Adaptive baseline values ​​in automated drug delivery devices based on the user's past drug delivery amounts

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 on March 9, 2022, and U.S. Provisional Patent Application No. 63 / 369,790, filed on July 29, 2022, the contents of which are hereby incorporated by reference in their entirety.

Background Art

[0002] An automatic insulin delivery (AID) device, such as an insulin pump, enables both insulin bolus delivery and basal insulin delivery. Basal insulin delivery continuously delivers small amounts of insulin periodically. An insulin bolus is administered to suppress a rise in blood glucose level due to a meal intake or normalize a blood glucose level that is too high.

[0003] Conventionally, an AID device determines the amount of basal insulin to be administered to a user based on the total daily insulin dose (TDI). The TDI is the total amount of insulin delivered to the user per day. The TDI may be initially set based on the user's weight. The amount of insulin delivered by the basal delivery per day is derived from the TDI. Conventionally, the amount of insulin delivered by the basal delivery per day is set to half of the user's TDI.

[0004] According to one aspect of the present invention, a drug delivery system includes at least one non-temporary storage device for storing computer program instructions, and at least one processor for executing computer program instructions, wherein the computer program instructions cause the processor to perform automated basic drug delivery to a user of the drug delivery system based on at least one basic profile, and to acquire drug delivery data over a recent period, particularly the most recent day or multiple days, the drug delivery data including past bolus drug delivery amounts and past basic drug delivery amounts delivered to a user of the drug delivery system in the recent period, and to calculate the total of past basic delivery amounts, the sum of past bolus delivery amounts and past basic delivery amounts, and to acquire a new automated basic drug delivery amount and / or a new basic profile, by dividing the sum of past basic delivery amounts by the sum of past bolus delivery amounts and past basic delivery amounts (TDM) to obtain a past basic ratio (BR old The system adjusts automated basal drug delivery based on the following: ) or based on the total of past basal deliveries relative to the total of past bolus deliveries or the ratio of past bolus deliveries to the total of past basal deliveries.

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

[0006] In particular, new automated basal drug delivery doses and / or new basal profiles can be adjusted so that subsequent basal drug delivery doses become a new basal ratio, which is the sum of subsequent basal delivery doses divided by the sum of subsequent bolus delivery doses and subsequent basal delivery doses. For example, the new basal ratio can be calculated by multiplying the previous basal ratio by a first weighting coefficient, multiplying the adjustment coefficient by a second weighting coefficient, and adding the resulting values. The sum of the first and second weighting coefficients may be 1. Furthermore, the first and second weighting coefficients may depend on the length of the recent period, with the first weighting coefficient decreasing and the second weighting coefficient increasing as the period lengthens or the recent period lengthens. This approach improves reliability and stability in drug delivery.

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

[0008] The sum of subsequent bolus doses and subsequent basal doses may be the same as the sum of past bolus doses and past basal doses. Alternatively, the sum of subsequent bolus doses and subsequent basal doses may be adjusted by the user via a user interface, or automatically by computer program instructions, particularly based on past blood glucose measurements, such that the sum of subsequent doses increases if the average of past blood glucose measurements regularly exceeds the target blood glucose level, and decreases if the average of past blood glucose measurements regularly falls below the target blood glucose level.

[0009] A drug delivery system may include a drug delivery device comprising a reservoir for storing drugs, a delivery mechanism or pump mechanism for delivering drugs from the reservoir to a user, and / or a management device. At least one non-temporary storage device and at least one processor for executing computer program instructions may be provided in either the drug delivery device or the management device, or if there are two or more non-temporary storage devices and two or more processors for executing computer program instructions, at least one storage device and at least one processor may be provided in the drug delivery device, and at least one additional storage device and at least one additional processor may be provided in the management device.

[0010] According to another aspect of the present invention, the drug delivery system comprises a non-temporary storage device for storing computer program instructions and a processor for executing computer program instructions. The computer program instructions cause the processor to calculate a new base ratio for the user, which specifies what percentage of the user's total daily drug dose should be delivered by a base delivery dose based on the user's previous base ratio and adjustments. The adjustments include a ratio of the amount of drug delivered to the user as a base drug delivery dose via an automated drug delivery device over a period of time, and at least one adjustment limit that restricts how much the new base ratio may change from the previous base ratio. The computer program instructions also cause the processor to determine the dose for the next base drug delivery to the user by the automated drug delivery device using the new base ratio.

[0011] The drug may be insulin. The drug may include at least one of the following: a glucagon-like peptide-1 (GLP-1) agonist, a pramulintide, or another drug that affects the user's blood glucose level. Dosage determination for subsequent basal drug delivery may include multiplying the user's total daily insulin amount by the new basal ratio. At least one adjustment limit may include the maximum and / or minimum values ​​that the adjustment assumes. At least one adjustment limit may limit the difference between the previous basal ratio and the new basal ratio to a predetermined amount. At least one adjustment limit may be a scaling factor that expands or contracts the adjustment.

[0012] According to another aspect of the present invention, a drug delivery system comprises a non-temporary memory for storing computer program instructions and a processor for executing computer program instructions. The computer program instructions cause the processor to determine the average amount of insulin delivered to the user per day to compensate for carbohydrates ingested in a meal, and to determine the average amount of insulin delivered to the user per day to correct hyperglycemia experienced by the user. The computer program instructions also cause the processor to determine the average amount of insulin delivered by the user as the basal delivery amount, and to calculate the sum of the average daily amounts of insulin delivered to the user to adjust for carbohydrates ingested in a meal, the average daily amount of insulin delivered to the user to correct hyperglycemia experienced by the user, and the average amount of insulin delivered to the user as the basal delivery amount. Furthermore, the computer program instructions cause the processor to determine a basal partial coefficient as a ratio to the sum of the average amounts of insulin delivered to the user as the basal delivery amount, and to determine the user's updated basal delivery rate using the basal partial coefficient.

[0013] Determining the updated basal delivery rate for a user may include determining the updated hourly basal delivery rate for the user. Alternative interval rates can be determined, for example, every two 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 partial coefficient and the user's total daily insulin dose (TDI), and then dividing the product by 24 to obtain the hourly basal delivery rate. Other intervals of the basal delivery rate may be calculated in a similar manner. This method may include updating the basal partial coefficient and using the updated basal partial coefficient to update the user's basal delivery rate. Updating the basal partial coefficient may include increasing the basal partial coefficient by a first predetermined fixed amount if the basal partial coefficient is less than a threshold. Updating the basal partial coefficient may include decreasing the basal partial coefficient by a second predetermined fixed amount if the basal partial coefficient is greater than a threshold.

[0014] According to a further aspect of the present invention, the drug delivery system includes a display and a non-temporary storage device for storing computer program instructions. The drug delivery system also includes a processor for executing computer program instructions. The computer program instructions cause the processor to compare the average meal bolus portion of the patient's total daily insulin intake over the past few days with the average meal bolus portion of the patient's total daily insulin intake in the past. If the average meal bolus portion of the total daily insulin intake over the past few days is 1 percentage higher than the average postprandial bolus portion of the total daily insulin intake in the past, the processor suggests on the display that the insulin amount for the meal bolus be reduced by 1 percentage. If the average meal bolus portion of the total daily insulin intake over the past few days is 2 percentage lower than the average meal bolus portion of the total daily insulin intake in the past, the processor suggests that the insulin amount for the meal bolus be reduced by 2 2 The system will suggest to the user on the display that they increase the amount by a percentage.

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

[0016] Furthermore, according to one aspect of the present invention, a drug delivery device for delivering a drug to a user includes a non-temporary storage medium for storing computer program instructions. The drug delivery device further includes a processor configured to execute computer program instructions such that the processor uses a first base partial value representing a portion of the user's total daily drug dose (TDM) to determine the amount of base drug that the drug delivery device will deliver during a first operating period. This instruction causes the processor to determine an adjusted base partial value for the next operating period after the first operating period, based on the magnitude of the most recent base drug delivery by the drug delivery device, and the processor uses the adjusted base partial value to determine the amount of base drug that will be delivered by the drug delivery device during the next operating period. This instruction causes the processor to deliver the determined base drug delivery amount by the drug delivery device during the next operating period.

[0017] Determining the adjusted baseline partial value for the next operating period may include: assigning a first weight to the first baseline partial value for the first operating period to obtain a first weight value; determining a calculated ratio of the total amount of baseline drug delivered to the user by the drug delivery device during the operating period to the total amount of baseline drug that would have been delivered over that period if the initial baseline partial value had been used; assigning a second weight to that calculated ratio to generate a second weight value; and determining the adjusted baseline partial value by summing the first weight value and the second weight value. The initial baseline partial value is the baseline / TDM ratio, and the baseline / TDM ratio to the initial baseline partial value may be 0.5. The initial baseline partial value may be tailored to the user's insulin sensitivity. The first weight may be at least four times the second weight. The drug may be insulin, a glucagon-like peptide 1 (GLP-1) agonist, pramulintide, or a combination of at least two of these. The drug delivery device may be an insulin patch pump. Determining the adjusted baseline partial value for the next action period after the first action period may include calculating the TDM based on recent drug delivery amounts and using the calculated TDM to determine the adjusted baseline partial value.

[0018] Furthermore, according to another aspect of the present invention, a drug delivery device for delivering drugs to a user includes a non-temporary storage medium for storing computer program instructions and a processor configured to execute computer program instructions, wherein the processor can be made to perform operations such as: determining the amount of basic drug to be delivered by the drug delivery device during a first operating period using a first basic partial value representing a portion of the total daily drug dose (TDM) of the user delivered in basic form; determining an adjusted basic partial value for the interval between operations after the first operating period based on the magnitude of the most recent bolus delivery by the drug delivery device; determining the amount of basic drug to be delivered by the drug delivery device during the next operating period using the adjusted basic partial value; and causing the drug delivery device to deliver the determined amount of basic drug during the next operating period.

[0019] The first baseline partial value can be a baseline to TDM ratio of 0.5. Determining the adjusted baseline partial value for the next operating period involves assigning a first weight to the first baseline partial value for the first operating period to obtain a first weight value; determining the ratio of the total amount of bolus drug delivered to the user by the drug delivery device during a given operating period to the total amount of bolus drug that would be delivered over that period if the predicted baseline partial value were used; subtracting the determined ratio from 1 to calculate the difference; assigning a second weight to that difference to calculate a second weight value; and summing the first weight value and the second weight value to determine the adjusted baseline partial value.

[0020] The first baseline value may be adjusted to the user's drug sensitivity. The drug may be insulin, a glucagon-like peptide-1 (GLP-1) agonist, pramulintide, or a combination of two or more of the above. The drug delivery device may be an insulin patch pump. The first weight may be at least four times the second weight.

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

[0022] The insulin delivery device may have cycles of a fixed length, and the total predicted basal delivery amount in a time frame may be half of 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 amount of insulin delivered to the user by the insulin delivery device in a time frame. Weighting the previous basal-to-TDI ratio may include applying a weight to the previous ratio that is at least four times the weight applied to that ratio. The previous basal-to-TDI ratio may be customized for the user. [Brief explanation of the drawing]

[0023] [Figure 1]Figure 1 shows a drug delivery system suitable for an exemplary embodiment. [Figure 2] Figure 2 shows a flowchart of exemplary steps that can be performed to apply a baseline partial value from a drug delivery device to a user in an exemplary embodiment. [Figure 3] Figure 3 shows a flowchart of exemplary steps that can be taken to determine a new underlying partial value according to the first option in an exemplary embodiment. [Figure 4] Figure 4 shows a flowchart of exemplary steps that can be performed to determine a baseline dose for delivery by a drug delivery device in an exemplary embodiment. [Figure 5] Figure 5 shows a flowchart of exemplary steps that can be taken to determine a new adjustment coefficient having minimum and maximum values ​​in an exemplary embodiment. [Figure 6A] Figure 6A shows a flowchart of exemplary steps that can be taken to determine a new adjustment coefficient by averaging empirically based partial values ​​with ideal partial values, in an exemplary embodiment. [Figure 6B] Figure 6B shows a flowchart of exemplary steps that can be taken to determine a new underlying partial value according to a second option in an exemplary embodiment. [Figure 7] Figure 7 shows a flowchart of exemplary steps that can be taken to determine an adjustment coefficient with a constant value option in an exemplary embodiment. [Figure 8] Figure 8 shows a flowchart of exemplary steps that can be taken to determine an adjustment factor having a scaled value in an exemplary embodiment. [Figure 9] Figure 9 shows a flowchart of exemplary steps that can be taken to notify the user of the need to adjust the bolus dose in an exemplary embodiment. [Figure 10] Figure 10 shows a flowchart of exemplary steps that can be taken to determine the base rate per hour in an exemplary embodiment. [Figure 11] Figure 11 shows a flowchart of exemplary steps that can be taken to apply incremental adjustments to the base partial value in an exemplary embodiment. [Figure 12] Figure 12 shows a flowchart of exemplary steps that can be taken to propose adjusting the bolus quantity based on the average underlying partial value in an exemplary embodiment. [Figure 13] Figure 13 shows a flowchart 1300 of exemplary steps that can be performed to apply the basic partial values ​​and TDM to a user in an exemplary embodiment. [Figure 14] Figure 14 shows a flowchart of exemplary steps that can be taken to adjust the underlying partial values ​​for a shortened period in an exemplary embodiment. [Figure 15A] Figure 15A shows a flowchart of exemplary steps that can be taken to determine a baseline partial value adjusted from the user's recent drug delivery history in an exemplary embodiment. [Figure 15B] Figure 15B shows a flowchart of exemplary steps that can be taken to allow a user to adapt the underlying partial values ​​in an exemplary embodiment. [Figure 16] Figure 16 shows a flowchart of the steps that can be taken to adapt TDM to a user in an exemplary embodiment. [Figure 17] Figure 17 shows a flowchart of exemplary steps that can be taken to use the adjusted TDM for determining the underlying partial values ​​in an exemplary embodiment. [Modes for carrying out the invention]

[0024] Exemplary embodiments may provide adaptability in a baseline portion value that identifies what proportion of the total daily drug delivery to the user the baseline delivery amount represents (e.g., a “baseline ratio” of the daily baseline delivery amount to the total daily drug delivery (TDM)). More generally, the baseline portion value represents the total dose of baseline drug delivery over a period such as a day. The “baseline ratio” may be used herein as an example of a baseline portion value. However, it should be understood that the baseline portion value does not have to be expressed solely as a baseline ratio. For example, the baseline portion value may be a decimal value, or in some embodiments, it may be the absolute amount of baseline drug over a day or other period.

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

[0026] An exemplary embodiment can adapt a base partial value to a user based on the user's historical drug delivery data. Furthermore, the exemplary embodiment can update the base partial value based on more recent trends that deviate from the historical drug delivery data. The degree of adaptability provided by the exemplary embodiment can be limited so as not to exceed upper and / or lower thresholds. Furthermore, the rate of adaptability may be adjusted by controlling the degree of adaptability to very small increments each time the base ratio is updated. The increment may be set to a constant size or may be adjusted by a scaling factor, etc.

[0027] In some exemplary embodiments, the size of the drug bolus dose delivered to the user may be adjusted based on recent drug bolus history and drug delivery history data, or adjustment of the bolus may be suggested. The drug bolus dose may be adjusted upward or downward based on how much the ratio of the average daily drug bolus dose to the TDM ratio has changed from the historical mean of that ratio. Thus, the bolus dose may be adjusted to reflect changes in the difference between the average daily basal drug delivery and the average daily drug bolus delivery.

[0028] In exemplary embodiments, the user's baseline partial values ​​can be adjusted based on the user's recent drug sensitivity. This adjustment can be performed continuously throughout the lifespan of the drug delivery device. Furthermore, adjustments can be made rapidly to quickly respond to changes in the user's drug needs. For example, some insulin pumps have an effective lifespan of approximately 3 days. Rather than keeping the user's baseline partial values ​​and / or TDM constant only when the insulin pump is first fitted to the user and activated, as in some conventional drug delivery devices, in exemplary embodiments, the baseline partial values ​​and / or TDM can be adjusted at shorter intervals, such as every hour, every 3 hours, or every 12 hours. If the drug is insulin, for example, the drug delivery device can better account for changes in the user's insulin sensitivity, for example, some users may experience abnormal changes in insulin sensitivity between 2 a.m. and 8 a.m. due to exercise or dawn phenomenon.

[0029] Figure 1 shows 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 attached to the user 108's body or may be a wearable device carried by the user. The drug delivery device 102 may be directly attached to the user without the use of a tube (for example, so as to be directly attached to a part of the user 108's body and / or skin via an adhesive, etc.), and the injection site may be located directly below the drug delivery device 102, or it may be carried by the user (e.g., on a belt or in a 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, the surface of the drug delivery device 102 may contain 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, a logic circuit, a field-programmable gate array (FPGA), an application-specific integrated circuit (ASIC), or a microcontroller. The processor 110 can record the date and time and also perform other functions (e.g., calculations). The processor 110 can operate by executing a control application 116 encoded with computer program instructions stored in a memory device 114, so that the processor 110 can direct the operation of the drug delivery device 102. The control application 116 may be a single program, multiple programs, modules, libraries, 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 can display information to the user 108 and can also receive input from the user 108, such as when the display 127 is a touchscreen.

[0031] A control application 116 can control the delivery of the drug to the user 108 according to a control approach such as those described herein. The control application can provide the basal ratio, total daily drug dose, and adaptability in bolus doses as described below. A storage device 114 can maintain the user's history 111, including a history of basal deliveries, a history of bolus deliveries, and / or other histories such as a history of meal events, exercise events, and blood glucose levels. Furthermore, the processor 110 can be made operable to receive data or information. The storage device 114 may include both primary and secondary memory. The storage device 114 may include random access memory (RAM), read-only memory (ROM), optical memory, magnetic memory, removable storage media, semiconductor memory, and the like.

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

[0033] For example, there may be one or more communication links with one or more devices physically separated from the drug delivery device 102, including a user and / or caregiver management device 104, a sensor 106, a smartwatch 130, a health status monitor 132, and / or various other devices 134. The communication links may be any wired or wireless communication links that operate according to a well-known communication protocol or standard, such as Bluetooth®, Wi-Fi, a near-field 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 link. The network 122 may include a local area network (LAN), a wide area network (WAN), or a combination thereof. The 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 sensors 106 may be attached to the user 108 by means of, for example, an adhesive, and may provide information or data about one or more medical conditions and / or physical attributes of the user 108. The sensors 106 may be physically separate from the drug delivery device 102 or may be an integrated component thereof. The sensors 106 may include, for example, blood glucose monitors such as continuous glucose monitors (CGMs) and non-invasive blood glucose monitors. The sensors 106 may also include ketone body sensors, analyte sensors, heart rate monitors, respiratory rate monitors, motion sensors, temperature sensors, sweat sensors, blood pressure sensors, alcohol sensors, and the like.

[0036] The drug delivery system 100 may or may not include a control device 104. In some embodiments, the control device is not necessary because the drug delivery device 102 can manage itself. The control device 104 may be a dedicated device, such as a dedicated personal diabetes management (PDM) device. The control device 104 may be a programmed general-purpose device, such as any portable electronic device including a dedicated controller, such as a processor or microcontroller. The control device 104 may be used to program or adjust the operation of the drug delivery device 102 and / or the sensor 106. The control device 104 may be any portable electronic device, such as a dedicated device, smartphone, smartwatch, or tablet. In the illustrated embodiment, the control device 104 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 drugs to the user 108. The drug delivery device 102 can provide data from the sensor 106 and other data to the control device 104. The data can be stored in the storage device 118. The processor 119 may be operable to execute programming code stored in the storage device 118. For example, the storage device 118 may be operable to store one or more control applications 120 executed by the processor. The control application 120 may play a role in controlling the drug delivery device 102, for example, by controlling the delivery of insulin AID to the user 108. In some exemplary embodiments, the control application 120 provides the adaptability described herein. The storage device 118 may store the control application 120, the history 121 relating to the drug delivery device 102 as described above, and other data and / or programs.

[0037] A display 140, such as a touchscreen, may be provided to display information. The display 140 can display a user interface (UI) 123. Furthermore, if the display 140 is a touchscreen, it can also be used to receive input. The management device 104 may further include input elements 125, such as a keyboard, buttons, or knobs, to receive input from the user 108.

[0038] The management device 104 can communicate with a network 124, such as a LAN, WAN, or a combination of such networks, via a wired or wireless link. 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 transmitted 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 smartwatch 130, a health monitor 132, and other devices 134 may be part of the drug delivery system 100. These devices 130, 132, and 134 can communicate with the drug delivery device 102 and / or the control device 104 to receive information and / or send commands to the drug delivery device 102. These devices 130, 132, and 134 can execute computer program instructions via control applications 116 and 120 to perform some of the control functions performed by the processor 110 or the processor 119. These devices 130, 132, and 134 may include a display for displaying information. The display may show a user interface for providing user input to request a change or pause in dosage, request, start, or confirm a bolus delivery of the drug, or display output such as a change in dosage (e.g., basal delivery dose) determined by the processor 110 or the control device 104. These devices 130, 132, and 134 can also be wirelessly connected to the sensor 106 to directly receive measurement data of the analyte. Other delivery devices 105, such as a drug delivery pen, can also be provided to deliver the drug to the user 108.

[0040] A wide variety of drugs can be delivered by drug delivery devices 102 and 105. The drug may be insulin for the treatment of diabetes. The drug may be glucagon, which raises the user's blood glucose level. Alternatively, the drug may be a glucagon-like peptide (GLP)-1 receptor agonist, which delays the rapid rise in blood glucose levels after meals by lowering blood glucose levels or slowing gastric emptying. Or, the drug delivered by drug delivery device 102 may be analgesics, chemotherapeutic agents, antibiotics, anticoagulants, hormones, antihypertensives, antidepressants, antipsychotics, statins, anticoagulants, anticonvulsants, antihistamines, anti-inflammatory agents, steroids, immunosuppressants, anxiolytics, antivirals, nutritional supplements, or vitamins. The drug may be a combination of several of the drugs listed above.

[0041] The functions described below in the exemplary embodiments 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 functions may be controlled by, or performed by, a cloud service / server 128, a computing device 126, or other listed devices including a smartwatch 130, a health monitor 132, or other wearable devices 134.

[0042] In closed-loop mode, control applications 116 and 120 continuously determine the amount of drug delivered to user 108 based on the feedback loop. In the case of an insulin delivery device, the purpose of closed-loop mode is to bring the user's blood glucose level to the target blood glucose level.

[0043] As described above, exemplary embodiments can provide adaptability to the TDM, baseline partial values, and bolus drug delivery doses provided by the drug delivery device 102. Control applications 116 and 120 can be configured to provide such adaptability, as described below. Several methods exist for providing adaptability in exemplary embodiments, as described below.

[0044] Figure 2 shows a flowchart 200 of exemplary steps that can be taken to adjust the daily basal dose of a drug in an exemplary embodiment. In 202, a new basal fraction, expressed as a basal ratio, may be determined based on drug delivery data collected over the past few days. In 204, once the new basal ratio is determined, a new daily basal dose may be determined using the new basal ratio, as detailed below. The basic formula for this determination is as follows: DB new =BR new *TDM new (Formula 1) Here, DB new This is the new daily baseline delivery amount, BR new This is a new base ratio, TDMnew is the new total drug amount per day.

[0045] FIG. 3 shows an exemplary flowchart 300 of exemplary steps executable in a first option for determining a new base portion value represented as a base ratio in an exemplary embodiment. The new base ratio BR new A suitable 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 for which the adjustment is made, and BR old is the base ratio before adjustment. The adjustment factor is based on data regarding the recently collected drug delivery amount and is aimed at adjusting the base ratio to approach the base ratio based on the experience reflected in the collected data. At 302, weighting is performed on the previous base ratio BR old . In Equation 2 above, the weight is (1 - A r * N days ), and the adaptation rate A r controls the rate at which the adjustment factor is incorporated into the new base ratio, and its standard value is 0.2. The adaptation rate may be variable. When the period is short, the influence of the previous base ratio is greater. For example, if the period is only 1 day, the weight is 0.8 (i.e., 1 - 0.2 * 1), but if the period is 3 days, the weight decreases to 0.4. At 304, weighting is performed on the adjustment factor. The adjustment factor reflecting more recent collected drug delivery data remains the same with the standard value of the adaptation rate being 0.2, and the weighting of A old * N r with respect to BR days is in the reverse configuration. As the number of days in the period increases, the weight of the adjustment factor also increases. If it is 1 day, the weight is 0.2, but if the period is 3 days, the weight increases to 0.6. At 306, the weighted previous base ratio (e.g., (1 - A r * N days ) * BRold ) is a weighted adjustment factor (for example, A r *N days *This is added to the adjustment coefficient. In 308, the sum of these is the new base ratio BR new This is the result.

[0046] Figure 4 shows a flowchart 400 of exemplary steps that can be performed to determine the dosage of basal delivery using a new basal ratio (see 204 in Figure 2) in an exemplary embodiment. In 402, drug delivery data for the user is collected over a recent period. This recent period is a period following a longer period in which historical data was previously collected. In 404, from the data collected over the recent period, a new total daily drug dose (TDM) is calculated. new ) is determined. TDM new The preferred equation is as follows:

number

[0047] TDM new To calculate the daily bolus drug delivery amount and basal drug delivery amount for the recent period (

number

[0048] In 408, the next basal delivery dose is determined from the adjusted daily basal dose. Specifically, it is assumed that the drug delivery device 102 delivers the basal drug in cycles, and each cycle lasts 5 minutes. In this case, there are 180 cycles per day. That is, the basal dose per cycle can be determined by dividing the adjusted basal delivery dose by 180 (e.g., DBD). new ( / 180).

[0049] In exemplary embodiments, as described above, various types of adjustment factors can be used to adjust the underlying partial values. Figure 5 shows a flowchart of exemplary steps that can be performed when limited adjustment factors are used in exemplary embodiments. 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 that period, the relative adjustment coefficient, and BR. old It depends on the difference in size.

[0051] As shown in flowchart 500 of Figure 5, in 502, the base ratio based on experience (i.e.,

number

[0052] Another option for the adjustment coefficient is to use an ideal base ratio of 0.5 and an empirically based average base ratio. The formula for this adjustment coefficient is:

number

number

[0053] This adjustment coefficient formula changes the adjustment coefficient by half as it approaches the ideal value of 0.5.

[0054] Figure 6A shows a flowchart 600 of exemplary steps that can be performed using these various adjustment coefficients. In 602, an empirically based base ratio is added to the ideal base partial value (for example,

number

[0055] Furthermore, the Adjustment Factor can be a constant value in several exemplary options. For example, the Adjustment Factor can be assumed to be a positive constant if the empirically based ratio is above a certain threshold, a negative constant if the empirically based ratio is below another threshold, and zero or a standard value if it is between the thresholds. One exemplary formula for this option is as follows:

number

number

[0056] Figure 6B shows a flowchart of exemplary steps that can be taken to calculate a new base ratio according to this second option, as shown in Equation 8. First, in 622, the past base ratios are added to the adjustment coefficient to calculate the total. In 624, it is determined whether the total is lower than the lower threshold. If so, in 626, the lower value is used as the new base ratio. For example, if the lower value is 1 / 3 and the total is less than 1 / 3, the new base ratio is set to 1 / 3. If the total is greater than the lower threshold, in 628, it is determined whether the total exceeds the upper threshold. If so, in 630, the new base ratio is set to the upper threshold (e.g., 2 / 3). Otherwise, in 632, the total is used as the new base ratio.

[0057] Figure 7 provides a flowchart 700 of exemplary steps that can be performed in an exemplary embodiment with such adjustment coefficient options. In 702, it is determined whether the empirically based base partial value (i.e., the empirically based base ratio) is greater than the ideal base ratio (e.g., +0.05). If so, in 704, a positive adjustment coefficient (e.g., 0.05) is used. Otherwise, a negative adjustment coefficient (e.g., -0.05) is used.

[0058] As an additional option, there is a method of using an adjustment factor with a scaling value. The scaling value can be, for example, 0.5. An example formula for the adjustment factor in this option is as follows:

number

[0059] This exemplary adjustment coefficient adjusts the adjustment coefficient for the ideal value of 0.5 based on the square root of the difference between the empirically based base ratio and the ideal value. Equation 2 can be applied to determine the new base ratio.

[0060] Figure 8 shows a flowchart 800 of exemplary steps that can be taken when this option for determining the adjustment coefficient is used. In 802, an empirically based base ratio (e.g.,

number

number

number

[0061] In an exemplary embodiment, the user may be notified if the empirically based baseline ratio is outside the desired range. Figure 9 shows a flowchart of exemplary steps that can be performed when providing notification in an exemplary embodiment. In 902, it is determined whether the empirically based baseline ratio exceeds the upper limit. If so, in 904, the user is notified that an insufficient bolus dose may not have been administered. The notification may be displayed on display 109. The notification may be sent using a means of communication such as text message or email. Next, in 906, it is determined whether the empirically based baseline ratio falls below the lower limit. If so, in 908, the user is notified that the bolus dose may be too high. Otherwise, in 910, no notification is generated.

[0062] Figure 10 shows another way to adapt the basal delivery rate to the user's customized needs. In an exemplary embodiment, Figure 10 shows a flowchart of exemplary steps that can be taken to determine the user's basal rate per hour based on historical average values ​​over a period of time. In 1002, drug delivery data for the user is collected over a period of time. The drug delivery data may include the basal drug delivery amount, the meal bolus drug delivery amount delivered to address the rise in blood glucose levels due to carbohydrate intake, the corrected bolus drug delivery amount delivered to address hyperglycemia, and so on.

[0063] In step 1004, the user's daily meal bolus during that period is calculated. If the period is m days, this value can be calculated using the following formula.

number

[0064] In step 1006, the average daily correction bolus amount for users during that period is calculated. The appropriate equation for this average is as follows:

number

[0065] In 1008, the average daily basal drug delivery rate is calculated. The average can be calculated using the following formula:

number

[0066] In 1010, the base portion coefficient can be calculated as the average daily base delivery divided by the sum of the other average values ​​calculated in 1004, 1006, and 1008. The base portion coefficient is related to a new base ratio adapted to the data collected during that period. This calculation can be expressed as follows:

number

[0067] In 10¹², the base rate per hour is determined using the basal portion factor. The base rate per hour can be expressed as follows:

number

[0068] In exemplary embodiments, the bolus amount delivered to the user can also be adjusted based on the basal portion value. Given the wide range of deviations in the user's daily bolus requirement, rather than directly converting the user's immediate basal insulin delivery rate into a change in the user's basal percentage, in exemplary implementations, if the user's insulin requirement deviates by 10% or more (0.05 is 10% of 0.5) from the baseline value (50 / 50 division) in one direction, the basal portion percentage can be increased by a certain amount. The adjustment of the basal portion value can be expressed, for example, as follows:

number

[0069] Therefore, as shown in flowchart 1100 of Figure 11, the base partial coefficient can be calculated in 1102 using equation 13, for example. In 1104, it is determined whether the base partial coefficient is smaller than the lower threshold (e.g., 0.45). Such a value indicates that the user's actual base partial coefficient is smaller than 0.45 and should be adjusted downward. If so, in 1106, the adjustment value becomes 1-increment (e.g., 0.05). Otherwise, in 1108, it is checked whether the base partial coefficient is greater than or equal to the upper threshold (e.g., 0.55) and should be adjusted upward. If so, in 1110, the adjustment value is adjusted to 1+increment. Otherwise, in 1112, the base partial coefficient is close to ideal and the adjustment value is set to 0. In 1114, a new adjustment coefficient b is set. factor past base ratio b old Multiply by this to obtain the new base ratio. bnew =b old ·b factor (Formula 16)

[0070] In other exemplary embodiments, deviations from a standard base correction coefficient are used to detect bolus overload or bolus underload from historical data. If a dynamically calculated base correction coefficient is unavailable, the amounts of bolus underload and bolus overload can be determined and the user can be alerted. Figure 12 shows a flowchart 1200 of exemplary steps that can be performed in such exemplary embodiments. In 1202, the user's drug delivery history is collected for long-term and more recent short-term periods. This data is used to determine the mean, which can be used to determine bolus overload and bolus underload. In 1204, the average daily base drug delivery amount for the user over the long term is calculated, for example, using equation 12. In 1206, the average daily bolus drug delivery amount for the user over the long term is calculated, for example, by summing equations 10 and 11. In 1208, the average daily bolus drug delivery amount to the user over more recent short-term periods is calculated. In 1210, the average daily base drug delivery amount to the user over short-term periods is calculated. In step 1212, the average drug bolus portion over the short term and long term is calculated. These are the ratios of the average daily bolus dose to the TDM over the short term and long term. In step 1214, the percentage difference between the user's average short-term drug bolus portion and the user's average long-term drug bolus portion is determined. In step 1216, the user is notified via display 109 or 127, etc., to adjust the bolus dose by the determined percentage difference. This percentage difference can be positive or negative. For example, suppose 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 described above, the baseline partial value and / or TDM may be adjusted over shorter periods than those described above, for example, over a period of one hour. Figure 13 shows a flowchart 1300 of exemplary steps that can be performed to adjust the baseline partial value and TDM for the user in an exemplary embodiment. In 1302, the next period is reached. This period can be, for example, a period of one hour, a period of three hours, a period of six hours, or a period of twelve hours. The period can also be a shorter period, for example, a period of 30 minutes. The arrival of the next period triggers the adjustment of the baseline partial value in 1304. In 1306, the TDM may also be adjusted as needed. In 1308, a check is performed to see if the last period has been reached. For example, if this period is the last period immediately before the drug delivery device is replaced, then this period is the last period. Otherwise, in 1302, the process is repeated when the next period arrives.

[0072] Figure 14 shows a flowchart 1400 of exemplary steps that can be performed to adjust the baseline partial value over a short period in an exemplary embodiment. In 1402, the initial baseline partial value is used to determine the baseline delivery amount of the drug over the operating period. In 1404, the adjusted baseline partial value for the next operating period is determined. The adjusted baseline partial value may 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, and time of day may affect insulin sensitivity. In 1406, the adjusted baseline partial value is used to determine the amount of drug delivered to the user over the next operating period. In 1408, the control application 116 or 120 administers the determined baseline drug amount to the user over the next period.

[0073] The adjusted baseline partial 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 can be performed to determine the adjusted baseline partial value from the user's recent drug delivery history in an exemplary embodiment. The following formula may be used to determine the user's adjusted baseline partial value.

number

[0074] Therefore, in 1502, the total basic delivery amount of the drug in time frame N is calculated (i.e.,

number

number

[0075] The base portion value can be adjusted using recent bolus delivery history instead of recent base delivery history. A relationship exists between the base portion value and the bolus portion value, representing the TDM portion attributable to manual bolus deliveries. Specifically, the base portion value is equal to 1 minus the bolus portion value. This relationship can be used to determine the base portion value. A suitable equation for determining the user-adjusted base portion value from recent bolus delivery history is:

number

[0076] Figure 15B shows a flowchart 1520 of exemplary steps that can be performed to adjust the user's underlying partial values ​​in an exemplary embodiment. In 1522, the bolus delivery amounts manually delivered to the user over the time frame are summed up over all cycles of the time frame (i.e.,

number

number

[0077] The TDM value can also be adjusted frequently, either per cycle or per period. Figure 16 shows a flowchart 1600 of the steps that can be taken to adapt TDM to a user in an exemplary embodiment. In 1602, the doses of all drug deliveries to the user (i.e., all manual deliveries and all automated deliveries) over the most recent time frame are summed up. In some embodiments, the most recent time frame should be one day or more. Therefore, if the drug delivery device cycle is 5 minutes, the time frame should be 288 cycles (i.e., the number of cycles in a day) or more. In 1604, the resulting sum is normalized to obtain a value per day. If the time frame M is greater than 288 cycles, the sum can be normalized by dividing by M / 288. In 1606, the normalized sum is used as the TDM.

[0078] Adjusted TDM (or TDI in the case of insulin) can be used to determine the baseline portion of the adjusted TDM. Figure 17 shows a flowchart 1700 of a feasible exemplary step in which adjusted TDM is used to determine the baseline portion value in an exemplary embodiment. In 1702, the baseline portion value is determined based on the most recent baseline delivery using the adjusted TDM value. Substituting the above equation into equation 16 for determining the baseline portion value from the most recent baseline delivery, we obtain the following equation:

number

[0079] In 1704, the underlying partial value is determined using the most recent bolus delivery quantity with the adjusted TDM value. The formula for determining the underlying partial value from the most recent bolus delivery quantity is given below. 18 Substituting the above equation into the given expression, we obtain the following equation.

number

number

number

[0080] In this application, the term “non-temporary storage device” should be understood as either a single non-temporary storage device, multiple non-temporary storage devices contained in a single device, or multiple non-temporary storage devices contained in (or separated from) different devices, for example, one non-temporary storage medium contained in a distribution device and another non-temporary storage medium contained in a management device. Similarly, the term “processor” refers to a single processor or multiple processors, which may be contained in a single device or contained in (or separated from) different devices, for example, one processor in a distribution device and another processor in a management device.

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

[0082] 1. A drug delivery system, A non-temporary memory device that stores computer program instructions, A processor that executes computer program instructions, wherein the computer program instructions are performed by the processor, A new baseline ratio (BR) is used to specify what portion of the total drug delivery amount should be delivered to the user as the baseline drug delivery amount within a subsequent period, particularly within one or more days. new ) is the calculation, and the calculation is, The user's previous base ratio (BR old ), Adjustments including the ratio of the amount of drug delivered to the user as a base drug delivery amount via an automated drug delivery device over a period of time to the total amount of drug delivered to the user over that period of time, New base ratio (BR new ) is the previous base ratio (BR old ) at least one adjustment limit that restricts how much it can change from, Based on this, calculation and New base ratio (BR new ) is used to determine the next baseline drug delivery amount to the user by the automated drug delivery device, A drug delivery system that enables this process.

[0083] 2. Previous base ratio (BR old The drug delivery system according to Embodiment 1, wherein ) is a portion of the total amount of drug delivered to the user as the basal drug delivery amount within a prior period, particularly within one or more days.

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

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

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

[0087] 6. The first weighting coefficient (1-A r *N days ) and the second weighting coefficient (A r *N days The drug delivery system according to Embodiment 5, wherein the sum of ) is 1.

[0088] 7. The first weighting coefficient (1-A r *N days ) and the second weighting coefficient (A r *N days ) is an adjustment coefficient for the new base ratio (BR new Adaptive rate (A) that controls the rate incorporated into ) r A drug delivery system according to embodiment 5 or 6, which depends on ).

[0089] 8. A drug delivery system according to any of the above embodiments, wherein determining the dose for the next basal drug delivery includes multiplying the user's total daily insulin dose by a new basal ratio.

[0090] 9. A drug delivery system according to any of the above embodiments, wherein at least one adjustment limit includes the maximum and / or minimum values ​​that the adjustment can take.

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

[0092] 11. A drug delivery system according to any of the above embodiments, wherein at least one adjustment limit is a scaling factor that expands or contracts the adjustment.

[0093] 12. A drug delivery system according to any of the foregoing embodiments, wherein the drug is insulin, a glucagon-like peptide-1 (GLP-1) agonist, a pramulintide, or another drug that affects the user's blood glucose level.

[0094] 13. A drug delivery system, A non-temporary memory device that stores computer program instructions, A processor that executes computer program instructions, wherein the computer program instructions are performed by the processor, To compensate for the carbohydrates consumed in the diet, determine the average amount of insulin delivered to the user per day, To correct the hyperglycemia experienced by the user, the average amount of insulin delivered to the user per day is determined, The basal delivery dose is determined by determining the average amount of insulin delivered by the user, This involves calculating the average amount of insulin delivered to the user per day to compensate for carbohydrates consumed in meals, the average amount of insulin delivered to the user per day to improve hyperglycemia experienced by the user, and the sum of the average amount of insulin delivered by the user as a basal delivery. The basal portion coefficient is determined as the ratio of the average amount of insulin delivered by the user to the total amount of insulin delivered by the user, Using the underlying partial coefficients to determine the user's update base delivery rate, A drug delivery system that enables this process.

[0095] 14. Determining the user's refresh base delivery rate includes determining the user's refresh base delivery rate per hour, as described in Embodiment 13.

[0096] 15.1 A drug delivery system according to Embodiment 13 or 14, wherein determining the basal delivery rate per hour includes determining the product of a basal partial coefficient and the user's total daily insulin dose (TDI), and then dividing the product by 24 to obtain the basal delivery rate per hour.

[0097] 16. A drug delivery system according to any one of embodiments 13 to 15, further comprising updating the base partial coefficient and updating the user's base delivery rate using the updated base partial coefficient.

[0098] 17. A drug delivery system according to any one of embodiments 13 to 16, wherein updating the base partial coefficient includes increasing the base partial coefficient by a first predetermined fixed amount if the base partial coefficient is below a threshold.

[0099] 18. A drug delivery system according to any one of embodiments 13 to 17, wherein updating the base partial coefficient includes reducing the base partial coefficient by a second predetermined fixed amount if the base partial coefficient is greater than a threshold.

[0100] 19. A drug delivery system, The display and A non-temporary memory device that stores computer program instructions, A processor that executes computer program instructions, and the computer program instructions are to the processor, This involves comparing the average daily meal bolus portion of the patient's total insulin intake over the past few days with the average daily meal bolus portion of the patient's total insulin intake over the past few days, If the average daily meal bolus portion of a patient's total daily insulin intake over the past few days is greater than the average daily meal bolus portion of a patient's total daily insulin intake in the past by a first percentage, the system will generate a suggestion on the display to reduce the amount of insulin given by meal boluses by a first percentage. If the average daily meal bolus portion of a patient's total daily insulin intake over the past few days is two percentage points lower than the average daily meal bolus portion of a patient's total daily insulin intake in the past, then the amount of insulin due to meal bolus is second 2 To generate on-screen suggestions for the user by increasing them by that percentage, A drug delivery system that enables this process.

[0101] 20. The drug delivery system according to Embodiment 19, wherein the drug delivery system includes one of an insulin pump, an insulin pump controller, or a portable calculator.

[0102] 21. A drug delivery system according to Embodiment 19 or 20, wherein a computer program instruction causes the processor to further calculate the average daily basal insulin delivery amount to the patient in the past.

[0103] 22. A drug delivery system in any of embodiments 19 to 21, wherein a computer program instruction further causes the processor to calculate the average daily meal bolus insulin delivery amount to the patient over the past period.

[0104] 23. A drug delivery system according to any one of embodiments 19 to 22, wherein a computer program instruction further causes the processor to calculate the average total daily insulin dose to the patient in the past as the sum of the average daily basal insulin delivery dose to the patient in the past and the average daily meal bolus insulin delivery dose to the patient in the past.

[0105] 24. A drug delivery system according to any one of embodiments 19 to 23, wherein a computer program instruction further causes the processor to calculate the average meal bolus portion of the total daily insulin amount to the patient as the ratio of the average daily meal bolus insulin delivery amount to the patient to the average daily total insulin amount to the patient.

[0106] 25. A drug delivery system according to 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 drugs to a user, A non-temporary storage medium for storing computer program instructions, A processor configured to execute computer program instructions, and the processor, The amount of basal drug delivered by the drug delivery device during the first operating period is determined using a first basal partial value that represents a portion of the user's total daily drug dose (TDM), The drug delivery device determines an adjusted baseline portion value for the next operating period after the first operating period, based on the magnitude of the most recent baseline delivery amount. Using the adjusted baseline partial value, the amount of baseline drug to be delivered by the drug delivery device during the next operating period is determined, During the next operating period, the drug delivery device will deliver the determined amount of the base drug. A drug delivery device configured to perform the following action.

[0108] 27. Determining the adjusted baseline partial values ​​for the next operating period is: The first weight is obtained by assigning a first weight to the first basic partial value during the first operating period, and To determine the calculated ratio of the total amount of basal drug delivered to the user by the drug delivery device during the operating period to the total amount of basal drug that would have been delivered over that period if the initial basal partial value had been used, The calculated ratio is then given a second weight to generate a second weight value, The first weight value and the second weight value are added together to determine the adjusted base partial value, A drug delivery device according to embodiment 26, including the above.

[0109] 28. A drug delivery device according to Embodiment 26 or 27, wherein the initial baseline portion value is the baseline / TDM ratio, and the baseline / TDM ratio for the initial baseline portion value is 0.5.

[0110] 29. A drug delivery device according to any one of embodiments 26 to 28, wherein the initial baseline portion is adjusted 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, a pramulintide, or a combination thereof.

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

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

[0115] 34. A drug delivery device for delivering drugs to a user, A non-temporary storage medium for storing computer program instructions, In the processor, The amount of basal drug delivered by the drug delivery device during the first operating period is determined using a first basal partial value that represents a portion of the total daily drug dose (TDM) of the user delivered in basal form, Based on the magnitude of the recent bolus delivery volume by the drug delivery device, the adjusted baseline partial value for the next operating period after the first operating period is determined, Using the adjusted baseline partial value, the amount of baseline drug to be delivered by the drug delivery device during the next operating period is determined, The determined amount of the base drug is delivered by the drug delivery device during the next operating period, A processor configured to execute computer program instructions to cause the execution of, A drug delivery device equipped with the following features.

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

[0117] 36. Determining the adjusted baseline partial values ​​for the next operating period is: The first weight value is calculated by assigning a first weight to the first basic partial value during the first operating period, Determining the ratio between the total amount of bolus drug delivered to the user by the drug delivery device during the operating period and the total amount of bolus drug that would be delivered over that period if a predicted bolus portion value were used, Subtracting the determined ratio from 1 to calculate the difference, This involves applying a second weight to the difference to generate a second weight value, The first weight value and the second weight value are added together to determine the adjusted base partial value, A drug delivery device according to embodiment 34 or 35, including the drug delivery device described in embodiment 34 or 35.

[0118] 37. A drug delivery device according to any one of embodiments 34 to 36, wherein the first baseline value can be adjusted 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, a pramulintide, or a combination thereof.

[0120] 39. The drug delivery device is an insulin patch pump, as described in any one of embodiments 34 to 38.

[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 for controlling the dosage of basal insulin delivery performed by a processor in an insulin delivery device or one or more processors in an insulin delivery system, The amount of basal insulin delivered to the user from the insulin delivery device is stored in a non-temporary computer-readable storage medium. Based on at least some of the memorized basal insulin delivery doses, the total amount of basal insulin delivered within a time frame is determined, To determine the ratio between the total amount of the determined base delivery and the total amount of the predicted base delivery within the time frame, To weight that ratio, Weighting the previous ratio of basal insulin dose to total daily insulin dose (TDI) used by one or more processors to determine the basal delivery dose in a previous time frame, The weighted ratio is summed with the previous weighted ratio to calculate a new ratio of TDI to basal insulin delivery in the next period, To determine the basal insulin delivery amount in the following period using a new ratio of basal insulin delivery amount to TDI, The insulin delivery device will deliver the determined basal insulin dose over the following period: Methods that include...

[0123] 42. The method according to Embodiment 41, wherein the insulin delivery device has cycles of a certain length, and the total expected basal delivery amount in a time frame is half the TDI, which is obtained by dividing the number of cycles per day by the ratio of the number of cycles in the time frame.

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

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

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

Claims

1. A drug delivery system, A non-temporary memory device for storing computer program instructions, The system comprises at least one processor that executes the computer program instructions, and the computer program instructions are performed by the processor, To have the user of the drug delivery system perform automated basic drug delivery, To obtain drug delivery data over a recent period, wherein the drug delivery data includes past bolus drug deliveries and past base drug deliveries delivered to the user of the drug delivery system over the recent period. To calculate the total amount of past basic delivery amounts and the total amount of past bolus delivery amounts over the aforementioned recent period, During closed-loop operation, the sum of the past base delivery amounts and the past bolus delivery amounts over the recent period, divided by the number of intervals in the recent period (TDM) ｎｅｗ ) to a new base ratio (BR ｎｅｗ Adjusting the automated basal drug delivery dose to obtain a new automated basal drug delivery dose by multiplying by the new basal ratio, where the new basal ratio is The sum of past automatic base delivery amounts over past periods is the sum of the past bolus delivery amounts and the past base delivery amounts over the said past period (TDM). ｏｌｄ The previous base ratio (BR) obtained by dividing by ) ｏｌｄ ) and an adjustment coefficient that reflects the ratio of the total past basic delivery amounts over the recent period to the total past bolus delivery amounts and past basic delivery amounts over the recent period, A drug delivery system that enables this process.

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

3. The new automated basal drug delivery system uses the new basal ratio (BR) for subsequent basal drug delivery. ｎｅｗ The drug delivery system according to claim 1, which is adjusted to be such as

4. The new base ratio (BR ｎｅｗ ), multiplying the previous base ratio (BR ｏｌｄ ) by a first weighting factor (1 - A ｒ *N ｄａｙｓ ), multiplying the adjustment coefficient by a second weighting factor (A ｒ *N ｄａｙｓ ), and adding the obtained value (BR ｎｅｗ = (1 - A ｒ *N ｄａｙｓ ) * BR ｏｌｄ + A ｒ *N ｄａｙｓ *the adjustment coefficient), the drug delivery system according to claim 3.

5. The first weighting coefficient (1 - Ar*N) ｄａｙｓ ) and the second weighting coefficient (Ar*N ｄａｙｓ The drug delivery system according to claim 4, wherein the sum of the above is 1.

6. The first weighting coefficient (1-A ｒ *N ｄａｙｓ ) and the second weighting coefficient (A ｒ *N ｄａｙｓ ) is the most recent period (N ｄａｙｓ ) depends on the duration, and the longer the duration, or the more recent period (N ｄａｙｓ The more the first weighting coefficient (1-A) is equal to the value of the first weighting coefficient (1-A) ｒ *N ｄａｙｓ ) decreases, and the second weighting coefficient (A ｒ *N ｄａｙｓ The drug delivery system according to claim 4, wherein the amount increases.

7. The first weighting coefficient (1-A ｒ *N ｄａｙｓ ) and the second weighting coefficient (A ｒ *N ｄａｙｓ ) is when the adjustment coefficient is the new base ratio (BR ｎｅｗ The adaptive rate (A) that controls the rate incorporated into ) ｒ A drug delivery system according to claim 4, which depends on ).

8. The aforementioned adaptive rate (A ｒ The drug delivery system according to claim 7, wherein the coefficient is in the range of 0.05 to 0.

8.

9. The drug delivery system according to claim 4, wherein the adjustment coefficient is in the range of 0.3 to 0.

7.

10. The adjustment coefficient is the ideal value of the base ratio and the previous base ratio (BR ｏｌｄ The drug delivery system according to claim 4, which is the average of ).

11. The sum of the subsequent bolus delivery amount and the subsequent base delivery amount (TDM) ｎｅｗ ) is the sum of the past bolus delivery amount and the past base delivery amount (TDM) ｏｌｄ The drug delivery system according to claim 1, which is identical to the one described above.

12. The sum of the subsequent bolus delivery amount and the subsequent base delivery amount (TDM) ｎｅｗ ) can be adjusted by the user via the user interface, or the sum of the subsequent bolus delivery amount and the subsequent base delivery amount (TDM ｎｅｗ ) is automatically adjusted by the computer program instructions based on past blood glucose measurements, and if the average of the past blood glucose measurements continues to exceed the target blood glucose level, the total (TDM) ｎｅｗ ) increases, and if the average of past blood glucose measurements remains consistently below the target blood glucose level, the total (TDM) ｎｅｗ The drug delivery system according to claim 1, wherein the amount of the drug is reduced.

13. The drug delivery system according to 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 according to claim 13, wherein the at least one non-temporary storage device and the at least one processor for executing the computer program instructions are included in the drug delivery device or the management device, or if there are two or more non-temporary storage devices and two or more processors 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. The drug delivery system according to any one of claims 1 to 14, wherein the drug is insulin, a glucagon-like peptide-1 (GLP-1) agonist, a pramulintide, or another drug that affects the user's blood glucose level.

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