Intradermal active ingredient delivery system

Abstract

The present invention relates to an intradermal active ingredient delivery system comprising an extraction device (10) having, interstitial fluid extraction, a plurality of hollow needles (30). A delivery device (14) is fluidly connected to the extraction device (10). The delivery device (14) is further fluidly connected to an active ingredient reservoir (16). The delivery device (14) is fluidly connected to a delivery device (26) for delivering the interstitial fluid containing the active ingredient. The delivery device (26) preferably has hollow needles (30) for delivering a liquid mixture intradermally.

Description

Technical Field

[0001] The present invention relates to an intradermal active ingredient delivery system that can deliver an active ingredient, particularly a medical active ingredient, intradermally to a patient.

Summary of the Invention

Problems to be Solved by the Invention

[0002] Transdermal therapeutic systems (TTS) are known for the delivery of active ingredients. For example, a transdermal patch can be applied to a patient's skin. The stored active ingredient is continuously absorbed through the skin. This form of administration, unlike an injection, has the advantage of being painless for the patient and allowing the drug to be administered over a longer period. However, the disadvantage is that drug regulation can only be done by removing or replacing the TTS. In particular, it is difficult to clearly determine the amount delivered to the patient.

[0003] Furthermore, it is known to administer an active ingredient via a microneedle. Here, the active ingredient is delivered to the dermis of the skin via a plurality of needles. Thus, since the delivery is performed in the outer layer of the skin where there are no nerves, this active ingredient delivery is also painless for the patient. In this context, needles configured as hollow needles are known, and the active ingredient is contained in the hollow needle and delivered through the needle opening at the tip of the needle. Furthermore, microneedles composed of a material that dissolves in the skin are known. In the case of microneedles, the active ingredient is incorporated into the needle material. There is also a problem with microneedles in that it is difficult to determine the exact amount of the active ingredient delivered to the patient, for example because the needle may not completely dissolve or may break.

[0004] An object of the present invention is to provide an intradermal active ingredient delivery system that makes it easier to determine the amount of the active ingredient delivered to a patient.

Means for Solving the Problems

[0005] According to the present invention, this objective is achieved by an intradermal active ingredient delivery system having the features of claim 1.

[0006] The intradermal active ingredient delivery system according to the present invention comprises an extraction device for extracting interstitial fluid. The extraction device preferably has a plurality of microneedles configured particularly as hollow needles. A transport device is fluidically connected to the extraction device. In particular, the transport device is used to draw interstitial fluid from the patient's tissue. Furthermore, the intradermal active ingredient delivery system comprises an active ingredient reservoir. The active ingredient reservoir is fluidly connected to the transport device. The active ingredient reservoir contains the active ingredient to be administered to the patient in solid and / or powder and / or liquid form. According to the present invention, a delivery device is further fluidly connected to the transport device. The delivery device is used for intradermal delivery of a mixture of the active ingredient and the extracted interstitial fluid, or for delivery of interstitial fluid rich in the active ingredient to the patient. The delivery device preferably has microneedles configured particularly as hollow needles.

[0007] Therefore, the intradermal drug delivery system according to the present invention makes it possible to administer a clearly defined amount of the active ingredient to the patient. Here, the active ingredient is concentrated in the active ingredient reservoir and is preferably diluted or dissolved in interstitial fluid.

[0008] In a particularly preferred further embodiment of the present invention, the extraction device has a plurality of microneedles. In a preferred embodiment, at least 4 needles / cm per microneedle array 2 Preferably at least 50 stitches / cm 2 Particularly preferably at least 100 needles / cm 2 It is preferable that one or more microneedle arrays having the following characteristics are provided.

[0009] In particular, when the extraction device has multiple microneedle arrays, it is preferable that the microneedle arrays are arranged parallel to each other and connected to the transport device via separate channels. Furthermore, it is possible to arrange multiple extraction devices in a circular pattern around the transport device at equal distances from it. Providing multiple microneedle arrays has the advantage that each microneedle array can be connected to the channel with a small cross-section, thus enabling the realization of a very compact intradermal active ingredient system. Providing multiple microneedle arrays has the further advantage that sufficient liquid supply is always ensured. In particular, in association with a liquid transport device having a pump with increased stroke and / or an increased number of strokes, it is possible to realize a liquid suitable for extraction.

[0010] The transport device preferably has at least one pump. The pump can be a diaphragm pump, etc., with a valve configured so that the liquid can only be transported in one direction. In particular, the diaphragm is provided at the inlet and outlet of the pump, respectively. This ensures that mixing with the active ingredient preferably takes place only within the pump or a space provided within the pump. In particular, dilution of the active ingredient without active delivery or administration is avoided. Furthermore, providing a diaphragm in the microneedle array has the advantage that the channel is always constantly filled with liquid or active ingredient solution, and backflow into the skin or chamber located in the pump is avoided. For example, the pump may be controlled by a piezoelectric actuator that causes a pressure change in the pump chamber to activate the delivery process. Delivery may further be performed by manually generated pressure in the corresponding chamber.

[0011] In a particularly preferred embodiment of the present invention, an active ingredient reservoir containing a liquid active ingredient is connected to the inlet of a transport device. Preferably, an extraction device is further connected to the inlet of the transport device, particularly to the inlet of a pump. While one inlet is preferred to miniaturize the active ingredient delivery system, the pump may have one or more inlets.

[0012] In this preferred embodiment of the present invention, a liquid active ingredient and interstitial fluid can be simultaneously drawn in by a transport device. Here, it is preferable that the two liquids are mixed. Optionally, a mixing chamber for mixing the two liquids may be provided, particularly within the transport device. The mixing chamber may be a pump chamber, particularly a diaphragm pump chamber. The two mixed liquids are then preferably delivered by the transport device to the dermis of the skin via a delivery device connected to the transport device.

[0013] In a more preferred embodiment, the active ingredient reservoir is connected to the outlet of a conveying device, particularly the outlet of the pump of the conveying device. Here, the active ingredient reservoir may contain a liquid, solid, or powdered active ingredient. In this preferred embodiment, the conveying device draws in interstitial fluid, preferably via an extraction device, and the interstitial fluid is conveyed to the active ingredient reservoir. In this embodiment, the active ingredient reservoir simultaneously functions as a mixing chamber, or mixing or dissolution of the active ingredient takes place in the active ingredient reservoir, respectively.

[0014] In a preferred embodiment, the transport device may have multiple pumps, particularly two pumps. In this embodiment, the active ingredient reservoir can be located between the two pumps. Thus, a pump located upstream of the active ingredient reservoir in the direction of flow draws in interstitial fluid and then delivers it to the active ingredient reservoir. A pump located downstream of the active ingredient reservoir in the direction of flow draws in interstitial fluid rich in the active ingredient and transports it to the delivery device.

[0015] In preferred embodiments, a delivery device having multiple hollow needles is directly or indirectly connected to a transport device, particularly via one or more channels.

[0016] In a more preferred embodiment, the delivery device may be directly or indirectly connected to the active ingredient chamber or mixing chamber, particularly via a channel. In this embodiment, it is preferable that the pump transports the drawn-in interstitial fluid through the active ingredient reservoir and mixing chamber. Here, the interstitial fluid absorbs the active ingredient so that the interstitial fluid rich in the active ingredient reaches the delivery device.

[0017] In a further preferred embodiment of the intradermal active ingredient delivery system according to the present invention, an active ingredient reservoir or a further active ingredient reservoir is integrated into the delivery device. Therefore, mixing of the active ingredient contained in such an active ingredient reservoir with interstitial fluid occurs immediately before delivery to the patient. In particular, the active ingredient may be directly contained in a hollow needle.

[0018] Optionally, the intradermal active ingredient delivery system may include a mixing chamber. Here, a mixing element, such as a piezoelectric actuator, may act on the mixing chamber to ensure thorough mixing of the active ingredient with the interstitial fluid. This further ensures the complete dissolution of the active ingredient, whether solid or powdered. Depending on the embodiment, the mixing chamber may be omitted or integrated, for example, with a transport device, active ingredient reservoir, and / or delivery device.

[0019] The active ingredient delivery system according to the present invention is small enough that the entire system can be easily and reliably placed on the patient's skin, just a few centimeters in size. 2In addition to the small configuration at the contact surface with the skin, the active ingredient delivery system can be further realized, for example, in the form of a wristband that wraps around the arm. What is particularly important for realizing the active ingredient delivery system according to the present invention is the flexibility of the system and the penetration depth of the needle. To achieve the required flexibility, the system is always very thin and thus always remains in contact with the entire surface of the skin even while moving. On the other hand, the patient's freedom of movement is only slightly restricted. Since the needle has a length that penetrates only into the dermis of the skin, contact with the nerves that may cause pain is avoided.

[0020] Hereinafter, the present invention will be described in more detail by preferred embodiments with reference to the accompanying drawings.

Brief Description of the Drawings

[0021] [Figure 1] It is a diagram showing a preferred embodiment of the intradermal active ingredient delivery system according to the present invention. [Figure 2] It is a diagram showing a preferred embodiment of the intradermal active ingredient delivery system according to the present invention. [Figure 3] It is a diagram showing a preferred embodiment of the intradermal active ingredient delivery system according to the present invention. [Figure 4] It is a diagram showing a preferred embodiment of the intradermal active ingredient delivery system according to the present invention. [Figure 5] It is a very simplified cross-sectional schematic view showing an extraction device or a delivery device. [Figure 6] It is a very simplified schematic view of a conveyance device in the form of a diaphragm pump.

Modes for Carrying Out the Invention

[0022] In various embodiments of the intradermal active ingredient delivery system according to the present invention shown in FIGS. 1 to 4, the same and similar components are assigned the same reference numerals.

[0023] In the embodiment shown in FIG. 1, an extraction device 10 having two microarrays including a plurality of hollow needles is provided. The two microarrays 10 are respectively connected to a pump or a conveyance device 14 via channels 12. An active ingredient reservoir 16 in which a liquid active ingredient is stored is further connected to the pump 14 via a channel 18. In the illustrated exemplary embodiment, all three channels 12, 18 are integrated upstream of the pump 14 and are connected to a single pump inlet 20.

[0024] In the illustrated exemplary embodiment, the pump 14 has two pump outlets 22 respectively connected to channels 24. Alternatively, the pump 14 may have one outlet connected to two channels 24. The channels 24 are connected to a delivery device 26. The delivery device 26 is a microarray having a plurality of hollow needles.

[0025] FIG. 5 schematically shows a cross section of a microarray that can be the microarray 10 of the extraction device or the microarray 26 of the delivery device. The microarrays 10, 26 have a plurality of hollow needles 28 having openings 30 at their tips. When the microarray is an extraction device, interstitial fluid can be drawn through the openings 30. When the microarray is a delivery device, interstitial fluid rich in the active ingredient is delivered to the patient through the openings 30. The hollow needles 28 are connected to channels 32 on the opposite side of the openings 30. The channels 32 preferably extend across the entire surface of the microarray and are connected to the channel 12 or the channel 24.

[0026] The intradermal active ingredient delivery system shown in Figure 1 allows interstitial fluid to be drawn in by a pump through the hollow needles of the microarray 10 via channels 12. Simultaneously, liquid active ingredients are drawn in from the active ingredient reservoir 16. The two liquids are mixed in the pump 14 or in the region where channels 12 and 18 are already merged. After closing the pump inlet 20, the pump 14 can be used to deliver the fluid mixture through two outlets 22 and channels 24 to the microneedles 30 of the delivery device 26 for injection into the patient.

[0027] For example, pump 14 may be a diaphragm pump schematically shown in Figure 6. In the state of pump 14 shown in Figure 6, both the outlet 22 and the inlet 20 are closed. Pump 14 is in an unloaded state. For example, force can be applied to the pump cavity 34 by a piezoelectric element (not shown). When negative pressure or vacuum is created in the pump cavity 34, the inlet 20 opens, and liquid can flow into the cavity 34 in the direction of arrow 36. To transport the liquid out of the pump cavity 34, pressure is applied to the cavity 34 again, for example, using a piezoelectric element. For this reason, the inlet 20 closes as shown in the lower part of Figure 6. Simultaneously, the outlet 22 opens so that the liquid flows in the direction of arrow 38.

[0028] According to another embodiment shown in Figure 2, the two microarrays 10 of the extraction device are also connected to the first pump 14 via channels 12. In this exemplary embodiment, the outlet 22 of the first pump 14 is connected to the active ingredient reservoir 16. The active ingredient reservoir 16 is then connected to the second pump 40 via an inlet 42 in the direction of flow, i.e., to the right in Figure 2. The outlet 44 of the second pump 40 is connected to the delivery device 26 via channels 24.

[0029] Accordingly, in the exemplary embodiment shown in Figure 2, the first pump 14 draws in interstitial fluid via the extraction device 10 and delivers it to the active ingredient reservoir 16. The active ingredient reservoir 16 contains the active ingredient in liquid, solid, or powder form. Accordingly, in the exemplary embodiment shown in Figure 2, the active ingredient reservoir 16 also functions as a mixing chamber. The second pump 40 draws in the liquid mixture from the active ingredient reservoir 16 and delivers it via the channel 24 to the delivery device 26.

[0030] The exemplary embodiment shown in Figure 3 is substantially equivalent to the exemplary embodiment shown in Figure 2, except that a second pump is not provided. The interstitial fluid drawn in by pump 14 is delivered by pump 14 through the active ingredient reservoir 16, where the interstitial fluid absorbs the active ingredient. The pump 14 then continues to deliver the liquid mixture directly through channel 24 to the delivery device 26.

[0031] The embodiment shown in Figure 4 is substantially equivalent to the embodiment shown in Figure 1, except that the active ingredient reservoir 16 is not connected to the pump inlet 20. Rather, in this exemplary embodiment, the active ingredient reservoir is integrated with the delivery device 26. For example, the active ingredient is contained in the hollow needle 30 and / or channel region 32 (Figure 5) and is absorbed into the interstitial fluid immediately before injection.

Claims

1. An extraction device for extracting interstitial fluid, A transport device fluidly connected to the extraction device for transporting interstitial fluid, The active ingredient reservoir is fluidly connected to the aforementioned transport device, A delivery device fluidly connected to the transport device for intradermal delivery of interstitial fluid containing the active ingredient and An intradermal active ingredient delivery system equipped with this system.

2. The extraction device has microneedles, and in particular, at least 4 needles / cm. 2 , especially at least 50 stitches / cm 2 , especially at least 100 stitches / cm 2 The intradermal active ingredient delivery system according to claim 1, comprising a microarray having the following characteristics.

3. The extraction device in particular has at least 4 needles / cm 2 , especially at least 50 stitches / cm 2 , especially at least 100 stitches / cm 2 The intradermal active ingredient delivery system according to claim 2, comprising two microarrays, each having a different characteristic.

4. The intradermal active ingredient delivery system according to any one of claims 1 to 3, wherein the transport device has at least one pump.

5. An intradermal active ingredient delivery system according to any one of claims 1 to 4, wherein a solid, liquid, or powdered active ingredient is stored in the active ingredient reservoir.

6. The intradermal active ingredient delivery system according to any one of claims 1 to 5, wherein the active ingredient reservoir containing the liquid active ingredient and the extraction device are connected to the inlet of the transport device, particularly the pump inlet.

7. The intradermal active ingredient delivery system according to claim 6, wherein the active ingredient reservoir and the extraction device are connected to the inlet of the transport device, particularly the pump inlet, so that the active ingredient and the initial liquid are drawn in simultaneously.

8. The intradermal active ingredient delivery system according to any one of claims 1 to 5, wherein the active ingredient reservoir is connected to the outlet of the transport device, particularly the pump outlet.

9. The intradermal active ingredient delivery system according to any one of claims 1 to 8, wherein the transport device has two pumps, and the active ingredient reservoir is located between the two pumps.

10. The delivery device has micro needles, particularly at least 4 needles / cm 2 , particularly at least 50 needles / cm 2 , particularly at least 100 needles / cm 2 and has a microarray having the same, the intradermal active ingredient delivery system according to any one of claims 1 to 9.

11. The intradermal active ingredient delivery system according to any one of claims 1 to 10, wherein the delivery device is connected to the outlet of the transport device, particularly to the pump outlet.

12. The intradermal active ingredient delivery system according to any one of claims 1 to 11, wherein the active ingredient reservoir is integrated with the delivery device, and the active ingredient is contained in the needle of the delivery device.

13. An intradermal active ingredient delivery system according to any one of claims 1 to 12, comprising a mixing chamber for mixing interstitial fluid and an active ingredient.

14. The intradermal active ingredient delivery system according to claim 13, wherein the active ingredient reservoir forms the mixing chamber.

15. The intradermal active ingredient delivery system according to claim 13 or 14, wherein the mixing chamber is integrated with the transport device.

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