Adaptive basal fraction values ​​in an automated drug delivery device based on a user's past drug delivery amounts - Patents.com

Abstract

Exemplary embodiments may provide adaptability in basal fraction values. Exemplary embodiments may also provide adaptability in total daily drug delivery (TDM). The adaptability provided by exemplary embodiments helps customize drug delivery to the needs of a user of a drug delivery device. Exemplary embodiments may adapt a user's basal rate based on the user's drug delivery history data. Additionally, exemplary embodiments may update the basal rate based on more recent trends that deviate from the drug delivery history data. The degree of adaptability provided by exemplary embodiments may be limited to not exceed upper and / or lower thresholds. The degree of adaptability may be adjusted by controlling the rate of adaptability to a sufficiently small increment each time the basal rate is updated.

Description

[Technical field]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 318,217, filed March 9, 2022, and U.S. Provisional Patent Application No. 63 / 369,790, filed July 29, 2022, the contents of which are incorporated by reference in their entireties herein. [Background technology]

[0002] Automated insulin delivery (AID) devices, such as insulin pumps, allow for both bolus and basal insulin delivery, which delivers small, regular, continuous doses of insulin, and bolus insulin, which is administered to counteract food-induced increases in blood glucose levels or to normalize blood glucose levels that are too high.

[0003] Traditionally, AID devices determine how much basal insulin to administer to a user based on a total daily insulin amount (TDI). The TDI is the total amount of insulin delivered to a user per day. The TDI may be initially set based on the user's weight. The amount of insulin delivered by basal delivery per day is derived from the TDI. Traditionally, the amount of insulin delivered by basal delivery per day is set to half the user's TDI.

[0004] According to one aspect of the present invention, a drug delivery system includes at least one non-transitory storage device storing computer program instructions and at least one processor executing the computer program instructions, the computer program instructions causing the processor to perform an automatic basal drug delivery to a user of the drug delivery system based on at least one basal profile; acquiring drug delivery data over a recent period of time, in particular a recent one or more day period, the drug delivery data including past bolus drug delivery amounts and past basal drug delivery amounts delivered to the user of the drug delivery system during the recent period; calculating a sum of past basal delivery amounts and a sum of past bolus delivery amounts and past basal delivery amounts; and calculating a past basal ratio (BR ) by dividing the sum of past basal delivery amounts by the sum of past bolus delivery amounts and past basal delivery amounts (TDM) to obtain a new automatic basal drug delivery amount and / or a new basal profile. old ) or based on a ratio of a sum of past basal deliveries to a sum of past bolus deliveries or a sum of past bolus deliveries and past basal deliveries.

[0005] The present invention is based on the idea of ​​improving the allocation of basal and bolus drug delivery to a user of a drug delivery system. The drug delivery system can be designed to automatically deliver a bolus to the user based on blood glucose measurements or based on estimated blood glucose values ​​and / or user input, particularly via a user interface. This may result in deviations in the basal and bolus drug delivery compared to the physiologically ideal drug delivery over a period of time, particularly a day. In particular, if the basal drug delivery is too low during a day, it may be necessary to increase the bolus drug delivery during that day, which is not optimal for maintaining the user's blood glucose level within the target range. Therefore, in the present invention, the past basal and past bolus deliveries, as well as the past basal deliveries, are analyzed and the automatic basal drug delivery is adjusted to obtain a new automatic basal drug delivery and / or a new basal profile.

[0006] In particular, the new automatic basal drug delivery amount and / or the new basal profile can be adjusted such that the subsequent basal drug delivery amount is a new basal ratio, which is the sum of the subsequent basal delivery amount divided by the sum of the subsequent bolus delivery amount and the subsequent basal delivery amount. For example, the new basal ratio can be calculated by multiplying the previous basal ratio by a first weighting factor, multiplying the adjustment factor by a second weighting factor, and adding the resulting values. The sum of the first weighting factor and the second weighting factor can be 1. Furthermore, the first weighting factor and the second weighting factor can be dependent on the length of the recent period, such that as the period becomes longer or the recent period becomes longer, the first weighting factor decreases and the second weighting factor increases. This approach improves reliability and stability in drug delivery.

[0007] The first and second weighting factors may be dependent on an adaptivity rate, which controls the rate at which the adjustment factor is incorporated into the new basal rate. For example, the adaptivity rate may range from 0.05 to 0.8, in particular from 0.1 to 0.5, in particular from 0.2 to 0.4. Furthermore, the adjustment factor may range from 0.3 to 0.7, in particular from 1 / 3 to 2 / 3, in particular from 0.45 to 0.55. Alternatively or additionally, the adjustment factor may be the average of the ideal basal rate and the previous basal rate, in particular the ideal basal rate of 0.5 and the average of the previous basal rate.

[0008] The sum of the subsequent bolus delivery and the subsequent basal delivery may be the same as the sum of the previous bolus delivery and the previous basal delivery. Alternatively, the sum of the subsequent bolus delivery and the subsequent basal delivery may be adjusted by a user via a user interface, or automatically by computer program instructions based on, among other things, previous blood glucose measurements, in which the sum of the subsequent dose is increased if the average of the previous blood glucose measurements was regularly above the target blood glucose value, and the sum of the subsequent dose is decreased if the average of the previous blood glucose measurements was regularly below the target blood glucose value.

[0009] The drug delivery system may comprise a drug delivery device comprising a reservoir for storing the drug, a delivery or pump mechanism for delivering the drug from the reservoir to a user, and / or a management device. The at least one non-transitory storage device and the at least one processor for executing the computer program instructions may be comprised in either the drug delivery device or the management device, or, if there is more than one non-transitory storage device and more than one processor for executing the computer program instructions, the at least one storage device and the at least one processor may be comprised in the drug delivery device and the at least one additional storage device and the at least one additional processor may be comprised in the management device.

[0010] According to another aspect of the present invention, a drug delivery system includes a non-transitory storage device for storing computer program instructions and a processor for executing the computer program instructions. The computer program instructions cause the processor to calculate a new basal rate for a user, the new basal rate specifying what percentage of the user's total daily drug amount should be delivered by a basal delivery amount based on the user's previous basal rate and an adjustment value. The adjustment includes a percentage of the drug amount delivered as a basal drug delivery amount via the automatic drug delivery device over a period of time, and at least one adjustment limit that limits how much the new basal rate can vary from the previous basal rate. The computer programming instructions also cause the processor to determine a dosage for the next basal drug delivery to the user by the automatic drug delivery device using the new basal rate.

[0011] The drug may be insulin. The drug may include at least one of a glucagon-like peptide-1 (GLP-1) agonist, pramlintide, or other medication that affects the user's blood glucose level. Determining the dosage for the next basal drug delivery may include multiplying the user's total insulin amount per day by the new basal rate. The at least one adjustment limit may include a maximum and / or minimum value that the adjustment assumes. The at least one adjustment limit may limit the difference between the previous basal rate and the new basal rate to a predetermined constant amount. The at least one adjustment limit may be a scaling factor that scales the adjustment.

[0012] According to another aspect of the present invention, a drug delivery system includes a non-transitory storage device for storing computer program instructions and a processor for executing the computer program instructions. The computer program instructions cause the processor to determine an average amount of insulin delivered to a user per day to compensate for carbohydrates ingested in meals, and to determine an average amount of insulin delivered to a user per day to correct hyperglycemia experienced by the user. The computer program instructions also cause the processor to determine an average amount of insulin delivered by the user as a basal delivery rate, and to calculate a sum of an average amount of insulin delivered to the user per day to adjust for carbohydrates ingested in meals, an average amount of insulin delivered to the user per day to correct hyperglycemia experienced by the user, and an average amount of insulin delivered to the user as a basal delivery rate. The computer program instructions also cause the processor to determine a basal portion factor as a ratio of the sum of the average amount of insulin delivered to the user as the basal delivery rate, and to determine an updated basal delivery rate for the user using the basal portion factor.

[0013] Determining an updated basal delivery rate for the user may include determining an updated hourly basal delivery rate for the user. Alternate interval rates may be determined, for example, every 2 hours, every 30 minutes, every 15 minutes, every 5 minutes, etc. Determining the hourly basal delivery rate may include determining the product of the basal portion factor and the user's total daily insulin (TDI) and dividing the product by 24 to determine the hourly basal delivery rate. Other intervals of the basal delivery rate may be calculated in a similar manner. The method may include updating the basal portion factor and updating the user's basal delivery rate using the updated basal portion factor. Updating the basal portion factor may include increasing the basal portion factor by a first predetermined constant amount if the basal portion factor is less than a threshold value. Updating the basal portion factor may include decreasing the basal portion factor by a second predetermined constant amount if the basal portion factor is greater than a threshold value.

[0014] According to a further aspect of the invention, the drug delivery system includes a display and a non-transitory storage device for storing computer program instructions. The drug delivery system also includes a processor for executing the computer program instructions. The computer program instructions cause the processor to compare an average meal bolus portion of the patient's total daily insulin amount for the last few days with a past average meal bolus portion of the patient's total daily insulin amount. If the average meal bolus amount of the total daily insulin amount for the last few days is higher than the average post-meal bolus amount of the total daily insulin amount by a first percentage, the processor suggests to the user on the display to reduce the amount of insulin for the meal bolus by a first percentage. If the average meal bolus amount of the total daily insulin amount for the last few days is lower than the average meal bolus amount of the total daily insulin amount by a second percentage, the processor suggests to the user on the display to increase the amount of insulin for the meal bolus by a first percentage.

[0015] The drug delivery system may include an insulin pump, a controller for an insulin pump, or a portable computing device such as a smartphone. The computer program instructions may further cause the processor to calculate a historical average daily basal insulin delivery to the patient. The computer program instructions may further cause the processor to calculate a historical average daily prandial bolus insulin delivery to the patient. The computer program instructions may further cause the processor to calculate a historical average daily total insulin amount for the patient as the sum of the historical average daily basal insulin delivery to the patient and the historical average daily prandial bolus insulin delivery to the patient. The computer program instructions may further cause the processor to calculate a historical average prandial bolus portion of the daily total insulin amount for the patient as a ratio of the historical average daily prandial bolus portion of the daily insulin delivery to the patient and the historical average daily total insulin amount for the patient. The first percentage may be equal to the second percentage.

[0016] Further, according to an aspect of the present invention, a drug delivery device for delivering a drug to a user includes a non-transitory storage medium for storing computer program instructions. The drug delivery device further includes a processor configured to execute the computer program instructions such that the processor uses a first basal fraction value indicative of a portion of the user's total daily medication (TDM) to determine an amount of basal drug to be delivered by the drug delivery device during a first operating period. The instructions cause the processor to determine an adjusted basal fraction value for a next operating period after the first operating period based on a magnitude of a recent basal delivery amount by the drug delivery device, and the processor uses the adjusted basal fraction value to determine an amount of basal drug to be delivered by the drug delivery device during the next operating period. The instructions cause the processor to deliver the determined basal drug delivery amount by the drug delivery device during the next operating period.

[0017] Determining an adjusted basal fraction value for a next operating period may include: applying a first weighting to the first basal fraction value for the first operating period to obtain a first weighting value; determining a calculated ratio of a total amount of basal drug delivered by the drug delivery device to the user during the operating period to a total amount of basal drug that would be delivered over the period if the initial basal fraction value was used; applying a second weighting to the calculated ratio to generate a second weighting value; and summing the first weighting value and the second weighting value to determine the adjusted basal fraction value. The initial basal fraction value may be a basal / TDM ratio, and the basal / TDM ratio for the initial basal fraction value may be 0.5. The initial basal fraction value may be tailored to the insulin sensitivity of the user. The first weighting may be at least four times the second weighting. The drug may be insulin, a glucagon-like peptide 1 (GLP-1) agonist, pramlintide, or a combination of at least two of these. The drug delivery device may be an insulin patch pump. Determining the adjusted basal portion value for the next operating period after the first operating period may include calculating a TDM based on the recent drug delivery amount and using the calculated TDM in determining the adjusted basal portion value.

[0018] Furthermore, according to another aspect of the present invention, a drug delivery device for delivering a drug to a user includes a non-transitory storage medium for storing computer program instructions and a processor configured to execute the computer program instructions, and is capable of causing the processor to perform the following operations: determine an amount of basal drug to be delivered by the drug delivery device during a first operating period using a first basal portion value indicative of a portion of the user's total daily drug dosage (TDM) delivered in basal form; determine an adjusted basal portion value for a next operating interval after the first operating period based on a magnitude of a recent bolus delivery by the drug delivery device; determine an amount of basal drug to be delivered by the drug delivery device during the next operating period using the adjusted basal portion value; and cause the drug delivery device to deliver the determined amount of basal drug during the next operating period.

[0019] The first basal fraction value may have a basal-to-TDM ratio of 0.5. Determining the adjusted basal fraction value for the next operating period includes applying a first weighting to the first basal fraction value for the first operating period to obtain a first weighting value, determining a ratio of a total amount of bolus drug delivered by the drug delivery device to a user during an operating period to a total amount of bolus drug that would be delivered over that period if the predicted basal fraction value were used, subtracting the determined ratio from 1 to obtain a difference, applying a second weighting to the difference to obtain a second weighting value, and summing the first weighting value and the second weighting value to determine the adjusted basal fraction value.

[0020] The first basal portion value may be tailored to a drug sensitivity of the user. The drug may be insulin, a glucagon-like peptide-1 (GLP-1) agonist, pramlintide, or a combination of two or more of the above. The drug delivery device may be an insulin patch pump. The first weighting may be at least four times the second weighting.

[0021] According to yet another aspect of the present invention, a method for managing a basal insulin delivery dose is performed by a processor of an insulin delivery device. The method includes storing a basal insulin delivery dose delivered to a user by the insulin delivery device in a non-transitory computer-readable storage medium. The method also includes determining, by the processor, a total basal insulin delivery amount for a time period based on at least some of the stored basal insulin delivery doses, and determining, by the processor, a ratio of the determined total basal delivery amount to a predicted total basal delivery amount for the time period. The method further includes weighting the ratio and weighting the previous basal to TDM ratio or, if used in the future, the total daily insulin amount (TDI) used by the processor to determine the basal delivery amount for the previous time period. The method further includes summing, by the processor, the weighted ratio and the previous weighted ratio to generate a new ratio of basal insulin delivery amount to TDI for a next time period, and determining, by the processor, the basal insulin delivery amount for the next time period using the new ratio of basal insulin delivery amount to TDI. The method further includes delivering, by the insulin delivery device, the determined basal insulin delivery amount for a next period of time.

[0022] The insulin delivery device may have a cycle of a certain length, and the sum of the predicted basal delivery in the time frame may be one-half the TDI divided by the ratio of the number of cycles per day to the number of cycles in the time frame. The method may further include calculating the TDI from the insulin delivery to the user by the insulin delivery device in the time frame. Weighting the previous ratio of basal to TDI may include applying a weight to the previous ratio that is at least four times the weight applied to the ratio. The previous ratio of basal to TDI may be customized for the user. [Brief description of the drawings]

[0023] [Figure 1]FIG. 1 illustrates a drug delivery system suitable for an exemplary embodiment. [Diagram 2] FIG. 2 shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to cause a drug delivery device to apply basal portion values ​​to a user. [Diagram 3] FIG. 3 shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to determine a new basis portion value according to the first option. [Figure 4] FIG. 4 shows a flow chart of exemplary steps that can be performed to determine a basal dose for delivery by a drug delivery device in an exemplary embodiment. [Diagram 5] FIG. 5 shows a flow chart of exemplary steps that can be performed in an exemplary embodiment to determine new adjustment factors having minimum and maximum values. [Figure 6A] FIG. 6A shows a flow chart of exemplary steps that can be performed in an exemplary embodiment to determine new adjustment factors by averaging empirical basal fraction values ​​with ideal basal fraction values. [Figure 6B] FIG. 6B shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to determine a new basis portion value according to the second option. [Figure 7] FIG. 7 illustrates a flow chart of exemplary steps that may be performed in an exemplary embodiment to determine an adjustment factor having a constant value option. [Figure 8] FIG. 8 shows a flowchart of exemplary steps that can be performed to determine adjustment factors having scaled values ​​in an exemplary embodiment. [Figure 9] FIG. 9 illustrates a flow chart of exemplary steps that may be taken in an exemplary embodiment to notify a user of the need to adjust a bolus dose. [Figure 10] FIG. 10 shows a flow chart of exemplary steps that can be performed to determine an hourly basal rate in an exemplary embodiment. [Figure 11] FIG. 11 shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to apply incremental adjustments to base portion values. [Figure 12] FIG. 12 shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to suggest bolus amount adjustments based on average basal portion values. [Figure 13] FIG. 13 shows a flowchart 1300 of exemplary steps that may be performed to have a user apply the basal fractional value and TDM in an exemplary embodiment. [Figure 14] FIG. 14 illustrates a flow chart of exemplary steps that may be performed in an exemplary embodiment to adjust basal portion values ​​for a shortened period of time. [Figure 15A] FIG. 15A shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to determine adjusted basal portion values ​​from a user's recent drug delivery history. [Figure 15B] FIG. 15B shows a flowchart of exemplary steps that may be performed to adapt a basis portion value to a user in an exemplary embodiment. [Figure 16] FIG. 16 shows a flow chart of steps that can be performed to adapt TDM to a user in an exemplary embodiment. [Figure 17] FIG. 17 shows a flow chart of exemplary steps that can be performed in an exemplary embodiment to use the adjusted TDM in determining the basal fraction value. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0024] Exemplary embodiments may provide flexibility in basal fractional values ​​(e.g., a "basal ratio" of daily basal delivery to total daily drug delivery (TDM)) that identify what percentage of the total daily drug delivery to the user the basal delivery represents. More generally, a basal fractional value represents a total dose of basal drug delivery over a period of time, such as a day. A "basal ratio" may be used herein as an example of a basal fractional value. However, it should be understood that a basal fractional value need not be expressed solely as a basal ratio. For example, a basal fractional value may be a decimal value or, in some embodiments, an absolute amount of basal drug over a day or other period of time.

[0025] Exemplary embodiments can also provide adaptability of TDM to accommodate changing insulin needs of a user. As mentioned above, conventional drug delivery devices such as AID devices can operate with a constant TDI and a constant basal value. The difficulty with operating with a constant TDI and a constant basal value is that the TDI and / or the constant basal value may not always be suitable for a user. For example, a user may be better suited to a higher or lower basal value. Similarly, the TDI may be too high or too low for a user.

[0026] Exemplary embodiments may adapt the basal portion value for a user based on the user's historical data of drug delivery rates. Additionally, exemplary embodiments may update the basal portion value based on more recent trends that deviate from the historical data of drug delivery rates. The degree of adaptability provided by exemplary embodiments may be limited to not exceed upper and / or lower thresholds. Additionally, the rate of adaptability may be adjusted by controlling the degree of adaptability to very small increments each time the basal rate is updated. The increments may be set to a fixed magnitude, adjusted by a scaling factor, or the like.

[0027] In some exemplary embodiments, the size of the drug bolus dose delivered to the user may be adjusted, or a suggestion to adjust the bolus may be made, based on recent drug bolus history and drug delivery history data. The drug bolus dose may be adjusted upwards or downwards based on how much the ratio of the average daily drug bolus dose to the TDM ratio has changed from the historical average value of that ratio. Thus, the bolus dose may be adjusted to reflect the change in the difference between the average daily basal drug delivery and the average daily drug bolus delivery.

[0028] In an exemplary embodiment, the user's basal fractional value may be adjusted based on the user's recent drug sensitivity. This adjustment may be made continuously over the life of the drug delivery device. Additionally, adjustments may be made rapidly to quickly accommodate changes in the user's drug needs. For example, some insulin pumps have a useful life of about three days. Rather than making the user's basal fractional value and / or TDM constant only when the insulin pump is first donned and activated by the user, as in some conventional drug delivery devices, in an exemplary embodiment, the basal fractional value and / or TDM may be adjusted at shorter intervals, such as every hour, every three hours, every twelve hours, etc. If the drug is insulin, for example, the drug delivery device may better account for changes in the user's insulin sensitivity, where some users may experience abnormal changes in insulin sensitivity between 2:00 a.m. and 8:00 a.m., such as due to exercise or due to the dawn phenomenon.

[0029] FIG. 1 illustrates an exemplary drug delivery system 100 suitable for delivering a drug to a user 108 according to an exemplary embodiment. The drug delivery system 100 comprises a drug delivery device 102. The drug delivery device 102 may be a wearable device worn on the body of the user 108 or carried by the user. The drug delivery device 102 may be directly coupled to the user without the use of a tube (e.g., attached directly to a body part and / or skin of the user 108 via adhesive or the like), with an injection location located directly below the drug delivery device 102, or may be carried by the user (e.g., on a belt or pocket) with the drug delivery device 102 connected to an injection site where the drug is injected using a needle and / or cannula. In a preferred embodiment, a surface of the drug delivery device 102 may include an adhesive to facilitate attachment to the user 108.

[0030] The drug delivery device 102 may include a processor 110. The processor 110 may be, for example, a microprocessor, logic circuit, field programmable gate array (FPGA), application specific integrated circuit (ASIC), or microcontroller. The processor 110 may record date and time and perform other functions (e.g., calculations, etc.). The processor 110 may operate to execute a control application 116 encoded with computer program instructions stored in the memory device 114 to enable the processor 110 to direct the operation of the drug delivery device 102. The control application 116 may be a single program, multiple programs, a module, a library, etc. The processor 110 may also execute computer program instructions stored in the memory device 114 for a user interface (UI) 117, which may include one or more display screens displayed on a display 127. The display 127 may display information to the user 108 and, in some examples, may also receive input from the user 108, such as when the display 127 is a touch screen.

[0031] The control application 116 can control the delivery of drugs to the user 108 according to the control approach as described herein. The control application can provide flexibility in basal rates, total daily drug amounts, and boluses as described below. The storage device 114 can maintain a user history 111, such as a history of basal delivery, a history of bolus delivery, and / or other history such as a meal event history, an exercise event history, a blood glucose history, etc. Additionally, the processor 110 can be operable to receive data or information. The storage device 114 can include both primary and secondary storage devices. The storage device 114 can include random access memory (RAM), read only memory (ROM), optical storage device, magnetic storage device, removable storage media, semiconductor storage device, etc.

[0032] The drug delivery device 102 may include one or more housings for housing various components, including a pump 113, a power source (not shown), and a reservoir 112 that stores a drug for delivery to the user 108. A fluid pathway to the user 108 may be provided, and the drug delivery device 102 may use the pump 113 to pump the drug from the reservoir 112 via the fluid pathway to deliver the drug to the user 108. The fluid pathway may include, for example, tubing connecting the drug delivery device 102 to the user 108 (e.g., tubing connecting a cannula to the reservoir 112) and may include conduits to other injection sites.

[0033] There may be one or more communication links with one or more devices physically separate from the drug delivery device 102, including, for example, the user and / or the user's caregiver's management device 104, the sensor 106, the smart watch 130, the health monitor 132, and / or various other devices 134. The communication link may be any wired or wireless communication link operating according to a known communication protocol or standard, such as Bluetooth, Wi-Fi, a short-range wireless communication standard, a cellular standard, or other wireless protocol.

[0034] The drug delivery device 102 can communicate with the network 122 via a wired or wireless communication link. The network 122 can include a local area network (LAN), a wide area network (WAN), or a combination thereof. A computing device 126 can communicate with the network 122, and the computing device can communicate with the drug delivery device 102.

[0035] The drug delivery system 100 may include one or more sensors 106 for sensing the level of one or more analytes. The sensor(s) 106 may be coupled to the user 108, for example, by adhesive, and may provide information or data regarding one or more medical conditions and / or physical attributes of the user 108. The sensor(s) 106 may be physically separate from the drug delivery device 102 or may be an integrated component thereof. The sensor(s) 106 may include, for example, a blood glucose monitor, such as a continuous glucose monitor (CGM) or a non-invasive blood glucose monitor. The sensor(s) 106 may include a ketone body sensor, an analyte sensor, a heart rate monitor, a respiration rate monitor, a motion sensor, a temperature sensor, a sweat sensor, a blood pressure sensor, an alcohol sensor, and the like.

[0036] The drug delivery system 100 may or may not include a management device 104. In some embodiments, a management device is not needed since the drug delivery device 102 is self-managing. The management device 104 may be a dedicated device, such as a dedicated personal diabetes management (PDM) device. The management device 104 may be a programmed general-purpose device, such as any portable electronic device that includes a dedicated controller, such as a processor, microcontroller, etc. The management device 104 may be used to program or coordinate the operation of the drug delivery device 102 and / or the sensor 106. The management device 104 may be any portable electronic device, such as a dedicated device, a smartphone, a smartwatch, a tablet, etc. The management device 104 in the illustrated embodiment may include a processor 119 and a storage device 118. The processor 119 may perform processing to manage the user's blood glucose level and control the administration of medication to the user 108. The drug delivery device 102 may provide data from the sensor 106 and other data to the management device 104. The data may be stored in the storage device 118. The processor 119 may be operable to execute programming code stored in the memory 118. For example, the memory 118 may be operable to store one or more control applications 120 for execution by the processor. The control application 120 may be responsible for controlling the drug delivery device 102, for example, by controlling AID delivery of insulin to the user 108. In some exemplary embodiments, the control application 120 provides the adaptability described herein. The memory 118 may store the control application 120, history 121 as described above for the drug delivery device 102, and other data and / or programs.

[0037] A display 140, such as a touch screen, may be provided for displaying information. The display 140 may display a user interface (UI) 123. If the display 140 is a touch screen, it may also be used to receive input. The management device 104 may further include input elements 125, such as a keyboard, buttons, knobs, etc., for receiving input from a user 108.

[0038] The management device 104 can communicate with a network 124, such as a LAN or WAN, or a combination of such networks, via wired or wireless communication links. The management device 104 can communicate with one or more servers or cloud services 128 via the network 124. In some embodiments, data such as sensor values ​​can be sent directly from the drug delivery device 102 to the cloud service / server(s) 128 or from the management device 104 to the cloud service / server(s) 128 for storage and processing.

[0039] A smart watch 130, a health monitor 132, and other devices 134 may be part of the drug delivery system 100. These devices 130, 132, 134 may communicate with the drug delivery device 102 and / or the management device 104 to receive information and / or send instructions to the drug delivery device 102. These devices 130, 132, 134 may execute computer program instructions to perform some of the control functions performed by the processor 110 or the processor 119 via the control applications 116 and 120. These devices 130, 132, 134 may include a display for displaying information. The display may display a user interface for providing input by a user to request a change or pause of a dosage, to request, start, or confirm a bolus delivery of a drug, or to display an output such as a change in a dosage (e.g., a basal delivery rate) determined by the processor 110 or the management device 104. These devices 130, 132, 134 may also be in wireless communication communication with the sensor 106 to directly receive analyte measurement data. Another delivery device 105, such as a drug delivery pen, may also be provided to deliver drugs to the user 108.

[0040] A wide variety of drugs can be delivered by the drug delivery device 102 and the delivery device 105. The drug can be insulin for the treatment of diabetes. The drug can be glucagon, which increases the user's blood glucose levels. The drug can also be a glucagon-like peptide (GLP)-1 receptor agonist, which lowers blood glucose levels or slows gastric emptying, slowing the spike in blood glucose levels after a meal. Alternatively, the drug delivered by the drug delivery device 102 can be a painkiller, a chemotherapy drug, an antibiotic, an anticoagulant, a hormone, an antihypertensive, an antidepressant, an antipsychotic, a statin, an anticoagulant, an anticonvulsant, an antihistamine, an anti-inflammatory, a steroid, an immunosuppressant, an anti-anxiety drug, an antiviral, a nutritional supplement, or a vitamin. The drug can also be a combination of several of the drugs listed above.

[0041] The functionality described in the exemplary embodiments below may be under the control of or performed by the control application 116 of the drug delivery device 102 or the control application 120 of the management device 104. In some embodiments, all or part of the functionality may be controlled by or performed by a cloud service / server 128, a computing device 126, or other enumerated devices, including a smart watch 130, a health monitor 132, or other wearable device 134.

[0042] In closed loop mode, the control application 116, 120 continually determines the amount of drug delivered to the user 108 based on a feedback loop. In the case of an insulin delivery device, the goal of closed loop mode is to bring the user's blood glucose level to a target blood glucose level.

[0043] As discussed above, the exemplary embodiments may provide adaptability to the TDM, basal fractional values, and bolus drug delivery dosages provided by the drug delivery device 102. As described below, the control applications 116 and 120 may be configured to provide such adaptability. As described below, there are several ways in which the exemplary embodiments provide adaptability.

[0044] 2 shows a flow chart 200 of exemplary steps that can be performed to adjust the basal daily delivery rate of a drug in an exemplary embodiment. At 202, a new basal portion value, expressed as a basal rate, may be determined based on drug delivery data collected over the last few days. Once the new basal rate is determined, at 204, a new basal daily delivery rate may be determined using the new basal rate, as described in more detail below. The basic formula for this determination is: DB new =BR new *TDM new (Formula 1) Here, DB new is the new daily basal dose, BR new is the new basic ratio, TDMnew is the new total daily dose.

[0045] 3 shows a flow chart 300 of exemplary steps that may be performed in an exemplary embodiment in a first option for determining a new basal portion value expressed as a basal ratio. new The preferred equation for calculating BR new =(1-A r *N days )*BR old +A r *N days *Adjustment factor (Equation 2) where N days is the number of days in the period in which the adjustment is made, and BR old is the basal rate before adjustment. The adjustment factor is based on recently collected data on the amount of drug delivered and is intended to adjust the basal rate closer to the empirical basal rate reflected in the collected data. old In the above formula 2, the weights are (1-A r *N days ) and the adaptation rate A r controls the rate at which the adjustment factor is incorporated into the new basal rate, with a nominal value of 0.2. The adaptation rate may be variable. If the time period is short, the influence of the previous basal rate is greater. For example, if the time period is only 1 day, the weighting will be 0.8 (i.e., 1-0.2*1), but if the time period is 3 days, the weighting will be reduced to 0.4. At 304, the adjustment factor is weighted. The adjustment factor, which reflects the more recently collected drug delivery data, is adjusted so that the nominal value of the adaptation rate remains the same at 0.2, while the BR old A for r *N days The weighting of the adjustment factor is reversed. As the number of days in the period increases, the weight of the adjustment factor also increases. If the period is 1 day, the weight is 0.2, but if the period is 3 days, the weight increases to 0.6. In 306, the weighted previous base ratio (e.g., (1-A r *N days )*BRold ) is added to the weighted adjustment factor (e.g., A r *N days *Adjustment factor) is added to the new base ratio BR at 308. new It becomes.

[0046] 4 illustrates a flow chart 400 of exemplary steps that may be performed in an exemplary embodiment to determine a basal delivery dosage using a new basal rate (see 204 in FIG. 2). At 402, drug delivery data for a user is collected over a recent period of time. This recent period is a period following a long-term period during which historical data was previously collected. At 404, a new total daily drug dose (TDM) is calculated from the collected data from the recent period. new ) is determined. new A suitable equation for is:

number

[0047] TDM new To calculate the daily bolus and basal drug deliveries (

number

[0048] At 408, the next basal delivery rate is determined from the adjusted daily basal rate. Specifically, assume that the drug delivery device 102 delivers the basal drug every cycle, and each cycle is 5 minutes. In this case, there are 180 cycles per day. That is, the adjusted basal delivery rate can be divided by 180 to determine the basal dose per cycle (e.g., DBD new / 180).

[0049] In an exemplary embodiment, various types of adjustment factors can be used to adjust the basis portion value, as described above. Figure 5 shows a flow chart 500 of exemplary steps that can be performed when a limited adjustment factor is used in an exemplary implementation. Examples of such adjustment factors are:

number

number

[0050] Therefore, the magnitude of the change in the base ratio depends on the number of days in the period, the relative adjustment factor and the BR old It depends on the difference in size.

[0051] As shown in flow chart 500 of FIG. 5, at 502, an empirical basal ratio (i.e.

number

[0052] Another option for the adjustment factor is to take the average of the ideal basal ratio of 0.5 and the empirical basal ratio. The formula for this adjustment factor is:

number

number

[0053] This adjustment factor formula varies the adjustment factor by 1 / 2 towards the ideal value of 0.5.

[0054] 6A shows a flow chart 600 of exemplary steps that can be performed using the various adjustment factors. At 602, an empirical basal ratio is added to the ideal basal portion value (e.g.,

number

[0055] Additionally, the Adjustment Factor may apply a constant value option in some exemplary options. For example, the Adjustment Factor may assume a positive constant when the Empirical Basal Ratio is above a certain threshold, a negative constant when the Empirical Basal Ratio is below another threshold, and zero or a standard value when between the thresholds. One exemplary formula for this option is as follows:

number

number

[0056] FIG. 6B shows a flow chart of exemplary steps that may be performed to calculate a new basal rate according to this second option, as shown in Equation 8. First, at 622, the past basal rates are added to an adjustment factor to calculate a sum. At 624, it is determined whether the sum is lower than a lower threshold. If so, at 626, the lower threshold is used as the new basal rate. For example, if the lower threshold is 1 / 3 and the sum is less than 1 / 3, the new basal rate is set to 1 / 3. If the sum is greater than the lower threshold, it is determined at 628 whether the sum exceeds an upper threshold. If so, at 630, the new basal rate is set to an upper threshold (e.g., 2 / 3). If not, at 632, the sum is used as the new basal rate.

[0057] 7 provides a flowchart 700 of example steps that may be performed in an example embodiment involving such an adjustment factor option. At 702, it is determined whether the empirical basal portion value (i.e., the empirical basal rate) is greater than the ideal basal rate (e.g., +0.05). If so, at 704, a positive adjustment factor (e.g., 0.05) is used. Otherwise, a negative adjustment factor (e.g., -0.05) is used.

[0058] An additional option is to use an adjustment value with a scaling value, which may be, for example, 0.5. An exemplary formula for the Adjustment Factor in this option is:

number

[0059] This exemplary adjustment factor adjusts the adjustment factor for an ideal value of 0.5 based on the square root of the difference between the empirical basal rate and the ideal value. Equation 2 can be applied to determine the new basal rate.

[0060] 8 shows a flow chart 800 of exemplary steps that may be performed when this option to determine an adjustment factor is used. At 802, an empirical basal ratio (e.g.,

number

number

number

[0061] In an exemplary embodiment, a user may be notified that the empirical basal rate is outside of a desired range. FIG. 9 illustrates a flow chart of exemplary steps that may be performed in providing a notification in an exemplary embodiment. At 902, it is determined whether the empirical basal rate is above an upper limit. If so, at 904, the user is notified that they may not have received enough bolus. The notification may be displayed on the display 109. The notification may be sent using a communication method such as a text message or email. Next, at 906, it is determined whether the empirical basal rate is below a lower limit. If so, at 908, the user is notified that they may have received too much bolus. If not, at 910, no notification is generated.

[0062] Another method of adapting the basal delivery rate to a user's customized needs is shown in Figure 10. Figure 10 shows a flow chart of exemplary steps that may be performed in an exemplary embodiment to determine a user's hourly basal rate based on historical average values ​​over a period of time. At 1002, drug delivery data for a user is collected over a period of time. The drug delivery data may include a basal drug delivery amount, a meal bolus drug delivery amount delivered to address a rise in blood glucose level due to carbohydrate ingestion, a correction bolus drug delivery amount delivered to address hyperglycemia, etc.

[0063] The user's daily food bolus for the period is calculated at 1004. If the period is m days, this value can be calculated as follows:

number

[0064] The user's average daily correction bolus amount for the time period is calculated at 1006. The equation suitable for this average is:

number

[0065] At 1008, the average daily basal drug delivery is calculated. The average can be calculated as follows:

number

[0066] At 1010, a basal portion factor can be calculated as the average daily basal delivery divided by the sum of the other average values ​​calculated at 1004, 1006, and 1008. The basal portion factor relates to the new basal rate adapted to the data collected during that time period. This calculation can be expressed as:

number

[0067] At 1012, an hourly basal rate is determined using a basal portion factor. The hourly basal rate can be expressed as:

number

[0068] Exemplary embodiments may also adjust the bolus amount delivered to the user based on the basal portion value. Given the wide variation in a user's daily bolus requirements, rather than directly translating the percentage of the user's instantaneous basal insulin delivery into a change in the user's basal rate, an exemplary implementation may increase the basal portion rate by a fixed amount if the user's insulin requirements deviate from the baseline (50 / 50 split) by 10% or more in one direction (0.05 is 10% of 0.5). The adjustment of the basal portion value may be expressed, for example, as follows:

number

[0069] Thus, as shown in flow chart 1100 of FIG. 11, at 1102, the base partial coefficient may be calculated, such as by using Equation 13. At 1104, it is determined whether the base partial coefficient is less than a lower threshold (e.g., 0.45). Such a value indicates that the user's actual base partial coefficient is less than 0.45 and should be adjusted downward. If so, at 1106, the adjustment value is 1-increment (e.g., 0.05). If not, at 1108, it is determined whether the base partial coefficient is greater than or equal to an upper threshold (e.g., 0.55) and should be adjusted upward. If so, at 1110, the adjustment value is adjusted to 1+increment. If not, at 1112, the base partial coefficient is close to ideal and the adjustment value is set to 0. At 1114, the new adjustment coefficient b factor Past basic ratio b old Multiply by to get the new base ratio. bnew =b old b factor (Formula 16)

[0070] In another exemplary embodiment, deviations from a standard basal correction factor are used to detect bolus overage or underage from historical data. If a dynamically calculated basal correction factor is not available, the amount of bolus underage and overage can be determined and the user can be alerted. FIG. 12 shows a flow chart 1200 of exemplary steps that can be performed in such an exemplary embodiment. At 1202, the user's drug delivery history is collected for a long term and a more recent short term. This data is used to establish average values ​​that can be used to determine bolus overage and underage. At 1204, the average daily basal drug delivery of the user over the long term is calculated, such as by using Equation 12. At 1206, the average daily bolus drug delivery of the user over the long term is calculated, such as by summing Equations 10 and 11. At 1208, the average daily bolus drug delivery to the user over the more recent short term is calculated. At 1210, the average daily basal drug delivery to the user over the short term is calculated. At 1212, the short and long term average drug bolus portions are calculated. These are the ratios of the short and long term average daily bolus amount to the TDM. At 1214, a percentage difference between the user's short term average drug bolus portion and the user's long term average drug bolus portion is determined. At 1216, a notification is sent to the user, such as through the display 109 or 127, to adjust the bolus amount by the determined percentage difference. This percentage difference can be a positive or negative value. For example, assume the TDM is 140, the long term bolus portion is 100 / 140, and the short term bolus portion is 105 / 140. The percentage difference is approximately +3.5%.

[0071] As mentioned above, the basal fractional value and / or the TDM may be adjusted for shorter periods than those mentioned above, for example, periods over an hour. FIG. 13 shows a flow chart 1300 of exemplary steps that can be performed to adjust the basal fractional value and the TDM for a user in an exemplary embodiment. At 1302, the next period is reached. This period can be, for example, a period of 1 hour, a period of 3 hours, a period of 6 hours, or a period of 12 hours. The period can also be a shorter period, for example, a period of 30 minutes long. The arrival of the next period triggers an adjustment of the basal fractional value at 1304. At 1306, the TDM can also be adjusted if necessary. At 1308, a check is performed to see if the last period has been reached. For example, if this period is the last period just before the drug delivery device is replaced, this period is the last period. If not, at 1302, the process is repeated at the arrival of the next period.

[0072] FIG. 14 shows a flow chart 1400 of exemplary steps that can be performed to adjust a basal fractional value over a short period of time in an exemplary embodiment. At 1402, the initial basal fractional value is used to determine a basal delivery amount of the drug over an operating period. At 1404, an adjusted basal fractional value for the next operating period is determined. The adjusted basal fractional value can reflect changes in the user's drug sensitivity acquired by recent drug delivery to the user. For example, if the drug being delivered is insulin, factors such as exercise, menstrual cycle, time of day, etc. can affect insulin sensitivity. At 1406, the adjusted basal fractional value is used to determine the amount of drug delivered to the user in the next operating period. At 1408, the control application 116 or 120 causes the user to administer the determined basal drug amount over the next period.

[0073] The adjusted basal portion value may be determined based on the user's recent drug delivery history (see 1406). Figure 15A shows a flowchart 1500 of exemplary steps that may be performed in an exemplary embodiment to determine the adjusted basal portion value from the user's recent drug delivery history. The following formula may be used to determine the user's adjusted basal portion value:

number

[0074] Thus, in 1502, the sum of the basal delivery rate of the drug for time period N is calculated (i.e.,

number

number

[0075] The basal portion value can be adjusted using recent bolus delivery history instead of recent history of basal delivery rates. There is a relationship between the basal portion value and the bolus portion value, which represents the portion of the TDM that is attributable to manual bolus delivery. In particular, the basal portion value is equal to 1 minus the bolus portion value. This relationship can be used to determine the basal portion value. A suitable equation for determining the user adjusted basal portion value from recent bolus delivery history is:

number

[0076] 15B shows a flow chart 1520 of exemplary steps that may be performed to adjust a user's basal portion value in an exemplary embodiment. At 1522, the bolus delivery amounts manually delivered to the user over the time frame are summed for all cycles of the time frame (i.e.,

number

number

[0077] The TDM value can also be adjusted frequently, for each cycle or for a period of time. FIG. 16 shows a flow chart 1600 of steps that can be performed to adapt the TDM to a user in an exemplary embodiment. At 1602, the dosages of all drug deliveries (i.e., all manual deliveries and all automatic deliveries) to the user over a recent time frame are summed. In some embodiments, the recent time frame should be greater than or equal to one day. Thus, if the cycle of the drug delivery device is 5 minutes, the time frame should be greater than or equal to 288 cycles (i.e., the number of cycles in a day). At 1604, the resulting sum is normalized to obtain a daily value. If the time frame M is greater than 288 cycles, the sum can be normalized by dividing by M / 288. At 1606, the normalized sum is used as the TDM.

[0078] The adjusted TDM (or TDI in the case of insulin) can be used in determining the adjusted TDM basal portion. Figure 17 shows a flow chart 1700 of exemplary steps that can be performed in an exemplary embodiment to use the adjusted TDM in determining the basal portion value. At 1702, the adjusted TDM value is used to determine the basal portion value based on the recent basal delivery. Substituting the above equation into Equation 16 for determining the basal portion value from the recent basal delivery, the following equation is obtained:

number

[0079] The recent bolus delivery with the adjusted TDM value is used to determine the basal fractional value at 1704. Substituting the above equation into Equation 17 for determining the basal fractional value from the recent bolus delivery, we obtain the following equation:

number

number

number

[0080] In this application, the term "non-transitory storage device" should be understood to mean either a single non-transitory storage device, or multiple non-transitory storage devices contained in a single device, or multiple non-transitory storage devices contained (or split) in different devices, e.g., one non-transitory storage medium contained in a distribution device and another non-transitory storage medium contained in a management device. Similarly, the term "processor" can refer to a single processor or multiple processors, which may be contained in a single device or contained (or split) in different devices, e.g., one processor in a distribution device and another processor in a management device.

[0081] Although exemplary embodiments have been described herein, it should be understood that various changes in form and detail may be made therein without departing from the intended scope as defined in the appended claims. While the invention has been described herein above and defined in the appended claims, the invention may additionally and alternatively be defined as set forth in the following embodiments.

[0082] 1. A drug delivery system comprising: a non-transitory storage device for storing computer program instructions; a processor for executing computer program instructions, the computer program instructions causing the processor to: A new basal ratio (BR) is provided to the user that specifies how much of the total drug delivery is to be delivered to the user as a basal drug delivery within a subsequent period of time, particularly within one or more days. new ), the calculation comprising: The user's previous base ratio (BR old ), an adjustment that includes a ratio of the amount of drug delivered as a basal drug delivery amount to the user via the automated drug delivery device over a period of time to a total amount of drug delivered to the user over the period of time; New base ratio (BR new ) was the previous basic ratio (BR old ), Calculating based on New base ratio (BR new determining a next basal drug delivery amount to the user by the automated drug delivery device using the A drug delivery system that performs the above steps.

[0083] 2. Previous base ratio (BR old ) is the portion of the total delivery of drug delivered to the user as a basal drug delivery within a previous period, particularly within one or more days.

[0084] 3. The drug delivery system of embodiment 1 or 2, wherein the total delivery amount of drug delivered to the user as a basal drug delivery amount within a previous period, particularly within one or more days, is the sum of the basal drug delivery amount and the bolus drug delivery amount within the previous period.

[0085] 4. A drug delivery system as described in any one of embodiments 1 to 3, wherein the total delivery amount of drug to be delivered to the user as a basal drug delivery amount within the next time frame, particularly within one or more days, is the sum of the basal drug delivery amount and the bolus drug delivery amount within the next time frame.

[0086] 5. New base ratio (BR new ) is the previous base ratio (BR old ) plus the first weighting factor (1-A r *N days ), and multiplying the adjustment factor by the second weighting factor (A r *N days ) and adding the resulting value (BR new =(1-A r *N days )*BR old +A r *N days *Adjustment factor), the drug delivery system in one of the above embodiments.

[0087] 6. First weighting factor (1-A r *N days ) and the second weighting factor (A r *N days 6. The drug delivery system of embodiment 5, wherein the sum of

[0088] 7. First weighting factor (1-A r *N days ) and the second weighting factor (A r *N days ) is adjusted by the new base ratio (BR new The adaptation rate (A r The drug delivery system of embodiment 5 or 6, wherein the drug delivery system is

[0089] 8. A drug delivery system according to any of the preceding embodiments, wherein determining the dosage for the next basal drug delivery comprises multiplying the user's total amount of insulin per day by the new basal rate.

[0090] 9. The drug delivery system according to any of the previous embodiments, wherein at least one adjustment limit comprises a maximum and / or minimum value to which the adjustment can be taken.

[0091] 10. A drug delivery system according to any of the previous embodiments, wherein at least one adjustment limit limits the difference between the previous basal rate and the new basal rate to a predetermined constant.

[0092] 11. The drug delivery system according to any of the previous embodiments, wherein at least one tuning limit is a scaling factor that scales the tuning.

[0093] 12. The drug delivery system according to any of the previous embodiments, wherein the drug is insulin, a glucagon-like peptide-1 (GLP-1) agonist, pramlintide, or other medication that affects the user's blood glucose levels.

[0094] 13. A drug delivery system comprising: a non-transitory storage device for storing computer program instructions; a processor for executing computer program instructions, the computer program instructions causing the processor to: determining an average amount of insulin to be delivered to a user per day to compensate for carbohydrates ingested in a meal; determining an average amount of insulin to be delivered to the user per day to correct hyperglycemia experienced by the user; determining an average amount of insulin delivered by a user as a basal delivery rate; calculating the sum of an average amount of insulin delivered to the user per day to compensate for carbohydrates ingested in meals, an average amount of insulin delivered to the user per day to correct hyperglycemia experienced by the user, and an average amount of insulin delivered by the user as a basal delivery; determining a basal portion factor as a ratio of the sum of the average amount of insulin delivered by the user as a basal delivery; determining an updated basal delivery rate for the user using the basal portion factor; A drug delivery system that performs the above steps.

[0095] 14. The drug delivery system of embodiment 13, wherein determining an updated basal delivery rate for the user comprises determining an updated hourly basal delivery rate for the user.

[0096] 15. The drug delivery system of embodiment 13 or 14, wherein determining the hourly basal delivery rate comprises determining the product of the basal portion factor and the user's total daily insulin (TDI) and dividing the product by 24 to determine the hourly basal delivery rate.

[0097] 16. A drug delivery system as described in any one of embodiments 13 to 15, further comprising updating the basal portion coefficient and updating the user's basal delivery rate using the updated basal portion coefficient.

[0098] 17. A drug delivery system described in any one of embodiments 13 to 16, wherein updating the basal partial coefficient includes increasing the basal partial coefficient by a first predetermined constant amount if the basal partial coefficient is less than a threshold value.

[0099] 18. A drug delivery system described in any one of embodiments 13 to 17, wherein updating the basal partial coefficient includes decreasing the basal partial coefficient by a second predetermined constant amount if the basal partial coefficient is greater than a threshold value.

[0100] 19. A drug delivery system comprising: A display and a non-transitory storage device for storing computer program instructions; a processor for executing computer program instructions, the computer program instructions causing the processor to: comparing the average meal bolus portion of the patient's total daily insulin amount for the last few days with the average meal bolus portion of the patient's historical total daily insulin amount; generating a suggestion on the display to the user to reduce the amount of insulin from the meal bolus by a first percentage if the average meal bolus portion of the patient's total daily insulin amount for the last few days is greater than the average meal bolus portion of the patient's historical total daily insulin amount by a first percentage; generating a suggestion on the display to the user to increase the meal bolus insulin amount by a first percentage if the average meal bolus portion of the patient's total daily insulin amount for the last few days is less than the average meal bolus portion of the patient's historical total daily insulin amount by a second percentage; A drug delivery system that performs the above steps.

[0101] 20. The drug delivery system of embodiment 19, wherein the drug delivery system includes one of an insulin pump, a controller for an insulin pump, or a portable computing device.

[0102] 21. The drug delivery system of embodiment 19 or 20, wherein the computer program instructions further cause the processor to calculate an average historical daily basal insulin delivery amount to the patient.

[0103] 22. The drug delivery system of any of embodiments 19 to 21, wherein the computer program instructions further cause the processor to calculate an average past daily meal bolus insulin delivery to the patient.

[0104] 23. The drug delivery system of any one of embodiments 19 to 22, wherein the computer program instructions further cause the processor to calculate an average total insulin amount per day in the past for the patient as the sum of an average basal insulin delivery amount per day in the past for the patient and an average prandial bolus insulin delivery amount per day in the past for the patient.

[0105] 24. The drug delivery system of any one of embodiments 19 to 23, wherein the computer program instructions further cause the processor to calculate the average meal bolus portion of the patient's historical total daily insulin amount as a ratio of the patient's historical average meal bolus insulin delivery amount per day to the patient's historical average total daily insulin amount.

[0106] 25. The drug delivery system of any one of embodiments 19 to 24, wherein the first percentage is equal to the second percentage.

[0107] 26. A drug delivery device for delivering a drug to a user, comprising: a non-transitory storage medium storing computer program instructions; a processor configured to execute computer program instructions, the processor comprising: determining an amount of basal drug to be delivered by the drug delivery device during a first operating period using a first basal fraction value indicative of a portion of the user's total daily medication (TDM); determining an adjusted basal portion value for a next operating period after the first operating period based on a magnitude of the most recent basal delivery rate, the drug delivery device; using the adjusted basal portion value to determine an amount of the basal drug to be delivered by the drug delivery device during a next operating period; during a next operating period, the drug delivery device delivers the determined delivery amount of the basal drug; The drug delivery device is configured to:

[0108] 27. Determining the adjusted basis portion value for the next operating period includes: performing a first weighting on the first basic portion value in the first operating period to obtain a first weighting value; determining a calculated ratio of a total basal drug amount delivered to a user by the drug delivery device during an operational period to a total basal drug amount that would be delivered over that period if the initial basal portion values ​​were used; applying a second weighting to the calculated ratio to generate a second weight value; summing the first weight value and the second weight value to determine an adjusted basis portion value; 27. The drug delivery device of embodiment 26, comprising:

[0109] 28. The drug delivery device of embodiment 26 or 27, wherein the initial basal fractional value is a ratio of basal / TDM, and the ratio of basal / TDM for the initial basal fractional value is 0.5.

[0110] 29. A drug delivery device according to any one of embodiments 26 to 28, wherein the initial basal fraction value is adapted to the user's insulin sensitivity.

[0111] 30. A drug delivery device according to one of embodiments 26 to 29, wherein the first weight is at least four times the second weight.

[0112] 31. A drug delivery device according to any one of embodiments 26 to 30, wherein the drug is insulin, a glucagon-like peptide 1 (GLP-1) agonist, pramlintide, or a combination thereof.

[0113] 32. A drug delivery device according to any one of embodiments 26 to 31, wherein the drug delivery device is an insulin patch pump.

[0114] 33. A drug delivery device described in any one of embodiments 26 to 32, wherein determining an adjusted basal portion value in a next operating period after a first operating period includes calculating a TDM based on a recent drug delivery amount and using the calculated TDM to determine the adjusted basal portion value.

[0115] 34. A drug delivery device for delivering a drug to a user, comprising: a non-transitory storage medium storing computer program instructions; The processor: determining an amount of basal drug to be delivered by the drug delivery device during a first operating period using a first basal fraction value indicative of a portion of the user's total daily medication (TDM) delivered in basal form; determining an adjusted basal portion value for a next operating period after the first operating period based on a magnitude of a recent bolus delivered by the drug delivery device; using the adjusted basal portion value to determine an amount of the basal drug to be delivered by the drug delivery device during a next operating period; delivering the determined amount of basal drug by the drug delivery device during a next operating period; a processor configured to execute computer program instructions to cause A drug delivery device comprising:

[0116] 35. The drug delivery device of embodiment 34, wherein the first basal portion value is a basal to TDM ratio having a value of 0.5.

[0117] 36. Determining the adjusted basis portion value for the next operating period includes: performing a first weighting on the first basic portion value in the first operating period to calculate a first weighting value; determining a ratio between a total amount of bolus medication delivered to a user by the medication delivery device during an operational period and a total amount of bolus medication that would be delivered over that period if the predicted bolus fraction value were used; subtracting the determined ratio from 1 to calculate a difference; applying a second weighting to the difference to generate a second weighting value; summing the first weight value and the second weight value to determine an adjusted basis portion value; 36. The drug delivery device of embodiment 34 or 35, comprising:

[0118] 37. A drug delivery device as described in any one of embodiments 34 to 36, wherein the first basal portion value is adapted to the user's insulin sensitivity.

[0119] 38. A drug delivery device according to any one of embodiments 34 to 37, wherein the drug is insulin, a glucagon-like peptide-1 (GLP-1) agonist, pramlintide, or a combination thereof.

[0120] 39. A drug delivery device according to any one of embodiments 34 to 38, wherein the drug delivery device is an insulin patch pump.

[0121] 40. A drug delivery device according to any one of embodiments 34 to 39, wherein the first weight is at least four times the second weight.

[0122] 41. A method of managing a dosage of basal insulin delivery executed by a processor of an insulin delivery device or one or more processors of an insulin delivery system, comprising: storing in a non-transitory computer readable storage medium a dose of basal insulin delivery delivered to a user from the insulin delivery device; determining a total amount of basal insulin delivery for the time period based at least in part on the stored doses of basal insulin delivery; determining a ratio of the determined total basal delivery rate to a predicted total basal delivery rate for the time frame; Weighting that ratio, and weighting a previous ratio of basal insulin to total insulin per day (TDI) that the processor or processors used to determine the dose of basal delivery in the previous time frame; and summing the weighted ratio and the previous weighted ratio to calculate a new ratio of TDI to basal insulin delivery for the next time period; determining a basal insulin delivery rate for a next time period using the new ratio of basal insulin delivery rate to TDI; causing an insulin delivery device to deliver the determined basal insulin delivery amount over a period of time; A method comprising:

[0123] 42. The method of embodiment 41, wherein the insulin delivery device has a cycle of fixed length and the sum of the predicted basal deliveries in the time frame is half the TDI divided by the ratio of the number of cycles per day to the number of cycles in the time frame.

[0124] 43. The method of embodiment 41 or 42, further comprising calculating the TDI from insulin delivery to the user by the insulin delivery device over a time axis.

[0125] 44. The method of any one of embodiments 41 to 43, wherein weighting the previous ratio of basal to TDI comprises applying a weight to the previous ratio that is at least four times the weight applied to that ratio.

[0126] 45. The method of any one of embodiments 41 to 44, wherein the previous basal ratio to TDI is customized for the user.

Claims

1. 1. A drug delivery system comprising: at least one non-transitory storage device for storing computer program instructions; and at least one processor for executing the computer program instructions, the computer program instructions causing the processor to: executing an automated basal drug delivery to a user of the drug delivery system based on at least one basal profile (115); obtaining drug delivery data over a recent period, in particular a recent one or more day period, said drug delivery data including past bolus drug deliveries and past basal drug deliveries delivered to a user of said drug delivery system over said recent period; calculating a sum of a past basal delivery and a sum of a past bolus delivery and a past basal delivery; A previous basal ratio (BR) is obtained by dividing the sum of the previous basal delivery by the sum of the previous bolus delivery and the previous basal delivery (TDM). ｏｌｄ ) or based on the sum of the past basal deliveries or a ratio of the sum of the past bolus deliveries and the past basal deliveries; adjusting said automatic basal drug delivery rate to obtain a new automatic basal drug delivery rate and / or a new basal profile; A drug delivery system.

2. 2. The drug delivery system of claim 1, wherein the drug delivery system is designed to automatically perform a bolus delivery to the user based on a blood glucose measurement or estimated blood glucose value and / or based on user input, in particular via a user interface, of a bolus delivery amount to the user.

3. The new automatic basal drug delivery and / or the new basal profile determines whether a subsequent basal drug delivery is greater than or equal to the sum (TDM) of the subsequent bolus delivery and the subsequent basal delivery. ｎｅｗ A new basal rate (BR) is the sum of the subsequent basal deliveries divided by ｎｅｗ 3. The drug delivery system of claim 1 or 2, wherein the drug delivery system is adjusted to have a molecular weight of 1000 or more.

4. The new basic ratio (BR ｎｅｗ ) is the previous basic ratio (BR ｏｌｄ ) with a first weighting factor (e.g., 1-A ｒ *N ｄａｙｓ ), multiplying the adjustment coefficient by a second weighting coefficient (e.g., A ｒ *N ｄａｙｓ ) and adding the obtained values ​​(e.g., BR ｎｅｗ = (1-A ｒ *N ｄａｙｓ ) *BR ｏｌｄ +A ｒ *N ｄａｙｓ *Adjustment factor).

5. The first weighting factor (for example, 1-Ar*N ｄａｙｓ ) and the second weighting factor (e.g., Ar*N ｄａｙｓ 5. The drug delivery system of claim 4, wherein the sum of is 1.

6. The first weighting factor (e.g., 1-A ｒ *N ｄａｙｓ ) and the second weighting factor (e.g., A ｒ *N ｄａｙｓ ) is the most recent period (N ｄａｙｓ ) depending on the duration of the last period (e.g., N ｄａｙｓ ), the greater the first weighting factor (for example, 1-A ｒ *N ｄａｙｓ ) is decreased, and the second weighting factor (e.g., A ｒ *N ｄａｙｓ 6. The drug delivery system of claim 4 or 5, wherein the ratio of the stoichiometric amount of the drug to the total stoichiometric amount of the drug is increased.

7. The first weighting factor (e.g., 1-A ｒ *N ｄａｙｓ ) and the second weighting factor (e.g., A ｒ *N ｄａｙｓ ) is the adjustment coefficient of the new basic ratio (BR ｎｅｗ ) ｒ 7. The drug delivery system of claim 4, wherein the drug delivery system is based on

8. The adaptation rate (A ｒ 8. The drug delivery system of claim 7, wherein q is in the range of 0.05 to 0.8, in particular 0.1 to 0.5, in particular 0.2 to 0.

4.

9. 9. A drug delivery system according to any one of claims 4 to 8, wherein the adjustment factor is in the range of 0.3 to 0.7, in particular 1 / 3 to 2 / 3, in particular 0.45 to 0.

55.

10. The adjustment factor is the ratio between the ideal value of the basal ratio and the previous basal ratio (BR ｏｌｄ ) and, in particular, the average of the ideal basal ratio of 0.5 and the previous basal ratio (BR ｏｌｄ 9. The drug delivery system of claim 4, wherein the average

11. The sum of the subsequent bolus delivery and the subsequent basal delivery (TDM ｎｅｗ ) is the sum of the past bolus delivery and the past basal delivery (TDM ｏｌｄ 11. The drug delivery system of claim 1 , wherein the drug delivery system is identical to the drug delivery system of claim 1 .

12. The sum of the subsequent bolus delivery and the subsequent basal delivery (TDM ｎｅｗ ) is adjustable by the user via a user interface, or the sum of the subsequent bolus delivery and the subsequent basal delivery (TDM ｎｅｗ ) is automatically adjusted by the computer program instructions based on past blood glucose measurements, and, in particular, when the average of the past blood glucose measurements is consistently above the target blood glucose level, the total (TDM ｎｅｗ ) is increased and the sum (TDM ｎｅｗ 11. The drug delivery system of claim 1, wherein the .alpha.-hydroxylation constant is reduced.

13. 13. The drug delivery system of claim 1 , comprising a drug delivery device comprising a reservoir for storing a drug, a delivery or pump mechanism for delivering the drug from the reservoir to a user, and / or a management device.

14. The drug delivery system of claim 13, wherein the at least one non-transitory storage device and the at least one processor for executing the computer program instructions are included in a drug delivery device or a management device, or, if there is more than one non-transitory storage device and more than one processor for executing the computer program instructions, at least one storage device and at least one processor are included in the drug delivery device and at least one other storage device and at least one other processor are included in the management device.

15. 15. The drug delivery system of any one of claims 1 to 14, wherein the drug is insulin, a glucagon-like peptide-1 (GLP-1) agonist, pramlintide, or other drug that affects the user's blood glucose level.

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