examination, monitoring, or supervision by a qualified healthcare professional. This is particularly advantageous for longer or repeated administrations, as the patient or individual does not need to be monitored repeatedly or for extended periods by a qualified healthcare professional. This is possible because the needles of the MNA can be easily inserted into the stratum corneum and can remain there for a longer period of time even without additional compression, thereby ensuring that the desired amount of medicament, active substance, pharmaceutical composition or other substance is delivered by the patient or the individual himself using the MNA according to the invention.

The subject of the present invention is therefore a microneedle system for intradermal delivery, comprising:

i.) a cover element above the active substance container, wherein the active substance container is accommodated in a frame having the microneedle array; and

ii.) a substrate, wherein the substrate has an opening for accommodating the microneedle array, and the cover element and the substrate are movably connected to each other;

iii.) the substrate is fully or partially connected to the fixing tape; and

iv.) The frame and the substrate are movably connected to each other, wherein the frame with the microneedle array can be linearly moved in the direction of the opening of the substrate.

Furthermore, the cover elements are movably connected to one another on the base plate, preferably by means of a thread.

According to the present invention, the term "intradermal delivery (synonym: intradermal administration)" means that a substance is administered into the skin via MNA and requires the insertion of microneedles into the skin.

According to the invention, after fixation on the skin by means of a fixing tape for the microneedle system, in a first step the cover element is screwed on the base plate and in this way the frame with the microneedle array is moved towards the opening of the base plate.

During this movement or stroke, the frame with the microneedle array reaches the plane of the substrate's opening, where the protruding microneedles penetrate the skin. Simultaneously, the accompanying active substance container reaches one or more opening elements (such as a needle), causing it to rupture and release the solution or formulation, specifically, into the provided MNA. The opening elements are positioned so that, as soon as the microneedle array reaches the plane of the substrate's opening (the so-called delivery position), they contact and open the active substance container.

In a preferred embodiment of the present invention, the frame of the microneedle system has at least one or more latching hooks, which preferably protrude and can engage in the base plate. The base plate may have corresponding recesses. Furthermore, the latching hooks serve as the aforementioned points of engagement during the rotational movement of the cover element relative to the base plate.

The latching hooks provide the frame with a defined position relative to the base plate and also prevent the frame from being (completely) rotated, more precisely (completely) rotated on the base plate. At the same time, the latching hooks on the frame and the recesses in the base plate are designed so that the frame can be movably mounted in the base plate.

If the frame is in the plane of the substrate or mounting tape, the MNA is positioned in the opening of the substrate.

The frame and the base plate are movably connected to one another, but can be linearly displaced relative to one another, wherein the one or more latching hooks are intended to prevent a rotational movement or a rotation of the frame on the base plate.

In a particularly preferred embodiment of the microneedle system, the cover element and the base are movably connected to each other via a thread. In a preferred embodiment of the microneedle system, the active substance container is opened with a quarter turn of the thread. The preferred rotation angle is 90°. Depending on the design, the rotation angle can range from 10° to 350°. Reaching the maximum rotation angle can be indicated to the user, in the simplest case, for example, by a position marking in the stop.

In another preferred embodiment of the microneedle system, the fixing adhesive tape is protected by a protective film.

In another preferred embodiment of the microneedle system, the diameter of the microneedle system is at least 10 mm, preferably at least 25 mm, particularly preferably at least 50 mm.

In another preferred embodiment of the microneedle system, the height of the microneedle system is a maximum of 30 mm, preferably a maximum of 20 mm, particularly preferably a maximum of 10 mm.

In another preferred embodiment of the microneedle system, the active substance container is a blow-fill-seal container or a disposable container.

In another preferred embodiment of the microneedle system, the active substance container has one or more substances, medicaments, active substances, solutions or (liquid) preparations, in particular pharmaceutical active substances or pharmaceutical ingredients, in particular antibiotics, antiviral active substances, analgesics, anesthetics, appetite suppressants, antirheumatic drugs, antidepressants, antihistamines, anti-inflammatory agents, antitumor agents, vaccines (including DNA vaccines), etc., proteins, peptides or peptide fragments, nucleic acids or nucleic acid parts, as well as cosmetics, nutritional supplements, sunscreens, insect repellents, free radical scavengers, moisturizers, colorants.

Preferably, the active substance container contains a solution or a (liquid) preparation comprising the active substance and auxiliary substances.

The term "solution" or "(liquid) formulation" refers to one or more substances having at least one aggregated state that enables the substance or substances to be delivered intradermally via an MNA at room temperature within a predetermined delivery time. Suitable viscosities are values between 0 and 200 mPa*s.

The present invention also provides a method for producing a microneedle system according to the invention, comprising the following steps:

a) providing an active substance container, preferably by means of a blow-and-seal process;

b) providing a microneedle array; and

c) Connecting the active substance container and the microneedle array to the frame, substrate and fixing tape to form a microneedle system.

The subject of the present invention is also a method for carrying out intradermal delivery, comprising

a) fixing the microneedle system according to the present invention on the skin by means of a fixing tape;

b) Transferring the microneedle system from the storage position (first position) into the delivery position (second position), for example by rotating the cover element relative to the base plate.

A preferred embodiment of the present invention relates to a method for performing intradermal delivery, the method comprising:

a) fixing the following microneedle system on the skin with a fixing tape, wherein the microneedle system comprises

i.) a cover element above the active substance container, wherein the active substance container is accommodated in a frame having a microneedle array, and

ii.) a substrate, wherein the substrate has an opening for accommodating the microneedle array, and the cover element and the substrate are movably connected to each other,

iii.) the substrate is fully or partially connected to the fixing tape, and

iv.) the frame and the substrate are movably connected to each other, wherein the frame having the microneedle array can be linearly moved toward the opening of the substrate; and

b) The microneedle system is transferred from the storage position (first position) into the delivery position (second position), for example by rotating the cover element (1) relative to the base plate, wherein the active substance container is opened by the opening element.

The subject of the present invention is also a method for intradermal delivery, comprising:

a) fixing the microneedle system according to the present invention on the skin by means of a fixing tape;

b) transferring the microneedle system according to the invention from the storage position into the delivery position, for example by rotating a thread between the cover element and the base plate;

c) delivering one or more substances to selected areas of an individual's skin.

Likewise, the present invention relates to one or more substances, medicaments, active ingredients, solutions or (liquid) preparations to be delivered intradermally in the microneedle system according to the invention.

The MNS according to the present invention can include one or more MNAs and one or more active substance containers. The MNS according to the present invention enables painless piercing of the stratum corneum and allows microneedles to penetrate the skin with minimal effort. The MNS according to the present invention is particularly advantageous for achieving a constant force connection with the skin and maintaining a constant and lasting force connection between the skin and the MNA during delivery. The MNS according to the present invention is designed so that, during use, it is first positioned and secured on the skin. The MNA is in a first position—the storage position. By rotating the cover element about the base plate, the frame (delivery mechanism) is linearly moved toward the base plate. The MNA is moved from the storage position to the delivery position, and the active substance containers are simultaneously opened by the opening element. The solution contained in the active substance containers flows from the active substance containers into the MNA or into the microneedles. In the delivery position, the microneedles have already pierced the stratum corneum and penetrated into the skin. The liquid is delivered intradermally via the microneedles. By operating the delivery mechanism, a constant tension is generated and maintained between the skin and the MNS. As a result, there is a permanent force-locking connection between the MNA and the skin during the entire intradermal delivery, so that the solution can also be administered over a longer period of time. The MNA remains in the skin during the entire delivery period, but the needles of the MNA do not come loose from the skin.

The cover element has a shape and size that complements the shape and size of the base plate. The cover element and the base plate form a housing. Preferably, the cover element has a thread for locking the cover element in the closed position and for transferring the MNA from the storage position to the delivery position.

The cover element has an upper side and an underside, with the underside pointing inward toward the base plate and preferably contacting the latching hooks. The cover element may, for example, have the shape of a dome-shaped cover. Preferably, the cover element has features on its upper side that facilitate transfer from the storage position to the delivery position. For example, the cover element may have one or more grooves on its upper side to prevent slippage. Furthermore, the cover element may have one or more markings that specify how the MNS can be transferred from the storage position to the delivery position. The underside has a circumferential thread that complements the thread of the base plate, allowing the cover element and base plate to be connected by rotating the thread. Simultaneously, rotating the thread between the cover element and base plate causes the MNS to transfer from the storage position to the delivery position.

The cover element and the base plate form a housing having a cavity inside, which is suitable for accommodating the frame, the MNA and the active substance container.

The base plate has a circumferential projection with an opening that is offset inward from the base plate edge. This projection serves as a distance element for creating a cavity. Threads complementary to the threads of the cover element are provided on the outer side of the edge. To create the cavity, the cover element is placed onto the base plate without turning the threads. A partial or complete thread turn, or multiple thread turns, reduces the cavity defined by the cover element and base plate.

In the storage position, the MNA is above the skin, and the microneedles do not penetrate the stratum corneum. During the transition to the delivery position, the cavity decreases and the MNA descends. The microneedles then penetrate the skin, preferably into or through the stratum corneum, and remain in this position for the duration of the delivery or use of the MNS.

The frame is dimensioned in such a way that it can accommodate the active substance container. The active substance container is preferably placed or fastened in the frame in such a way that it is also linearly displaced relative to the base plate when the thread is turned.

The active substance container is made of a material that can be opened by at least one opening element. In a preferred embodiment of the present invention, the active substance container is manufactured using a blow-fill-seal process. Corresponding methods are known in the art and are described, for example, in Andrew W. Goll (International Pharmaceutical Engineering Association (2012) Knowledge Brief, KB-0025-Jun 12). A particularly preferred embodiment of the MNS according to the present invention involves such an embodiment using a blow-fill-seal container.

The MNS according to the present invention also includes a fixing patch for fastening the MNS to the skin. The term "fixing patch" herein encompasses any fastening device suitable for fastening the MNS to the skin surface. The fixing patch can, for example, include a fixing carrier and a chemical or biological substance, preferably an adhesive. The fixing patch can also simply include or consist of one or more chemical and/or biological substances, wherein the one or more chemical and/or biological substances are applied directly to the underside of the substrate and are suitable for fastening the MNS to the skin surface. The fixing patch can also have or consist of a structured surface, such as nanostructures suitable for fastening the MNS to the skin surface. It is important that the fixing patch creates a sufficiently strong fastening and fixation on the skin surface, thereby creating a constant force-locking connection between the skin and the MNS, and that this force-locking connection between the skin and the MNS is maintained during delivery. Suitable fixing tapes are selected based on the skin tension in the affected area (e.g., the abdomen or back), the amount of fat tissue in and beneath the stratum corneum in the affected area, the individual's body mass index (BMI), their age, their dietary habits (e.g., fluid intake), their lifestyle (e.g., sun exposure of the affected skin area), and optionally other factors. Accordingly, a professional can select suitable fixing tapes for different individuals or patients and/or skin areas. Furthermore, the fixing tape is selected based on the size of the MNS and the materials used therein or the weight of these materials. Examples of suitable fixing tapes are common commercially available (adhesion) adhesives applied to a carrier, optionally also applied to both sides of the carrier.

The fixing tape is fixedly connected to the substrate. In a particular embodiment, the fixing tape is an integral part of the substrate. The fixing tape has one or more interstices through which the microneedles of the MNA are guided when adjusting the delivery position and protrude during delivery. The interstices of the fixing tape can optionally be protected by a protective film or the like before delivery or before being fixed to the skin.

According to the present invention, a microneedle array (MNA) (synonyms: microneedle patch or microneedle pad) has one or more skin-penetrating elements. In some embodiments, the skin-penetrating elements are arranged in an array of rows and columns that are spaced apart by substantially uniform distances from one another. The actual length and spacing of the skin-penetrating elements may depend on the solution to be administered and the site of administration on the body of the individual or patient. Typically, the skin-penetrating elements are needles, preferably hollow needles, that are affixed to or adjacent to a support and protrude from the support. The skin-penetrating elements are arranged in an array configured to administer an effective amount of solution through the skin of the individual/patient over a defined period of time. Typically, the microneedle array has an area of about 1 cm ² to about 10 cm ² and preferably has an area of about 2-5 cm ² .

Preferably, the skin penetrating elements are hollow needles, each having an axial channel and an inclined, tapering external tip for piercing the skin of the individual/patient. The skin penetrating elements are arranged in a hole in the fixed carrier in such a way that a solution can flow from the active substance container through the axial channel of the hollow needle. The skin penetrating elements can be fastened in the opening of the fixed carrier by means of a suitable adhesive or by means of a press fit. In an alternative embodiment, the miniature skin penetrating elements can be integrally formed with the fixed carrier. Preferably, each skin penetrating element has an inclined, tapering external tip and an axial channel in order to establish a fluid connection between the active substance container and the intradermal site in the patient's skin.

The skin-penetrating element preferably has a length suitable for achieving the desired skin penetration depth. The length and thickness of the skin-penetrating element are selected based on the solution to be administered, the thickness of the skin, and the target area where the MNS is to be placed. In embodiments of the present invention, the skin-penetrating element may be a microneedle, microtube, solid or hollow needle, lancet, or the like. In a preferred embodiment, the skin-penetrating element is a hollow needle or hollow cannula made of stainless steel. The needle is approximately 24 gauge to 50 gauge, preferably approximately 30 gauge to approximately 36 gauge, and in the most preferred embodiment, approximately 34 gauge. Smaller needles penetrate the skin surface more easily than larger needles and are generally preferred. The needle is positioned in the MNS on the underside of the frame to provide an effective length of approximately 50 microns to approximately 5000 microns. In another embodiment, the needle has an effective length of approximately 500 microns to approximately 3000 microns. In other embodiments, the needle may have an effective length ranging from approximately 1000 microns to 2000 microns. Typically, the needle has an effective length of about 500 microns to about 1000 microns.

The components of the MNS, in particular the cover element, the frame, the base plate, the optional carrier material of the MNA, and/or the optional carrier material of the adhesive patch, can be made of a suitable plastic material. Typically, non-reactive, inert, well-tolerated, biocompatible plastic materials, for example those tested in dermatology, are used for this purpose. Suitable plastic materials include polyethylene, polypropylene, polyester, polyamide, polycarbonate, and copolymers thereof.

In an MNA, the skin-penetrating elements are formed into an array (i.e., an arrangement) in the form of rows and columns spaced apart from one another. In this context, an MNA may include one, at least two, a plurality, or a large number of skin-penetrating elements, for example, 10-1,000,000, preferably 50-100,000, and particularly preferably 100-10,000 skin-penetrating elements. An MNA may be manufactured, for example, from a silicon wafer that has been machined and etched to form the individual needles. In alternative embodiments, an MNA may be manufactured from stainless steel, tungsten steel, and alloys including nickel, molybdenum, chromium, cobalt, and titanium. In other embodiments, an MNA may be manufactured from ceramic materials, glass, polymers, and other non-reactive materials.

The skin penetration element array is typically arranged in rows and columns, but the skin penetration elements can be arranged in other suitable patterns. Preferably, the skin penetration elements are spaced apart from each other to a sufficient degree so that each skin penetration element can penetrate the skin to a depth substantially uniform across the entire array without interfering with each other. The preferred penetration depth of the needle is derived from the stratum corneum, which is preferably pierced completely or almost completely. In a preferred embodiment, the skin penetration elements penetrate the skin to a uniform depth and/or pierce the skin to allow for administration of a solution at a selected skin depth and to reduce the risk of leakage when administering a substance. The number of skin penetration elements in the array can vary according to the size of the skin penetration element, the substance to be administered, and the penetration depth.

The MNS according to the present invention can include one or more active substance containers. These active substance containers can have different volumes or be designed to be filled with different volumes of solution. The volume is selected based on the (active) substance or medicament to be administered, the selected formulation, dosage, treatment regimen, and other factors. The duration of delivery depends on the volume of the active substance container, the (active) substance to be administered, the selected formulation, dosage, treatment regimen, the selected MNA (e.g., the inner diameter of the skin-penetrating element), the skin condition in the area involved, and other factors. For example, the MNS is suitable for a delivery period of 0.5 minutes to 10 days, preferably 5 minutes to 1 day, preferably 1 to 5 hours, and particularly preferably approximately 2 hours. During this time, the MNS according to the present invention ensures a constant force lock between the skin and the MNA, without the need for additional compression of the needle.

BRIEF DESCRIPTION OF THE DRAWINGS

An embodiment of the MNS according to the present invention is explained by way of example using the following figures and examples.

FIG1 shows an exploded view of the components of the MNS according to the invention. In the exemplary embodiment shown, the entire system has a maximum diameter of 50 mm with the component fixing adhesive and protective film and an overall height of approximately 7 mm.

FIG. 2 shows a cross-sectional view of the MNS in the storage position.

Figure 3: A cross-sectional view showing the MNS in the delivery position.

DETAILED DESCRIPTION

Example 1: Based on the structure of the MNS in Figure 1:

The active substance solution is contained in a blow-fill-seal container 2, which is housed in a frame 3. An MNA 4 is connected to the underside of the frame 3. The frame 3 is movably mounted in a base plate 5. The frame 3 and base plate 5 can be moved linearly relative to each other. Latching hooks on the frame 4 limit the travel and prevent rotational movement. The base plate 5 is securely connected to a fixing tape 6 and protected by a protective film 7 before use. The lid 3 and base plate 5 are movably connected via threads.

Example 2: Use of delivery agencies:

Starting from the sectional view of the MNS in the storage position according to FIG. 2 , the protective film 7 is first removed and the MNS is fixed to the skin by means of the fixing adhesive tape 6 .

By rotating the cover 3 by a quarter of a thread turn about the base plate 5 , the blow-fill-seal container, the frame 3 and the MNA 4 are moved linearly toward the base plate 5 and the active substance container 2 is opened by the piercing element (opening element 8 ) on the base plate 5 .

Claims (19)

1. A microneedle system for intradermal delivery, the microneedle system comprising: i.) A covering element (1) above the active substance container (2), wherein the active substance container (2) is housed in a frame (3) having a microneedle array (4); and ii.) substrate (5), wherein the substrate (5) has an opening for receiving a microneedle array (4), the substrate (5) has a surrounding protrusion offset inward relative to the edge of the substrate, the protrusion surrounding the opening, and the substrate has a thread on the outside of the surrounding protrusion that is complementary to the thread of the cover element (1), and the cover element (1) and the substrate (5) are movably connected to each other by the thread. iii.) The substrate (5) is completely or partially connected to the fixing tape (6); and iv.) The frame (3) and the substrate (5) are movably connected to each other, wherein the frame (3) having the microneedle array (4) is linearly movable toward the opening of the substrate (5) and the substrate (5) has at least one opening element (8) for opening the effective substance container (2). 2. The microneedle system according to claim 1, characterized in that the frame (3) has one or more locking hooks (9) that can be engaged into a gap (10) in the substrate (5). 3. The microneedle system according to claim 1 or 2, characterized in that the covering element (1) has a circumferential thread on the bottom side that is complementary to the thread of the substrate (5) on the outside of the circumferential protrusion. 4. The microneedle system according to claim 1 or 2, characterized in that the covering element (1) has one or more marking portions that specify how the microneedle system can be transferred from a storage location to a delivery location. 5. The microneedle system according to claim 1 or 2, characterized in that the fixing tape (6) is protected by a protective film (7). 6. The microneedle system according to claim 1 or 2, characterized in that the diameter of the microneedle system is at least 10 mm. 7. The microneedle system according to claim 1 or 2, characterized in that the diameter of the microneedle system is at least 25 mm. 8. The microneedle system according to claim 1 or 2, characterized in that the diameter of the microneedle system is at least 50 mm. 9. The microneedle system according to claim 1 or 2, wherein the height of the microneedle system is a maximum of 30 mm. 10. The microneedle system according to claim 1 or 2, wherein the height of the microneedle system is a maximum of 20 mm. 11. The microneedle system according to claim 1 or 2, wherein the height of the microneedle system is a maximum of 10 mm. 12. The microneedle system according to claim 1 or 2, characterized in that the effective substance container (2) is a blow-fill-seal container or a disposable container. 13. The microneedle system according to claim 1 or 2, characterized in that the effective substance container (2) comprises one or more substances. 14. The microneedle system according to claim 1 or 2, characterized in that the active substance container (2) comprises one or more pharmaceutical agents. 15. The microneedle system according to claim 1 or 2, characterized in that the active substance container (2) comprises one or more active substances. 16. The microneedle system according to claim 1 or 2, characterized in that the effective substance container (2) comprises one or more solutions. 17. The microneedle system according to claim 1 or 2, characterized in that the active substance container (2) comprises one or more liquid formulations. 18. A method for manufacturing a microneedle system according to any one of claims 1 to 17, wherein a) Provide effective material containers (2); b) Provide a microneedle array (4); and c) Connect the active material container (2) and the microneedle array (4) with the frame (3), the substrate (5) and the fixing tape (6) to form a microneedle system; The feature is that the covering element (1) and the substrate (5) are movably connected to each other by threads, and the effective substance container (2) is opened by the opening element (8) by rotating the covering element (1) relative to the substrate (5). 19. The method according to claim 18, characterized in that an effective material container is provided by means of manufacturing using a blown-sealing process.