WO2021159191A1

WO2021159191A1 - Blister pack holder device connected to an external server

Info

Publication number: WO2021159191A1
Application number: PCT/BR2020/050579
Authority: WO
Inventors: Rodrigo Hernandez DE LUZIA GURDOS; Gabriela DE OLIVEIRA AMANCIO BALAZINI
Original assignee: Smartpills Serviços De Informação Ltda.
Priority date: 2020-02-13
Filing date: 2020-12-23
Publication date: 2021-08-19
Also published as: BR202020003089U2

Abstract

The present model relates to a blister pack holder device that is customized such that each type of blister pack requires a blister pack holder designed according to the dimensions thereof for a perfect fit, emphasizing that the patient only has to open the device once during the usage cycle of a blister pack, removing the pill by means of an extraction button (2). The device is characterized by having macro functions, two of which are described below: using one or more light emitters, preferably LEDs, to visually inform the patient of the time to take their pill, the number of pills to be taken, the time left before the patient can take the pill within the correct timescale, and whether the patient is at risk as a result of incorrect treatment (4); and using a real-time blister-pack scanning system to monitor occurrence of a pill extraction event. The device contains a microcontroller (14) with a program.

Description

BLISTER HOLDER DEVICE CONNECTED TO THE EXTERNAL SERVER APPLICATION FIELD

[001] The present model refers to an electronic blister pack iot (internet of things) device, adaptable to the portfolio, which signals and monitors the use of the drug, reusable that is produced to adapt to the layout of the drug brand portfolio specific.

HISTORIC

[002] The World Health Organization (WHO) reported that non-adherence of chronic disease patients is on average 50% in developed countries, and as a result more than 30% of hospital admissions occur due to this cause (LAM E FRESCO, 2015), reaching 70% in the case of treatment for hypertension, being the major cause of uncontrolled blood pressure (SA TSCHI ET AL, 2007),

[003] The WHO defines adherence as the extent to which people's behavior (including medication consumption) corresponds to the recommendations agreed with a health provider (SABATÉ, 2003). Monitoring medication adherence can be done with direct measures or indirect. Direct ones include expected concentrations of drug markers from laboratory tests with patient fluids, which are impractical on a large scale due to the high associated costs. Indirects include secondary database analysis, based on the amount of refills ordered versus the amount predicted as per the medical prescription.

[004] The accuracy of this method depends on a centralized and consistent system between healthcare providers and patients, which are not always available and do not provide healthcare analysts with tips on the pattern of non-adherence during the study period. Another indirect method that suffers from the same problem is counting the remaining capsules between medical appointments, in addition to not considering the possibility of replacing the drug before the end of the package (LAM E FRESCO, 2015). Subjective methods of measuring adherence (based on the declaration of patients and/or service providers) are highly subject to bias (BRUXVOGRT ET AL, 2015). Also according to the systematic review of the state of the art by Lam and Fresco (2015), indirect measures involving electronic drug packaging devices in general have the following features:

- Recording of dosage events and storage of adherence records;

- Audiovisual reminders to signal the time for the next dose;

- Digital dispays;

- Real-time monitoring;

- Feedback on medication adherence performance,

[GG5]Among the available devices, there are two main models, known in the literature as MEMS (Medication Events Monitoring System) and Smart Blister. MEMS are composed of drug containers with electronic caps in which whenever a capsule is removed, an embedded microprocessor records the date and time, assuming that the patient took a specific dose at that particular moment. The disadvantages of this method are that the capsules must be removed from their original packaging and placed in the container, as well as the possibility of opening the packaging accidentally or out of curiosity without meaning that a dose was taken,

[Q06]Even with these disadvantages, MEMS is recognized as the most reliable non-invasive method for assessing patient adherence (BERTHOLET ET AL, 2000), and is therefore commonly used as a reference for testing the effectiveness of other methods and in trials. clinical trials. However, its cost according to Lam and Fresco (2015) reaches $274 per user, being impractical in many cases. Smarts are blister packs with a look identical to the originals in which when a pill is detached a signal is emitted to a device with microcontroller that records the event. In this case, there is the advantage of using the original drug packaging and less propensity for the user to activate the mechanism out of curiosity or accident,

[OG7JO contraceptive universe

[0G8]The emergence of the contraceptive pill, in the early 1960s, allowed women to control their fertility, conquer their sexual freedom with safety and practicality and, more recently, combine contraception with other benefits provided by the pill. According to the Guttmacher Institute, a sexual health organization in the United States, approximately 100 million women used the contraceptive pill in the world in 2006, while in the same period there were 10.4 million. women making use of this type of medicine in Brazil, according to data from the IBGE's Household Sampling Survey (Pnad). More recently, a survey carried out in 2014 by Bayer in conjunction with Unifesp revealed that 51% of women in fertile period use this medicine, that is, approximately 25 million. [GG9] According to Manuel Cavalcante, marketing manager at Medley, the market for contraceptives reached R $ 2 billion in sales in 2012, thus becoming the second largest market of the national pharmaceutical industry, behind only painkillers.

[OOlOjAccording to Perpétuo and Aguirre (1998), the percentage of users of contraceptive methods grows according to their socioeconomic level. It is noteworthy that this last mentioned index shows significant growth in Brazil, especially in large metropolises,

[0011] Brazil, we live in a time "sexually active" protected by contraception of only 50% and of these, it can be expected that the minority makes the correct use of the method in use. Access to contraception, a constitutionally guaranteed right, is not widely attended to. There are problems in production, quality control, procurement, input distribution logistics and maintenance of continuity in the supply of contraceptive methods. The result is precarious and excluding care, or even non-existent in some locations (ALI; CLELAND, 2005).

[0012] Unplanned pregnancy

[0013JO Family Planning (PF), currently defined as a citizen's right, was extremely debated, going through a political process, which involved several groups with different thoughts on the theme of reproduction. The notion of reproductive rights as a human right developed after the struggles of social movements, which influenced international conferences and were related to changes in the role of women and their value in society and the development of medical technologies (VIEIRA, 2004).

[0014JO PF was regulated in Brazil through Law 9,263 of January 12, 1996, which states that this is a set of actions for the regulation of fertility, through preventive and educational activities that ensure equal access to information, means, methods and techniques available, guaranteeing the right of constitution, limitation or increase of offspring by women, men or couples, within a vision of global and comprehensive health care, with the use of actions for any type of demographic control being prohibited (DEPARTAMENTO, 2005).

[GG15] In 2001, the last Health Assistance Operational Standard (NOAS-2001) of the Ministry of Health established that assistance in family planning was among the minimum actions that should be implemented in all municipalities (MINISTÉRIO DA SAÚDE, 2001) . In this context, freedom of choice is fundamental in the sphere of fertility regulation. To choose a contraceptive method in a free and informed way, women need to know and have access to all scientifically approved and available contraceptive methods, choosing the one that is best suited to their characteristics and their living conditions at any given time. Within this proposal, family planning aims to guarantee women and men a basic right to citizenship: the right to have children or not (MINISTÉRIO DA SAÚDE, 2002).

[0016] Regarding the reproductive planning of Brazilian women, the National Demographic and Health Survey (PNDS), conducted in 2006, found a high prevalence of use of contraceptive methods such as contraceptives, IUD, vaseciomia and condoms in the country (81%) , reinforcing that between 1996 and 2006 this prevalence increased, due to the expansion of the use of methods in the lower socioeconomic strata, reaching 80.6% of sexually active women and 75.2% of those who had a marital status without a partner (BRASIL , 2008).

[0G17] It was observed, however, that 46% of births were unplanned, of which 28% were wanted later and 18% were unwanted. It is important to emphasize that the occurrence of unplanned pregnancy remains throughout the reproductive life of women. According to the 2006 PNDS data, there is a trend towards an increase in the lack of desire for pregnancy with the increase in women's age, increasing from 9.4% between 15 and 19 years old to 20.3% between 30 and 49 years old (BERQUÓ; LIMA, 2009) and, still, the proportion of unwanted births reaches 40% among women over 35 years old (BRASIL, 2008).

[0018JA each year, at least 80 million women worldwide experience the situation of having an unplanned pregnancy, a number that has been growing in recent decades. The occurrence of this phenomenon is responsible for an additional risk in the number of abortions and, in addition to the episode itself, increases the risk of morbidity and mortality related to abortion. This situation is quite relevant in South America, where the number of clandestine abortion procedures is close to four million per year (LANGER, 2002).

[0019J Unplanned pregnancy, if it is also unwanted, can prove to be a serious problem for the sexual and reproductive health of Brazilian adolescents and youth, as evidenced by the number of abortion-related visits in the SUS, as well as the rates of juvenile maternal deaths ( BRAZIL, 2006).

[0020] This contradiction between the high prevalence of use of contraceptive methods in the Brazilian context and the difficulty in preventing an unplanned pregnancy reveals that women lack information and tools to fully satisfy their reproductive rights (BRASIL, 2008).

[0Q21]Effects on women's health

[0022] The result is that often, even using contraceptives for years and even decades, women lack basic information about their medication, which can be verified through the 72.7% index of women who were taking use of contraceptive method when they discovered the unplanned pregnancy. (Sanches, Natalia Canella, 2014).

[GG23]Even with the availability of safe contraceptive options to maintain family planning, many women in Brazil and around the world still face unplanned pregnancies. The study "Born in Brazil", by the Oswaldo Cruz Foundation, points out that 55% of Brazilian pregnant women do not have a planned pregnancy.

[0024] A survey conducted by UNIFESP (Federal University of São Paulo), in partnership with Bayer, pointed out that 76% of respondents said that an unplanned pregnancy would disrupt their future life plans. The survey, carried out with 2,000 women, aged between 14 and 30, in the cities of São Paulo and Rio de Janeiro, shows that 76% of the interviewees know someone who became pregnant before the age of 16. When it comes to teenagers, unplanned pregnancy can be even more devastating. According to the report "State of World Population 2013" by the United Nations Population Fund (UNFPA), about 20,000 girls, under the age of 18, give birth every day in developing countries, with the lack of information being the main obstacle to contraception,

[GG25] There are some devices used commercially such as the "Med-ic" (Med-ic from Information Mediary Corporation, Ottawa, Canada) is composed of a thin wire connected to a microchip that crosses each capsule of the card and breaks when the capsule is removed. The packages in this case need to be activated by an Information Mediary Corporation device and then the packages must be scanned by the same device to collect the data recorded on the microchip. In a study with malaria treatment patients in Tanzania, data from 21% of the packages could not be used due to a defect in the card or inability to download the data. Even so, it was possible to carry out the study that revealed a significant difference in adherence to medication at the prescribed time between the subjective measures and measures with the device, evidencing possible bias of the participants when answering the questionnaires. In the conclusions, they add that the number of capsules scanned as taken did not correspond to the number presented by the software in some cases, indicating the need for improvements in the device design (BRUXVOORT ET AL, 2015). The HeÍping Hand™ device from Bang & Oíufsen Medi com, Denmark, developed its bespoke solution for the pharmaceutical industry AstraZeneca with the aim of being a "new patient monitor that measures patient compliance". The "Helping Hand ™" is a product that reminds the patient when to take medication/pills. The purpose behind the device is to motivate and guide the patient to seek and maintain a high rate of compliance with the prescribed medication. In addition, the device can be used by physicians to help motivate their patients to continue taking their full course of medication. The unique software reminds the user to take the medication and helps the patient keep track of how well they are taking the medication. The patient receives feedback via a visual signal (red, yellow or green). To upload data there is a bluetooth application. Alternatively, the device can work via a USB wired cable or via a wireless transponder solution. [0026JO Clyk is the smart pill dispenser from Bayer Healthcare Pharmaceuticals - Bayer Pharma AG co-developed with Balda Medical. This pill dispenser comes with an LCD display and is designed to be used for 2 years. It is specifically designed to help women follow a new oral treatment within a single flexible long-term consumption regimen to give the woman the option to plan her menstruation period. The dispenser can be used globally due to the use of universal symbols. Clyk provides a daily reminder through its visual and audible alarm, but also advises the woman if the pills are wrong and advises her if additional supportive contraception is needed. The dispenser guides the woman through her cycle and the 4-day free interval. It has no internet connection and no bluetooth or wi-fi modules, so it is offline,

[0027J The state of the art comprises documents that teach about this type of devices such as US 2013319902 that teaches about a pocket-size blister box designed to receive a blister of a known type with a plurality of cells, each containing a product, for example a pharmaceutical product in the form of a pill or tablet, has a plurality of capabilities and/or optical sensors to count and display the number of pills taken from the respective cell, as well as the date and time they were taken , and is able to communicate with a control center that can verify the patient's degree of compliance with the prescribed therapy and can dialogue with the patient himself.

[0028JO US20170465G1 document teaches devices for monitoring the distribution of a fluid from a container employing a sensor unit that may include a light emitting diode in the opposite direction of the photodetector and also communication via 3G with a cell phone. The document also teaches alert sent to the user which can be a light emitter such as an LED, or a signal sent to a remote computer. [0029JO document WO 2017176571 deals with method and apparatus for automatic monitoring of the drug status content of a blister card. Each tablet location on the blister card is operatively coupled to a different sensor that detects whether the tablet location is occupied and/or a dispensing event at the tablet location. Alternative detection approaches are based on optical, acoustic and tactile sensors which interrogate the dispensing region at each pill location or the pills themselves to determine if the pills were dispensed. The sensors interface with a mobile app that provides user instructions to help improve drug regimen compliance.

[0030JO document 3P 2018068743 deals with a portable drug management device capable of easily and accurately acquiring a drug state stored in a package as a PTP sheet (press-pack) and, in addition, acquiring distribution of which drug in any position of the package is taken; and a system comprising a light emitting unit and light receiving unit. [003!] Documents BR112018015571 and US10185311 also teach devices that support blisters and feature pill removal timers and emit reminder signals to the user.

GOALS

[0032JO the device has advantages over existing products on the market such as:

- there is no need to develop a disposable printed circuit interface as in the case of Med-ic, as it uses optical sensing / permissiveness of the environment where the tablet is located to identify whether it was removed (ie, this or not present), with this there is a reduction in costs;

- there is no change in the layout (dimensions) or headspace of the blister, avoiding the need for new studies on the stability of the molecule, unlike Clyk;

- use of real-time data transmission technology, which can be, but not limited to, wi-fi, bluetooth, low-frequency radio, RFID, 2,3,4 and 5g, avoiding the need for daily pairing of the application with the device;

- takes advantage of native cell phone features to generate alerts and reminders, such as the display, speaker and vibration engine, making the device more efficient, since it does not need to use battery to maintain these features, while it also makes hardware simpler and therefore cheaper;

- Use of cell phone metadata to identify and obtain information about the patient; - it is possible to create feature upgrades on the mobile application and make them available at any time through Play Stores and also update the device firmware via bluetooth, wi-fi or 4g, depending on which technology was used;

- possibility for health service providers to obtain continuous medication use information in real time, instead of just when there is an appointment or meeting to read the device;

- possibility of creating a system of automatic and personalized messages/alerts in the mobile app, email or other forms of communication with the patient to motivate the user to adhere, Fioravanti et al (2015) and Sabin et al (2015) indicate that sending personalized content in text has proven to have a positive impact on patient empowerment, self-management and adherence to prescriptions;

- visual alert system on the device through flashing light, thus generating convenience and intelligence, as the user knows exactly which, when and how many pills to take;

- closed system, the user does not need to remove and place the biister in the device every time she takes the tablet, in such a way that she only needs to perform this activity when the card runs out, thus inserting a new one;

- the device was designed to be recharged every 3 months, using a rechargeable lithium battery;

- the product is designed to have a shelf life of 36 months.

BRIEF DESCRIPTION OF THE FIGURES?

[0G33] Attached are figures depicting the device, as listed below:

-Figure 1: Front view of the device turned off (Figure IA), schematic with all lights on (Figure 1B);

Figure 2: Operation of the signaling/timer light bar, where at 5 the bar is completely lit and at 6 completely off, the middle images being the intermittent intervals, The way the lights come on and off, as well as its intensity and color, can signal from time to synchronization, among other things. In 7 the "unprotected" icon is displayed, which signals when the treatment is no longer highly efficient according to the package insert and, due to the incorrect use of the treatment. recommended, was considered at risk;

-Figure 3: PCB board and its main electronic components, its function is, on a single board, to scan the bister tablets that are coupled/aligned to the perforations of the same through optical sensor/permissiveness of the medium, to memorize the information of the moment changing the state of the card (status is understood as the quantity and position of tablets present and/or absent), processing the information and remotely sending this data to an external receiver;

Figure 4: Schematic of the electronic circuit of the optical sensor that identifies the presence or absence of the bister pill at a pre-established frequency of time. There is a previous calibration of the sensor according to each type of bister, since there is a difference in the dimensions of the tablet, in addition modulated light is used to avoid interference from external (environmental) light. For electrical permittivity of the medium a capacitive sensor would be used instead of an optical sensor;

Figure 5: Format of the printed circuit board with the function of the individual reading of a tablet;

Figure 6: Prototypes for testing individual reading for the presence or absence of a pill;

-Figure 7; Represents the biister test;

-Figure 8: Illustrates in the image on the left the reading pattern of the optical signal when the tablet is present, on the right the signal when the tablet is not present, the axes. The firmware identifies the difference to conclude whether or not the tablet is present. The x axis is time and the y amplitude of the signal measured in electrical voltage of the received signal, in this graph 1024 will represent about 3.3V;

-Figure 9; Test model with extractor buttons with a 5mm stroke and 90 shore for a 3.4 mm high tablet,

SUMMARY DESCRIPTION

[0034] This model is a custom-designed blister holder device in such a way that each type of card needs a bister holder designed according to its dimensions, for the perfect fit, emphasizing that the patient does not need to open more than once the device during the use cycle of a card, performing the extraction of the compressed via an extractor button (2). The device is characterized by having four macro functions, namely:

1) visually inform the patient through one or more light emitters, preferably LEDs, the time to take their pill, the number of pills to be taken, how much time is left for them to take the pill within the time interval correct and whether the patient is at risk due to poor treatment adherence (4);

2) monitor in real time through a blister scanning system when a pill extraction event occurs;

3) the patient extracts the tablet through an extractor button, with it being expelled through a hole in the device (with this the patient only needs to open and close the device, to insert a card in it, once per cycle of use , for example a pack of 30 pills, with the use of 2 pills a day, only needs to be changed every 15 days, like a refill);

4) memorize these data and send them to an external server so that the data can be compiled and transformed into relevant information for the patient's health.

[0G35] Internally it has a microcontroller (14) with a program that:

(a) indicates pill consumption status;

(b) indicates the safe time interval for consumption in case of forgetting;

(c) indicates when the user is at risk because he/she has poorly adhered to the treatment according to the package insert of his medicine;

(d) detects the presence/absence of each pill;

(e) performs such aforementioned detection at pre-programmed time intervals;

(f) plan actions with time intervals;

(g) check the time scheduled for taking the pill;

(h) it has a clock that updates itself with the server, always keeping the current time;

(i) periodically sampling the presence of each pill;

(j) indicates the battery charge through the RGB LED, alternating its color to indicate that the battery has a low charge, that the device is charging and finally when the battery is already fully recharged;

(k) knows when the device drawer is opened and closed due to an electronic contact switch.

DETAILED DESCRIPTION

[0036JO This model refers to a reusable electronic blister pack iot (internet of things) device that is produced to adapt to the layout of the portfolio of specific drug brands, employable in particular in the pharmaceutical industry. need to take the tablets from the original bister and insert it into the device, in addition it requires the patient to open and close the device, inserting the card inside it, just once per cycle of use, with the extraction of the tablet being performed by pressure in one of the faces of the device and the tablet being expelled immediately against the applied force. The device has light emitters that create a visible communication with the patient, a communication that alerts the patient when to take the pill, which or which pills should be taken at that moment and informs, also visually, how much time is left for the pill yet can be taken correctly according to the patient's treatment. The device then monitors in real time when a tablet is extracted from the pack using optical sensors positioned on an electronic pcb, in such a way that for each tablet there is a light emitter and a light receiver positioned diametrically opposite, whose tablet is the physical barrier . Once the tablet is extracted, light arrives at its receiver and the microcontroller + program understands which tablet was extracted and at what time. This is only possible because the microcontroller performs a card scan at costly time intervals. Once the extraction event occurs, the device sends and stores data to an external server through machine to machine (iot) communication protocols such as wi-fi, blueiooth, beacon, radio and other available data transmission technologies. Finally, it signals the patient when the use of his card due to the treatment was wrong, alerting him that he is at risk.

[0037J The device represents an evolution in relation to the state of the art presented for continuous use medicines that are in the bister format because through optical sensors it identifies in real time when a tablet is extracted from its original bister, in addition to having a visual alert system that signals to the patient, through a series of light emitters, when, which and how many pills he should use at that moment, while monitoring the pill extraction event, all using the same light emission system and without the need for any type of change in the blister. It is important to mention that the light emitter is positioned 180 degrees from the board to optimize the arrival of light on the receiver.

[0038J The device also requires the least possible amount of interaction on the part of the patient, in addition to being careful not to change their routine and habits that affect the use of their medicine, thus seeking only to offer tools that help them to improve their treatment adherence and get information on when she is not protected, which in the medical literature, for oral contraceptives, means below 91% effectiveness. [0039] Additionally, the device sends personalized messages to the user and displays to her in the format of a visual, sound or smartphone vibration message, in order to remind her to take her medication at the correct time and what do when one or more pills are not taken, always following the directions of the medicine package insert.

[0G40]Among the functions of the application or program used in the device, we can indicate: a. Indicate the consumption status of each pill

Remind the user to medicate herself with the contraceptive and alert her regarding the pills that were not consumed. B. Indicate safe time interval for consumption in case of forgetting Allow the signal bar to light up at the exact moment when the pill is needed (according to the respective treatment) and gradually turn off as time passes, like a timer, until that goes off completely, indicating that the pill is no longer suitable for consumption. ç. Indicate when the user is unprotected

Allow the 'unprotected' icon to light up on the device and concomitantly on the app in cases of incorrect use of the drug exactly as it is in the package insert e. Detect the presence of each pill Let the device know if the indicated pill is present or not in the blister. f. Detect if the pill has been removed

Allow the device to stop indicating consumption if the pill has already been removed by the user. g. Plan actions with time intervals

Allow the device to differentiate 3 times of indication: the pill must be consumed and it is within the scheduled time; the pill must be taken, but it is outside the scheduled time; the pill is late and its consumption should be as recommended by the medicine's package insert, h. Consult the scheduled time for taking the pill

Allow the device to know the scheduled time for pill consumption. i. Having a watch that keeps the current time

Allow the device to have an absolute time reference, performing periodic server queries. j. Sampling the presence of each pill periodically

Allow the device to scan the entire card in triplicate to validate the reading is correct k. Indicate battery charge

Allow the device to recognize 3 battery charge statuses: no charge, charging and charged, sending this information also to the server if we want to alert the patient through other channels such as app, email and the like.

L. Signaling different situations using different colors, frequencies and intensity of light emitters.

[0041J The device can also be customized for continuous use oral contraceptives, provided they are sold in the form of a card. Therefore, the blister pack device must be specially designed for each type/layout of contraceptive pack, taking into account the width, length, height and dimension of the pills, all with the aim of achieving a perfect fit. It is highlighted again that the patient does not need to open the device more than once during the cycle of using a card, removing the pill through an extractor button (2). The device is then characterized by the same functions described above, as follows:

(a) the risk icon lights up only when the user is unprotected, which means that the contraceptive, due to misuse, is showing an efficacy equal to or less than 91%, that is, about 100 times more risk than in protection with correct use (99.8%), according to the package insert,

(b) Indicates the safe time interval for consumption in case of forgetting through a timer bar that decreases over time.

[0042] According to a preferential way, the bister-carrier device connected to an external server comprises: a) a device that needs to be sized/designed for each different type of card layout, as it requires a perfect fit between the card and it, thus preventing the pharmaceutical industry from changing the shape of their blister packs on the production line; b) a signaling/timer light bar (3) indicative of safe time interval of pill consumption according to the medicine package insert; c) individual light signals on each pill cap, informing which, how many and when to take them, and may also use different signaling colors, personalized according to the patient's treatment; d) a "risk" icon (4) that signals when the patient, due to poor adherence to treatment, is at risk according to their package insert/clinical studies, also informing via application what should be done; e) pill extractor button (2) which prevents the pack from having to be removed from the device daily, in such a way that the pack is placed in full inside it and is only removed after all the pills have been taken. The user presses the extractor button, which in turn is made of a flexible polymer and with that it ejects the tablet through a hole in the vector; f) a microcontroller (14) with an application capable of:

® have a personalized interface to receive patient information, store it and transmit it to the device; ® manage points a, b _; ced above;

® detect the presence of each pill and, in real time, if it has been removed, using an optical sensor for this purpose;

® detect if the pill has been removed in real time;

® plan actions with time intervals;

® check the scheduled time for taking the pill;

® update your internal clock via the server to keep the time always up to date;

® periodically sample the presence of each pill; and ® indicate battery charge.

[0043JA Figure 1 attached shows a front view of the device, turned off (Figure IA), schematic (Figure !B), comprising a flexible synthetic polymer cover that allows light to pass only in specific places, which are recessed into the part for this purpose. leaving the site thinner and thus translucent (1), the pill or pill extractor button and pill or pill taking indicator (2), indicator/timer bar indicative of the safe pill consumption interval (3) and the "unprotected" icon.

[0044JA Figure 2 in the annex indicates the operation of the timer bar and "unprotected" icon that, through the emission of internal light of the device, indicates the maximum time for the pill to be consumed (5), the timer bar completely erased, indicates the end the time of ingestion of the pill (6) and the "unprotected" icon lit, which indicates low adherence to the treatment and/or misuse of the medication (7),

[0045] Figure 3 attached indicates the PCB board (8) comprising a rechargeable lithium battery (9), a phototransistor that identifies the passage of light (10), the side light emitter (11), wireless communication module (bluetooth, low frequency radio, wifi, 3g, 4g, 5g,...) (12), the USB output for battery charging (13) and the microcontroller (14). [0046] Below the numbers referring to the figures:

(1) Flexible synthetic polymer cover

(2) Pill extractor button and pill-taking indicator

(3) Light bar indicative of safe pill consumption time interval (4) "unprotected" icon

(5) Full light bar, indicates the maximum time for the pill to be consumed

(6) Light bar completely off, indicates the end of safe pill ingestion time.

(7) "unprotected" icon lit, indicates low adherence to treatment and/or misuse of the drug

(8) PCB board

(9) Lithium battery

(10)Phototransistor that identifies the passage of light

(11) Side light emitting source

(12) Wireless communication module (bluetooth, radio frequency, wifL)

(13)USB output for battery charging

(14) Microcontroller

[0047JA follow examples that illustrate the model, but that should not serve to restrict its scope.

Example 1

[0G48] One of the embodiments of the device uses a light source, which has the function of signaling the moment of taking the tablet visually to the user through the selective permissiveness of light on the polymer membrane (in specific places where we want it to the light passes), and to determine, in conjunction with a phototransistor that acts as a receiver, whether the pills are present or not. This alternative is only possible because the blister is made of transparent pvc plastic, where the tablets are stored, sealed by aluminum. Thus, as the emitted light source and the phototransistor are positioned in the same plane as the tablet, but diametrically opposite, the light emitted by the emitter only fully reaches the phototransistor when the tablet is not present, as it acts as a barrier . Importantly, the technology can be used both in plastic-aluminum and aluminum-aluminum blisters. While in the first case the light passes through the plastic due to its translucency property, in the second case the light passes through a permanent channel in the aluminum that is generated by deformation by the impact of the internal pin of the extractor button, which through the pressure exerted by the patient's finger to extract the tablet, it deforms a channel shape in the aluminum, which thanks to its inelastic property, allows light to pass from the emitter to the receiver in a continuous way.

[0049] Tests were performed with several LEDs and phototransistors to determine effectiveness in detecting the presence of pills in contraceptive packs.

[0050]Each test case had its result evaluated as adequate or inadequate according to a pre-established evaluation criterion.

[005!] For the evaluation of the devices, a table was created that correlates the emitters and receivers in test cases. These test cases consider the sending and receiving capability of each device to combine them in tests that can provide satisfactory results. Some cases will be assembled in such a way as to allow performing more than one test with a single prototype, accelerating the evaluation of different combinations.

[0G52] Table 1 of test cases can be seen below:

TABLE 1

[0053] To reduce the interference caused by external light sources, the tests were carried out with modulation of the emitted light. Modulation allows that, even with external light similar to that emitted by the emitter used, it is possible to identify if the emitter is performing a test.

[G054]Also in order to reduce interference caused by external light, the polymer should have an ideal combination of thickness and opacity, such that the lighter the shade used in the polymer, the thicker it needs to be.

[G055]G The endpoint was the difference between the signal received with the pill and without the pill of at least 5% of the maximum scale. If the test had a higher result or equal to this value, it would be considered adequate. If the test presented a result lower than this value, it would be considered inadequate.

[G056]For the validation of each test case, prototypes for the test cases were designed and manufactured. Such prototypes allowed the performance of the specified tests, implementing the minimum circuit for the use of the components and also allowing the implementation of an external auxiliary circuit.

[G057JA Figure 4 attached represents the schematic of the electronic circuit of the optical sensor. [0058J The circuit implements only the power of the emitters and polarization of the receivers, allowing to control the emitters as desired and treat the signal received from the receivers before analyzing them, if necessary.

[0059] The attached Figure 5 shows the format of the printed circuit board for individual reading of a tablet.

[0Q6Q] The prototype's printed circuit board has a circular hole in the center to fit a pack of test pills and exposes the component connections on the edge for use in the test equipment.

[OG61]The test prototypes were individually implemented following the pattern presented above, manufacturing a board for each test case.

[0G62]The attached Figure 6 shows the prototypes for the test.

[0G63]Gs tests were performed using a microcontroller connected to the prototype boards. This microcontroller is responsible for generating the modulated signal to be transmitted by the emitters and for capturing the signal received by the receivers.

[The OG64JO test was characterized by the positioning of the prototypes with the components facing outside the pill pack, just as the prototype was originally conceived, facilitating the use of the emitters for the main function of the device. Â Figure 7 shows a Blister Test.

[0065] In this example, the prototype of case 1 was used, with lateral emission and a pack of 30 pills. The green line represents the signal received by the receiver and the yellow signal represents the signal of interest, obtained by processing the received signal. The blue and red lines are for reference only and do not represent obtained values. Â Figure 8 on the left indicates the pattern of reading the signal when there is the presence of the tablet, to the right the signal when the tablet is not present.

[0066] It can be observed difference in the amplitude of the received signal (green) and the treated signal (yellow) between the case with and without compressed.

[GG67]Tests were performed with packs of 21 pills. Table 2 below shows the difference between the signal received with and without the pill for each test case. Prototypes that have more than one receiver presented independent results, one for each sensor.

[0068] The values can range from 0 to 1023.

TABLE 2

[0G69]Gs tests performed on the 7 prototypes, indicated in Table 2, allowed the evaluation of a range of devices. These tests allowed us to evaluate each case in different situations and determine which devices present a better overall result.

[0070] It is noticed, when observing the evaluation tables, that cases 2, 3 and 5 do not work properly and can be discarded.

[QG71]The best results are obtained with prototype 1 (with lateral receiver) and 4. [QG72]It was also dimensioned that the extracting pin of the tablet needs to have shore (hardness) above 80 to guarantee an ideal extraction. In addition, it is necessary to have a height of at least 1.5 times the size of the tablet to ensure a minimum stroke to meet the goal of complete drug extraction, since this relationship was noted empirically according to tests performed on the deformation of the bister headspace , It is important to note that each blister has a headspace with different material and dimensions, requiring extraction pins with shapes, hardness and dimensions customized to them.

[0073J The tablet exit hole has also been sized both in width and depth to ensure that the tablet does not get stuck in it when ejected, resulting in the patient's eminent need to use the finger/nail to detach it from the hole. This feature is very important because this action can lead to pushing part of the aluminum from the blister into the cavity where the tablet was accommodated, generating noise in the light passage between the emitter and receiver, which can produce false negatives in the system's scanning. For this purpose, the orifice has a radius 25% greater than the tablet and its depth cannot exceed 75% of the height of the tablet.

Example 2 - Case study with oral contraceptive

[0074] To better illustrate the functioning of the product, the case of the use flow of a woman who uses oral contraceptives was chosen. Below is the step-by-step journey of the user in the interaction with her device: a) patient downloads the application on your mobile through one of the stores available for your mobile operating system; b) fill in the Information on: a. contraceptive brand b. if you are already using that card c. if you have already taken the pill that day d. what time do you use your pill e. if you take all the pills in the portfolio (if the brand has a placebo) f. if you splice one card into the other or pause to menstruate c) open the device drawer; d) inserts the card inside the blister pack; e) closes the device drawer; f) in the application, it pairs the device with the cell phone via bluetooth, rfid, wi-fi network, 4g, 5g, 2g, radio frequency, or other forms of communication available on the market, depending on the device version; g) the device scans the card and sends the information to the server or application; h) the application, in turn, starts to exactly mirror the current state of the card with the same quantity and sequence of pills; i) at the time of taking the next pill, a light signal on the cap of the respective pill to be taken will light up; j) at the same time, the timer bar will also light up, indicating how much time is left for taking the tablet within a safe interval; k) when extracting the tablet by squeezing the cap, the user removes the tablet through the exit hole, the sensor identifies that the tablet has been removed, turns off the light signal both on the cap of the tablet and on the timer bar;

L) the information goes in real time to the server or mobile application; m) the cycle from i to I repeats until the end of the card or until the user makes any change in her treatment via the app, in which case the device is immediately updated to reflect the change; n) if the user forgets to take her pill and falls into a case of risk, according to the package insert of her medicine, a light signal will light up an icon on the device and in the application, informing her that she is unprotected. The application informs you what should be done in accordance with the best practices described in the package insert of your respective contraceptive; o) when using all the pills in the pack, the user opens the drawer, removes the pack, inserts a new one and closes the drawer, thus the cycle from i to I is repeated.

[GG75] In the application, the user has the time information that she took each of her pills, available in the form of a history on a calendar, in such a way that she can identify patterns that are useful for her treatment. The application also has the intelligence to suggest changing the tablet's usage time from the moment it registers that there is a usage pattern different from the one configured. [0076]In the same app she can enter additional information about her menstrual and sexual cycle, making it a complete schedule.

Claims

1. Blister device connected to an external server characterized by comprising:

1) a device that needs to be dimensioned/designed for each type of different card layout, as it requires a perfect fit between the card and the card, thus preventing the pharmaceutical industry from changing the shape of its blister packs on the production line;

2) a signaling/timer light bar (3) indicative of safe pill consumption time interval according to the medicine package insert;

3) individual light signals on each pill cap, informing which, how many and when to take them, and may also use different signaling colors, personalized according to the patient's treatment;

4) a "risk" icon (4) that signals when the patient, due to poor adherence to treatment, is at risk according to their buia/clinical studies, also informing via application what should be done;

5) pill extractor button (2) that prevents the pack from having to be removed from the device daily, in such a way that the pack is placed in its entirety inside it and is only removed after all the pills have been taken;

6) a microcontroller (14) with an application or program capable of:

® have a personalized interface to receive patient information, store it and transmit it to the device;

® manage points a, b, c and d above;

® detect if the pill has been removed in real time;

® plan actions with time intervals;

® check the scheduled time for taking the pill;

® update your internal clock via the server to keep the time always up to date; ® periodically sample the presence of each pill; and ® indicate battery charge.

2. Blister device connected to an external server, according to claim 1, characterized by having four main macro functions, as indicated below:

- visually inform the patient, through one or more light emitters, the time to take their pill, the number of pills to be taken, how much time is left for them to take the pill within the correct time interval and if the patient is at risk due to poor adherence to treatment (4);

- monitor in real time through a blister scanning system when a pill extraction event occurs;

- the patient extracts the tablet through an extractor button, with it being expelled through a hole in the device;

- memorize these data and send them to an external server so that the data can be compiled and transformed into relevant information for the patient's health; and further comprises a microcontroller (14) with program.

3. Blister device connected to an external server, according to claim 2, characterized by comprising a program that:

(a) indicates pill consumption status;

(b) indicates the safe time interval for consumption in case of forgetting;

(d) detects the presence/absence of each pill;

(e) performs it! above-mentioned detection at pre-programmed time intervals;

(f) plan actions with time intervals;

(g) check the time scheduled for taking the pill;

(i) periodically sampling the presence of each pill;

(j) indicates the battery charge, alternating the color of the battery to indicate that the battery is low, that the device is charging and finally when the battery is already fully recharged;

4. Blister device connected to an external server, according to claim 1, characterized by signaling different situations using different colors, frequencies and intensity of light emitters.

5. Blister device connected to an external server, according to claim 1, characterized in that it comprises a flexible polymer cover.

6. Blister device connected to an external server, according to claim 1, characterized in that it internally comprises a PCB board (8), phototransmitters that identify the passage of side light (10) and side light emitting sources (11) .

7. Blister device connected to an external server, according to claim 1, characterized in that it comprises a wireless communication module (12),

8. Blister device connected to an external server, according to claim 1, characterized in that it comprises USB output for charging battery (13) and battery (18).

9. Blister device connected to an external server, according to claim 1, characterized by employing contraceptive bisters.