Patch delivery device with skin contact sensor

The present invention relates to a drug delivery system for delivering, administering, injecting, injecting, and / or dispensing a liquid containing a drug or active ingredient. The present invention is a development of a patch delivery device having means for detecting proper adhesion to a patient's skin.

There are various diseases that require regular treatment by subcutaneous, intradermal, or intramuscular administration of the drug. Accordingly, a number of drug delivery devices have been developed to assist patients in delivering the correct amount of drug in a convenient and controllable manner during the self-administration process. Delivery devices include injection devices that are removed from the injection site after each dosing treatment event or drug delivery process, and infusion or pumping devices that have a fluid channel into the patient's body that will continue to be used for extended periods of time.

Disposable, single-use injection devices include self-injectors and patch injection devices for delivering fixed or variable doses of drug from a container through a cannula or needle. Neither the cannula or the needle nor the container is intended to be replaced or manipulated by the user of the self-injection device or patch injection device. A patch injection device, or a ready-to-use pre-filled Wearable Bolus Injector (WBI) or On-Body Delivery System (OBDS), provides an imminent extended single dose injection. Attached, adhered, patched, or adhered to the patient's skin, taking into account that it will take at least 30 seconds to complete. Patch injection devices have been developed for the treatment of diseases such as cardiovascular disease, autoimmune disease, or cancer, containing injectable liquids with high viscosity, and / or up to 5 ml or Suitable for delivery of drugs that will be administered in single dose volumes as large as 10 ml.

Infusion devices include pump devices for continuous delivery of normal or basal doses (basal doses) of drug through a cannula that remains within the injection site for extended periods of up to 3 days. Disposable, single-use or semi-disposable infusion devices are worn and adhered to the patient's skin for continuous infusion and delivery of multiple adjustable doses that are superposed at the basal rate. Includes patch, or patched, patched injection pumps or wearable basal injection devices. Disposable parts include at least skin contact areas and cannulas that are not intended to be replaced and are discarded after being used for a period of 30 minutes to several days. Patch pumps have remote controls and are worn directly on the body, thus eliminating the need for long catheters and direct pump access and are being used preliminaryly in the treatment of diabetes.

WO2006067217A2 relates to a skin-worn medical device equipped with sensor means adapted to detect properties that can indicate a problematic situation related to the interface between the patient and the device. The device further comprises a circuit for processing the signal from the sensor means and for indicating that a predetermined situation associated with the interface between the patient and the device has been detected. The sensor means includes first and second capacitor plates placed laterally adjacent to the mounting surface, and a capacitive circuit is established when the mounting surface is placed on the skin surface.

US Patent Application Publication No. 2017/259015 comprises an adhesive surface for adhesion to the skin and multiple capacitive, resistant, or temperature contact sensors located at discrete locations on the contact surface of the device. Disclosed for single-use skin patch-type high-capacity or bolus injection devices. Multiple contact sensors are configured to output a signal indicating the degree of separation of the device from the injection site, which separation is due to deterioration of the adhesive layer that attaches the device to the injection site, which would not be noticed without this signal. Can occur. Alarm and control functions alert the user based on the signal received from the sensor, delaying or even interrupting the injection if the degree of separation jeopardizes a safer injection. be. A contact sensor is placed around a hole in the bottom of the device through which the delivery cannula protrudes into the patient's tissue during use of the device and delivery of the drug.

The EP3260151A1 has an adhesive patch with a bottom housing, a capacitance sensor, a first adhesive layer to contact the bottom housing and a second adhesive layer to contact the target, and a second before use of the device. Disclosed are patch devices with a stripping liner made of coated paper or a thin plastic sheet covering the adhesive layer of the. The conductive element of the sensor is embedded in the adhesive patch, integrated into the bottom housing, or otherwise attached to the patch or bottom housing. The peel liner or peel-off foil prevents unintended adhesion and contamination of the second adhesive layer. Detachment liner removal can be combined with other functionality such as switching or activating electrical circuits, or removing sterile barriers in fluid or cannula passages.

WO2008 / 068695A1 discloses a stripping liner for an ECG monitoring device that can be used for patient investigation prior to removal of any stripping liner moiety. The peel liner has an electrode area that aligns with and covers the electrodes of the ECG monitoring device. The electrode region is formed of a conductive material such as metal foil and extends from one side of the peel liner to the other with the same lateral elongation as the coated electrode. The electrode region provides a conductive path, which allows the ECG signal to be detected by the ECG monitoring device prior to any exfoliation liner removal.

In this context, the terms "substance", "drug", "drug", and "pharmaceutical" include any fluid medical formulation suitable for controlled administration through means such as, for example, a cannula or a hollow needle. , Also to be understood to include liquids, solutions, gels, or microsuspensions containing one or more medically active ingredients. The agent can be a composition comprising a single active ingredient, or a premixed or simultaneously formulated composition using two or more active ingredients present in a single container. Pharmaceuticals are based on peptides (eg, insulin, insulin-containing drugs, GLP-1 -containing drugs, or derivatives or similar formulations), proteins and hormones, active ingredients derived from or harvested from biological sources, hormones or genes. Not only drugs such as active ingredients, nutritional preparations, enzymes, and other substances both in solid (suspended) or liquid form, but also polysaccharides, vaccines, DNA, RNA, oligonucleotides, antibodies. , Or an antibody portion, as well as suitable basic, auxiliary, and carrier substances.

<p>An object of the present invention is to improve the safe use of the patch delivery device and to remove the peeling liner covering the patient-side mounting layer or adhesive layer before the attachment of the mounting layer or adhesive layer to the patient's skin. To identify. This object is achieved by the patch delivery device and sensor patch described in the independent claims. A preferred embodiment is evident from the dependent claims.</p>

<p>According to the present invention, a patch delivery device such as a patch pump or patch syringe attaches the bottom housing portion or base plate, a delivery element or cannula for subcutaneous delivery of liquid to the patient, and the bottom housing portion to the patient's skin. An adhesive patch for, and a capacitance sensor having an electrode configuration that includes multiple skin contact sensitive electrodes as separate areas that are independently connected to or interface with the capacitance measuring unit of the device. Includes a peel liner that coats and protects the patient-side adhesive layer of the adhesive patch before adhering to the patient's skin. The stripping liner comprises a conductive region that extends or covers at least a portion of the electrode configuration of the capacitive sensor before it is removed from the adhesive patch. Preferably, the conductive region is provided on and / or embedded in the non-conductive layer of the stripping liner and is printed, coated or glued, in particular on the surface of the non-conductive layer. , Or be added in another way.</p><p>The plurality of electrodes are arranged laterally offset from each other in an electrode layer parallel to the skin contact surface of the bottom housing portion. The non-conductive layer is made of a non-conductive material such as a piece of kraft paper, a thin plastic sheet, or a polymer film so that the conductive region does not provide a conductive path between the two surfaces of the stripping liner. In its entirety. By providing a conductive region in the peel liner that is electrically insulated from the sensor electrode when covering the adhesive layer on the patient side in the intended orientation or the original orientation, it is possible to discriminate in the capacitance reaction of the sensor electrode when the peel liner is removed. It causes change and thus allows the device to automatically detect the removal of the peel liner. As an additional advantage, a larger relative change in capacitance is observed when attaching the device without the detachment liner to the injection site compared to the previous test approach of the injection site with the detachment liner still in place. can. In addition to, or in addition to, the use of capacitive electrodes to determine degradation in adhesion to human skin, patch delivery devices according to the invention already utilize electrode signals prior to device adhesion. Therefore, test or dummy skin contact can be identified and inadvertent triggers or other operational errors are prevented.</p><p>In a preferred variant of the invention, the capacitance sensor includes an open electrode and an auxiliary electrode, which are adjacent to or adjacent to each half of the skin contact area of the bottom housing. They are placed facing each other, and preferably separated from each other by at least half the maximum linear dimension of the bottom housing portion. The conductive exfoliation liner region extends at least partially over both corresponding electrode regions. In addition to confirming perfect adhesion and / or no partial separation, such electrode configurations provide stripping liner removal or peel-off in one direction between the two electrodes through time-resolved capacitance tracking. Allows to be detected.</p><p>In a preferred embodiment of the invention, the capacitance sensor comprises a first aperture electrode and a second aperture electrode located on either side of the hole in the adhesive patch corresponding to the location of the delivery element, the conductive region of the peel liner. Extends over the electrode area of both open electrodes. Preferably, the conductive region extends substantially over the entire surface region of the non-conductive layer of the stripping liner and / or the skin contact surface of the bottom housing portion.</p><p>In an advantageous embodiment of the invention, the capacitance sensor comprises a first aperture electrode and a second aperture electrode, when the stripping liner is mounted on the sensor electrode in the intended or original configuration. The conductive region of the stripping liner covers the two corresponding electrode regions in different ranges or degrees or proportions. In the most asymmetrical coating, the first aperture electrode region is entirely covered or hidden by the conductive region, while the second aperture electrode region is completely uncovered or unshielded. Such distinct coating results in different capacitive reactions from the two electrodes during stripping liner removal, which allows the identification of stripping liner removal behavior in real time prior to device attachment. To. The difference in the response signal is most noticeable in the most asymmetric cases described above, while covering half of both electrode regions, for example, is unlikely to result in a distinguishable capacitance change. Different characteristic response signals are also present in the case of test prior to exfoliation liner removal or dummy patient skin approach.</p><p>In a further preferred embodiment, the patch drug delivery device is a patch injection device or a patch injection device for delivering a single dose or bolus dose volume from a container through a single use cannula in an injection process that takes at least 30 seconds and preferably 5-30 minutes. It is a wearable bolus syringe. The patch injection device is at least 1, preferably at least 15, and most preferably at least 50 cP (0.050 kgm).^-1s^-1) Was developed for injectable liquids with high viscosity. Alternatively, the patch drug delivery device may be a basal-type patch infusion pump device. The present invention may also be applied to an infusion set supporting a cannula connected to a non-patch pump device via a flexible catheter tube, and adhesion of the infusion set to the patient's skin must be monitored as well. For this reason, peeling liner removal shall be confirmed prior to needle insertion.</p><p>In the next preferred embodiment, at least the sensor electrodes of the capacitive sensor are, or are embedded in, a portion of an adhesive patch and, as such, are redesigned or shifted without fitting the housing of the device. Can be done. Alternatively, the sensor electrodes are integrated within the bottom housing portion of the device, making it easy to connect the electrodes to the capacitance measuring unit.</p><p>INDUSTRIAL APPLICABILITY According to the present invention, a sensor patch is provided for a patch delivery device having a bottom housing portion and a delivery element for subcutaneous delivery of a liquid to a patient. The sensor patch is adapted to be integrated into or printed on the adhesive patch and connected to the capacitance measuring unit of the delivery device with an adhesive patch for adhesion to the bottom housing section. It is equipped with a capacitance sensor having a plurality of electrodes. The sensor patch further comprises a peel liner, which includes a conductive region and covers the patient side or skin contact layer of the adhesive patch.</p><p>In an advantageous variant of the sensor patch, the patient side layer of the adhesive patch is a skin adhesive layer for adhering the sensor patch to the patient's skin. Alternatively, skin contact places the device in this position by attaching or attaching a device with a sensor patch to the patient's skin, and by wrapping a non-adhesive bandage, belt, or string tightly around the patient and device. Can be established by fixing to.</p><p>The subject matter of the present invention is described in more detail in the text below with reference to preferred exemplary embodiments exemplified in the accompanying drawings.</p>

<figref num="1">It is a figure which shows the side surface and the top surface of a patch delivery device.</figref><figref num="2">It is a figure which describes the exploded view of a patch delivery device.</figref><figref num="3">It is a figure which shows the electrode arrangement and the peeling liner of 1st Embodiment.</figref><figref num="4">It is a figure which shows the electrode arrangement and the peeling liner of 2nd Embodiment.</figref><figref num="5">It is a figure which shows the three self-capacitance signals of the electrode arrangement of FIG.</figref>

The reference codes used in the drawings and their main meanings are listed in summary form within the description of the code. As a rule, the same parts carry the same reference numerals in the drawings.

FIG. 1 shows a cover housing 10 including a window 11 for viewing the cartridge, a bottom housing or base plate 12, a release button 13 for activating the device and / or initiating injection, and a light indicator such as an LED. Includes side view (top half) and top view (bottom half) of a patch delivery device comprising housing 1 with 14 and. The patient-facing side or skin contact area of the bottom housing will be adhered or adhered to the patient's skin by an adhesive patch, and the detachable liner lid 310 of this adhesive patch extends laterally beyond the skin contact area. .. Exemplary subassemblies and components of the patch delivery device are a cartridge cage for holding the cartridge containing the liquid drug that will be released by the movable piston and a needle for inserting the cannula into the patient's skin. It includes an insertion mechanism, a fluid path for connecting the cannula to the cartridge, and a driving means for discharging the liquid and / or driving the needle insertion mechanism. These subassemblies are well described, for example, in EP3260151A1, and this disclosure is incorporated herein by reference in its entirety.

FIG. 2 is an exploded view showing the bottom housing portion 12, the capacitance sensor 2, the adhesive patch 30, the peeling liner or peel-off foil 31, and the auxiliary sticker or the adhesive foil 32. The adhesive patch 30 has a hole or passage 34, such as a puncture hole, that corresponds to the location of the cannula of the delivery device, and the cannula extends through this hole 34 during drug delivery. The capacitance sensor 2 comprises a conductive element that is embedded in, printed on, or otherwise adhered to an adhesive patch 30 to form a sensor patch. Alternatively, the capacitance sensor may be integrated within the bottom housing portion 12, printed on the patient-facing side of the bottom housing portion 12, or otherwise attached therein. The adhesive patch 30 typically attaches a device-side adhesive layer on both sides of the base layer to permanently attach the adhesive patch to the patient side of the delivery device, and a non-permanent adhesive patch to the patient's skin. Includes a multi-layer composite with a patient-side adhesive layer for. The adhesive patch may include additional layers, such as a shielding layer that protects the patch delivery device from electromagnetic fields or moisture. The peel liner is preferably made of coated paper or a thin plastic sheet to prevent unintended adhesion or contamination of the patient-side adhesive layer of the adhesive patch. The peeling liner has a lid (also called an ear or knob) 310 that extends laterally from the outer shape of the adhesive patch. The user can pinch the lid to easily remove the peel liner and thereby expose the patient-side adhesive layer. The bottom housing portion 12 has an opening as an outlet or inlet port for the cannula at a location corresponding to the hole 34, which opening is covered with a sterile cover or sterile barrier prior to needle insertion. An auxiliary sticker or adhesive foil 32 is provided to connect the peel liner 31 to the sterile cover, ensuring simultaneous removal of the peel liner and sterile cover. For that purpose, the peel liner may also include a passage through which the device-side adhesive portion of the auxiliary sticker contacts the sterile cover.

The activation of the device, even from a non-energized state, can be coupled to the cardboard box or flexible packaging of the delivery device that is removed via the button 13 or for the user to access the device. It can be done via a switch. Similarly, the strip liner 31 and especially the lid 310 are torn to a switch that can switch the power supply to a device operating state that connects to the control unit, or to a removable insulator that is located between the power supply and the control unit circuit. Can be connected in a difficult way. Alternatively, the delivery device may be activated or activated from a standby or low power consumption state in which the control unit continuously or continuously monitors the activation sensor. Specifically, for this purpose, RFID sensing circuits or electromagnetically actuated sensors that detect the removal of the stripping liner may be used.

The needle insertion mechanism for inserting the needle or cannula into the patient's skin additionally has a needle retracting function to pull the needle or cannula into the device before the device is removed from the injection site. obtain. The needle insertion mechanism first inserts the needle with a soft cannula surrounding the needle, and the needle is either retracted prior to delivery of the drug through the soft cannula, or, for example, a steel, hollow injection needle or A rigid cannula is either inserted into the tissue and used for subsequent delivery. The insertion mechanism for inserting the delivery element may be a mechanical spring mechanism. Alternatively, the insertion mechanism may include an electric motor and gear mechanism that causes the insertion of the insertion element into the user. Alternatively, the insertion mechanism can be a gas or fluid pressure operating mechanism, in which case the driving energy source is a reservoir of pressurized gas.

In any case, the initiation of drug delivery can only be performed after or as long as the device has been confirmed to adhere to the skin. Skin proximity, and thus the presumed adhesion of the delivery device, is conveniently detected by a capacitive sensor that measures the difference in capacitance between the non-skin adhesion state and the skin contact state of the delivery device. A preferred technique for detecting human skin is self-capacitance measurement, much like the capacitive sensing button solution on a touchpad. Capacitance sensors include conductive electrodes, traces, or pads that are placed in such a way as to create parasitic capacitance between each of the electrodes and the ground node. Since human skin has a small intrinsic capacitance and / or admittance to ground, the capacitance of parasitic capacitance is when the corresponding electrode is in contact with or in close proximity to the skin. And as long as it is, it will increase.

FIG. 3 illustrates a first embodiment of the invention using a first electrode arrangement of a capacitance sensor and a first peel liner. The capacitance sensor includes a first aperture electrode 20 and a second aperture electrode 21 located on either side of the circular hole or passage 34 of the adhesive patch. The hole corresponds to the location of the cannula of the delivery device, and the cannula extends through this hole during drug delivery. The two open electrodes are conductively connected via a corresponding trace to the sensor interface 24, which provides access to the capacitance measuring unit of the delivery device. If the sensor patch integrates the sensor electrode arrangement, this interface must provide reliable electrical contact, which can be established by spring-loaded contact pins within the bottom housing section. The first peel liner extends over the non-conductive layer or sheet 313 and the electrode regions of both the open electrodes 20 and 21, and substantially covers the entire region of the non-conductive layer 313 excluding the fringe region. Includes a first conductive region 311 to be covered.

In this embodiment, the signals provided by the two aperture electrodes are essentially identical. If the delivery device contacts the patient's skin with the detach liner still attached, the signal is somewhat diminished due to skin contact and the corresponding increase in self-capacitance. When the stripping liner containing the conductive region is removed, the signal value increases for both open electrodes following a discernible change in the capacitance reaction of the two electrodes. Subsequently, contact with the patient's skin for normal injection results in a simultaneous reduction in both electrode signals, which is clearly significantly greater than the test approach prior to removal of the exfoliated liner.

FIG. 4 illustrates a second embodiment of the invention using a second electrode arrangement (top) of the capacitance sensor and a matching second peel liner (bottom). The sensor includes three opening electrodes 20, 21, 22 that form a circular hole or passage corresponding to the location of the cannula of the delivery device, through which the cannula extends during drug delivery. The open electrode is placed adjacent to the first half of the two halves of the skin contact area, separated from each other by at least half the maximum linear dimension of the bottom housing. The auxiliary electrode 23 is provided adjacent to the second half region of the skin contact area of the bottom housing portion. All four open electrodes are conductively connected via a corresponding trace to the sensor interface 24, which provides access to the capacitance measuring unit of the delivery device. If the sensor patch integrates the sensor electrode arrangement, this interface must provide reliable electrical contact, which can be established by spring-loaded contact pins within the bottom housing section.

The second peel liner is shown superimposed on the second electrode configuration. The peel liner is a non-conductive layer or sheet 313, a first conductive region 311 adjacent to and covering the two open electrodes 21 and 22, and a second conductive region 311 adjacent to and covering the auxiliary electrode 23. Includes conductive regions 312 and. Both conductive regions 311, 312 are portions of the coating layer that are embedded in or printed on either side of the non-conductive layer 313 of the stripping liner and are electrostatic as will be apparent below. Capacitance Affects the capacitance of the sensor electrodes. The conductive region can take a different shape extending over at least a portion of the electrode configuration, and at least one electrode is preferably covered to a lesser extent than another electrode.

FIG. 5 depicts three measured signals 20', 21', 23 showing the self-capacitance of each of the three aforementioned electrodes 20, 21, 23 over time. The signal at electrode 22 is essentially equal to signal 21'and is therefore omitted. The three events are clearly distinguishable by the characteristic electrode signals. The first event (starting with T1) corresponds to a delivery device that approaches the patient's skin over a short period of time, such as the need to test whether the proposed injection site is not unpleasant for the patient. Such test or dummy contact is performed with the peel liner still attached and covering the patient-side adhesive layer of the adhesive patch attached to the contact side of the bottom housing portion. Due to skin contact, all signals are reduced, which corresponds to the increase in capacitance, and the signal 20'of the uncoated electrode is clearly larger than the other three signals. Shows a decline. The test contact sequence may be repeated to find a suitable injection site and is completed by removing the device from the injection site for exfoliation liner removal. The second event (starting with T2) is stripping liner removal, which results in an increase in signal values 21', 23' for the two previously coated electrodes, while on the uncoated electrode 20. The signal 20'remains essentially unchanged. A closer examination reveals that one signal 23'of the auxiliary electrode 23 lags behind the signal value 21', which is the last corresponding part of the strip liner. Indicates that it will be removed. Thus, the electrode configuration makes it possible to detect delamination liner removal or peel-off in one direction between two electrodes through time-resolved capacitance tracking. Finally, the third event (starting with T3) is a normal injection, with all four signals diminished at the same time. The signal shown is of a capacitive nature and depends on the galvanic insulation between the sensor electrode and the conductive region of the strip liner, eg, as a short circuit between the selected electrodes, in the conductive region.

The presence of a conductive region at stray voltage adjacent to and facing the sensor electrode tends to primarily increase the capacitance of the circuit with the electrode. Even when approaching or contacting the patient's skin, the expected increase in capacitance due to the capacitive properties of the skin is reduced as a result of the shielding effect of the conductive region. In other words, the conductive region has a relative increase in capacitance when approaching the patient's skin compared to a conventional exfoliation liner without a conductive region or compared to no exfoliation liner at all. Reduce. Therefore, it is possible to automatically distinguish between sequentially recorded patient skin approaches with and without a peel liner. Such a distinction may complement the independent detection of exfoliation liner removal occurring between two patient skin approaches. Such a distinction contributes to the reliable identification of the attachment of the delivery device to the patient's skin by the adhesive patch, as a requirement for subsequent needle insertion and as opposed to the approach of the test or dummy. Contributes to improved safety and usefulness. Therefore, the information from the capacitance measuring unit is shared with the control of the release button 13 and may only unlock the button upon proper removal of the peel liner or proper attachment to the skin as determined in accordance with the present invention. .. Information from the capacitance measuring unit can also be communicated to the user or patient through the status indicator 14. For example, the first visual signal can be emitted for approaching the body with the detached liner attached ("discovery of injection site") and the second signal for removing the detached liner ("attached"). "Ready"), a third signal can be emitted for attachment to the body ("adhesion"), and a fourth signal for removing the device from the body.

Although the invention is described in detail in the drawings and the aforementioned description, such description shall be deemed exemplary or exemplary and not restrictive. Modifications to the disclosed embodiments can be understood and achieved from the examination of the drawings, disclosures, and attachments, by those skilled in the art, and by practicing the claimed invention. In the claims, the term "provide" does not exclude other elements or steps, and the indefinite article "a (one)" or "an (one)" does not exclude more than one. The fact that a particular element or step is listed in different claims does not mean that the combination of these elements or steps cannot be profitable, especially the actual claim dependency. In addition, any further meaningful claim combination shall be deemed to be disclosed.

1 Device housing

Ten Cover housing part

11 11 window

12 Bottom housing part

13 Release button

14 Light indicator

2 Capacitance sensor

20, 21, 22 Aperture electrode

twenty three Auxiliary electrode

twenty four Sensor interface

30 Adhesive patch

31 Peeling liner

310 310 Peeling liner lid

311 and 312 Conductive regions

313 Non-conductive layer

32 Auxiliary foil

34 Hole