CH714300A2 - Printed circuit associated with the closure sheet of a blister, made with conductive paint, to detect the withdrawal of the product from the same blister. - Google Patents

Abstract

The purpose of the invention is to use the most widespread type of container for drugs, the blister, as a source that gives rise to the data to verify adherence to the therapy. The invention uses the "closure sheet" of the blister as a support for a "printed circuit", designed to create switches at each cavity containing the product. The printed circuit is made with a "conductive ink". This technology has a negligible impact on the cost of the blister itself, making it usable both for current use and as a tool for transferring information relating to the opening of each designed circuit. When the closure sheet is broken to allow the product to come out of the cavity that houses it, the circuit is thus "opened", and by means of its terminals it allows a service apparatus to detect that it has been taken. This service device can be designed to collect the data of each unit and maintain a diary which, once connected to an interface such as a smartphone, or other device, can be made available to both the patient and healthcare personnel that of the caregiver. Or remind the patient about the time of drug administration.

Description

Description

Definitions [0001] Blister, the cavity containing a drug unit or the blister complete with the closure sheet which closes all the cavities.

[0002] Closure sheet: the sheet of paper, aluminum, PVC or other material that closes the blister.

[0003] Conductive ink: the ink used to reproduce the printed circuit. It has characteristics that allow electrical conduction.

[0004] Contact combs: the terminal contacts in conductive ink, placed on the closure sheet of the blister that allow to detect, by means of a service apparatus, the interruption of a circuit in the printed circuit.

[0005] Service apparatus: an object powered by battery to be connected to the contact comb and able to detect and process circuit interruptions. 1. Introduction [0006] Adherence to the prescriptions of a therapy is fundamental to obtain the expected therapeutic result. Often the therapy is not followed as prescribed, consequently the expected result is less generating waste of time and resources, and not acting adequately on the health status of the patient. By adhesion to a therapy we mean the respect of the doses of a drug and the times and in some cases of the sequence of administration of the units placed in a blister.

[0007] Naturally, adherence to therapy takes priority both in the administration of drugs in which the mistake in recruitment can have health consequences; or drugs in the experimental phase.

[0008] The patient who receives the prescription from the attending physician usually provides the drug alone, sometimes it is administered by health personnel or by lay persons called "caregivers".

[0009] It is therefore important to remind the patient of the time of administration of the drug, and maintain a diary of the withdrawals from the package that is available both to the patient, to the healthcare personnel and to the caregiver.

[0010] The object of the invention is to use as the source of the data, the most widespread type of container for drugs, the blister which, specially modified by affixing a printed circuit, will be able to transfer the information to an apparatus of service allowing to obtain therapy monitoring in a more accessible way than it is today, and keeping production costs at current levels. 2. Therapy monitoring [0011] In support of this need there are apparatuses designed to remind patients and healthcare personnel of the punctuality in taking a therapy: obviously the drug withdrawal data is collected from the container, but it is not possible have reliable testimony of the assumption.

[0012] In order to monitor adherence to a therapy, many apparatuses are already able to remember to take the drug by means of an alarm, others to collect the time data in which the drug was taken and to show health personnel if the patient has joined the cure through appropriate communication systems such as websites, or apps. Studies show that adherence to therapy goes from 78% to 95%.

[0013] All existing devices for controlling drug withdrawal require removing the drug from its original container and placing it in the apparatus.

[0014] This practice is also applied in hospitals, to the point that there are "deblisterizers"; the drug thus released is then collected in containers, which in turn can also pack each patient's daily therapy back into sachets or other blisters.

[0015] These technological supports also have considerable dimensions and some of the most sophisticated must be connected to the electricity network. Not all of them are transportable. 2.1. The unmet need [0016] It seems clear that it would be much easier to leave the drug in its primary packaging, the blister, avoiding contact, contamination, possible transformations, pollution and errors that may occur in the transfer of the drug to its distributor. Furthermore the products currently in use are not able to detect the correct sequence of withdrawal in the case of differentiated dosage drugs such as - for example - for drugs prescribed for pregnancy control. 2.1.1. The applications studied [0017] In the past we have already set ourselves the goal of using the blister to draw information from the emptying of the cavity where the drug was located, but in any case it is necessary to intervene mediated apparatus that significantly modify the cost or yes clash with good manufacturing practices (Good Manufacturing Practice - GMP) or other regulatory aspects.

[0018] As an example the patents identified on ESPACENET: [0019] Patent US 2017 165 151 (A1) DEVICE FOR DETECTING THE REMOVAL OF DRUGS https.//worldwide.espacenet.com/publicationDetails/biblio?ll=1&ND= 3 & adjacent = true & local = en EP & FT = D & clate = 20170615 & CC = US & NR = 2017165151A1 & KC = A1 [0020] Patent WO 2016 135 306 (A1) ELECTRONIC DRUG PACKAGING FOR IMPROVED COMPLIANCE https: //worldwide.espacenet.com/publicationDetails/biblio?ll=25&ND=3&adjacent=true&locale=en EP & FT = D & date = 20160901 & CC = WO & NR = 2016135306A1 & KC = A1

[0021] Patent US 5 072 430 (A) COMPLIANCE METER FOR CLINICAL EVALUATION OF DRUGS https://worldwide.espacenet.com/publicationDetails/biblio?ll=25&ND=3&adjacent=true&locale=en EP & = D & date = 19911210 & CC = US & NR = 5072430A & KC = A 2.1.2. The position of industry [0022] It should be borne in mind that the industry cannot easily change the blisters, or the number of units per pack. The costs of regulatory compliance would be too expensive and the time dilated.

[0023] For this reason the modifications that can be made to the blister pack are limited and must allow both normal use and an information detection device, without having to differentiate the packs.

[0024] Thanks to these conditions, the blister pack, which is the result of the present invention, can be adopted in an industrially convenient manner, offering an objective and interesting plus both for the industry, for the patient and for the healthcare personnel. 3. The packaging of the drug in blisters [0025] The blister can perform a primary packaging function, in the case it is designed to contain, for example and not only, tablets, pills, capsules, confetti, or secondary packaging, if it contains vials, vials, pre-filled syringes, and more.

[0026] The drug, therefore, typically a tablet, a pill, a capsule, is dispensed by means of a primary container which in some countries is a nominative jar containing the therapy dedicated to the patient, but in many countries the drug is distributed through blisters. 3.1. The Blister [0027] Blisters are made up of two main parts: a part in which the individual cavities are obtained (which we continue to call blisters, which means bubble in English), obtained with a hot or cold process and which, once filled with the unit to be packaged are sealed with a multi-layer tape which we call the closure sheet. 3.1.1. The hot blister [0028] The hot blister is a container, consisting of a thermoformed sheet of PVC (or similar materials) to form many cavities with a size that can receive only one drug unit, whether it is a tablet, pill or capsule , or vial. This multiple container, once filled, is closed with the "closing sheet". To extract the drug from the blister, the patient or the healthcare personnel must break this closure sheet. See fig. 1 attached.

[0029] For a better understanding of the manufacturing procedures, we invite you to see the video illustrating the blistering process at: https://www.youtube.com/watch?v=S-N3Mr03Htl.

[0030] In particular we ask you to observe the section of the film 2.30-2.54 where it is clarified how the printing of the closure sheet is personalized, and positioned a way to coincide with each cavity of the blister. 3.1.2.1 cold-formed blisters [0031] These are aluminum-based laminates with different layers of PVC and other materials that allow their robustness. This is a cold processing that constitutes the beds for the drug by pressure modeling.

[0032] Also in this case there is a closing sheet. - In gray on the upper side of fig. 2 - Below the blister depicted in fig. 3. 3.2. The closing sheet [0033] The closing sheet is always an integral part of the complete blister. It consists of a multilayer support, often in paper, PVC, or consisting of a sheet of aluminum of about 20 microns laminated with other materials.

[0034] From the contact layer with the blister pack up to the outer surface many different layers can be found; for example: heat-sensitive lacquer for sealing, primer, aluminum, print, glossy finish.

[0035] For the purpose of the invention, the glossy finish can be obtained by means of a non-conductive varnish. 4. Description of the invention [0036] The invention proposes to use the "closure sheet" of the blister as a support for a "printed circuit".

[0037] The printed circuit is made using a "conductive ink".

[0038] The closure sheet is composed of many layers of different materials, the printed circuit will be affixed to one or more non-conducting states.

[0039] This printed circuit will cross the surface of the closure sheet at each cavity of the blister so as to create an independent circuit for each cavity. All circuits will have one end connected to a first «input» contact common to all circuits and will terminate independently «output».

[0040] The printed circuit will start and end on one side of the blister forming an aligned series of terminal contacts defined as a "contact comb". Each "output" contact refers to a single cavity containing the unit.

[0041] By coupling the blister pack with a service apparatus capable of connecting to the "contact comb", independent "closed" circuits are formed for each cavity.

[0042] When the closure sheet is broken to allow the product to come out of the cavity that houses it, the corresponding part of the circuit which is thus "opened" is also broken, and through its terminals it allows the service apparatus to detect it the opening and therefore the withdrawal, the times and sequence of the withdrawal of each unit contained in the blister.

[0043] (The description refers to Fig. 4 of the example.) 5. Recommendations for making the blister with a printed circuit.

[0044] The present invention is made possible by the availability on the market of inks with conductive capacities, and by materials constituting the closure sheet without electrical conduction capacity. 5.1. The ink [0045] Printing is carried out by means of an ink with electric conductive capacities. This ink is referred to as "conductive ink" in this text.

[0046] Typically, but only by way of example, the "bare conductive ink" produced by the Bare Conductive Society of London is cited: https://www.bareconductive.com.

[0047] This ink is no different from all other water-based inks, except that it conducts electricity. It can be used to design any contact or switch directly on each material. It is an electrical conductor, non-toxic, free of organic solvents, and water-soluble. It can be used with different printing techniques. It is adequate for low voltages. 5.2. The support (Lidding material) [0048] The material of the closure sheet is always made up of several layers. The closure sheet that can be used to carry out the invention must guarantee that the circuit can be printed so that it is not in contact with a conductive layer.

[0049] One of the purposes of the present invention is to intervene as little as possible on the manufacturing methods; in this perspective, if the material of the closure sheet does not include conductors, (for example when using PVC, paper), no precautions are necessary; it will be sufficient to affix the printing of the circuit on the external surface of the closure sheet, ie the one opposite to the blister cavity.

[0050] If in the stratification of the material of the closure sheet there is a conductor, for example aluminum, this stratification must be adequate so that the layer on which it is applied, painted, the printed circuit is not conductive. This varies at the discretion of the materials used and it will be the responsibility of the supplier to verify and guarantee their non-conductivity, as well as the adhesiveness of the conductive ink.

[0051] Nothing prevents the printed circuit from being affixed between two layers of non-conductive material between the many layers making up the closure sheet, provided that the parts of the contact comb remain connectable to the service apparatus. 5.3. Printed circuit board design. 5.3.1. The rules [0052] The design of the printed circuit board to be affixed to the closure sheet must comply with certain rules: - it must constitute an independent "semi-closed circuit" for each unit contained in the blister, crossing the surface of the closure sheet at the blister cavity . Semi-closed circuit means the connection between a contact - «input» - (red in the figures of examples 4 and 5) of the contact comb and the - «output» - corresponding to the cavity of each unit (in black in the figures examples 4 and 5). The circuit will be closed once connected to a service apparatus. - it must possibly present the QRcode, or other coding optical graphics, related to the drug / product. 5.3.2. Definition of the standards of connection with the service apparatus [0053] Maintaining these recommendations will allow the manufacturers àAIY service apparatus to access a standardized system. - On the side where the contact comb is placed, the distance between the edge of the blister pack and the cavity containing the nearest drug unit must allow sufficient «grip» for the attachment system of the service apparatus. A distance of at least 5 mm is recommended. - The contact ends of the contact comb, made with the same conductive ink, must be of such dimensions that they can be connected and activated by a metallic contact placed on the service apparatus. Indicatively a width of 1.5 mm placed between them a space of 1.5 mm, similar to a USB port. - The contact of the comb of the contacts, appointed to feed all the closed circuits, it is advisable to place it 10 mm from the edge of the proximal side. In the space between the edge of the blister pack and the first contact, the first pin can be placed on the service device. 5.3.3. Complexity and precautions [0054] Normally, in addition to the printed circuit, both the name of the drug and the name of the manufacturer can be printed with the conductive ink.

[0055] If the current good manufacturing standards provide for a widespread stamping of the name of the drug and of the manufacturer on the closure sheet, in such a dense manner as to interrupt or compromise the operation of the printed circuit, this stamp will be made - in a first printing passage - using paint not able to allow electrical conduction. While the printed circuit board will be affixed above it in a second printing step. 5.3.4. Opening the circuit [0056] When the blister is connected to the service apparatus, the circuits close and when the closure sheet is broken to allow the drug to flow out of the cavity that houses it, the circuit is "opened", allowing the service device to detect the withdrawal. 5.4. Description [0057] The printed circuit will begin terminating on one side of the blister forming a series of contacts defined herein in the present text as "contact comb".

[0058] In fig. 4 - example - the flat side of the blister is shown. On the (gray) surface of the closure sheet the continuous black lines representing the printed circuit are traced, and the blue dotted ellipsoidal shapes representing the surface of the closure sheet at the blister cavity. The dotted light surfaces are reserved: - for the dry punching of the blister as requested by some manufacturers and by some regulations to indicate lot and expiry date. - to the QRcode or other computer-readable code used to identify the product.

[0059] The lower left corner shows the contacts, printed by the conductive ink, which constitute the contact comb.

[0060] In fig. 4 a typical blister for a week's treatment is exemplified; the arrangement of the cavities of the blister, and consequently the layout of the printed circuits, will be adapted to the needs of the packaging without limitation of size or number.

[0061] In fig. 5 is exemplified, a blister with contacts for 14 administrations.

[0062] The inverted symmetry of the contact comb positioning allows avoiding contact fatigue when subjected to shocks and prolonged traction for two weeks, due to the transport of the blister when combined with the service apparatus. 6. Considerations on the possible increases in production costs [0063] While considering all the possible necessary modifications to the blister packaging system, the shared cost will be really insignificant. - The positioning of the closure sheet must strictly match the parts of the circuit which must open the contact in correspondence with the seats of the blister cavities. This technique is common, typically for birth control pills, but is not applied on all packaging lines. - The renewal of the stamp for the printing of the closing sheet including the printed circuit. - The ink for printing the printed circuit could have a different cost than the one normally used. - The insulating finish when the closure sheet includes a conductive layer. - The additional printing of the closing sheet when it is wanted to be stamped with diffuse written that can interfere with the printed circuit. - Normally no modification of the thermal modeling mold should be necessary. - Normally it should not be necessary to change the die cutter. - Normally it should not be necessary to change the secondary packaging, - Normally it should not be necessary to modify the illustrative leaflet, nor other regulatory adjustments. 7. Suggestions for the manufacture of a service apparatus [0064] This blister pack, coupled with a "service apparatus", can provide information on the opening of each circuit, and then record the withdrawal times of each unit of drug, and if necessary, the sequence of recruitment, as required for hormonal birth control therapies.

[0065] With the support of a smartphone, (or other reception / transmission system), and a dedicated Application, it will be possible to make this information available both to the patient and to the healthcare personnel so as to be able to verify the adhesion to the therapy.

[0066] This service apparatus, and the App are not the subject of the present patent application and do not form part of claims.

[0067] This service apparatus requires some precautions for manufacturing and may offer various services. A hypothetical scheme of a service apparatus and its coupling is presented in fig. 6 and 7. 7.1. Supply

[0068] On battery, eventually rechargeable via USB 7.2. Verification of contact openings [0069] Verification of the opening of the blister contacts will take place with a frequency of time defined by the firmware of the service apparatus (for example 30 minutes, 1 hour) by sending a low voltage pulse in the circuit. 7.3. Coupling technique [0070] The apparatus must be able to physically hold the blister pack. Typically with at least two points (pins) of contact that pierce the surface of the blister and fix it to the device itself and thus maintain contact between the comb of the contacts of the blister with the comb of the metal contacts of the service apparatus.

[0071] For this purpose, 10 mm are reserved before the first contact of the contact comb, to be able to position the first pin. See fig. 4 and 5. 7.4. Connection technique [0072] This apparatus will be provided with a "comb of the receiving contacts" and must be able to receive at least one blister for a single therapy. Depending on the characteristics of the object, more than one blister may be connected to the apparatus.

[0073] The manufacturer of the service apparatus is advised to prepare a comb of the receiver contacts for at least 14 contacts, usable for individual blisters containing up to 28 units. Then 14 + 1 = 15 contact points in the contact comb - receiver - placed on the service apparatus.

[0074] The first contact could be 10 mm from the left edge support point; the other metal contacts, spaced on their own 3 mm axis. Still referring to fig. Example 4. 7.5. Communication technology [0075] Bluetooth or similar radio system capable of connecting the service device with a smartphone or other telecommunication device. Communication will be both ways.

Claims (8)

claims 1. The idea of using the components of a blister as a printing medium for a printed circuit is claimed. 2. The idea of using a conductive ink affixed on any component layer of the closure sheet of a blister to form a printed circuit is claimed. 3. The idea of using this printed circuit to detect the opening of the blister cavity through the interruption of the printed circuit is claimed. 4. The idea is claimed that the terminals of this printed circuit can be connected to a service apparatus capable of closing the circuit and detecting its opening. 5. The idea of using a service device capable of coupling and connecting to this printed circuit to detect the opening of the circuits is claimed. 6. The idea of using a service apparatus is claimed which, if kept connected to the printed circuit board object of the invention, can detect the date, time and sequence of the opening of the circuits, of the withdrawal of the units. 7. The idea of having transformed a passive object such as the blister into a potentially active object capable of communicating both the interruption of a contact and the sequence of this interruption is claimed. 8. The idea that this technique described in the previous claims can be applied to blisters is claimed.