Abstract:
A liquid medication dispenser apparatus which provides for user-friendly medication measurement and compliance. The apparatus measures and dispenses liquid medication doses and records the time and dose sizes for up to one year. The recorded information can then be downloaded to a personal computer for evaluation of patient compliance. A disposable, motor driven pump is used to provide a very wide range of medication dispensation volumes, while maintaining full accuracy and reducing the risks of patient errors as might occur with a manual dispense system.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority from U.S. provisional application serial No. 60/030,641 filed on Nov. 8, 1996, entitled “Liquid Medication Dispenser Apparatus,” which is incorporated by reference herein in its entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention pertains generally to devices and methods for dispensing medication, and more particularly to a liquid medication dispenser apparatus that monitors compliance with a treatment plan and determines a compliance score indicative of whether the liquid medication was dispensed at predetermined times and at predetermined dose levels. 
     2. Description of the Background Art 
     Medication recipients frequently need to take a set dose of medication or medications at regular intervals of time. Failure by persons to take the required medication dosages at the appropriate time intervals results in incorrect blood serum levels of the medication, and can ultimately lead to unfavorable clinical outcomes. For several reasons, incorrect liquid medication dosages are often taken by patients. Liquid medication dosages are typically measured by pouring the medication into a tea spoon or small container prior to taking the medication. This manner of dosage measurement is prone to inaccuracy and can result in wasted medication and unpleasant messes due to spills during measurement. Further, the amount of liquid medication remaining in a container cannot be easily determined, unlike solid medications wherein the patient can count the number of pills present, and thus the patient can run out of medication, resulting in missed or skipped medication dosages. Additionally, patients who must take numerous medications on a regular basis can easily loose track of the time at which a particular medication was most recently taken, resulting in omission by the patient of required dosages or exceeding the dosage requirement. Frequently, the timing requirements vary for dosages of different medications and further lead to patient confusion and error in taking the different medications at correct time intervals. 
     Accordingly, there is a need for a liquid medication dispenser which alerts patients of the correct time intervals for taking liquid medications, which keeps track of and displays the number of dosages of liquid medication taken, and which quickly, consistently and accurately measures and dispenses dosages of liquid medication. The present invention satisfies these needs, as well as others, and generally overcomes the deficiencies found in the background art. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention pertains to a liquid medication dispenser that monitors treatment compliance. It is designed to be extremely convenient and easy to use by the patient, while still providing state-of-the-art features for the health care provider. It measures and dispenses liquid medication doses, recording the time and sizes of doses, as well as information pertaining to compliance with a programmed treatment plan, for up to one year or longer. The device can be programmed, and information retrieved from the device, using a personal computer. Information downloaded from the device can then be used to evaluate patient compliance with the programmed treatment plan. The device utilizes a disposable, motor driven pump and medication reservoir to provide a very wide range of volumes, while maintaining full accuracy and reducing the risks of patient errors as might occur with a manual dispensing system. 
     In general terms, the invention comprises a medication cassette with an interchangeable and disposable reservoir and fluid path assembly, means for adjusting the amount of medication delivered, timer means for measuring time, memory means for storing data, display means for providing visual and audio output to a user, and control processor means for monitoring and recording the time and number of medication dosages dispensed, for alerting the user of the time for taking medication dosages, for monitoring he amount of medication remaining in the medication cassette, and for computing a compliance score. Preferably audible alarm means for alerting a user, and a communications interface for linking the control processor means with an external computer, are also included with the invention. A liquid dispensing valve assembly and pump are used for dispensing liquid medication from the reservoir and through the fluid path assembly. 
     By way of example, and not of limitation, the control processor means preferably comprises a conventional microprocessor, or other programmable data processor, which may be in digital or analog format. The timer means comprises first and second timers interfaced with the microprocessor, with the first timer preferably comprising a 32 KHz timing circuit for real time monitoring by the microprocessor, and the second timer preferably comprising a 4 MHz clock for basic processing by the microprocessor. The microprocessor may additionally include an internal “watchdog” timer. The display means preferably comprises a multi-field liquid crystal display (LCD) or light emitting diode (LED) display operatively connected to the microprocessor. The audio alarm means preferably comprises a conventional piezoelectric watch alarm device, and is operatively coupled to the microprocessor. The liquid dispensing pump has a pump motor with a rotation sensor associated with the rotating shaft of the motor. The rotation sensor is preferably an optical rotation encoder and is operatively coupled to the microprocessor to allow monitoring of medication dispensing events. The memory means preferably comprises at least 2K of random access memory (RAM) which is accessible by the microprocessor. The communications interface preferably comprises an optical interface operatively coupled to the microprocessor, and which receives an interface cable for connection to a personal computer. 
     It is an object of the invention to provide a liquid medication dispensing apparatus which uses standard 50 ml medication bottles, has a disposable fluid path fully enclosed in the dispenser&#39;s plastic case for easy carrying, has a 0.1 ml to 5 ml dose range, has 0.1 ml resolution, exhibits high accuracy at 5 ml, has only two user keys—a Display/Dose key and an Alarm/Increment key, employs a liquid crystal display (LCD), has at least one year memory at 2 doses per day (uploadable to a personal computer), has at least several months of battery life, uses common “AA” type alkaline batteries for power, and uses a pump technology for wide volume range and less patient error. 
     The invention provides for dispensing a measured dose of a liquid therapeutic drug to a patient and records the timing and amount of dose dispensed. The dose and/or timing history can be reviewed by a patient, physician or other health care provide, either as raw data or as a calculated “compliance score.” The invention is particularly suited for dispensing a liquid immunosuppressive drug to a transplant patient, and can be adapted for dispensing multiple drugs. 
     Further objects and advantages of the invention will be brought out in the following portions of the specification, wherein the detailed description is for the purpose of fully disclosing preferred embodiments of the invention without placing limitations thereon. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will be more fully understood by reference to the following drawings which are for illustrative purposes only: 
     FIG. 1 is a functional block diagram of a liquid dispensing apparatus in accordance with the present invention. 
     FIG.  2 A through FIG. 2C is a schematic diagram of a liquid dispensing apparatus in accordance with the present invention corresponding to the functional block diagram shown in FIG.  1 . 
     FIG. 3 is a side elevation view of a liquid dispensing apparatus in accordance with the present invention. 
     FIG. 4 is a front elevation view of a liquid dispensing apparatus in accordance with the present invention. 
     FIG. 5 is a top plan view of a liquid dispensing apparatus in accordance with the present invention. 
     FIG. 6 is a cross-sectional view of a liquid dispensing apparatus in accordance with the present invention taken through line  6 — 6  showing the disposable cassette assembly in place with a liquid medication bottle attached. 
     FIG. 7 is a partial cross-sectional view of the disposable cassette assembly portion of FIG. 6 with the liquid medication bottle removed. 
     FIG. 8 is a diagrammatic view of a basic screen display in accordance with the invention showing three viewing fields. 
     FIG. 9 is a diagrammatic view of a second screen display in accordance with the present invention. 
     FIG. 10 is a diagrammatic view of a third screen display in accordance with the present invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring more specifically to the drawings, for illustrative purposes the present invention is embodied in the apparatus generally shown in FIG.  1  through FIG.  10 . It will be appreciated that the apparatus may vary as to configuration and as to details of the parts without departing from the basic concepts as disclosed herein. 
     Referring first to FIG. 1, there is shown generally in block diagram form a liquid medication dispenser  10  in accordance with the present invention. Dispenser  10  generally comprises a control microprocessor  12  which provides the overall control functions of the device, including monitoring and recording the number of medication doses dispensed from a medication cassette  14 , alerting the user of the time for taking medication dosages, monitoring the amount of medication remaining in the medication cassette  14 , and computing a compliance score. User feedback from the device is provided both by a visual display  16  and an audible alarm  18 . Memory  20  is provided for storage and retrieval of data, and various keys/switches  22 ,  24 ,  26 ,  28  are provided for user and/or general operation. Timing and clock operations are provided by a pair of clocks  30 ,  32 . A serial interface  34  is also provided for linking the device to an external computer. Liquid medication is dispensed by operation of pump motor  36  which is mechanically coupled to the medication cassette  14 . A rotation sensor  38  monitors shaft rotation of pump motor  36  to sense the amount of liquid dispensed. 
     Referring also to FIG.  2 A through FIG. 2C, which shows an exemplary schematic diagram corresponding to the control circuitry shown in FIG. 1, control microprocessor  12  preferably comprises a conventional microprocessor, or other programmable data processor, which may be in digital or analog format. In the embodiment shown, control microprocessor  12  comprises a Microchip PIC16LC64A or like device. Pump motor  36  is preferably coupled to control microprocessor  12  by driver in the form of a simple transistor pair wherein one transistor turns the motor on in one direction, and the other transistor shorts out the motor to apply an electronic brake function. Alternative microprocessors which may be used with the invention include National Semiconductor COP842CJ and COP988CS, Microchip PIC16C57, NEC 75304, Motorola 68HC05, Phillips 80C51, Toshiba TMP87CH800LF, Oki MSM64162 and Hitachi micros. Control microprocessor  12  preferably includes a built-in independent watchdog oscillator and timer as conventionally found in such devices. The watchdog timer runs continuously, uses very little power and, if the watchdog timer is not cleared periodically as may occur if the software hangs up for some reason, it will timeout and cause a processor reset. The microprocessor preferably provides flags to differentiate between a watchdog reset and a power up reset, allowing the software to simply continue if a failure occurs. Thus, the clock and other current data is not lost or corrupted. 
     Display  16  is preferably a conventional commercial grade multi-field liquid crystal display (LCD) with a reflective viewing mode, a 12-o&#39;clock view angle, and a multiplexed electrical drive. Preferably display  16  is software driven directly from the pins of control microprocessor  12  to reduce circuit board space and the number of solder joints required. Alternatively, display  16  could be driven using a conventional driver circuit, either internal or external to control microprocessor  12 . However, microprocessors with LCD drivers tend to increase cost. 
     Audible alarm  20  preferably comprises a conventional small, low-cost, low power piezoelectric element that can be used to generate alarms in the form of high frequency tones in the range of 3 to 4 KHz. The device is similar to those used in watches with alarms and small clocks. 
     For storage of important data, memory  20  preferably comprises non-volatile random access memory (RAM) or the like, which allows the batteries to be changed or power disturbances to occur without loss of data or clock time. The preferred memory is a conventional 2K EE memory chip such as the Microchip 24LC16B, which operates in a low voltage range. Memory internal to the particular microprocessor selected may alternatively be used. 
     Timing functions are carried out by two time-base clocks. For the microprocessor shown in FIG. 2, clock  28  is preferably a 4 MHz clock that is used for basic processing when the microprocessor is awake. On the other hand, clock  30  is preferably a 32 KHz clock that runs continuously to provide a time base for a real time ten minute clock. By stopping the faster 2 MHz clock most of the time, substantial battery power is saved. 
     Referring also to FIG.  3  through FIG. 5, a hand-held housing  40  contains the functional components of dispenser  10 . Housing  40  includes a physical dispense trigger  42  which operates dispense switch  26  (FIG.  1  and FIG.  2 B). Referring more particularly to FIG. 5, the upper portion  44  of housing  40  includes a user control panel  46 . Control panel  46  includes display  16 , which has three viewing segments  48   a ,  48   b ,  48   c . Control panel  46  also includes alarm/increment key  22 , display/dose key  24 , a “take dose” alarm light  50  which is a conventional light emitting diode (D 3  in FIG.  2 B), and a conventional phototransistor  52  (D 4  in FIG.  2 B). Liquid medication is dispensed through the lower portion  54  of housing  40 . 
     Note that alarm light  50  also functions as the emitter portion of serial interface  34 , while phototransistor  52  functions as the receiver portion of serial interface  34 . Alternatively, a dedicated light could be used for alarm light  50  and serial interface  34  could comprise a conventional infrared transceiver mounted in the case of dispenser  10 . In any of these embodiments, to communicate with a personal computer (PC) or the like an interface cable (not shown) is used. The interface cable preferably has an infrared transceiver in a small housing on one end, and either a 9 pin or 25 pin serial connector on the other end. The housing on the interface cable would be adapted to fit over housing  40  so that the infrared transceiver can be positioned adjacent to emitter  50  and receiver  52 . Conventional communications timing and command protocol is then used for communications. It will be appreciated that other conventional communications means could be employed, including serial cables that plug into dispenser  10 , modems, telephone links, radio links, printer connections and the like. 
     Referring to FIG. 6, dispenser  10  is preferably constructed on two printed circuit boards (PCB)  56 ,  58 . PCB  56  carries most of the electronic components while PCB  58  primarily carries display  16 . Display  16  is preferably connected to control microprocessor  12  and related components through a flexible connector or the like (not shown) and is preferably mounted at a right angle to PCB  56 . Alternative configurations could also be used. 
     Dispenser  10  is preferably powered by one or more batteries  60  such as “AA” alkaline. “AAA” alkaline, or “2/3 A” lithium batteries. Various other batteries, such as 9 volt versions, button cells, etc. may alternatively be used. Generally, consideration must be given to the voltages required by the microprocessor used with the invention, the life of the battery with a given electronic configuration, and constraints on size, cost, and replacement availability. The alkaline cell batteries are presently preferred due to their low cost, long life, and correct voltage for the microprocessor. 
     Rotation sensor  38  preferably comprises an optical sensor that senses each revolution of shaft  62  of pump motor  36 . Shaft  62  is in turn coupled to a connecting rod  64  that operates a pump piston  66  in medication cassette  14 . This in turn senses each stroke of pump piston  66  during dispensing. The output from rotation sensor  38  is used by control microprocessor  12  to monitor the medication doses dispensed and to calculate the remaining doses in medication cassette  14 . The optical sensor preferably comprises a half-moon shaped disk  68  coupled to shaft  62  that interrupts the light path between a conventional optical emitter/sensor pair  70  (D 1 , D 2  in FIG. 2A) during rotation of shaft  62 . It will be appreciated that magnetic rotational sensors or other techniques could be used as alternatives to optical emitter/sensor pair  70 . 
     Referring also to FIG. 7, medication cassette  14  comprises a removable assembly that snaps into the bottom portion  54  of housing  40  by means of a resilient latch  72  that engages a corresponding slot  74  in housing  40 . Medication cassette  14  includes a liquid medication bottle  76  or like reservoir for storage of the medication to be dispensed. The size of liquid medication bottle  76  is preferably approximately 50 ml, which is a standard size. Liquid medication bottle  76  screws into a receptacle  78  where it is secured in place and positioned adjacent to pump orifice  80 . An air vent tube  82  coupled to a hydrophobic vent  84  is provided for extending into liquid medication bottle  76  to assist with pumping operation. Connecting rod  64  is coupled to shaft  62  of motor  36  by means of a reciprocating crank  86  for operation of pump piston  66 , and liquid medication is dispensed through a flapper valve  88 . Bottle switch  28  (FIG. 1, FIG. 2B) is toggled by a switch lever  90  that contacts liquid medication bottle  76  whenever medication cassette  14  is installed or removed. 
     Referring also to FIG.  8  through FIG. 10, dispenser  10  generally operates in accordance with the following criteria. 
     1. Alarm and Timer Functions 
     Dispenser  10  includes alarm and timer functions which provide a simple reminder to the patient to take medication regularly. These reminders comprise a count down timer, dose size indicator and visual and audible prompts. FIG. 8 shows the basic screen display configuration for dispenser  10 , where an upper digit set  92  is shared between a count down timer value, doses left value, and dose size value. Pressing the display/dose key  24  will toggle through these displays. 
     The count down timer is displayed in hours and minutes and represents the time until the next dose. It is started each time a dose is dispensed with a time value programmed by the health care provider. The count down timer is not visible when dispenser  10  is in a power saving sleep mode, but the time value is maintained continuously in memory. The count down timer value is displayed whenever dispenser  10  is awakened from the sleep mode or when the count down timer counts down to zero signaling that it is time to take a dose. 
     The dose size value is an integer number in milligrams that is programmed by the health care provider and displays the dose size along with an “mg” icon  94  to shown the amount of liquid medication to be dispensed. The count down timer and dose size values are also displayed during the last hour prior to the dose time, alternating between each other approximately every three seconds. In addition, if dispenser  10  is in a sleep mode it can be awakened by pressing any key, and the count down timer will display until dispenser  10  goes to sleep again or until the display/dose key  24  is pressed to toggle to another screen display. Those skilled in the art will appreciate that other display parameters could easily be programmed into the apparatus. 
     When the time value counts down to zero as shown in FIG. 9, the “Take Dose” icon  96  begins to flash on display  16 , an audible tone is heard from alarm  18  (FIG. 1, FIG.  2 A), the take dose light  50  (FIG. 5) flashes, and an alarm icon  98  flashes. Until the dose is taken, the visual indicators continue to flash and the audible tone repeats once every 10 minutes. Note that the patient may take the dose at any time, and the count down timer will not prevent early dose taking. Note also that the alarm can be toggled on and off by depressing alarm/increment key  22 . 
     2. Dosage Dispensing 
     To dispense a dose of medication, the patient holds dispenser  10  over a drinking cup or other container. Dispense button  42  (FIG. 3, FIG. 4) is then pressed and held depressed for one to two seconds until a audible prompt is heard. Dispense button  42  is then released to start the dispense action. For safety, dispense button  42  must preferably be released within one second or dispensing action will occur. This timed interaction will help prevent accidental dispensations of medication that might occur from moving or bumping dispense button  42 . Alternatively, a safety latch or locking mechanism could be employed instead of the foregoing press and release mechanism. Once started, dispenser  10  will always dispense the programmed volume of medication. Dispenser  10  will then sound a completion tone at the end of the dose. 
     After the dose, digit set  92  will automatically display the integer number of doses left and a “Doses Left” icon  100  will appear as shown in FIG.  8 . If no other keys are pressed, dispenser  10  will automatically go to sleep after a preset timeout period. Additionally, once a dose is dispensed, for safety and compliance purposes a subsequent dose cannot be dispensed until after a preset time period elapses as determined by an internal timer. That time period can, if desired, be set short of the next dose time; doing so will permit the patient to take the next dose earlier than scheduled if desired, but not so early that the patient will overdose. Alternative, the timer can be disabled altogether, thus overriding this protection. 
     3. Dosage Display Icons 
     The invention displays the doses to be taken in a given day in viewing segment  48   b  of display  16  as shown in FIG.  8 . The dose number is displayed as an integer value  102 , and a check mark  104  is used to identify each dose taken in a twenty-four hour period since 1 AM. Therefore, the display will be in the form of “1”, “2” and so forth for doses taken. The check marks are cleared at 1 AM of each day, and each dose causes another icon to light (whenever the display is awake). Up to four doses can be prescribed per day, and FIG.  8  through FIG. 10 show the display format after four doses have been taken. 
     4. Setting Dosages 
     The dose size is initially set by the health care provider using a personal computer coupled to serial interface  34 . The dose sizes can be set in 0.1 ml increments from 0.1 ml to 5.0 ml. Display  16  shows this value in terms of milligrams at a rate of 100 mg per milliliter. 
     Referring also to FIG. 5, the patient can change the dose size by pressing and holding the display/dose key  24  and the alarm/increment key  22  together for approximately three seconds. Any other sequence will abort the change. Display  16  will then automatically switch to show the dose size, the “mg” icon  94  will flash, and an audible tone will be heard. While the display/dose key  24  is held down, the alarm/increment key  22  is then pressed repeatedly to increment the dose size to the desired amount in 10 mg steps. The value will wrap from 500 mg back to 10 mg and then repeat the 10 mg incremental steps for a total of fifty steps. While changing the dose size, pressing and holding the alarm/increment key  22  will automatically increment the value about two or three steps per second. The dose size is incremented in a temporary register during this procedure. 
     Referring also to FIG. 10, an example of a display screen showing the number of doses left in medication cassette  14  can be seen. The actual volume drawn from medication cassette  14  is maintained internally and the remaining doses at the current dose size is computed and displayed. Since the starting volume and dose sizes are known, the remaining doses are easily determined. Preferably, the starting volume is divided by the dose size to determine the total number of doses available, and then the number of dispensed doses subtracted from the starting number. Alternatively, the volume of dispensed doses could be subtracted from the starting volume, and the remaining volume divided by the dose size to determine the remaining number of doses. No dose will be dispensed and an audible alarm will sound if there is insufficient medication to give a full dose. The dose size and doses left icon  100  are always shown after a dose is taken. 
     5. Cassette Removal Alarm 
     An audible alarm is sounded if medication cassette  14  is removed with more than 6 ml left in bottle  76 . When medication cassette  14  is replaced, the supply counter will be retained at its previous value. This sequence presumes that medication cassette  14  was removed for inspection only, and reinstalled partially full. For this sequence of early removal and re-installation, the number of doses left and the doses left icon  100  will flash until medication cassette  14  is replaced. However, if the user presses the display/dose key  24  during the first five seconds after removal of medication cassette  14 , the counter will reset back to 50 ml. This is an override of the default value, allowing early cassette replacement by a properly instructed user or health care provider. 
     If medication cassette  14  is changed with less than 6 ml left, the counter will reset back to 50 ml, assuming a normal new cassette replacement. The user should be instructed not to remove the cassette until the doses left value in display  16  indicates one or zero doses and to install only full medication supply bottles. 
     6. Compliance Memory 
     Dispenser  10  preferably includes sufficient non-volatile memory in RAM  20  to maintain a compliance history of up to approximately nine hundred and fifty doses being dispensed. Two doses per day results in over fifteen months of compliance history, and three doses per day results in over ten months of compliance history. Each dose is recorded as a time event with a resolution of ten minutes and a maximum time span of fifteen months, based on the internal clock as set by the health care provider, patient or other user via a personal computer and serial interface  26 . The actual values stored must be interpreted by the personal computer software upon downloading to establish actual days and months. 
     In addition to storing the time of each dose dispensed, the compliance memory also stores the dose sizes. To save memory, it only stores a new dose size in the compliance memory when the health care provider, patient or other user changes it. The values stored range from one to fifty, corresponding to 10 mg to 500 mg. Changing the dose size uses the equivalent of one time recording, reducing the maximum number of doses recorded by one for each change. Even in unusual cases where the dose changes frequently, this should not impact the usefulness of the product. 
     Optionally, the compliance memory could also store the time of each any medication supply change to confirm correct usage of each supply. 
     If the compliance memory has thirty or less memories available, the “service” icon  106  shown in FIG. 8 will flash on the display and an audible alarm will sound after each dose is taken. 
     7. Compliance Score 
     Dispenser  10  also keeps a running history of the number of doses taken each day for a compliance score period; for example, thirty days. From that history, it computes a percentage of compliance from the number of prescribed doses versus the actual number taken. Referring to FIG. 8, this value is then displayed as a score  108  in viewing segment  48   c  of display  16  for monitoring. The compliance score is updated as a function of time and dosing, and changes if dosing does not occur on specified times or at specified does. The values are in increments of 1% steps, so score steps include 0% through 100%. Note that this information is maintained in a separate portion of RAM  20  than the compliance memory for computation purposes, but can also be cleared independent of the compliance memory. As a result, a patient&#39;s score can continue uninterrupted even after uploading the compliance data. 
     In order to determine the compliance score, when a dose is taken the “today&#39;s dose” count is incremented, up to a maximum of four doses per day. At 1 AM of each day, the dose count is set to zero. Where the compliance score is computed over a thirty day running period, the past thirty days of counts are summed and the total days are counted. If the total number of days counted is less than five, the count is forced to five so that a 100% compliance score is not reached until five days of medication. The compliance score is then computed according to: 
     
       
         Score=(sum of doses)/(doses per day * total day count) 
       
     
     and rounded to the nearest 1% increment. 
     As can be seen, the compliance score is a critical indicator that the patient, health care provider or other person responsible for monitoring treatment can use to determine if proper drug therapy is taking place. 
     8. General Memory 
     Dispenser  10  also includes general memory in RAM  20  that allows programming of the patient name or identification (30 characters), the pharmacy name or identification (30 characters), the device serial number (10 characters), the last date and time that the unit was programmed, the number of doses per day prescribed, and time interval presets (useful when 3 or 4 doses per day are prescribed). 
     9. Internal Clocks 
     Dispenser  10  maintains a real time clock that is set via a personal computer and serial interface  26 . It does not regard date or months or time changes. It simply counts up every ten minutes to a maximum count of 65,530, or 10,922 hours, or 455 days. The time of day for day zero is recorded upon programming. It is used to establish when the day rollover occurs to reset the “doses today” check marks  104 . 
     When data is uploaded to a personal computer via the serial interface  26 , the personal computer receives the current real time clock value from dispenser  10  and computes actual days and times with this real time clock value relative to the real time and date from within the personal computer. To establish the actual time and date of a particular dose, the dose time is subtracted from the current real time clock value to determine how much time has elapsed since the dose. The elapsed time is then used to determine an actual calendar date and time within the personal computer. This ten minute clock is kept in non-volatile memory, so a battery power loss due to a drop, bump, or the patient changing the battery will not result in a full reset of the clock or confusion within the compliance data. Optionally, when the clock is at a predetermined number of days, such as three hundred and sixty-five days, or greater since a service by the health care provider, the service icon  106  will flash on the display and an audible alarm will sound after each dose is taken. 
     10. Sleep Mode and Timeout 
     Dispenser  10  enters a sleep mode when not in use between doses to save battery power. During that time, display  16  is blank and the only internal activity is clock maintenance. Pressing either the alarm/increment key  22  or the display/dose key  24 , or removing medication cassette  14 , will wake up dispenser  10  and activate display  16 . Also, one hour prior to the time for dosing, dispenser  10  will automatically wakeup and activate display  16 . Dispenser  10  will go back to sleep after two minutes of non-activity, termed the sleep “timeout” period. 
     11. Programming and Uploading Data 
     The health care provider would generally run a software program on an external personal computer to communicate with dispenser  10  for programming and reading the compliance history. To enter the communications mode, the alarm/increment key  22  is held down for three seconds until display  16  goes blank. This indicates that dispenser  10  is ready to talk to the personal computer. The software on the personal computer is then run (or the correct function activated within software that is already running). The personal computer then transmits various commands to dispenser  10  and establishes communications. When all communications are finished, pressing dispense button  42  (which in turn activates dispense switch  26 ) causes dispenser  10  to exit the communications mode and return to normal operation. Preferably, the communications mode operates with the following safeguards: 
     (a) The communications mode cannot be entered if dispenser  10  is in the process of setting a dose or dispensing a dose. 
     (b) The alarm/increment key  22  does not need to be held down during communications. 
     (c) The internal clocks are suspended during the communications mode. 
     The personal computer always acts as the master and issues commands to either read data from or write data to dispenser  10 . A complete data transfer will take approximately four to twenty seconds, depending upon the amount of data transferred. Simply programming dispenser  10  will be almost instantaneous since little data is transferred. For compatibility, a data rate of 2400 baud is used. 
     12. Programming Command Set 
     Control microprocessor  12  includes programming which will generally carry out the operations of: 
     (a) Programming patient name and identification (ID). 
     (b) Programming pharmacy name and ID. 
     (c) Programming serial number (only used in production). 
     (d) Resetting real-time clock to current time, day zero (10 minute clock). 
     (e) Programming the dose size. 
     (f) Programming doses per day (one to four). 
     (g) Programming dose intervals (4 two digit hours values. ex: 04,04,04,12). 
     (h) Resetting the battery timer (new battery installed). 
     (i) Clearing the compliance history memory. 
     (j) Clearing the compliance score memory (30 day histogram data). 
     (k) Reading data: This operation includes reading the compliance memory of all doses taken since compliance memory was last cleared (time for each dose and all dose sizes used), patient and pharmacy names and ID&#39;s, device serial number, battery life timer, current real time clock, and time value when unit was last programmed. All data is uploaded at one time, allowing the personal computer to be used to further manipulate the data for displaying and/or printing. 
     13. Battery Change Timer 
     To save power and cost, dispenser  10  preferably does not utilize a battery voltage detector. Instead, it senses when the battery is removed and starts a timer when the new battery is installed. After a preset period of time (e.g., six months) or after a certain number of dispenses since a battery change, service icon  106  (FIG. 8) will light anytime the unit is awake. Note that this timer is independent of the clock. This timer value can also be read by a personal computer over serial interface  26  so the health care provider can view it. 
     As a routine, the health care provider should change the batteries regularly, even if the battery timer has not timed out, to insure reliable operation. 
     14. Replacing the Medication Cassette 
     The empty medication cassette  14  is removed from dispenser  10  by squeezing the two side latches  74  (FIG. 6) at the bottom portion of dispenser  10  and removing the entire medication cassette  14 . This includes the liquid medication bottle  76  and disposable fluid path components. To load a new medication cassette  14  into dispenser  10 , the cassette assembly is inserted into dispenser  10  until the two side latch assemblies  72 ,  74  engage. 
     Medication cassette  14  is assembled using a standard bottle of the medication and a disposable fluid path assembly. The medication cassette is automatically primed during the first dose after it is installed, eliminating any pre-priming by the health care provider or the patient. The accuracy of the priming action may introduce a small degree of error on smaller doses, and compensation may be necessary. Note that if medication cassette  14  is removed and then reinstalled, the first dose administered will be over-dosed by the priming volume, which is in the range of approximately 0.1 ml to 0.2 ml. 
     15. Possible Hazards Overcome by the Invention 
     Table 1 lists various hazards or dangers associated with the taking of medications, and indicates how the present invention overcomes or avoids these hazards. Preferably, a user manual is provided with the invention which explains the solution provided by dispenser  10 . The “level of concern” column shown in Table 1 corresponds to the FDA&#39;s definitions regarding the potential harm done to a patient. In all hazard cases, the mitigated level of concern is reduced to MINOR CONCERN, causing little or no harm to the patient. 
     Accordingly, it will be seen that this invention provides a liquid medication dispenser which alerts patients of the correct time intervals for taking liquid medications, which keeps track of and displays the number of dosages of liquid medication taken, which quickly, consistently and accurately measures and dispenses dosages of liquid medication in a user friendly manner, and which records the date, time and dose level so that treatment compliance can be reviewed by the patient and/or healthcare professional supervising the treatment. The invention is particularly suited for immunosuppressive therapy in transplant patients. Using an immunosuppressive drug such as cyclosporine, tacrolimus, mycophenolate mofetil, mycophenolate acid, raapamycin or azathioprine, steroids, leflumomide, on a daily basis (e.g., once, twice or four times a day) at the appropriate dose is essential to transplant outcome. Insufficient dosing can result in acute graft rejection and graft loss. Excessive dosing can result in nephrotoxicity, liver toxicity, infectious cancer or neurotoxicity. Patients need specific education and monitoring; they typically have three to ten medications per day to use on a chronic basis. Measuring compliance, or lack of compliance, can help healthcare professionals to better direct their education and monitoring efforts toward certain patients. 
     Although the description above contains many specificities, these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of this invention. Thus the scope of this invention should be determined by the appended claims and their legal equivalents. In addition, those skilled in the art will appreciate that various forms of circuitry can be used for the invention, and that the schematic diagram shown in FIG. 2 is but one embodiment that could be employed. For example, circuit elements could be replaced with digital or analog equivalents. Furthermore, it will be appreciated that control microprocessor  12  and its associated programming and relate components provides the means for carrying out the timing, recording and dose tracking functions, and related computations described above, as well as control of medication cassette  14  and communications with external devices such as a personal computer. Also, the programming sequences and steps for control processor  12  can vary without departing from the scope of the invention. Those skilled in the art will appreciate that conventional programming techniques would be employed to implement the functions described herein with respect to remotely programming and interrogating dispenser  10  with an external personal computer. The design and coding of such software to carry out those functions could be readily developed by a person having ordinary skill in the art and, are not described herein. 
     
       
         
               
               
               
               
             
           
               
                   
               
               
                 Potential 
                 Level of 
                 Potential 
                 Solution Provided by the 
               
               
                 Hazard 
                 Concern 
                 Cause 
                 Invention 
               
               
                   
               
             
             
               
                 Dose too 
                 Moderate 
                 Incorrect dose 
                 The actual dose size is always 
               
               
                 Small 
                   
                 size pro- 
                 displayed prior to dispensing. 
               
               
                   
                   
                 grammed by 
                 The dose size is initially 
               
               
                   
                   
                 PC. 
                 programmed by a professional 
               
               
                   
                   
                   
                 pharmacy. The patient is instruc- 
               
               
                   
                   
                   
                 ted to observe the dose size. 
               
               
                   
                   
                 Incorrect dose 
                 The actual dose size is always 
               
               
                   
                   
                 size pro- 
                 displayed prior to dispensing. 
               
               
                   
                   
                 grammed by 
                 The patient is instructed to 
               
               
                   
                   
                 patient. 
                 observe the dose size. 
               
               
                   
                   
                 Patient does 
                 Patient is instructed on use of 
               
               
                   
                   
                 not allow com- 
                 the device when issued. The 
               
               
                   
                   
                 plete dispense 
                 instruction manual contains the 
               
               
                   
                   
                 into glass. 
                 same instructions. Housing 40 
               
               
                   
                   
                   
                 can include an arrow (not 
               
               
                   
                   
                   
                 shown) indicating the dispense 
               
               
                   
                   
                   
                 location on the bottom to insure 
               
               
                   
                   
                   
                 the medication goes into the 
               
               
                   
                   
                   
                 glass. 
               
               
                   
                   
                 Disposable 
                 The disposable and motor cam 
               
               
                   
                   
                 pump not 
                 are designed to self-fit, provided 
               
               
                   
                   
                 properly mated 
                 the disposable fluid path is fully 
               
               
                   
                   
                 to motor cam 
                 inserted. The software monitors 
               
               
                   
                   
                   
                 the proper insertion of the 
               
               
                   
                   
                   
                 medication supply and will not 
               
               
                   
                   
                   
                 dispense and will cause an alarm 
               
               
                   
                   
                   
                 if not properly inserted. 
               
               
                   
                   
                 Medication 
                 The software maintains a record 
               
               
                   
                   
                 supply goes 
                 of the quantity of medication left 
               
               
                   
                   
                 empty during 
                 in the medication cassette and 
               
               
                   
                   
                 dispense. 
                 will not dispense and will cause 
               
               
                   
                   
                   
                 an alarm if there is insufficient 
               
               
                   
                   
                   
                 solution in the supply. 
               
               
                   
                   
                 Fluid path 
                 The dispenser automatically 
               
               
                   
                   
                 not primed 
                 primes the fluid path with the 
               
               
                   
                   
                   
                 first dispense after changing the 
               
               
                   
                   
                   
                 medication cassette. 
               
               
                   
                   
                 Electronic 
                 The electronics use a full time 
               
               
                   
                   
                 failure 
                 watchdog to reset the micro 
               
               
                   
                   
                   
                 upon program failure. The soft- 
               
               
                   
                   
                   
                 ware uses timeouts to insure that 
               
               
                   
                   
                   
                 the motor is rotating and alarm if 
               
               
                   
                   
                   
                 there is a motor failure. 
               
               
                 No dose 
                 Moderate 
                 No medication 
                 The software monitors the prop- 
               
               
                 delivered 
                   
                 supply present 
                 er insertion of the medication 
               
               
                   
                   
                 or not inserted 
                 supply and will not dispense and 
               
               
                   
                   
                 fully. 
                 will cause an alarm if a dispense 
               
               
                   
                   
                   
                 is attempted when the supply is 
               
               
                   
                   
                   
                 not present or not fully inserted. 
               
               
                   
                   
                 Medication 
                 The software keeps a record of 
               
               
                   
                   
                 supply empty 
                 the remaining medication supply 
               
               
                   
                   
                   
                 and will not dispense and will 
               
               
                   
                   
                   
                 cause an alarm if a dispense is 
               
               
                   
                   
                   
                 attempted when the record 
               
               
                   
                   
                   
                 indicates an empty supply. 
               
               
                   
                   
                 Disposable 
                 The disposable and motor cam 
               
               
                   
                   
                 pump not 
                 are designed to self-fit, provided 
               
               
                   
                   
                 properly mated 
                 the disposable fluid path is fully 
               
               
                   
                   
                 to motor cam 
                 inserted. The software monitors 
               
               
                   
                   
                   
                 the proper insertion of the 
               
               
                   
                   
                   
                 medication supply and will not 
               
               
                   
                   
                   
                 dispense and will cause an alarm 
               
               
                   
                   
                   
                 if not properly inserted. 
               
               
                   
                   
                 Battery too 
                 The software detects when the 
               
               
                   
                   
                 low for 
                 battery has been removed and 
               
               
                   
                   
                 operation 
                 times the total operation time 
               
               
                   
                   
                   
                 since the new battery was 
               
               
                   
                   
                   
                 inserted. An alarm is given on 
               
               
                   
                   
                   
                 the display when the battery has 
               
               
                   
                   
                   
                 been in place for 365 days. The 
               
               
                   
                   
                   
                 actual expected battery life is 
               
               
                   
                   
                   
                 longer than this, insuring correct 
               
               
                   
                   
                   
                 operation for the full time. In 
               
               
                   
                   
                   
                 addition, the user&#39;s manual 
               
               
                   
                   
                   
                 instructs both the health care 
               
               
                   
                   
                   
                 provider and the patient to only 
               
               
                   
                   
                   
                 replace the batteries with new 
               
               
                   
                   
                   
                 ones. 
               
               
                 Dose too 
                 Moderate 
                 Incorrect 
                 The actual dose size is always 
               
               
                 big 
                   
                 dose size 
                 displayed prior to dispensing. 
               
               
                   
                   
                 programmed 
                 The dose size is initially 
               
               
                   
                   
                 by PC 
                 programmed by a professional 
               
               
                   
                   
                   
                 pharmacy. The patient is in- 
               
               
                   
                   
                   
                 structed to observe the dose size. 
               
               
                   
                   
                 Incorrect 
                 The actual dose size is always 
               
               
                   
                   
                 dose size 
                 displayed prior to dispensing. 
               
               
                   
                   
                 programmed by 
                 The patient is instructed to 
               
               
                   
                   
                 patient 
                 observe the dose size. 
               
               
                   
                   
                 Electronic 
                 The electronics use a full time 
               
               
                   
                   
                 failure 
                 watchdog to reset the micro 
               
               
                   
                   
                   
                 upon program failure. The soft- 
               
               
                   
                   
                   
                 ware uses timeouts to insure that 
               
               
                   
                   
                   
                 the rotation sensor is working 
               
               
                   
                   
                   
                 correctly and alarms if there is a 
               
               
                   
                   
                   
                 sensor failure. 
               
               
                 Accidental 
                 Minor 
                 Dispense 
                 The software requires that the 
               
               
                 Dose 
                   
                 button 
                 Dispense button is pressed and 
               
               
                 dispense 
                   
                 accidentally 
                 held for 2 seconds, and then 
               
               
                   
                   
                 pressed 
                 released within 1 second after an 
               
               
                   
                   
                 or bumped. 
                 audio prompt to validate a 
               
               
                   
                   
                   
                 dispense request. A latch or lock 
               
               
                   
                   
                   
                 mechanism could alternatively 
               
               
                   
                   
                   
                 be used. 
               
               
                 Doses 
                 Minor to 
                 Patient does 
                 The device displays a count 
               
               
                 missed 
                 moderate 
                 not dispense 
                 down timer and alarms when it 
               
               
                   
                   
                 dose when 
                 is time for the patient to take a 
               
               
                   
                   
                 prescribed 
                 dose. The device continues to 
               
               
                   
                   
                   
                 alarm every 10 minutes until the 
               
               
                   
                   
                   
                 dose is taken. The device also 
               
               
                   
                   
                   
                 displays a record of the doses 
               
               
                   
                   
                   
                 taken today and a score of 
               
               
                   
                   
                   
                 patient compliance within the 
               
               
                   
                   
                   
                 last 30 days (or other preset 
               
               
                   
                   
                   
                 period). The compliance mem- 
               
               
                   
                   
                   
                 ory also provides the health care 
               
               
                   
                   
                   
                 professional with complete 
               
               
                   
                   
                   
                 dose taking history for patient 
               
               
                   
                   
                   
                 counseling. 
               
               
                 Doses 
                 Minor 
                 Patient dis- 
                 The count down timer does not 
               
               
                 taken too 
                   
                 penses early 
                 instruct the user to take 
               
               
                 soon 
                   
                   
                 medication until the prescribed 
               
               
                   
                   
                   
                 time. 
               
               
                 Dose 
                 Minor 
                 Patient 
                 When the prescribed time has 
               
               
                 taken late 
                   
                 delays dosing 
                 elapsed since the last dose, the 
               
               
                   
                   
                   
                 device alarms every 10 minutes 
               
               
                   
                   
                   
                 until a dose is taken. 
               
               
                 Remaining 
                 Minor 
                 Supply was 
                 An alarm is sounded if a 
               
               
                 supply 
                   
                 removed and 
                 medication cassette is removed 
               
               
                 counter 
                   
                 reinstalled 
                 with more than 6 ml left in the 
               
               
                 has incor- 
                   
                 partially filled. 
                 bottle. When the cassette is then 
               
               
                 rect value. 
                   
                   
                 reinstalled, the supply counter is 
               
               
                   
                   
                   
                 retained at its previous value. 
               
               
                   
                   
                   
                 The “Doses Left” display 
               
               
                   
                   
                   
                 flashes with until the cassette is 
               
               
                   
                   
                   
                 replaced. If the user presses and 
               
               
                   
                   
                   
                 holds the display/dose key dur- 
               
               
                   
                   
                   
                 ing the first 5 seconds after 
               
               
                   
                   
                   
                 removal of the cassette, the 
               
               
                   
                   
                   
                 counter will reset back to 50 ml. 
               
               
                   
                   
                   
                 If the cassette is changed with 
               
               
                   
                   
                   
                 less than 6 ml left, or the Dis- 
               
               
                   
                   
                   
                 penser is allowed to go to sleep, 
               
               
                   
                   
                   
                 the counter will reset back to 50 
               
               
                   
                   
                   
                 ml. The instruction manual shall 
               
               
                   
                   
                   
                 include a warning not to remove 
               
               
                   
                   
                   
                 the cassette until the “Doses 
               
               
                   
                   
                   
                 Left” display indicates 
               
               
                   
                   
                   
                 on or zero doses and to install 
               
               
                   
                   
                   
                 only full medication supply 
               
               
                   
                   
                   
                 bottles. 
               
               
                 Compli- 
                 Minor 
                 Electronic 
                 The electronic design and 
               
               
                 ance 
                   
                 failure 
                 battery operation insure 
               
               
                 Memory 
                   
                   
                 minimal memory corruption. 
               
               
                 corrupted 
                   
                   
                 The software stores the data in a 
               
               
                   
                   
                   
                 format whereby data points 
               
               
                   
                   
                   
                 are not interdependent and a 
               
               
                   
                   
                   
                 failure will most likely only 
               
               
                   
                   
                   
                 cause one data point to fail. 
               
               
                 Health 
                 Minor 
                 Patient records 
                 The device allows important 
               
               
                 care provi- 
                   
                 are not 
                 patient and prescription 
               
               
                 der cannot 
                   
                 available 
                 information to be held within the 
               
               
                 interpret 
                   
                   
                 device memory and is recovered 
               
               
                 compli- 
                   
                   
                 whenever the compliance 
               
               
                 ance data 
                   
                   
                 memory is read. 
               
               
                 Internal 
                 Minor to 
                 Electronic 
                 The device utilizes a full time 
               
               
                 clock 
                 moderate 
                 failure 
                 watchdog to reset the micro if a 
               
               
                 stops 
                   
                   
                 clock failure occurs. 
               
               
                 Dispenser 
                 Minor 
                 Electronic 
                 The device utilizes a full time 
               
               
                 will not 
                   
                 failure 
                 watchdog to reset the micro if a 
               
               
                 operate 
                   
                   
                 clock failure occurs. 
               
               
                 Compli- 
                 Minor 
                 Patient has 
                 When the compliance memory is 
               
               
                 ance 
                   
                 not seen 
                 within 30 doses of being full 
               
               
                 Memory is 
                   
                 health care 
                 (about 2 weeks), an alarm is set 
               
               
                 full 
                   
                 provider 
                 after each dispense, indicating 
               
               
                   
                   
                   
                 that the device must be serviced. 
               
               
                   
                   
                   
                 The compliance memory can 
               
               
                   
                   
                   
                 hold up to about 15 months of 
               
               
                   
                   
                   
                 data with a typical prescription. 
               
               
                   
                   
                   
                 A typical patient will have to see 
               
               
                   
                   
                   
                 the health care provider for other 
               
               
                   
                   
                   
                 reasons before this time. The 
               
               
                   
                   
                   
                 software utilizes a circular 
               
               
                   
                   
                   
                 memory configuration in the 
               
               
                   
                   
                   
                 compliance memory. If the 
               
               
                   
                   
                   
                 memory is full and is not 
               
               
                   
                   
                   
                 serviced, the software will over 
               
               
                   
                   
                   
                 write the oldest data points with 
               
               
                   
                   
                   
                 the newer ones. Thus, only the 
               
               
                   
                   
                   
                 more recent doses can be read. 
               
               
                 Clock 
                 Minor 
                 Patient has 
                 The device alarms for service 
               
               
                 time 
                   
                 not seen 
                 after 365 days upon each 
               
               
                 wraps 
                   
                 health care 
                 dispense. If the patient continues 
               
               
                 back to 
                   
                 provider. 
                 to avoid service beyond 455 
               
               
                 zero. 
                   
                   
                 days, the internal clock and 
               
               
                   
                   
                   
                 compliance data time values will 
               
               
                   
                   
                   
                 simply wrap around to zero and 
               
               
                   
                   
                   
                 start again. The health care 
               
               
                   
                   
                   
                 provider or the host PC software 
               
               
                   
                   
                   
                 may have to do some additional 
               
               
                   
                   
                   
                 interpretation to decipher this.