CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Serial No.

62/700,183, which was filed on July 18, 2018.

[0002] The present application also claims priority as a continuation-in-part of

International Patent Application SER. NO. PCT/US18/40150, filed June 28, 2018, and titled "System. Methods, & Device for Managing a Product", which claims priority to U.S. Provisional Serial No. 62/525,806 filed on June 28, 2017, and U.S. Provisional Serial No. 62/665,504 filed on May 2, 2018, and U.S. Provisional Serial No. 62/688,976 filed on June 22, 2018.

[0003] The present application also claims priority as a continuation-in-part of U.S.

Utility Patent Application Serial No. 14/824,231, filed 8/12/2015, know allowed, and titled “System and Method for Monitoring Pill Container Activity”, which claims priority to U.S. Provisional 62/036,272, filed on August 12, 2014.

[0004] All aforementioned applications are herein incorporated by reference in their entirety.

FIELD

[0005] The various embodiments of the present disclosure are generally related to smart drug delivery systems for pills.

BACKGROUND

[0001] Many people have stated that smart pill caps and reminder devices have not had a significant impact on medication adherence, or on healthcare outcomes. For example, Choudry et al found that,“no statistically significant difference in adherence was found between those in the control group and those who received a reminder device (pill bottle strip with toggles, digital timer cap, or standard pillbox)” [1].

[0002] Volpp et al concluded,“A compound intervention integrating wireless pill bottles, lottery-based incentives, and social support did not significantly improve medication adherence or vascular readmission outcomes for AMI survivors.” [2]. [0003] What is needed within the vitamin and pharmaceutical industry is an improved drug delivery device for use with medications and vitamins to safely store, automatedly remind the user of a dose, monitor remotely adherence of dosing by caregivers/family/clinicians for improved adherence, and allow user auto-refilling by activating a refill mechanism on the device.

SUMMARY

[0004] Disclosed herein is a drug delivery device comprising a smart cap with a generic vial or a compatible vial (e.g. with childproof hooks and/or push tab) that stores a pill (vitamin or prescription drug), a kit comprising the device and pills, a networked system and a method of treating a disorder by utilizing the device. The various embodiments comprise a wireless pill cap that connects to smartphones, and an accompanying software platform, that can be used as a method to improve medication adherence, and thus health outcomes.

[0005] In an embodiment, the pill within the vial is a brand name drug, or a generic version thereof, or an over-the-counter supplement (e.g. vitamin), for the treatment or prevention of one or more diseases and disorders, such as the non-limiting examples listed in Table 1.

[0006] In another embodiment, the present disclosure comprises a drug delivery device comprising at least one statin compounds able to treat and/or prevent the diseases hyperlipidemia and/or coronary artery disease, wherein the pharmaceutical compound is at least one of: rosuvastatin, atorvastatin, simvastatin, pravastatin, lovastatin, pitavastatin, and/or Fluvastatin; or an extended release version of thereof. The embodiment further comprises a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device and the dosing schedule of the compound.

[0007] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease hypertension, wherein the pharmaceutical compound is at least one of one of Lisinopril, benazepril, enalapril, Ramipril, quinapril, fosinopril, captopril, tradolapril, moexipril, or perindopril. The embodiment further comprises a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device with the system, and the dosing schedule of the compound.

[0008] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease of heart failure, wherein the pharmaceutical compound is at least one of: sacubitril, valsartan, subitril/valsartan (e.g. a ratio of 1:1) (Entresto®), lisinopil, metoprololer, hydroclorothiazide, furesemide, carvedilol, spironolactone, enalapril, chlorthalidone, digoxin, digitek, torsemide, bumetanide, quinapril, metolazone, telmisartan, indapmide, fosinopril, candesartan, carvedilol, corlanor, bidil, ethacrnic acid, dyrenium, carospir, gonitro, ibuprofen lysine, neoprofen or isuprel. The embodiment further comprises a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device with the system, and the dosing schedule of the compound.

[0009] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease schizophrenia, and further comprising a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device with the system, and the dosing schedule of the compound. Non- limiting exemplary compounds are: Aripiprazole; Asenapine; Brexpiprazole; Cariprazine; Clozapine; Iloperidone; Lurasidone; and Olanzapine.

[0010] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease depression and the pharmaceutical compound is one of sertraline, fluoxetine, trazodone, duloxetine, escitalopram, citalopram, bupropion xl, venlafaxine er, amitriptypline, amitriptyline, bupropion sr, paroxetine, mirtazapine, aripiprazole, nortriptyline, bupropion, venlafaxine, doxepin, desvenlafaxine succinate er, vortioxetine, viibryd, quetiapine er, imipramine hydrochloride, brexpiprazole, norpramin, fetzima, nefazodone, levomefolate, perphenazine / amitriptyline, chlordiazeproxide / amitriptyline, forfivo XL, protriptyline, phenelzine, emsam, imipramine pamoate, tranylcypromine, olanzapine/fluoxetine, desvenlafaxine, pamprotiline, aplenzin, amoxapine, paroxetine, trimipramine, isocarboxazid and/or trazodone.

[0011] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease multiple sclerosis and the pharmaceutical compound is one of fingolimod, and/or dimethyl fumarate, and/or teriflunomide; and further comprising a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device with the system, and the dosing schedule of the compound.

[0012] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease breast cancer and the pharmaceutical compound is one of Ribociclib, and/or Abemaciclib; and further comprising a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device with the system, and the dosing schedule of the compound.

[0013] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent an adverse immune response in a patient with an organ transplant, and the pharmaceutical compound is one of Everolimus; and further comprising a kit containing at least one drug delivery device containing a plurality of doses of the compound, and printed instructions, or a web link to instructions, on how to use the device with the system, and the dosing schedule of the compound.

[0014] In embodiment, the present disclosure comprises a method of treatment of a disease or disorder, such as one disclosed herein, the method comprising providing a smart cap drug delivery device comprising: 1) a therapeutically effective amount of a pharmaceutical compound or vitamin in at least one of a tablet, a pill, or a capsule formulation for oral administration to a patient in need thereof; and 2) a drug delivery device able to store the compound or vitamin, and wherein the device comprises an electronic pharmaceutical packaging. The packaging further comprises: a) a smart cap with a secured generic pill vial (device 200, 300, 400 disclosed herein) or a smart bottle, and the cap is capable of detecting interaction with the vial/bottle for removal of a compound dose and transmitting data wirelessly to a first remote computer (e.g. a user smartphone); or wherein the electronic pharmaceutical packaging is a smart pill bottle (e.g. the vial is not generic). Alternatively, the electronic pharmaceutical packaging is a blister card with a uniquely identifiable printed electronic circuit covering each dose.

[0015] The method of treatment further comprises: 3) using the smart cap drug delivery device to perform one or more of the following: a) schedule alarms that cause audio or visual cues to be emitted by either the cap or a remote computer (e.g. a user’s smartphone); b) monitor drug taking adherence by recording when the cap is opened and closed, and relying data to a remote computer (e.g. caregiver/clinician/pharmacy); and/or c) activate a prescription refill request via a user predefined action on the cap or blister card or case/holder.

[0016] In another embodiment, the smart drug delivery device comprises: 1) a therapeutically effective or prophylactic effective pharmaceutical compound or vitamin in at least one of a tablet, a pill, or a capsule formulation for oral administration to a patient in need thereof; and 2) a drug delivery device storing the compound and comprising an electronic pharmaceutical packaging comprising: a) a cap unit comprising a housing with a cover portion removably attached to a bottom portion, and encasing a printed circuit board and a power source in-between the cover portion and the bottom portion, wherein the printed circuit board comprises at least one sensor for detecting an open state and a closed state of the cap unit from a container unit, a wireless radio transmitter, a microprocessor, and a local memory; b) a push- plate disposed relative to the printed circuit board for movement of the push-plate to activate the sensor when the cap unit is either secured to the container unit in a closed state or is removed from the container unit in an open state; and c) wherein the microprocessor is configured to store in memory information corresponding with the push-plate activating and/or deactivating the contact sensor, and the radio transmitter is able to wirelessly transmit the information to a user electronic computing device. The cap’s printed circuit board may further comprise one or more of the following: a global positioning sensor (e.g. a GPS chip) for the system to detect the location of the cap; an accelerometer to wake the device from a low-power state, or to detect a pre-defined action (e.g. a shake or a top to initiate a refill); and a display screen for a user to see the time, remaining doses, etc., and comprising for example, LED’s or a low power screen (e.g. e-ink).

[0017] Additionally, the sensor is activated when the cap unit is in the closed position and is deactivated when the cap unit is removed from the container in the open state. Information stored by the microprocessor comprises an access event log of opening and closing events of the cap unit, and/or double tapping on the cap unit to order a smart monitor device refill. The printed circuit board local memory comprises non-transitory, tangible computer- readable storage medium comprising a data storage unit and a data monitoring module. The data storage unit further comprises a token comprising a device identifier unique to the smart monitor device. The sensor comprises a depressor switch connected to the printed circuit board on one side, and in contact with the push-plate on a switch opposing side. The printed circuit board is oriented horizontally to the cover portion, and wherein the printed circuit board is between about 25 and 45 mm in diameter. The sensor is placed on the side of the printed circuit board that is facing the container unit.

[0018] Additionally, the microprocessor comprises a Bluetooth chip; and the wireless radio transmitter operates at 2.4 GHz and is able to transmit the open and closed state of the cap unit, and/or double pressing of the cap unit, to a user electronic computing device. The wireless radio transmitter sends wireless advertisement packets at a first interval when there is no new data to sync, and at a second interval when there is un-synced data remaining in the memory. And/or the wireless radio transmitter transmits at a first energy level when there is no new data to sync, and at a second energy level when there is un-synced data remaining in memory. An electrical current supplied to the wireless radio transmitter from the power source and through the printed circuit board is between about 0.5mA and 25 mA when the wireless radio transmitter is advertising or is connecting to a user electronic computing device. The electrical current supplied to the wireless radio transmitter from the power source and through the printed circuit board is between about 0.5mA and 10 mA when the wireless radio transmitter is receiving a wireless signal from the user electronic computing device.

[0019] Additionally, the cap comprises an alert indicator comprising an audio indicator, a visual indicator, or a combination thereof to generate a signal to a user indicating the occurrence, or lack thereof, of a smart monitor device access event comprising a missed dose, an early dose, a late dose, and a scheduled dose. The audio indicator comprises a piezo buzzer and speaker able to generate an audible noise upon the microprocessor’ s determination of the occurrence, or lack thereof, of the container unit access event.

[0020] The cap further comprises a user control mechanism to automatedly order a smart monitor device refill, the mechanism comprising the microprocessor detecting the cap unit being depressed and released two sequential times, in rapid succession. The user control mechanism comprises the upper surface of the depressor switch connected to the printed circuit board, and the lower surface in contact with a push-plate, and wherein the microprocessor is able to receive a signal from the depressor switch when compressed by the push-plate upon a user depressing and releasing the cap unit two sequential times, in rapid succession. The microprocessor is configured to: store in memory information corresponding with the push- plate pressing against the contact sensor, the information indicative of the user pressing and releasing the cap unit two sequential times, in rapid succession; and in response, configured to wirelessly transmit a refill request. The bottom portion comprises a cylindrical adapter ring configured to hold the push-plate in position. The sliding push-plate is non-flexible with or without springs, or is flexible between a center region thereof and an outer periphery thereof in response to engagement with the container unit.

[0021] The various embodiments of the present disclosure further comprise a computer program product (e.g. non-transitory computer readable medium) for the smart device and networked system, and able to carry out any of the methods disclosed herein.

[0022] Further areas of applicability will become apparent from the description provided herein. It should be understood that the description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The above, as well as other advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description when considered in light of the accompanying drawings.

[0024] FIG. 1 is a block diagram depicting an exemplary networked system for managing a product, in accordance with certain example embodiments, comprising a smart cap/vial, a first remote computer (user device), second remote computer (Dose Management System), and Provider computer (e.g. Pharmacy).

[0025] FIG. 2A is a top perspective view of the smart drug delivery of one embodiment comprising: 1) a cap with a flexible sliding push-plate (without springs) activating a switch contact sensor, and a vial with child proof hooks; and 2) a plurality of tablets of a vitamin or a prescription drug.

[0026] FIG. 2B is a longitudinal cross-sectional side view of the smart cap/vial drug delivery device of FIG. 2A taken along line C-C, illustrating the electrical-mechanical components within the cap unit with the flexible push-plate.

[0027] FIG. 2C is an exploded see-through view of the cap and vial of FIGS. 2A-2B.

[0028] FIG. 2D is a perspective view of the inside of the cap of FIGS. 2A-2D illustrating the childproof catch protrusions.

[0029] FIG. 2E is a side elevational view of the vial with childproof hooks that fit into the cap catch protrusions.

[0030] FIG. 2F is an illustration of a cross-sectional view of the printed circuit board, the flexible push-plate, and the depressor switch when the cap is removed from the pill container (open).

[0031] FIG. 2G is an illustration of a cross-sectional view of the printed circuit board, the flexible push-plate and the depressor switch when the cap is securely fastened to the pill container (closed) or is being double tapped by the user to wirelessly, automatedly order a prescription refill.

[0032] FIG. 3A is a top perspective view of the cap comprising the bottom portion with the top portion removed, exposing the printed circuit board with the replaceable battery.

[0033] FIG. 3B is a top plan view of an exemplary printed circuit board.

[0034] FIG. 3C is a bottom perspective view of the printed circuit board that includes a depressor switch. [0035] FIG. 4 illustrates an embodiment of the smart drug delivery device comprising a top perspective view of an exemplary smart monitor device comprising a cap unit connected to a pill container, and able to wirelessly communicate with a user’s electronic computing device, as disclosed in U.S. Patent Application Serial No. 14/824,231, now allowed, and filed 8/12/2015 and published as US 20160048657 Al, wherein the cap comprises a non-flexible sliding push-plate without springs.

[0036] FIGS. 5A-5F illustrate another embodiment of the cap/vial comprising a non- flexible sliding push-plate with springs and a vial with threads to twist onto the cap

[0037] FIG. 5A is a top perspective view of another embodiment of the smart drug delivery device 300, comprising: 1) a cap with a non-flexible sliding push-plate with springs activating a switch contact sensor, and a vial with threads; and 2) a plurality of tablets of a vitamin or a prescription drug.

[0038] FIG. 5B is a longitudinal cross-sectional side view of the smart cap/vial drug delivery device of FIG. 5A taken along line C-C, illustrating the electrical-mechanical components within the cap unit with the flexible push-plate.

[0039] FIG. 5C is an exploded see-through view of the cap and vial of FIGS. 5 A or 5B.

[0040] FIG. 5D is a side elevational view of a bottle with external threads that is used in lieu of the vial, for smart caps disclosed herein comprising internal matching threads.

[0041] FIG. 5E is a bottom perspective view of the cap of FIGS. 5A-5C comprising inner threads matching the vials external threads, and two childproof notches requiring the user to push down and rotate the cap.

[0042] FIGS. 6A-6G comprise electric schematic illustrations of components of the printed circuit board within the cap unit and the blister card or holder.

[0043] FIG. 6A illustrates an exemplary electrical schematic for the microprocessor comprising flash memory and antenna for short range wireless transmissions.

[0044] FIG. 6B illustrates an electric circuit schematic able to connect a button (or the internal contact sensor) to one of the general-purpose input-output pins of the SoC.

[0045] FIG. 6C is an exemplary electrical circuit schematic illustrating the LED on the printed circuit board, which can be used to notify or reminder the user.

[0046] FIG. 6D exemplary electrical circuit schematic illustrating a power circuit that is used to connect the coin cell battery.

[0047] FIG. 6E is an electrical circuit schematic of the programming port on the printed circuit board (PCB).

[0048] FIG. 6F is an electrical circuit schematic of the PCB real-time clock (RTC). [0049] FIG. 6G illustrates an exemplary electrical schematic for the piezo buzzer.

[0050] FIG. 7 is an illustration on one embodiment of the blister card comprising the electronic, wireless circuit that communicates with the user’s smartphone.

[0051] FIG. 8 is an illustration of a blister card holder (e.g. a carrier case) in which the holder comprises the wireless electronic circuitry.

[0052] FIG. 9 is a block diagram, depicting a computer components for network of computers of FIG. 1, in accordance with certain example embodiments.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0053] The following description is merely exemplary in nature and is not intended to limit the present disclosure, application, or uses. It should be understood that throughout the drawings, corresponding reference numerals indicate like or corresponding parts and features.

[0054] Throughout this specification and in the claims that follow, the following terms are defined with the following meanings, unless explicitly stated otherwise.

[0055] The term“prevention” refers to prophylactic administration to a healthy subject to prevent the development of the conditions mentioned herein. Moreover, the term “prevention” means prophylactic administration to patients being in a pre-stage of the conditions to be treated.

[0056] The term“treatment” is understood the management and care of a patient for the purpose of combating the disease, condition or disorder.

[0057] The term“therapeutically effective amount” refers to an amount of a drug or a therapeutic agent that will elicit the desired biological and/or medical response of a tissue, system or an animal (including man) that is being sought by a researcher or clinician.

[0058] The terms“patient” include, but are not limited to, humans, dogs, cats, horses, pigs, cows, monkeys, rabbits and mice. The preferred patients are humans.

[0059] The terms“administration of’ and or“administering a” compound should be understood to mean providing a compound of the invention or a pharmaceutically acceptable salt or ester thereof, or a pro-drug thereof to a subject in need of treatment. The administration of the composition of the present invention in order to practice the present methods of therapy is carried out by administering a therapeutically effective amount of the compounds in the composition to a subject in need of such treatment or prophylaxis. The need for a prophylactic administration according to the methods of the present invention is determined via the use of well-known risk factors. The effective amount of an individual compound is determined, in the final analysis, by the physician in charge of the case, but depends on factors such as the exact disease to be treated, the severity of the disease and other diseases or conditions from which the patient suffers, the chosen route of administration, other drugs and treatments which the patient may concomitantly require, and other factors in the physician's judgment.

[0060] The term“prophylactically effective amount” as used herein means the amount of the active compounds in the composition that will elicit the biological or medical response in a tissue, system, subject, or human that is being sought by the researcher, veterinarian, medical doctor or other clinician, to prevent the onset of a disease characterized and/or manifested by atrial enlargement and/or remodeling.

[0061] As used herein, the term“about” or“approximately” refers to +1-20%, +/- 10%, or +1-5% of a value.

[0062] As used herein, the term“pharmaceutical” refers to a brand name drug and/or it generic version. It may be a prescription or an over-the-counter drug.

[0063] The term “pharmaceutically acceptable”, as used herein, refers to those compounds, materials, compositions and/or dosage forms, which are, within the scope of sound medical judgment, suitable for contact with the tissues of mammals, especially humans, without excessive toxicity, irritation, allergic response and other problem complications commensurate with a reasonable benefit/risk ratio.

[0064] As used herein, the term“vitamin” is a prescription or over-the-counter supplement to facilitate improving a user’s health.

[0065] As used herein, the term“compound” refers to both a prescription or over-the-counter pharmaceutical and a vitamin.

Device of Drug and Pill Container

[0063] A smart drug delivery device, a kit comprising at least one smart device, and a method for treatment or prevention of a disease using the smart device, the smart drug delivery device comprising: 1) a therapeutically effective amount and/or a prophylactically effective amount of pharmaceutical compound or vitamin in at least one of a tablet, a pill, or a capsule formulation; 2) an electronic pharmaceutical packaging (smart cap device- cap w / generic vial, or specialized vial w / hooks and/or push tab) that’ s capable of detecting interaction with the packaging for removal of a dose and transmitting data wirelessly to a first remote computer; 3) at least one scheduled alarm that causes audio or visual cues to be emitted by either the pharmaceutical packaging or a remote computer. The pharmaceutical compound is deemed safe and effective for treating or preventing at least one medical condition or a user’s overall health.

[0064] In an embodiment, that pharmaceutical compound is one or more of those listed in Table 1, although it is understood that the present disclosure covers any pharmaceutical or vitamin pill for use in the smart drug delivery device.

TABLE 1

[0064] In an embodiment, the pharmaceutical sacubitril and valsartan at a ratio between

40:60 and 60:40, by mass or weight. In an embodiment, this combination is used with the connected smart cap device platform described herein as a method for treating heart failure and/or hypertension. The smart device, kit and method of treatment further comprise the administration of a therapeutically effective amount, or a prophylactically effective amount, of a combination of sacubitril or a pharmaceutically acceptable salt thereof and valsartan or a pharmaceutically acceptable salt thereof in a 1:1 molar ratio to said patient.

[0065] In the context of the present invention, the“sacubitril and valsartan in a 1:1 molar ratio” are delivered to a patient in need thereof, in the form of a pharmaceutical composition comprising (i) valsartan or a pharmaceutically acceptable salt thereof; and (ii) sacubitril or a pharmaceutically acceptable salt thereof. And the sacubitril and valsartan in a 1 : 1 molar ratio may be in the same tablet or capsule.

[0066] In an embodiment, a patient in need of treatment for heart failure comprises at least one of the following characteristics: 1) heart failure of NYHA class II, III or IV; 2) an elevated plasma BNP or NT-proBNP level, preferably a plasma BNP >100 pg/mL (or NT- proBNP >400 pg/mL), more preferably a plasma BNP >150 pg/mL or NT-proBNP >600 pg/mL; and 3) a reduced left ventricular ejection fraction (LVEF) of <40%, preferably <35%.

[0067] In an embodiment, the present disclosure comprises a method of treatment or prevent heart failure and/or hypertension, comprising orally administering from a smart drug delivery device disclosed herein (e.g. 101, 300, 400) to a patient in need thereof a twice- daily target dose of 200 mg of sacubitril and valsartan in a 1:1 molar ratio (e.g. LCZ696). The smart drug delivery device additionally performs one or more of the following tasks: 1) schedules alarms that cause audio or visual cues to be emitted by either the cap or a remote computer; 2) monitors drug taking adherence by recording when the cap is opened and closed, and relies upon data to remote a computer (e.g. caregiver/clinician/pharmacy); and/or 3) activates a prescription refill request via a user predefined action on the cap or blister card or case/holder. [0068] In an embodiment, this combination is used with the connected smart cap device platform described herein as a method for treating heart failure, and where medication adherence to the drug combination is greater than 80% on average, as measured by the drug device combination.

[0069] In an embodiment, this combination is used with the connected device platform described herein as a method for treating heart failure, and where there is a significant difference in ejection fracture before and after treatment. Exemplary drugs suitable for use in the present invention comprise: U.S. Patent Application 20180125820 Al, May 9, 2016, by Novartis, entitled“SACUBITRIL-VALSARTAN DOSAGE REGIMEN FOR TREATING HEART FAILURE”; U.S. Patent 8,796,331 B2 filed by Novartis, that issue Aug 5, 2014, entitled“Methods of treatment and pharmaceutical composition”; and U.S. Patent Application 20180140579 Al by Novartis, that published on May 24, 2018, entitled“SACUBITRIL AND VALSARTAN FOR TREATING METABOLIC DISEASE”. The aforementioned publications are hereby incorporated by reference in their entirety.

[0070] In an embodiment, the SACUBITRIL-VALSARTAN pills, tablets (e.g. coated) or capsules are administered in one unit dose form at 1 : 1 molar ratio, or in two separate unit dose oral forms.

[0071] In an embodiment, the SACUBITRIL-VALSARTAN pills, tablets (e.g. coated) or capsules are administered in the two separate unit oral dose forms are in a kit.

Multiple Sclerosis

[0072] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease multiple sclerosis; and the pharmaceutical compound is one of fingolimod, and/or dimethyl fumarate, and/or teriflunomide.

[0073] In an embodiment, the pharmaceutical compound is Ribociclib provided in a tablet or capsule form at a dosage per tablet or capsule is between about fingolimod 0.25mg or 0.5mg.

[0074] In an embodiment, the pharmaceutical compound is dimethyl fumarate provided in a tablet or capsule form and wherein the dosage per tablet or capsule is between about 50mg and 250 mg. [0075] In an embodiment, the pharmaceutical compound is dimethyl fumarate provided in a tablet or capsule form and wherein the dosage per tablet or capsule is between about 120 mg and 240 mg.

[0076] In an embodiment, the pharmaceutical compound is teriflunomide provided in a tablet or capsule form and wherein the dosage per tablet or capsule is between about 3mg and 25 mg.

[0077] In an embodiment, the pharmaceutical compound is teriflunomide provided in a tablet or capsule form and wherein the dosage per tablet or capsule is one of about 7 mg and 14 mg.

Breast Cancer

[0078] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent the disease breast cancer and the pharmaceutical compound is one of Ribociclib, and/or Abemaciclib.

[0079] In an embodiment, the pharmaceutical compound is Ribociclib provided in a tablet or capsule form at a dosage per tablet or capsule is between about lOOmg and 800 mg.

[0080] In an embodiment, the pharmaceutical compound is Ribociclib provided in a tablet or capsule form at a dosage per tablet or capsule of one of about 200mg, 300mg, 500mg, 600mg, or 800mg.

[0081] In an embodiment, the pharmaceutical compound is Abemaciclib provided in a tablet or capsule form and wherein the dosage per tablet or capsule is between about 25 and 400 mg.

[0082] In an embodiment, the pharmaceutical compound is Abemaciclib provided in a tablet or capsule form and wherein the dosage per tablet or capsule is one of about 25mg, 50mg, lOOmg, 150mg, 200mg, 250mg, or 300mg.

Organ Transplantation

[0083] In an embodiment, the present disclosure comprises a drug delivery device comprising at least one compound able to treat and/or prevent an adverse immune response in a patient with an organ transplant, and the pharmaceutical compound is one of Everolimus.

[0084] In an embodiment, the Everolimus compound is provided in a tablet or capsule form and wherein the dosage per tablet or capsule is between about 0.25 and 4 mg; or is one of 0.25mg, 0.5mg, 0.75mg or lmg. The resulting trough concentrations in the patient are within the 3-8 ng/mL target range using a LC/MS/MS assay method. And the recorded dose history that is recorded by the smart monitoring device is incorporated into an algorithm that is also informed, at least in part, by the resulting trough concentration levels as a method for adjusting and optimizing a patient’s dosing level or frequency.

Kits:

[0085] The invention also relates to combining at least one vitamin and/or pharmaceutical compositions in kit form, which includes at least one smart drug delivery device.

[0086] For example, a kit combines two separate units: e.g. a valsartan pharmaceutical composition and a sacubitril pharmaceutical composition, wherein at least one composition is in tablet or capsule from and is housed with a smart drug delivery device (101, 300, 400) disclosed herein. The kit form is particularly advantageous when the separate components must be administered in from different routes, or from different smart cap/vial devices as disclosed herein.

[0087] The invention also relates to combining separate pharmaceutical compositions in kit form, such as a kit combining two or three separate units of the same or of different routes of administration (tables in a smart caps/vials for one pharmaceutical, and parental or IV or other non-oral route for the other pharmaceutical). Although the kit form is particularly advantageous when the separate components must be administered in different dosage forms (e.g. parenteral valsartan formulation and oral other) or are administered at different dosage intervals, the administration of the single components of such a kit of parts may, without any restriction be affected simultaneously, sequentially or staggered with time.

[0088] All kits of the various embodiments disclosed herein, further comprise written instructions on the packaging of the kit on how to use the smart cap-vial drug delivery device, and the proper dose for the patient. In another embodiment, a link to a website is printed on the kit packaging for a method of use and precautions for using the smart cap-vial drug delivery device and/or pharmaceuticals or vitamins contained within the kit.

Example System Architecture

[0089] Turning now to the drawings, in which like numerals indicate like (but not necessarily identical) elements throughout the figures, example embodiments are described in detail. [0090] FIG. 1 is a block diagram depicting a wireless networked system for managing a smart drug delivery system, in accordance with certain example embodiments.

[0091] As described in FIG. 1, the exemplary operating system environment 100 includes a network computing user device 110 (e.g. their smartphone, tablet, etc.), a smart monitor device 120 (also known herein as a smart drug delivery device 120 per FIGS. 2A-8), a dose management system 130 (or“DMS”), and, in certain examples a medical provider system 140. In another example embodiment, two or more of these components (including components 110, 120, 130, and 140) or parts thereof can be integrated into the same system and/or device. In certain examples, a user 101 associated with a user device 110 must make a feature selection and/or install an application on the user device 110 to obtain the benefits of the methods described herein.

[0092] Each network component 110, 120, 130, and 140 of the example operating system environment 100 includes a device having a communication module (not shown) capable of transmitting and receiving data over the network 105. Further, each component 110, 120, 130, and 140 can include a server, desktop computer, laptop computer, tablet computer, a television with one or more processors embedded therein and/or coupled thereto, smartphone, handheld computer, personal digital assistant (“PDA”), smart watch, or any other wired or wireless, processor-driven device. In the example embodiment depicted in FIG. 1, the network components 110 and 120 can be operated, for example, by end-users or consumers or other end user operators. Likewise, the network components 130 and 140 can be operated by dose management system operators and provider system operators, respectively, or other end user operators.

[0093] The network 105 includes a wired or wireless telecommunication system or device by which network components (including components 110, 130, and 140) can exchange data. For example, the network 105 can include a local area network (“LAN”), a wide area network (“WAN”), an intranet, an Internet, storage area network (“SAN”), personal area network (“PAN”), a metropolitan area network (MAN), a wireless local area network (“WLAN”), a virtual private network (“VPN”), a cellular 2G, 3G, 4G, 5G, LTE, Narrowband IoT (“NB-IoT”) or other mobile communication network, Bluetooth, a wireless short-range 2.4 GHz connection, near field communication (“NFC”), or any combination thereof or any other appropriate architecture or system that facilitates the communication of signals, data, and/or messages.

[0094] As shown in FIG. 1, the user device 110 includes a communication application

111 and associated web browser (not shown) that can interact with web servers or other computing devices and systems connected to the network 105. For example, the communication application 111 can interact with web servers or other computing devices connected to the network 105, including web servers (not shown) of the dose management system 130 and the provider system 140. In certain examples, the communication application

111 can communicate directly, as shown, with the smart monitor device 120 via short-range data transmissions, such as via Bluetooth, near field communication, decodable audio signal, wireless short-range 2.4 GHz connection, or other short-range appropriate architecture or system that facilitates the communication of signals, data, and/or messages. A user 101 can use the communication application 111 of the user device 110, for example, to view, download, upload, or otherwise access information, web pages, or other data via a distributed network 105. For example, the user 101 may use the communication application 111 to receive data and information from the smart monitor device 120 (via short-range connections) and transmit those data to the dose management system 130 and/or the provider system 140.

[0095] As shown, the user device 110 can also include a dose management application

112 that is configured to interact and communicate with the smart monitor device 120, the dose management system 130, and the provider system 140 via communication application 111. For example, the dose management application 112 can be used and configured to receive and send device connection data to dose management system 130, such as data and information related to the connections status of the user device 110 to the smart monitor device 120 (e.g., when and for how long the user device 110 and the smart monitor device 120 were or have been connected). The dose management application 112 can also be used and configured to receive and send adherence data to the dose management system 130, such as data obtained from the smart monitor device 120 regarding access events and their associated timestamps. The dose management application 112 can also be used and configured to receive management parameters from the dose management system 130 and, thereby facilitating management of product on the user device 110. And, by communicating with the smart monitor device 120, the dose management application 112 of the user device 110 can receive a token from the smart monitor device 120 and communicate that token to the dose management system 130.

[0096] In certain example embodiments, the dose management application 112 can also be used and configured to receive, from the smart monitor device 120 and via the communication application 111, refill data or other information that can be transmitted to the dose management system 130, thereby triggering a refill request as described herein. The dose management application 112 can also be used and configured to provide notices to the user regarding a missed dose or a connection error, such as via providing a text notification or other alert on a user interface of the user device 110. In certain example embodiments, the dose management application 112 can include a user interface (not shown) that allows a user 101 or operator of the dose management system 130, for example, to input information into the dose management application 112. For example, a user 101 or other system operator may use a user interface of the dose management application 112 to input user credentials into the dose management application 112, which can then be used to authenticate the user device 110 as described herein. The user interface of the dose management application 112 can also be used and configured to receive, via the communication application 111, data or information regarding the product to be managed and associated management parameters, such desired reminder times and/or dosage time interval data or information.

[0097] As shown in FIG. 1, the user device 110 includes a data storage unit 113 that is accessible by the communication application 111 and the dose management application 112. In certain example embodiments, the data storage unit 113 can, at the option of the user 101, store user credentials in a user device log 114. The data storage unit can also store a token log 115 that can include one or more tokens associated with one or more smart monitors 120. For example, to manage multiple products, the token log may store multiple tokens, either for the same user or for different users. In certain examples, the data storage unit 113 can store connection content related to the connection of the user device 110 to other network devices, as well as adherence data received from the smart monitor device 120. The exemplary data storage unit 113 can include one or more tangible computer-readable media. The data storage unit 113 can be stored on the user device 110 or can be logically coupled to the user device 110. For example, the data storage unit 113 can include on-board flash memory and/or one or more removable memory cards or removable flash memory.

[0098] The smart monitor device 120 represents the component of the exemplary operating system 100 responsible for monitoring access event data, receiving a refill request from the user device 110 (e.g., via a user input into the device, such as via a button-click user control option) and initiating the refill request, and/or providing audio and/or visual alerts to the user 101 regarding a processed refill or a possible missed dose. The smart monitor device 120 can include a dose monitoring module 121 that performs the analytical functions of the smart monitor device, including, for example, identifying an access event and associating the access event with a timestamp. The dose monitoring module 121 may also receive and process alert instructions that direct the smart monitor device 120 to provide one or more alerts, such as alerts at different times. [0099] To provide an alert, the smart monitor device 120 can include an alert indicator 122 that operates to inform the user 101 of an event associated with management of the product. For example, upon receiving an instruction from the data management application 112 of the user device 110 to provide an alert for a missed dose, the dose monitoring module 121 can trigger the alert indicator to inform the user 101 of the possible missed dose. In another example embodiment, the dose monitoring module 121 may receive an instruction to notify the user 101 that a user-requested refill is ready, in which case the dose monitoring module 121 can trigger the alert indicator 122 to alert the user 101 regarding the refill. The alert provided by the alert indicator 122 can be any type of notification, such as an audio alert (e.g., a beep or buzz), a visual alert (e.g., a blinking light), or other detectable or perceptible alert (e.g., a vibration or haptic alert or notification).

[00100] In certain example embodiments, the smart monitor device 120 can include a clock or timer (not shown) that, for example, can be configured to trigger an event associated with the smart container 120 to occur at a certain time. The clock, for example, can be used to time-stamp events in real time and to manage alerts. For example, the clock or timer may trigger an alert at a specific time. And in certain example embodiments, the clock can be used to provide reminders to a user 101. For example, the smart monitor device 120 can, in certain example embodiments, provide reminders on its own via coordination with the clock or timer.

[00101] To communicate with other devices of the exemplary operating system environment 100, such as the user device 110, the smart monitor device 120 includes a short- range communication capability, such as Bluetooth, near field communication (“NFC”), a wireless short-range 2.4 GHz connection or any combination thereof or any other appropriate short-range architecture or system that facilitates the communication of signals, data, and/or messages to a computing device, such as the user device 110. Such short-range communication capabilities are beneficial, for example, as this provides a lower power burden, i.e., short-range transmissions use less power in comparison to longer-range transmissions. In certain example embodiments, the smart monitor device 120 can communicate directly with the network 105 and hence other devices on the network, such as via a low power cellular connection (e.g., NB- IoT) (dashed line, FIG. 1). In certain example embodiments, the short-range data communications between the user device 110 and the smart monitor device 120 are conducted at the 2.4 GHz wireless frequency, with an energy level provided by the electronic circuitry to provide a wireless transmission distance from the smart monitor device of between 50 and 1500 feet when transmitted in an open space, such as a range of between 50 and 300 feet. In certain example embodiments, a Bluetooth connection will be automatically established and held between the smart monitoring device 120 and the user device 110 whenever the two devices are in range of wireless communication, as according to protocols established in the Bluetooth 5.0 specification.

[00102] As shown in FIG. 1, the smart monitor device 120 includes a data storage unit 123 that is accessible, for example, by the dose monitoring module 121 and the communication module (not shown). The dosage storage unit 123 can include an access event log 124, such as a record of access events and associated timestamps for the access events associated with the smart monitor 120. The data storage unit 123 can also store a token, such as unique identifier for the smart monitor device 120 as described herein, the token being stored in a token storage 125. The exemplary data storage unit 123 can also include one or more tangible computer-readable media. The data storage unit 123 can be stored on the smart monitor device 110 or can be logically coupled to the smart monitor device 120. For example, the data storage unit 123 can include on-board flash memory and/or one or more removable memory cards or removable flash memory. In certain example embodiments, the data storage unit 123 may include between 100 and 5,000 kB of flash memory and between 24 and 1000 kB of RAM memory.

[00103] As will appreciated by those skilled in the art in view of this disclosure, the smart monitor device 120 described herein can be coupled to or otherwise associated with a container or dispenser, for example, such as a pill bottle or other receptacle. An example smart monitor device 120 that is compatible with the methods and systems described herein is disclosed in U.S. Pat. Pub. US20160048657, which is hereby expressly incorporated herein by reference in its entirety.

[00104] The dose management system 130 represents the component of the exemplary operating system 100 responsible for managing a product, such as in coordination with the user device 110, the smart monitor device 120, and the optional provider system 140. As shown in FIG. 1, the dose management system 130 includes a data processing module 131 that performs the analytical functions of the dose management system 130, such as authenticating the user device 110 of the user 101, managing a product associated with the user 101 (including a dose schedule for the product), processing refill requests received from the smart module 120, analyzing adherence data, verifying system connections, and/or triggering smart reminders.

[00105] As shown, the dose management system 130 can also include a web site 132 and an associated web server 133. The website 132, for example, can provide a user interface that can be accessed via the network 105. For example, a user 101, an operator (not shown) of the dose management system 130, and/or an operator of the provider system 140 (not shown) may access the dose management system 130 via the web site 132 to provide data and information to the dose management system 130, such as product characteristics for the product to be managed and/or credentials of the user 101. Such information can also include, for example, management parameters that can be input into the user interface of the website 132 and used to mage the product. The web server 133 , for example, can operate to provide content to the website 132, such as features and user- interface content that the user 101, operator of the dose management system 130, and/or operator of the provider system 140 can use to input information to the dose management system 130, thereby permitting the dose management system 130 to manage a product for the user 101.

[00106] As shown, the dose management system 130 can include a data storage unit 134 that is accessible by the data processing module 131 and the web server 133, for example. The data storage unit 134 can store information regarding a user 101, such as a dose schedule for a given medication or other product that is to be managed. In certain example embodiments, the data storage unit 134 can, at the option of the user 101, store user credentials in a user log 135. The data storage unit can also store a token log 136 that can include one or more tokens associated with one or more smart monitors 120. The exemplary data storage unit 134 can also include one or more tangible computer-readable media. The data storage unit 134 can be stored on a device of the dose management system 130 or can be logically coupled to the a devoice of the dose management system 130. For example, the data storage unit 134 can include on board flash memory and/or one or more removable memory cards or removable flash memory. In certain example embodiments, the dose management system 130 may be run on a series of distributed servers, sometimes referred to as“the cloud,” and may be managed by a third-party cloud services company, such as Microsoft AzureTM or AmazonTM Web Services.

[00107] In certain example embodiments, the exemplary operating system 100 can optionally include a provider system 140. The provider system 140, for example, represents a third-party system that can determine product characteristics and, via a communication application 143, for example, communicate the product characteristic to the dose management system 130, the user device 110, and/or the smart monitor device 120. For example, the provider system 140 may manufacture, supply, and/or provide access to one or more products, such as a medication or other product that can benefit from the product management methods and systems provided herein. The dose management module 141 of the provider system 140 can, for example, determine when a particular product should be taken or administered. The dose management module 141 can also determine dosage time interval information for the product and thereafter include such information with the management parameters. The dose management module 141 can also associate the product to be managed with a specific product identifier, such as a Universal Product Code (“UPC”) or, in the case of a medication, for example, and National Drug Code (“NDC”).

[00108] As shown, the provider system 140 can also include a web browser 142 that can be used to access the website 132 of the dose management system 130. For example, an operator (not shown) of the provider system 140 may use the web browser 142 to input information regarding the user 101 and/or the product characteristics into the dose management system 130 via the website 132 of the dose management system 130. The dose management system 130 can then use the received information according to methods and systems described herein. In certain examples, the provider system can also include a data storage unit (not shown), which can be used, for example, to store information regarding one or more products that may benefit from the product methods described herein. The data storage unit of the provider system 140 can be stored on a device of the of the provider system 140 or can be logically coupled to the a devoice of the of the provider system 140. For example, the data storage unit of the of the provider system 140 can include on-board flash memory and/or one or more removable memory cards or removable flash memory.

[00109] As those skilled in the art having the benefit of this disclosure will appreciate, all of the functions of the dose management system 130 can be performed on the user device 110, such as in conjunction with (or as integrated as part of) the dose management application 112. For example, the product characteristics and management parameters can be provided to the dose management application 112 of the user device 110, with the dose management application 112 thereafter managing the product as described herein. In certain other example embodiments, one or more of the functions of the dose management system 130 can be performed separately and independently from the user device 110 and vice versa. In other example embodiments, all or part of the functions of the dose management system 130 can be performed on the provider system 140, such as in conjunction with (or as integrated as part of) the dose management module 141 of the provider system 140.

[00110] In certain example embodiments, information can be communicated between the dose management system 130 and the provider system 140 over the network 105. For example, the provider system 140 may be an electronic health records system used by prescribing doctors to send prescribing information to the dose management system, and to receive medication adherence information from the dose management system 130 that can be displayed in the patient’s personal electronic health record. Data generated by the dose management system 130 can be combined with information in the provider system 140 to calculate patient risk levels for medication non-adherence or other risk factors. Such patients may also be flagged for intervention by the healthcare provider.

[00111] It will be appreciated that the network connections shown in FIG. 1 are exemplary and that other means of establishing a communications link between the computers and devices can be used. Moreover, those having ordinary skill in the art having the benefit of the present disclosure will appreciate that the user device 110, the smart monitor device 120, the dose management system 130, and the provider system 140 illustrated in FIG. 1 can have any of several other suitable computer system configurations. For example, a user device 110 embodied as a mobile phone or handheld computer may or may not include all the components described herein.

Smart Pill Cap

[00112] In an embodiment, the smart pill cap 211, 311, and 411 disclosed herein comprises: 1) a low-power wireless radio, that is capable of transmitting a signal to a smartphone; 2) an energy storage device, ideally of lithium chemistry; 3) a switch, which is activated and deactivated by the opening or closing of the cap; 4) a thread, that is compatible with a medication vial; 5) a local memory; and 5) a microcontroller comprising a printed circuit board housing a memory, at least one processor/microprocessor, a wireless transceiver-radio (Bluetooth®, cellular, WiFi chip, non-infrared, etc.), and connected to a battery (e.g. replaceable coin-shaped, or rechargeable prismatic pouch cell battery, atop or above the PCB); and a speaker on the cap top portion/cover able to emit audio messages to the user.

[00113] The smart pill cap is programmed to connect to a remote application that is running on a smartphone or other peripheral device, the peripheral device being connected to the internet via a cellular or WiFi connection.

[00114] When connected, the smart pill cap syncs all data to the application. This is referenced in our earlier cloud sync application.

[00115] The smart pill cap may also be pre-programmed with scheduled doses. If a dose is taken within a pre-programmed dose interval then the dose will be automatically recorded and a reminder will not occur. If the dose is not taken, then the cap will emit a reminder. Optionally, the app may also emit a series of reminders if a dose is not registered by the preprogrammed time. Additionally, an application running on a server may send a reminder if a dose is not recorded by the pre-programmed time. [00116] Messaging may also be delivered depending upon the last time the data from device has been synced to the internet. For example, if the last time the user connected to the internet was 48 hours ago, then the user may receive a message asking them to connect to the internet, where if they are currently connected to the internet then the message may remind them to take their medication.

[00117] An important part of this application is the connection of data. In the preferred embodiment a remote caregiver, such as a pharmacist, has access to the data through a clinical support platform, the clinical support platform providing a) a way to view medication adherence data and b) (preferably) a way to communicate with the patient.

[00118] In another embodiment, an activation of the switch may initiate a refill request that is sent to the user’s pharmacy. For example, if the user presses the switch twice within a predefined period of time (e.g. 1 second) a refill signal may be sent to the mobile app. This signal may then be relayed to servers, which are relayed to the user’s pharmacy system. Alternatively, the timestamp of the button press may be recorded, with a filter running on the servers interpreting two clicks within a period of time (e.g. 1 second) as an indication to send a refill request to the user’ s pharmacy. Optionally, the user may receive a confirmation message via SMS or in their mobile app prior to sending the refill request to their pharmacy.

[00119] Additional rules may be deployed based on the user’s observed medication adherence data. For example, if the user misses a predefined number of doses, then a specific intervention can be triggered, such as notification of their caregiver or an automated series of text messages.

[00120] In another embodiment, an adaptable survey may be initiated that is based on measured medication adherence data. For example, if the user is determined to be non-adherent then the remote server may initiate a text message or push notification where they are asked why they are non-adherence. A different digital intervention pathway may be triggered upon the users response. For example, if they claim that cost is an issue then they may be sent a co pay card. If they claim that side effects are an issue than they may be referred to a remote counselor, with the adverse events being reported to the FDA via an API call.

Smart Blister Card and Case

[00121] Various embodiments of a smart blister card and/or holder (e.g. a card carrier case) are envisioned within the scope of the present invention that can wireless communicate with the system of FIG. 1, in a manner analogous to the smart cap device. [00122] Blister Cards: As illustrated in FIG. 7, one embodiment of the smart blister card comprises a plurality of solid medication doses 710 stored inside of a blister card 700. Each dose unit 710 within the blister card may contain either a single dose of a single oral solid medication or a plurality of oral solid medications. The blister card is comprised of a plastic encasement and a coating material (e.g. a metallic foil). The blister card can be filled either manually or by a robotic filling system.

[00123] One embodiment (design B) comprises a smart Blister Card with a printed circuit or antenna covering each dose (e.g. FIG. 7, 720 wireless passive or active), a battery 730, a microprocessor 740, and a switch 750. In another embodiment the smart blister card itself has a series of circuits printed on the flat side of the card. With this design, at least one circuit is designed to be broken when a dose unit is emptied.

[00124] Breaking of a specific circuit can be detected through one of several means. The circuit may also be printed such that a series of circuits come in contact with a pin-type receptacle, the microprocessor detected which circuits have been broken and which have not, each pin corresponding to a different dose unit on the pin care.

[00125] A second circuit may be printed with a known resistance at each circuit. An electronic unit that is in direct contact with the circuit measures resistance. An algorithm run by the microprocessor calculates the doses that are emptied based on the known resistance of the circuit.

[00126] The blister card may contain multiple circuits of varying resistance between dose pods. Because the circuit may also function as an antenna, the state of the dose units may also be detected by backscattering a wireless signal from the transmitting radio. For example, a Bluetooth radio may broadcast one or more known frequency wireless signals to the printed antenna on the blister card. The returned wireless frequency, which is determined by the combination of broken antenna circuits, may be known to correlate to which dose units have been broken and which have not. This can be associated via a lookup table stored on the computer readable storage medium. This method is valuable because it requires no direct, physical connection between the smart blister card case and the smart blister card.

[00127] Design C: comprises a smart blister card with a passive wireless tag that is placed over each dose pod, the wireless tag being broken or removed during the removal of a dose. One potential method for monitoring such a tag is: 1) the microprocessor“wakes up” based on detected activity or a preprogrammed schedule; 2) the microprocessor directors the passive tag reader inside of the smart blister card case to emit a signal; 3) the unique tag IDs of the various tags are returned when the wireless signal is reflected by the passive tags; or 4) the microprocessor receives the signal from the active tags. In a preferred embodiment the wireless tags may respond at varying frequencies, with the passive tag reader being capable of emitting such frequencies. This is preferable in that the tag reader could ping a range of frequencies without receiving“noise” from every single tag at the same time.

[00128] Design D comprises a smart blister card with active wireless tags. In another embodiment, actively transmitting wireless tags are printed onto the blister card, with a power source either printed onto the same blister card or supplied in attachment. The wireless tags may be programmed to emit their signals in response to a known input, such as a the pushing of a button, accelerometer, a change in heat, a change in conductance or a wireless signal that is transmitted by the smart case.

[00129] A mechanical input (e.g. a button or finger connecting a conductive circuit) may be required to connect the power source to the active tags, therefore enabling the user to decide when to activate the power source. In another embodiment, infrared light sensors may be used to detect the state of a dose unit.

[00130] Combination with asynchronous video medication monitoring. In another embodiment, data from the smart medication system may be combined with data captured by asynchronous video medication monitoring.

[00131] Blister Case: various embodiments of the case are disclosed herein. Design A comprises a wireless case, with a user’s button (FIG. 8, 810) that can be pressed one time to snooze an alarm of a dose missed, and pressed twice to indicate that the user has taken the dose. In one embodiment the blister card may be contained inside of a case that is designed to shield the blister card from view. This case may be made of either a flexible material such as silicone or a rigid material, such as plastic or metal.

[00132] An electronics unit is contained inside of the blister card case 800 that is in communication with at least a wireless radio (e.g. with a Bluetooth® chip), computer readable storage, a microprocessor, a power source, and a dose sensor that are connected by a printed circuit or flex board. In a preferred embodiment the dose sensor is a button 810 or switch that is designed to be manually pressed by the user after a dose is taken.

[00133] In another preferred embodiment the device also includes a speaker or buzzer within 830, the speaker or buzzer preferably being a low-power piezo-type buzzer (find speaker spec), the speaker or buzzer being programmed to emit a noise on a preprogrammed schedule (dose schedule) unless a dose is registered as being taken within the pre-programmed dose window. The button is ideally between 1 mm and 80mm in each dimension. [00134] The wireless radio may be one of either Bluetooth, WiFi, 3G, 4G, 5G or other cellular radio. In a most preferred embodiment the wireless radio is low-power (e.g. Bluetooth Low Energy standard), LTE-M or NbloT.

[00135] Optionally, the electronics unit may also contain a short-range wireless tag reader (e.g. NFC or RFID), the wireless tag reader intended to read wireless tags that are printed on the blister card. The wireless tag reader may also be intended to read wireless tags that are incorporated into the oral solid medication itself.

[00136] Optionally, the electronics unit may also include a plurality of infrared lights and infrared light sensors, the infrared lights emitting light onto the dose pods. The scattered light is then detected by infrared light sensors. The resulting readings are then analyzed by the microprocessor, which uses a known algorithm to correlate this data to determine the state of each dose unit. We have validated this method at the bench scale.

[00137] Optionally, the electronics unit may also include a wireless charger. The power source may be either a replaceable or rechargeable lithium-chemistry battery. In an ideal embodiment the anode of such a battery is made of non-doped lithium metal. In another embodiment a thin battery (e.g. thin film) may be printed directly onto the blister card itself.

[00138] Optionally, the electronics unit may also include an accelerometer. Data from the accelerometer may be used by the microprocessor to active the device into a high-powered, more active state (e.g. increasing wireless radio advertising frequency or strength, or activating a sensor) in response to movement detected by the accelerometer.

[00139] Optionally, the electronics unit may also include a display. Preferably, this display is low-power, such as an e-Ink or LED touchscreen display.

[00140] Optionally, a thumbprint scanner may also be included in the smart case. This could be beneficial for recording the identity of the person taking a dose. This information is particularly useful in research situations (e.g. a clinical trial), for controlled substances that have diversion issues (e.g. opioids) or when a patient may intend to be deceptive about whether or not they are taking their medications (e.g. medications for schizophrenia)

[00141] In a preferred embodiment the printed circuit board and all of the electronics are encased inside of a hard-plastic modularized encasement, the hard-plastic or metal modularized encasement, the modularized encasement being transferable into a plurality of case sizes or form factors. The modularized encasement can be secured into the modular encasement through a friction-type fit (if softer case), with an adhesive, or with a snap-fit (if harder plastic).

[00142] This modular approach has the benefit of reducing the cost of producing a single circuit board that can be used in a wide range of different sizes and shapes of blister cards. Without this approach manufacturing and regulatory costs of producing such a system that fits the wide range of blister card would be prohibitively high.

[00143] In an embodiment, the blister case is a drug delivery device case comprising: a therapeutically effective amount of a vitamin or pharmaceutical compound in at least one of a tablet, a pill, or a capsule formulation able to treat or prevent a disease or disorder, said compound contained inside of a blister pack; and a smart blister pack case device able to communicate via a wireless network. The device further comprises: a case for holding blister packs; a hard plastic or metallic module embedded inside the case with a printed circuit board contained within an internal cavity inside of the module; the printed circuit board connecting a battery, a microcontroller, a wireless radio, a memory, and a switch contact sensor that is pressed by the user to manually record when a dose is taken; and wherein the microcontroller is configured to non-infrared, wirelessly transmit information indicative of a dose being taken to at least one of an external computer and/or a cellular gateway device. Additionally, the wireless radio is a low-power cellular radio having bandwidth between 150 KHz and 1.6 MHz, with a peak data rate of between 5 kbps and 500 Kbps, and with uplink transmission power between 15 and 30 dBm.

Method of Treatment

[00144] A method for treatment of a disease disclosed herein, comprises providing a smart cap drug delivery device comprising: 1) a pharmaceutical compound in at least one of a tablet, a pill, or a capsule formulation, and that is securely stored in device (2); and 2) the drug delivery device storing the compound and comprising an electronic pharmaceutical packaging. The electronic pharmaceutical packaging comprises: 1) a smart cap with a secured pill vial or bottle, and the cap is capable of detecting interaction with the vial/bottle for removal of a compound dose and transmitting data wirelessly to a first remote computer; or wherein the electronic pharmaceutical packaging is a smart pill bottle; or 2) a blister card or holder with a uniquely identifiable printed electronic circuit covering each dose.

[00145] The method of treatment further comprises using the smart cap drug delivery device to perform one or more of the following: 1) scheduling at least one alarm that causes audio or visual cues to be emitted by either the cap or a remote computer; 2) monitoring drug taking adherence by recording when the cap is opened and closed, and relying data to remote computer (e.g. caregiver/clinician/pharmacy); and/or 3) activating a prescription refill request via a user predefined action on the cap or blister card or holder.

[00146] In an embodiment, the pharmaceutical compound is one as listed in Table 1. For example, it is a combination of sacubitril and valsartan; and at a ratio of sacubitril to valsartan is between 40:60 and 60:40, by mass. The combination is used with the connected smart device platform described herein as a method for treating heart failure, and where medication adherence to the drug combination is greater than 80% on average, as measured by the drug device combination; and/or where there is a significant difference in ejection fracture before and after treatment.

[00147] In an embodiment, the patient also receives monetary, or psychological rewards based on the frequency of taking their medication, and wherein the rewards are cellular credits that can be used for their cellular phone or smartphone.

[00148] In an embodiment, an application running on the first remote computer also contains a password protected login, and a means for securely sending messages to a pharmacist or healthcare provider through an application running on a second remote computer.

[00149] In an embodiment, the patient is also included in an online community of patients with similar medical conditions or similar drugs

[00150] The patient can also make refills by pressing a single button on at least one of a) the electronical pharmaceutical packaging (cap-predefined action); or b) their first remote computer, this action sending a refill request via a central API. Wherein a refill is automatically ordered when estimated pill count reaches a pre-defined refill threshold, the estimated pill count being calculated by subtracting doses that are recorded via electronic pharmaceutical packaging or pushing a button in the first remote computer

[00151] The patient can also record biometric data into an application running on a first remote computer that wirelessly connects to their electronic pharmaceutical packaging, including at least one of their mood, energy level, or filling out a depression scale survey (PHQ 9), with data sent to a healthcare professional using a second remote computer.

[00152] In an embodiment, the data is transmitted less than 5000 feet and the remote computer is a smartphone. IN another embodiment, the data is transmitted more than 5000 feet over a cellular network and where the remote computer is a remote server

[00153] In an embodiment, the pharmaceutical data is entered remotely in a separate application by a pharmacist, nurse or other professional healthcare provider, and where this data is synced to the patient’s remote computer and/or to their electronic pharmaceutical packaging [00154] In an embodiment, the unique device ID of the electronic pharmaceutical packaging is used as an authentication factor to sign the user into an app running on the first remote computer, the unique device ID being first entered and associated with the patient on a separate remote computer, such as in a pharmacy. The association being made by one of a) scanning a barcode associated with the unique device ID or b) wirelessly connecting to the electronic pharmaceutical packaging and reading the unique device ID.

Drug and behavior-specific educational messaging and surveys

[0066] The method of treatment may also contain displaying educational content or messaging to the user that is specific to the drug that is being managed by the smart medication device, by their behavior (e.g. medication adherence), or both. This content may be displayed on the remote computer (e.g. within a secure application running on a smartphone or tablet) or sent via another communication channel such as text message, email, or automated phone recording. In either case, the educational content and messaging are influenced by the specific drug being managed with the smart device, the MAC address (or unique device ID) of the smart medication device corresponding to a known drug that is stored in the dose management system.

[0067] For example, a user may have a smart medication device that is managing an oral solid medication for an anti-depressant medication. Educational information related to the specific medication may be displayed on their smartphone. Examples of educational information may include potential adverse events that are known to occur with this product, product ratings or reviews, pricing information, the length of time that is typically required to see results and commonly prescribed alternatives. This information may be synced to from other third party databases, with the unique device ID (MAC address) of the smart medication device being used to look up the name and dosage of the drug in the dose management system prior to requesting additional information from the third-party database using a secure, web- based request (API request). Educational content may also be delivered for specific classes of drugs (e.g. for anti-depressants). Educational content may also contain personal or contextual information, such as the user’s name or location.

[0068] Surveys may also be deployed that are linked to the specific MAC address and the inferred product contained in the smart medication device. For example, if the smart medication device is known to contain an anti-depressant then a PHQ-9 depression survey may be automatically delivered on a prescheduled basis. [0069] Educational information and surveys may also be customized and delivered in response to a user’s observed medication adherence behavior, as measured by the smart medication device. For example, if the user misses 4 consecutive scheduled doses they may receive a message that says something like,“Hello, John, it looks like you’ve 4 consecutive doses this week. What’ s the problem?”

[0070] If the user responds to a survey or message this information may be displayed to their professional health care team, either in the web application (website) of the dose management portal, or in the user’s electronic health record. Medication adherence data, survey data, physiological data, lab data, notes and other data may be synced to the user’s electronic health record from the dose management system via a web-based API, including by using the HL7 FHIR standard.

Mediated digital support groups

[0071] An additional component of the method of treatment may include automatic enrollment in digital support groups of people who have similar conditions, or who are taking similar classes (or even the same drug). In order to maintain quality interactions, enrollment into these groups is likely to be capped at a certain number (e.g. 50 patients) and to be mediated by a professionally-trained group mediator. In this embodiment the patients interact through a patient-facing version application (e.g. the smartphone application). The professional mediator is likely to interact with the group through the web application that is designed for professional caregivers. As part of the group interaction, group members may receive access to viewing each other’s medication adherence or other personal health information, including but not limited to blood pressure, weight, medication adherence, pulse oximetry, heart rate, heart rate variability, EKG, ECG, depression score, mood score, caloric intake, steps, calories burned, meditation data, or other exercise data. These groups are intended to provide social support and social accountability, both principles that are thought to improve healthy behavior and adherence. Inclusion into the digital support group is driven by users being assigned to specific health conditions or medications. In the case of user being driven by a specific medication, such medication is linked to a specific MAC address or device ID of the smart medication device within the dose management system’ s database. Display of physiological data to the user

[0072] Physiological data may also be displayed to the user in the smartphone application, ideally in the same screen as medication adherence so they can observe the cause- effect relationship between medication adherence as recorded by the smart medication device and their desired health outcome. For example, a graph of medication adherence to an anti hypertensive may be overlaid on a graph of their blood pressure. In another embodiment a graph of medication adherence to an anti-depressant may be overlaid on a graph of a mood score or PHQ-9 score that is also recorded in the same application.

EXEMPLARY EMBODIMENTS OF THE SMART DRUG DELIVERY DEVICE

[00155] Various exemplary embodiments of the smart drug delivery device are disclosed within, per FIGS. 2A-8, in which each functions as part of the computer network of FIG. l’s, Smart Monitor Device. Each Drug Delivery Device comprises the smart cap with matching vial, and housing at least one type of tablet or capsule comprising a prescription medication or vitamin. It is understood that one of skill in the art could readily modify the: cap (e.g. 101, 311, 411), the vial, the bottle , and/or switch and modify vials and caps (e.g. use threaded vial with cap 411, wherein internal threads are added to cap), and/or the blister card/case to have the same functionality as the devices disclosed herein.

[00156] Non-limiting examples of container units suitable for fitting a smart cap unit of the present disclosure (e.g. 211, 311,411) to as part of a smart drug delivery device comprises: a container for pills or tablets or capsules, a container for vitamins or supplements, an inhaler, a syringe, a container for liquid medication, a medicinal eye drop container, a nasal spray container, infant formula container, nutritional food packaging, water and nutraceutical bottles, and the like.

Embodiment- Flexible Sliding Plate

[00157] FIGS. 2A-2G and 3A-3C illustrate an embodiment of the smart drug delivery device 400 that is able to wirelessly communicate with the networked system of FIG. 1, and comprising a smart cap/vial container (comprising cap 910 and vial 920) and the plurality of tablets or capsules 430 housed within.

[00158] As illustrated in FIGS. 2A and 2B, the outer housing of cap unit 910 comprises a top portion, such as a cover 918; and a bottom portion comprising an adapter ring 917 that holds the push-plate 914 in position. The bottom portion may further comprise an optional seam cover 919 to conceal the joint between the cover 918 and the adapter ring 917. The cover 918 is a thin circular disc that is removeable to expose the underlying battery 932, such as for battery replacement (see FIG. 3A- top perspective view of cap battery on printed circuit board with cover 918 removed).

[00159] In an example embodiment, adapter ring 917 is a plastic ring with a selected internal thread pattern matching (i.e. configured to cooperate with) a container unit 920 external thread pattern. Adapter ring 917 can also be swapped out to fit multiple container unit 920 types (of similar diameter) without changing the other smart device components.

[00160] FIG. 2B is a cross-sectional view taken along line C-C of FIG. 2A, and of an exemplary smart monitor device 400 comprising the cap unit 910 on a pill container unit 920. Cover 918 includes an indicator or indicator window 915 for a visual indication to a user, such as a light emitter, and conceals a piezo buzzer 931 within an internal cavity 923 defined by the cap unit 910. The piezo buzzer 931 may lie directly beneath cover 918. The outer housing of the cap unit 910 further comprises the adapter ring 917 on the cap’s bottom portion, with the seal 919 disguising the seam between adapter ring 917 and cover 918. Battery 932 is housed within the internal cavity 923 to power the onboard circuitry, such as a PCB 934 (e.g. see also FIGS. 6A-6G). The battery 932 may lie beneath the piezo buzzer and atop the PCB 934. A switch 936, which is in electrical communication with the PCB 934, extends from an underside 937 of the PCB 934 that faces the push-plate 914 and extends toward the push-plate 914. The switch 936 may be integral with or connected to the PCB 934, and in one embodiment may be a depressor switch, such as one connected to a switch type contact sensor.

[00161] The push-plate 914 has a switch activator 933 and at least one stop 935 extending from an upper-side 939 thereof, which faces the underside 937 of the PCB 934. Each stop 935 has a predetermined length that enables the switch 936 to be activated or the switch 936 to be depressed a safe distance without applying a pressure to the PCB 934 that could damage or break the board. Each stop 935 has a free end that moves into direct contact against the underside 937 of the PCB 934 as a linear translation limiter for the push-plate 914. The switch activator 933 has a shorter length relative to each stop and is positioned in alignment with the switch 936 to activate the same when the push-plate is pushed (moved) toward the PCB 934, which has a fixed position within the internal cavity 923 of the cap unit 910. In one embodiment, the switch activator 933 has a depth of linear translation of about 0.1 to 2.5 mm into the switch 936.

[00162] FIG. 2C is an exploded see-through view of FIG. 2B showing the external device 400 housing components (918, 917, 920), and the internal cap unit 910 components. From top to bottom, the cap unit 910 comprises a cover 918 in the shape of a thin disc, covering a coin shaped battery 932, a seam cover 919, a thumb release mechanism 994 to assist in removing the cap unit, PCB 934 with a switch 936 attached on the underside and a battery connector 960 on the top side, a flexible push-plate 914, and the adapter ring 917.

[00163] FIG. 2D is an illustration of an exemplary embodiment of a container-receiving cavity 925 defined by the cap unit 910. In FIG. 2D, the following cap components are visible: the seam cover 919, adapter ring 917, a plurality of cap protrusions 915 protruding radially inward from a surface of the adapter ring 917 that defines the inner diameter of the adapter ring (and hence the outer diameter of the container receiving cavity 925), and a push-plate 914 defining a closed end of the container-receiving cavity 925. The push-plate 914 is positioned horizontally relative to the cover (not shown), and perpendicularly relative to the adapter ring 917. The cap further comprises a push-plate ejection stop 916.

[00164] FIG. 2E is a side elevational view of a vial 920 comprising a plurality of catch protrusions (hooks) 950 to secure a cap 910. The vial further comprises: mouth 951; rim edge 952; neck 953; catch protrusion container stop 954; container cavity 955; catch protrusion recess 956; and catch protrusion ramp 957.

[00165] FIG. 3A is a top perspective view of the cap comprising the bottom portion with the top portion removed, exposing the printed circuit board 934 with the replaceable battery. FIG. 3B is a top plan view of an exemplary printed circuit board 934, and FIG. 3C is a bottom perspective view of the same. As illustrated in FIG. 3 A, cap 910 with the cover 918 removed to expose the following cap top components within the adapter ring 917: circuit board mount insert 951; piezo pins 952; battery pry hole 953; battery contact 954; PCB mount snap fit 955; and adapter ring snap fit 956.

Switch Detector Sensor and Push-Plate

[00166] The smart drug delivery device 400 further comprises a contact sensor connected to, or in communication with, the PCB 934 (or a comparable printed circuit board that is readily discerned by one of skill in the art) to trigger an electrical signal to a microprocessor on the PCB 934 whenever the device 400 is opened (e.g. the cap unit 910 is removed from the container 920), and when the device is closed (e.g. the cap unit 910 is placed on container 920 and pressed down upon). As illustrated in FIG. 3B and 3C, the sensor comprises a depressor switch 936 connected to the bottom side of the PCB 934. The bottom end of the depressor switch 936 is touching a push-plate 914 in the assembled embodiment, as illustrated in FIGS. 2F and 2G.

[00167] The push-plate 914 is received in the internal cavity 923. The push-plate 914 is linearly translatable within the internal cavity 923 a preselected distance D at a periphery of the plate and less than the preselected distance D at a center region of the plate, thereby elastically flexing the plate between the center region and the periphery. The push-plate 914 is flexible between 0 mm and 5 mm inward toward the cover 918 at the push-plate center when the cap is in a closed position of FIG. 2G, thus requiring the user to push down on the cap 910 to remove the cap from container 920. In the longitudinal cross-section of FIG. 2F, the plate has a stepped- shoulder with a flange extending radially outward therefrom to define a seat to receive a rim of a container mouth, as subsequently shown in FIG. 2G. The center region comprises a stop 935 and a switch activator 933 both extending from an upper-side 939 of the plate facing the electronics, wherein the stop 935 has a predetermined length and the switch activator 933 has a length that is less than the predetermined length of the stop.

[00168] As illustrated in FIG. 2G, when the smart cap unit 910 is attached to the container unit 920, the depressor switch 936 is depressed by the flexible push-plate 914, triggering the attached microprocessor on the PCB 934 to read the device 110 as being in a “closed” position 952. When the cap unit 910 is removed from the container 920, the sensing switch 936 is released because the character of the push-plate in its flexed and/or elastically deformed condition inherently returns the push-plate back to its normal position 950 of FIG. 2F, triggering the attached microprocessor to read the vial as being“opened.”

[00169] In the various embodiments of the present invention, push-plate 914 extends the diameter of the internal cavity 923, and is between about 0.2 mm and about 2 mm thick, or between 0.5 mm and about 1.5 mm thick, or between about 0.1 mm to about 4 mm thick. The sliding plate is also about 1 mm thick in a preferred embodiment; and is made out of polypropylene or another food-grade polymer.

[00170] The push-plate 914 may also have a compressible seal on the ends that come in contact with the container 920 in order to create a tighter moisture-proof barrier that meets the requirements of moisture performance testing defined in USP 37 671. Embodiment - Flat, Non-Flexible Sliding Plate

[00171] In an embodiment illustrated in an exploded view FIG. 4, the device 200 is disclosed in detail as in US Patent Application 20160048657 (Serial No. 14/824,231 now allowed), the entirety of which is incorporated herein by reference. It comprises a non-flexible sliding push-plate 204 that activates a switch-type contact sensor 205, which in turn activates the printed circuit board 203 to record a closing of the cap (or if double tapped- an ordering of a refill), and to cause the microcontroller to wirelessly (via Bluetooth, internet, cellular, etc., but non-infrared) transmit to a first remote computer or hub.

[00172] The vial 220 comprises external threads 206 the match the cap’s internal threads; and the vial comprises a push down tab to pop the cap off, and houses a plurality of the compound 230.

[00173] The smart cap drug delivery device comprises: 1) a vitamin or pharmaceutical compound in at least one of a tablet, a pill, or a capsule formulation; 2) a vial securely connect able to a smart cap, able to store the compound; and 3) a smart cap. The smart cap comprises: 1) a housing with a top portion and a bottom portion and defining a cavity therebetween; 2) a sliding push-plate disposed in the cavity adjacent to the bottom portion; and 3) a microcontroller with a switch type contact sensor disposed in the cavity between the top portion and the sliding plate, the sliding plate configured to slide toward and activate the contact sensor where the cap is secured to the pill container in a closed state, and the sliding plate configured to slide away from and not activate the contact sensor where the cap is removed from the pill container in an open state. The microcontroller further comprises a printed circuit board that comprises a wireless radio (e.g. non-infrared), a memory, a speaker (optional), and wherein a battery is connected to the printed circuit board that is powered at least in part in both the opened state and the closed state; and is configured to wirelessly (e.g. non-infraredly) transmit information indicative of an opening and a closing of the pill container over time to at least one of an external computer and/or a cellular gateway device.

[00174] The smart cap drug delivery device further comprising that the microcontroller is configured to store in the memory information corresponding with the sliding push-plate pressing against the contact sensor, the information indicative of an opening and a closing of the medication container over time.

[00175] The smart cap drug delivery device further comprises a speaker (optional) beneath a top lid, and the microcontroller is configured to cause the speaker to emit an audio reminder to take a dose of the compound according to a predetermined schedule. Embodiment- Non-Flexible Sliding Plate with Springs

[00176] FIGS. 5A-5F illustrate another embodiment of the smart drug delivery device 300 comprising smart cap 310 connected to a vial container 320 and with a plurality of tablets or capsules 330 housed within. Referring to FIG. 3C, cap 310 further comprises a non-flexible sliding (up/down) push-plate 331 that compresses at least one spring 332 when the cap is closed (or tapped during refill ordering). When the spring(s) 332 are compressed fully, the plate 331 compresses and thus activates the switch type contact sensor 334, which is connected to the underside of the printed circuit board 336. This in turn activates the microcontroller on the PCB to record the closing or double tapping event in the board 336’s memory; and to cause the microcontroller to wirelessly transmit data to a first remote computer (per FIG. 1).

[00177] The smart cap 310 further comprises: 1) a cover (FIG 3C, 340); 2) a coin shaped battery (FIG 3C, 342) beneath the cover, and connected to a microcontroller on a battery bottom-side; 3) an adaptor ring (FIG 3C, 344) connected to the cover to define an internal cavity closed at a first end by the cover; 4) a non-flexible sliding push-plate 331 received in the internal cavity and biased by at least one spring 332 to a normal position; wherein the push- plate closes the internal cavity 346 opposite the cover and defines a container receiving cavity within the adaptor ring 344; and 5) electronics PCB 336 having a switch contact sensor 334 in operative engagement with the push-plate are enclosed within the internal cavity. Furthermore, in the normal position, the switch contact sensor is in a first position and in a container-closed position, the push-plate acts on the switch to place it in a second position, and the sliding push- plate is linearly translatable within the internal cavity.

[00178] The electronics further comprises a microcontroller located between the battery and the push-plate, and comprising a printed circuit board 336 that comprises a wireless radio, a memory, a speaker (optional), and wherein a battery is connected to the printed circuit board that is powered at least in part in both the opened state and the closed state. The microcontroller is configured to non-infrared, wirelessly transmit information indicative of an opening and a closing of the pill container over time to at least one of an external computer and/or a cellular gateway device.

[00179] The smart drug delivery device 300 further comprises a band 350 (e.g. rubber, silicone, etc.) disposed on an outer perimeter of the cap, flush to a cap side, covering a seam (e.g. groove) between the top portion/cover 340 and the bottom portion (adapter ring 344), and it may be colored to associate with a specific pill.

[00180] As illustrated in FIGS. 5D and 5E, the vial 320 comprises a push-tab 360 that the user forces downward to pop the cap 310 off of the device 300. The vial 320 further comprises external threads 370 wherein the bottom portion of the housing has internal threads 372 configured to cooperate with external threads 370 of the container. The vial may further comprise at least one protrusion (child release notch, FIG. 5E, 380) of plastic beneath the internal threads 372, configured to securely fasten the pill cap to the container until the user presses down on the cap in a one-click action and twists the cap to remove it from the container.

User Control Option for Refills

[00181] In an example embodiment, the smart monitor device (FIG. 1, 120), e.g. 200, 300, 400, comprises a user control mechanism to automatedly order a smart monitor device refill when the user depresses and releases the cap unit (e.g. FIG. 2B, 910) two sequential times, in rapid succession. The microprocessor is able to receive a signal from the switch 936 when compressed by the push-plate 914 upon a user depressing and releasing the cap unit. The microprocessor (FIG. 3C, 1010) is configured to then store in memory information corresponding with the push-plate 914 pressing against the switch 936, the information indicative of the user“double tapping” the cap. The PCB radio then relays the information wirelessly to the user electronic computing device (e.g. FIG. 1, 110).

Printed Circuit Board

[00182] Smart monitor device (FIG. 1, 120), e.g. 200, 300, 400, further comprises a printed circuit board (PCB) 934 positioned within the internal cavity 923 of the cap unit 910 to enable the device 120 to detect access events and to trigger alarms while communicating wirelessly with the user electronic computing device (FIG. 1, 110). In the exemplified embodiment, the PCB 934 is positioned horizontally in the cap unit 910, extending the diameter of the cavity, beneath the cover 918 and above the push-plate 914. In an embodiment, PCB 934 is oriented perpendicular to an inner side wall of the cap unit 910, or horizontally relative to the cover 918. PCB 934 is between about 25 and 45 mm in diameter.

[00183] PCB 934 contains a plurality of electrical components optimized to fit within the cap unit 910, such as a microprocessor, a coin cell type battery 932, an antenna for wireless communications with the user device (FIG. 1, 110), and an internal contact sensor. In an exemplary embodiment, the internal contact sensor comprises a depressor switch mechanism detecting movement of the cap unit 910 between an opened and closed position, and for user double tapping of the cover 918 to order a prescription refill wirelessly and automatedly. A number of capacitors and transistors will also populate the PCB 934 (e.g. see FIGS. 6A-6G).

[00184] FIGS. 6A-6G are exemplary illustrations of the various electrical components within the smart caps and blister cards and blister card holder of the present disclosure, which are able to communicate with the wireless networked system.

[00185] FIG. 6A is an illustration of an exemplary electrical schematic of the PCB 934 comprising a nRF chip, such as a Nordic nRF51822-QFAC or the nRF52810-QFAA microprocessor chip. Both of these system on chips devices support 2.4GHz wireless protocols (i.e. Bluetooth 4.1 or 5), have either a 16MHz or 32MHz microprocessor, and have onboard flash memory. Each chip comes pre-programmed with a unique MAC address stored in memory that is used when transmitting data wirelessly (e.g. to user electronic computing device 110, FIG. 1). This same MAC is used for unique device identification (e.g. a token). The antenna circuit is tuned for Bluetooth Low Energy and is capable of transmitting data approximately 100 meters.

[00186] FIG. 6B illustrates an electric circuit schematic able to connect a button (or the internal contact sensor) to one of the general-purpose input-output pins of the system on a chip (SoC). The button-sensor can be used to detect the opening and closing of container unit 920 in response to the movement of the push-plate 914.

[00187] In order to achieve wireless connectivity with a user device (FIG. 1, 110), such as a smart phone or in-home base station, PCB 934 contains at least a wireless radio able to connect via the cellular or intranet network (FIG. 1, 105), and/or via a short range wireless radios (e.g. Bluetooth® versions 4.1-5 pairing). The antenna is a pre-packaged chip that is soldered onto the PCB 934, or it may be etched directly into the PCB. Cap unit 910 is thus capable of wireless communication via at least one of the following: Bluetooth radio; ANT radio, cellular radio, WiFi radio, Near Field Communication radio, or RFID. In one embodiment, the wireless radio is a 2.4 GHz low-energy radio, which transmits and receives a signal from user device 110 at distance of no more than about 1500 feet. In another embodiment, the wireless radio transmits either at a narrow band of 200kHz spectrum, at 180kHz, or between 1.4 and 20 MHz, at an uplink peak rate of not more than 10 Mbit/s. As used herein, the term“about” refers to 5 percent plus or minus the stated value. [00188] FIG. 6E is an electrical circuit schematic of the programming port on the PCB 934, which is used to install firmware on the smart monitoring device 120 during manufacturing. It can also be used to read information from the device 120 during or after assembly.

[00189] FIG. 6F is an electrical circuit schematic of the PCB 934 real-time-clock (RTC). This optional circuit shows how a low power real-time-clock (RTC) can be connected to the SoC to keep accurate measurement of time. The RTC is also capable of triggering alarms on scheduled intervals.

Battery

[00190] As illustrated in FIGS. 2C, and 3A-3C, a battery connector 960 for holding battery 932, a microprocessor 110 having microprocessor memory and wireless antenna are each positioned to achieve a satisfactory connectivity range and battery life while maintaining a compact configuration. FIG. 6D exemplary electrical circuit schematic illustrating a power circuit that is used to connect the coin cell battery. PCB 934 may further comprise a battery holder clip 1103 shown in FIG. 3B on the top surface to fix battery 932 in position atop the PCB.

[00191] In one embodiment, the battery 932 is a non-rechargeable lithium battery cell (e.g. Coin cell battery (LiMn02), CR2450 or larger capacity), measuring no more than 24 mm in diameter and no more than 5 mm in thickness. In another embodiment, the battery 932 measures between 20 and 25 mm in diameter, and between 3.0 and 5.2 mm in thickness. In a battery-optimized system, the wireless radio is likely to transmit between 25 and 1500 feet, and most likely between 50 and 400 feet. In another embodiment, battery 932 is a rechargeable battery. In another embodiment there may be no battery required, such as in the case where there is mechanism for receiving wireless power on the printed circuit board 934 itself. In another embodiment, the battery is a rechargeable prismatic pouch cell battery.

Microprocessor Memory and Token

[00192] As illustrated in FIGS. 3B and 3C the microprocessor 1010 comprises the antenna and the memory (inside the microprocessor unit 1010), which in an embodiment comprises a combination of flash memory and RAM memory, e.g. the data storage unit (FIG. 1, 123) and the data monitoring module (FIG. 1, 121) as non-transitory, tangible computer- readable storage medium on which databases and processor-executable software are embodied. Additionally, or alternatively, the smart monitor device 120 further comprises one or more removable memory cards or removable flash memory comprising the data storage unit (FIG. 1, 123). The data storage unit 123 further comprises token storage 125 for storing a token, e.g., the token comprising a Bluetooth® SIG-assigned UUID unique to the smart monitor device 120. Additionally, the microprocessor further comprises at least one of a short-range, low- power wireless radio transmitter that operates between 2.4 and 2.485 GHz and transmitting data no more than 1000 feet; or a low-power cellular radio having bandwidth between 150 KHz and 1.6 MHz, with a peak data rate of between 5 kbps and 500 Kbps, and with uplink transmission power between 15 and 30 dBm.

[00193] In an additional embodiment, the wireless radio transmitter of device 120 transmits, or sends wireless advertisement packets, at a first interval when there is no new data to sync, and at a second interval when there is un-synced data remaining in the memory. The electrical current supplied to the wireless radio transmitter from the power source (battery 932) and through the printed circuit board 934 is between about 0.5 mA and 25 mA when the wireless radio transmitter is advertising or is connecting to a user electronic computing device 110. And the electrical current supplied to the wireless radio transmitter from the power source (battery 932) and through the printed circuit board 934 is between about 0.5 mA and 10 mA when the wireless radio transmitter is receiving a wireless signal from the user electronic computing device 110.

[00194] Light Pipe: Referring again to FIG. 2A, the cover 918 may further comprise a transparent light pipe 922, which conducts light from a light-emitting source, such as a light emitting diode (LED) (see FIG. 3B, 1102) that is connected to the printed circuit board 934. LED 1102 is powered by the battery 932 on the printed circuit board (PCB, 934). A blinking light may indicate a container access alert or dose scheduled reminder, in addition to, or in lieu of, the piezo buzzer. FIG. 6C is an exemplary electrical circuit illustrating LED 1102, which can be used to notify or reminder the user.

[00195] Piezo Buzzer: Referring again to FIG. 2 A, cover 918 further comprises a plurality of holes 921, to emit sound from the piezoelectric buzzer 931 located beneath the cover 918 within the internal cavity 923 of the cap unit 910. In an alternative embodiment, the piezoelectric buzzer 931 comprises a buzzer, speaker (optional), or other sound-emitting component that is directly mounted on the PCB 934 or connected to it through another conductive mechanism. Preferably, the sound-emitting component emits a sound between 75 decibels and 95 decibels, such as a reminder to take a scheduled dose. [00196] FIG. 6G illustrates an exemplary electrical schematic for the piezo buzzer on the printed circuit board, and comprising a 4kHz buzzer that can be driven by the SoC either directly, or by using a charge pump, which increases.

Other Example Embodiments Computers

[00197] FIG. 9 depicts a computing machine 2000 and a module 2050 in accordance with certain example embodiments. The computing machine 2000 may correspond to any of the various computers, servers, mobile devices, embedded systems, or computing systems presented herein (e.g. see FIG. 1). The module 2050 may comprise one or more hardware or software elements configured to facilitate the computing machine 2000 in performing the various methods and processing functions presented herein. The computing machine 2000 may include various internal or attached components such as a processor 2010, system bus 2020, system memory 2030, storage media 2040, input/output interface 2060, and a network interface 2070 for communicating with a network 2080.

[00198] The computing machine 2000 may be implemented as a conventional computer system, an embedded controller, a laptop, a server, a mobile device, a smartphone, a set-top box, a kiosk, a vehicular information system, one more processors associated with a television, a customized machine, any other hardware platform, or any combination or multiplicity thereof. The computing machine 2000 may be a distributed system configured to function using multiple computing machines interconnected via a data network or bus system.

[00199] The processor 2010 may be configured to execute code or instructions to perform the operations and functionality described herein, manage request flow and address mappings, and to perform calculations and generate commands. The processor 2010 may be configured to monitor and control the operation of the components in the computing machine 2000. The processor 2010 may be a general purpose processor, a processor core, a multiprocessor, a reconfigurable processor, a microcontroller, a digital signal processor (“DSP”), an application specific integrated circuit (“ASIC”), a graphics processing unit (“GPU”), a field programmable gate array (“FPGA”), a programmable logic device (“PLD”), a controller, a state machine, gated logic, discrete hardware components, any other processing unit, or any combination or multiplicity thereof. The processor 2010 may be a single processing unit, multiple processing units, a single processing core, multiple processing cores, special purpose processing cores, co-processors, or any combination thereof. According to certain embodiments, the processor 2010 along with other components of the computing machine 2000 may be a virtualized computing machine executing within one or more other computing machines.

[00200] The system memory 2030 may include non-volatile memories such as read-only memory (“ROM”), programmable read-only memory (“PROM”), erasable programmable read-only memory (“EPROM”), flash memory, or any other device capable of storing program instructions or data with or without applied power. The system memory 2030 may also include volatile memories such as random access memory (“RAM”), static random access memory (“SRAM”), dynamic random access memory (“DRAM”), and synchronous dynamic random access memory (“SDRAM”). Other types of RAM also may be used to implement the system memory 2030. The system memory 2030 may be implemented using a single memory module or multiple memory modules. While the system memory 2030 is depicted as being part of the computing machine 2000, one skilled in the art will recognize that the system memory 2030 may be separate from the computing machine 2000 without departing from the scope of the subject technology. It should also be appreciated that the system memory 2030 may include, or operate in conjunction with, a non-volatile storage device such as the storage media 2040.

[00201] The storage media 2040 may include a hard disk, a floppy disk, a compact disc read only memory (“CD-ROM”), a digital versatile disc (“DVD”), a Blu-ray disc, a magnetic tape, a flash memory, other non-volatile memory device, a solid sate drive (“SSD”), any magnetic storage device, any optical storage device, any electrical storage device, any semiconductor storage device, any physical-based storage device, any other data storage device, or any combination or multiplicity thereof. The storage media 2040 may store one or more operating systems, application programs and program modules such as module 2050, data, or any other information. The storage media 2040 may be part of, or connected to, the computing machine 2000. The storage media 2040 may also be part of one or more other computing machines that are in communication with the computing machine 2000 such as servers, database servers, cloud storage, network attached storage, and so forth.

[00202] The module 2050 may comprise one or more hardware or software elements configured to facilitate the computing machine 2000 with performing the various methods and processing functions presented herein. The module 2050 may include one or more sequences of instructions stored as software or firmware in association with the system memory 2030, the storage media 2040, or both. The storage media 2040 may therefore represent examples of machine or computer readable media on which instructions or code may be stored for execution by the processor 2010. Machine or computer readable media may generally refer to any medium or media used to provide instructions to the processor 2010. Such machine or computer readable media associated with the module 2050 may comprise a computer software product. It should be appreciated that a computer software product comprising the module 2050 may also be associated with one or more processes or methods for delivering the module 2050 to the computing machine 2000 via the network 2080, any signal-bearing medium, or any other communication or delivery technology. The module 2050 may also comprise hardware circuits or information for configuring hardware circuits such as microcode or configuration information for an FPGA or other PLD.

[00203] The input/output (“I/O”) interface 2060 may be configured to couple to one or more external devices, to receive data from the one or more external devices, and to send data to the one or more external devices. Such external devices along with the various internal devices may also be known as peripheral devices. The I/O interface 2060 may include both electrical and physical connections for operably coupling the various peripheral devices to the computing machine 2000 or the processor 2010. The I/O interface 2060 may be configured to communicate data, addresses, and control signals between the peripheral devices, the computing machine 2000, or the processor 2010. The I/O interface 2060 may be configured to implement any standard interface, such as small computer system interface (“SCSI”), serial- attached SCSI (“SAS”), fiber channel, peripheral component interconnect (“PCI”), PCI express (PCIe), serial bus, parallel bus, advanced technology attached (“ATA”), serial ATA (“SATA”), universal serial bus (“USB”), Thunderbolt, FireWire, various video buses, and the like. The I/O interface 2060 may be configured to implement only one interface or bus technology. Alternatively, the I/O interface 2060 may be configured to implement multiple interfaces or bus technologies. The I/O interface 2060 may be configured as part of, all of, or to operate in conjunction with, the system bus 2020. The I/O interface 2060 may include one or more buffers for buffering transmissions between one or more external devices, internal devices, the computing machine 2000, or the processor 2010.

[00204] The I/O interface 2060 may couple the computing machine 2000 to various input devices including mice, touch-screens, scanners, electronic digitizers, sensors, receivers, touchpads, trackballs, cameras, microphones, keyboards, any other pointing devices, or any combinations thereof. The I/O interface 2060 may couple the computing machine 2000 to various output devices including video displays, speakers, printers, projectors, tactile feedback devices, automation control, robotic components, actuators, motors, fans, solenoids, valves, pumps, transmitters, signal emitters, lights, and so forth.

[00205] The computing machine 2000 may operate in a networked environment using logical connections through the network interface 2070 to one or more other systems or computing machines across the network 2080. The network 2080 may include wide area networks (WAN), local area networks (LAN), intranets, the Internet, wireless access networks, wired networks, mobile networks, telephone networks, optical networks, or combinations thereof. The network 2080 may be packet switched, circuit switched, of any topology, and may use any communication protocol. Communication links within the network 2080 may involve various digital or an analog communication media such as fiber optic cables, free-space optics, waveguides, electrical conductors, wireless links, antennas, radio-frequency communications, and so forth.

[00206] The processor 2010 may be connected to the other elements of the computing machine 2000 or the various peripherals discussed herein through the system bus 2020. It should be appreciated that the system bus 2020 may be within the processor 2010, outside the processor 2010, or both. According to some embodiments, any of the processor 2010, the other elements of the computing machine 2000, or the various peripherals discussed herein may be integrated into a single device such as a system on chip (“SOC”), system on package (“SOP”), or ASIC device.

[00207] In situations in which the systems discussed here collect personal information about users, or may make use of personal information, the users may be provided with a opportunity or option to control whether programs or features collect user information (e.g., information about a user's social network, social actions or activities, profession, a user's preferences, or a user's current location), or to control whether and/or how to receive content from the content server that may be more relevant to the user. In addition, certain data may be treated in one or more ways before it is stored or used, so that personally identifiable information is removed. For example, a user's identity may be treated so that no personally identifiable information can be determined for the user, or a user's geographic location may be generalized where location information is obtained (such as to a city, ZIP code, or state level), so that a particular location of a user cannot be determined. Thus, the user may have control over how information is collected about the user and used by a content server.

[00208] Embodiments may comprise a computer program that embodies the functions described and illustrated herein, wherein the computer program is implemented in a computer system that comprises instructions stored in a machine-readable medium and a processor that executes the instructions. However, it should be apparent that there could be many different ways of implementing embodiments in computer programming, and the embodiments should not be construed as limited to any one set of computer program instructions. Further, a skilled programmer would be able to write such a computer program to implement an embodiment of the disclosed embodiments based on the appended flow charts and associated description in the application text. Therefore, disclosure of a particular set of program code instructions is not considered necessary for an adequate understanding of how to make and use embodiments. Further, those skilled in the art will appreciate that one or more aspects of embodiments described herein may be performed by hardware, software, or a combination thereof, as may be embodied in one or more computing systems. Moreover, any reference to an act being performed by a computer should not be construed as being performed by a single computer as more than one computer may perform the act.

[00209] The example embodiments described herein can be used with computer hardware and software that perform the methods and processing functions described previously. The systems, methods, and procedures described herein can be embodied in a programmable computer, computer-executable software, or digital circuitry. The software can be stored on computer-readable media. For example, computer-readable media can include a floppy disk, RAM, ROM, hard disk, removable media, flash memory, memory stick, optical media, magneto-optical media, CD-ROM, etc. Digital circuitry can include integrated circuits, gate arrays, building block logic, field programmable gate arrays (FPGA), etc.

[00210] The example systems, methods, and acts described in the embodiments presented previously are illustrative, and, in alternative embodiments, certain acts can be performed in a different order, in parallel with one another, omitted entirely, and/or combined between different example embodiments, and/or certain additional acts can be performed, without departing from the scope and spirit of various embodiments. Accordingly, such alternative embodiments are included in the inventions described herein.

[00211] Although specific embodiments have been described above in detail, the description is merely for purposes of illustration. It should be appreciated, therefore, that many aspects described above are not intended as required or essential elements unless explicitly stated otherwise. Modifications of, and equivalent components or acts corresponding to, the disclosed aspects of the example embodiments, in addition to those described above, can be made by a person of ordinary skill in the art, having the benefit of the present disclosure, without departing from the spirit and scope of embodiments defined in the following claims, the scope of which is to be accorded the broadest interpretation so as to encompass such modifications and equivalent structures.

[00212] From the foregoing description, one ordinarily skilled in the art can easily ascertain the essential characteristics of this disclosure and, without departing from the spirit and scope thereof, make various changes and modifications to the disclosure to adapt it to various usages and conditions.

[00213] A portion of the disclosure of this patent document contains material that is subject to copyright protection. This patent document may show and/or describe matter that is or may become a trademark and/or trade dress of the owner. The copyright, trademark and trade dress owner has no objection to the facsimile reproduction by anyone of the patent disclosure, as it appears in the U.S. Patent and Trademark Office patent files and records, but otherwise reserves all copyright, trademark and trade dress rights whatsoever.

References:

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