Ion electroosmosis drug delivery device

Abstract

This disclosure provides an iontophoresis drug delivery device. The iontophoresis drug delivery device includes: a power source for generating pulsed direct current required to penetrate a drug agent into a drug delivery area of ​​a biological organism, wherein the power source generates a positive pulsed direct current in a first time period and a reverse pulsed direct current in a second time period; a dielectric layer for contacting the drug delivery area, wherein the dielectric layer includes or has an active agent attached thereto, the active agent being used to penetrate into the drug delivery area via the pulsed direct current; and at least two electrodes for receiving the pulsed direct current output from the power source to provide the received pulsed direct current to the dielectric layer. The iontophoresis drug delivery device provided by this disclosure not only improves transdermal efficiency but also minimizes skin irritation or damage.

Description

Technical Field

[0001] This application relates to a drug delivery device, specifically to a drug delivery device for iontophoresis. Background Technology

[0002] Iontoosmosis is an electrotherapy in which an electric current is used to drive and propel an active agent (drug or other therapeutic agent) through the skin (typically, the stratum corneum of the skin acts as a barrier) and ultimately deliver the active agent (drug or other therapeutic agent) into the patient's bloodstream. Traditional iontoosmosis drug delivery devices, for example, continuously provide a direct current of a certain voltage amplitude to penetrate the drug into the target area of ​​the organism.

[0003] In traditional iontophoresis drug delivery devices, charge buildup occurs because the current flows in only one direction. Excessive charge buildup can lead to severe burns to the skin or tissue in the drug delivery area. Furthermore, continuous direct current can polarize the skin, limiting the amount of current that can be delivered over time due to the accumulated charge, thus restricting drug delivery efficiency.

[0004] Therefore, traditional iontophoresis therapy has at least the drawbacks of easily causing skin damage in the treatment area and low drug delivery efficiency. Summary of the Invention

[0005] According to an example embodiment of this disclosure, an iontophoresis drug delivery device is provided that can improve the efficiency of osmotic drug delivery and is less likely to cause damage to the skin in the drug delivery area.

[0006] In a first aspect of this disclosure, an iontophoresis drug delivery device is provided. The device includes: a power source for generating pulsed direct current required to penetrate a drug agent into a drug delivery area of ​​a living organism, wherein the power source generates a positive pulsed direct current in a first time period and a reverse pulsed direct current in a second time period; a dielectric layer for contacting the drug delivery area, wherein the dielectric layer includes or has an active agent attached thereto, the active agent being penetrated into the drug delivery area via the pulsed direct current; and at least two electrodes for receiving the pulsed direct current output from the power source to provide the received pulsed direct current to the dielectric layer.

[0007] In some embodiments, the current amplitude, frequency, and duty cycle of the forward pulse DC and the reverse pulse DC are preset or adjustable.

[0008] In some embodiments, the power supply alternately generates positive pulse DC and reverse pulse DC, and the difference between the amount of positive pulse DC generated by the power supply in a first time period and the amount of reverse pulse DC generated by the power supply in a second time period is less than or equal to a predetermined value.

[0009] In some embodiments, at least two electrodes meet at least one of the following: at least two electrodes are electrically connected to an integral dielectric layer; at least two electrodes are electrically connected to a plurality of independent dielectric layers; at least two electrodes are fixed to a dielectric layer; and at least two electrodes are detachably electrically connected to a dielectric layer.

[0010] In some embodiments, at least one of the forward pulsed DC and the reverse pulsed DC meets at least one of the following: at least one of the first time period and the second time period is between 1 second and 30 minutes; the frequency is between 100 Hz and 50 kHz; and the current amplitude is between 0.1 mA and 10 mA.

[0011] In some embodiments, the setting of at least one of frequency, current amplitude, and duty cycle is associated with characteristics of the drug delivery area, which are determined by measurement.

[0012] In some embodiments, in at least one of the first time period and the second time period, the duty cycle is a predetermined value for the first duty cycle, and the frequency varies between a first frequency threshold and a second frequency threshold.

[0013] In some embodiments, in at least one of the first time period and the second time period, the frequency is a predetermined value of the first frequency, and the duty cycle varies between a first duty cycle threshold and a second duty cycle threshold.

[0014] In some embodiments, during at least one of the first time period and the second time period, the frequency varies between a first frequency threshold and a second frequency threshold, and the duty cycle varies between a first duty cycle threshold and a second duty cycle threshold.

[0015] In some embodiments, the device further includes a gel containing or having one or more active agents attached.

[0016] It should be understood that the description in the Summary of the Invention section is not intended to limit the key or essential features of the embodiments of this disclosure, nor is it intended to restrict the scope of this disclosure. Other features of this disclosure will become readily apparent from the following description. Attached Figure Description

[0017] The above and other features, advantages, and aspects of the embodiments of this disclosure will become more apparent from the accompanying drawings and the following detailed description. In the drawings, the same or similar reference numerals denote the same or similar elements, wherein:

[0018] Figure 1 A schematic diagram of an iontophoresis drug delivery device 100 according to some embodiments of the present disclosure is shown;

[0019] Figure 2A schematic diagram of a pulsed direct current 200 according to an embodiment of the present disclosure is shown;

[0020] Figure 3 A schematic diagram of a pulsed direct current 300 according to an embodiment of the present disclosure is shown;

[0021] Figure 4 A schematic diagram of a pulsed direct current 400 according to an embodiment of the present disclosure is shown;

[0022] Figure 5 A schematic diagram of a pulsed direct current 500 according to an embodiment of the present disclosure is shown;

[0023] Figure 6 A schematic diagram of a pulsed direct current 600 according to an embodiment of the present disclosure is shown; and

[0024] In the various figures, the same or corresponding reference numerals indicate the same or corresponding parts. Detailed Implementation

[0025] Embodiments of this disclosure will now be described in more detail with reference to the accompanying drawings. While some embodiments of this disclosure are shown in the drawings, it should be understood that this disclosure can be implemented in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided to provide a more thorough and complete understanding of this disclosure. It should be understood that the accompanying drawings and embodiments of this disclosure are for illustrative purposes only and are not intended to limit the scope of protection of this disclosure.

[0026] In the description of embodiments of this disclosure, the term "comprising" and similar terms should be understood as open-ended inclusion, i.e., "including but not limited to". The term "based on" should be understood as "at least partially based on". The term "one embodiment" or "the embodiment" should be understood as "at least one embodiment". The terms "first", "second", etc., may refer to different or the same objects. Other explicit and implicit definitions may also be included below.

[0027] As described above, in traditional iontophoresis drug delivery devices, the fixed-amplitude current supplied by the device flows continuously in only one direction, which easily leads to charge accumulation. Excessive charge accumulation can cause severe burns to the skin or tissue in the drug delivery area. Furthermore, the continuous direct current can polarize the skin, limiting the amount of current that can be delivered over time, thus resulting in low drug delivery efficiency.

[0028] To address at least one of the aforementioned problems, and one or more other potential problems, exemplary embodiments of this disclosure provide an iontophoresis drug delivery device. This iontophoresis drug delivery device includes: a power source for generating pulsed direct current required to penetrate a drug agent into a drug delivery area of ​​a biological organism, wherein the power source generates a positive pulsed direct current for a first time period and a reverse pulsed direct current for a second time period; a dielectric layer for contacting the drug delivery area, wherein the dielectric layer includes or has an active agent attached thereto, the active agent being penetrated into the drug delivery area via the pulsed direct current; and at least two electrodes for receiving the pulsed direct current output from the power source to provide the received pulsed direct current to the dielectric layer.

[0029] In the above scheme, by utilizing a power source to generate a positive pulsed direct current in the first time period and a reverse pulsed direct current in the second time period, the iontophoresis drug delivery device can avoid problems caused by charge accumulation and skin polarization by using pulsed direct currents with varying directions over different time periods. Furthermore, it can adapt to individual differences among subjects by varying the current intensity (amplitude), frequency, and duty cycle of the pulsed direct current, thereby avoiding skin irritation or damage due to insufficient drug penetration or skin polarization. Therefore, the iontophoresis drug delivery device of this disclosure can improve the efficiency of transdermal drug delivery while minimizing damage to the skin in the drug delivery area.

[0030] Figure 1 A schematic diagram of an iontophoresis drug delivery device 100 according to an embodiment of the present disclosure is shown. In this example, the iontophoresis drug delivery device 100 includes at least: one or more power sources 110, a dielectric layer 114, and at least two electrodes 112-1 and 112-2. In some embodiments, the iontophoresis drug delivery device 100 further includes: a power control device 150 for controlling the power source 110, and a communication device 160. The power control device 150 is electrically connected to the power source 110 and the communication device 160. The power control device 150 is used to control the power source 110. The communication device 160 is used to receive data associated with transmitting iontophoresis drug delivery. It should be understood that the iontophoresis drug delivery device 100 may also include components not shown and / or may omit the shown components, and the scope of the present disclosure is not limited in this respect.

[0031] Regarding the power supply 110, it is used to generate pulsed direct current required to penetrate the drug substance into the treatment area of ​​the organism. For example, the power supply 110 generates a positive pulsed direct current in a first time period and a reverse pulsed direct current in a second time period. In some embodiments, the power supply 110 generates a reverse pulsed direct current in the first time period and a positive pulsed direct current in the second time period. In some embodiments, the iontophoresis drug delivery device 100 includes a single power supply. In some embodiments, the iontophoresis drug delivery device 100 includes multiple power supplies. These multiple power supplies may be connected in series and / or in parallel to provide appropriate voltage and current to penetrate the drug substance into the treatment area.

[0032] Regarding the medial layer 114, which is used to contact the drug delivery area, the medial layer includes or has an active agent attached thereto, which is used to be permeated into the drug delivery area via pulsed direct current. The medial layer 114 is typically covered over the drug delivery area 122 of the organism 120 and is adapted to the contour of the drug delivery area 122. The medial layer 114 is, for example, configured to conform to the contour of a face mask. In some embodiments, the medial layer 114 includes a porous structure (not shown) and a gel 118. The gel 118 includes a polar, free, permeable drug agent 130 dispersed in the skeletal structure of the gel 118. The medial layer 114 may have a predetermined resistance value. In some embodiments, the medial layer 114 is a monolithic medial layer electrically connected to the at least two electrodes described above. In some embodiments, the medial layer 114 is a plurality of independent medial layers, each electrically connected to the at least two electrodes described above. In some embodiments, the plurality of independent medial layers are, for example, in contact with the same body region, for example, all for facial drug delivery. In some embodiments, multiple independent media layers may contact different body regions, for example, one media layer for facial administration and another media layer for wrist or neck administration.

[0033] Regarding at least two electrodes 112-1 and 112-2, they are used to receive pulsed DC current from the power supply output in order to provide the received pulsed DC current to the dielectric layer. In some embodiments, the electrodes include a first electrode 112-1 and a second electrode 112-2, wherein the first electrode 112-1 is electrically connected to a first terminal of the power supply 110 via a connector 111-1 and a wire 113-1, and the second electrode 112-2 is electrically connected to a second terminal of the power supply 110 via a connector 111-2 and a wire 113-2. A backing layer 116 covers the first electrode 112-1 and the second electrode 112-2.

[0034] Regarding the connection method between electrodes 112-1 and 112-2 and dielectric layer 114, in some embodiments, at least two electrodes 112-1 and 112-2 are fixed (e.g., detachably) to the dielectric layer and electrically connected to it. For example, electrodes 112-1 and 112-2 are adhered to dielectric layer 114 and electrically connected to it, and the electrodes 112-1 and 112-2 adhered to dielectric layer 114 can be peeled off without affecting the dielectric layer 114 and the electrodes 112-1 and 112-2. For example, electrodes 112-1 and 112-2 can be detachably fixed to dielectric layer 114 via mutually coupled snap-fit ​​structures. Electrodes 112-1 and 112-2 can also be detachably fixed to dielectric layer 114 via magnetic structures. Electrodes 112-1 and 112-2 may also have a clamping structure, which can be clamped onto dielectric layer 114 to achieve electrical connection between electrodes 112-1 and 112-2 and dielectric layer 114.

[0035] Regarding the drug delivery area 122, in some embodiments, it is, for example, a localized area of ​​human skin, such as facial skin, neck skin, etc. The medium layer 114 is, for example, configured to resemble the outline of a face mask. Due to individual skin differences (e.g., differences in water-oil ratio, dryness, pore condition, etc.), individual skin characteristics vary. Therefore, considering these differences in characteristics of the drug delivery area, the iontophoresis drug delivery device of this disclosure includes a power source that generates pulsed direct current required to penetrate the drug delivery agent into the drug delivery area of ​​the organism, and this power source generates a positive pulsed direct current in a first time period and a reverse pulsed direct current in a second time period.

[0036] Regarding the penetrant 130, it may be, for example, but not limited to, a pharmaceutical agent for purposes such as pain relief, treatment of joint inflammation or asthma, hormone regulation, or cosmetic purposes. In some embodiments, the penetrant 130 may include, for example, vitamin C and arbutin, or vitamin C and tranexamic acid.

[0037] In some embodiments, the iontophoresis drug delivery device 100 of this disclosure further includes a gel 118, which contains or is attached with one or more active agents.

[0038] Regarding gel 118, it includes, for example but not limited to, a matrix, an active agent, and additives. In some embodiments, gel 118 includes, for example, at least one or more of the following components: polyethylene glycol, polyvinyl alcohol, polyhydroxyethyl methacrylate, polyacrylic acid, polymethacrylic acid, gelatin, and alginate.

[0039] The following combination Figure 2 Explain the characteristics of pulsed direct current in terms of current amplitude, frequency, and duty cycle. Figure 2A schematic diagram of a pulsed direct current 200 according to an embodiment of the present disclosure is shown. The power supply 110 of the iontophoresis drug delivery device 100 according to the present disclosure can provide pulsed direct current with a preset current amplitude, frequency, and duty cycle. For example, the current amplitude, frequency, and duty cycle of the positive pulsed direct current provided by the power supply 110 during a first time period are equal to or substantially equal to the current amplitude, frequency, and duty cycle of the reverse pulsed direct current provided by the power supply 110 during a second time period.

[0040] In some embodiments, the current amplitude, frequency, and duty cycle of the pulsed DC power supply may be adjustable during the period of the positive pulse or the period of the reverse pulse. For example, the current amplitude, frequency, and duty cycle of the positive pulsed DC power supply provided by power supply 110 during the first time period may be adjusted to values ​​different from preset values.

[0041] In some embodiments, the power supply 110 alternately generates forward pulsed DC and reverse pulsed DC, and the difference between the amount of the forward pulsed DC generated by the power supply 110 in a first time period and the amount of the reverse pulsed DC generated by the power supply 110 in a second time period is less than or equal to a predetermined value. For example, the predetermined value is zero. For example, the predetermined value is 0.01, 0.02, 0.03, ..., or 0.1 coulombs.

[0042] In some embodiments, the frequency of at least one of the forward and reverse pulsed DC currents generated by power supply 110 is between 100 Hz and 50 kHz. In some embodiments, the current amplitude of at least one of the forward and reverse pulsed DC currents generated by power supply 110 is between 0.1 mA and 10 mA. In some embodiments, at least one of the forward and reverse pulsed DC currents generated by power supply 110 conforms to the following: at least one of the first and second time periods is between 1 second and 30 minutes. By controlling the frequency, current amplitude, and duration of the forward and reverse pulsed DC currents, the drug delivery device of this disclosure is ensured to be able to match the individual skin characteristics differences caused by differences in water-oil ratio, dryness, pore condition, etc. Furthermore, studies have shown that the transdermal efficiency of different drug-administered components varies under different frequencies, current amplitudes, and durations of the forward and reverse pulsed DC currents. Typically, for different drug delivery purposes, the medium layer may include or be coated with different active agents or drug-administered components. Controlling the aforementioned electrical parameters of the positive and negative pulsed DC currents can help to specifically improve transdermal efficiency.

[0043] It should be understood that Figure 2The current amplitude, frequency, and duty cycle of the pulsed DC shown are merely illustrative and do not necessarily represent that the current amplitude, frequency, and duty cycle during the first time period of a positive pulse are equal to or substantially equal to the current amplitude, frequency, and duty cycle during the second time period of a reverse pulse.

[0044] Figure 3 A schematic diagram of a pulsed direct current 300 according to an embodiment of the present disclosure is shown. The setting of at least one of the frequency, current amplitude, and duty cycle of the pulsed direct current provided by the power supply 110 of the iontophoresis drug delivery device 100 is associated with characteristics of the drug delivery area, which can be determined by measurement. This is because the selection of the current amplitude, frequency, and duty cycle of the pulsed direct current depends heavily on several factors, including the active agent and medium formulation, and the user's skin condition. Therefore, a fixed frequency and duty cycle may not optimally or adequately penetrate the skin for all active agents as the user's skin condition changes. For example, different subjects may require different times to depolarize the skin to minimize resistance in the electric drive force, thereby better penetrating the active agent into the skin.

[0045] In some embodiments, the first time period corresponding to the positive pulsed DC current includes, for example, at least one scan segment, wherein each positive scan segment includes, for example, one or more positive scan rate segments. For example, the first positive scan segment includes, for example, a first scan rate segment, a second scan rate segment, and a third positive scan rate segment. Each of the first scan rate segment, the second scan rate segment, and the third scan rate segment... Figure 3Examples are given of positive pulses having different current amplitudes, frequencies, and duty cycles. For instance, a positive pulse DC in a first scan rate segment of a first positive scan segment has a current amplitude of a first current value, a frequency of a first frequency value, and a duty cycle of a first duty cycle value; a positive pulse DC in a second scan rate segment has a current amplitude of a second current value, a frequency of a second frequency value, and a duty cycle of a second duty cycle value; and a positive pulse DC in a third scan rate segment has a current amplitude of a third current value, a frequency of a third frequency value, and a duty cycle of a third duty cycle value. For example, in the first scan rate segment of the first positive scan segment, two positive pulses with the same current amplitude, frequency, and duty cycle are included. In the second scan rate segment of the first positive scan segment, four positive pulses with the same current amplitude, frequency, and duty cycle are included. In the third scan rate segment of the first positive scan segment, three positive pulses with the same current amplitude, frequency, and duty cycle are included. In some embodiments, the current amplitude, frequency, and duty cycle values ​​preset or adjusted for each segment are different. For example, in the first time period corresponding to a positive pulse, after experiencing a positive pulse with the same current amplitude, frequency, and duty cycle as the pulsed DC current of the first positive scan segment, a positive pulse with the same current amplitude, frequency, and duty cycle as the pulsed DC current of the first positive scan segment is experienced again. It should be understood that the corresponding positive pulse of the second positive scan segment (not shown) in the first time period may differ from the positive pulse of the first positive scan segment in terms of current amplitude, frequency, and duty cycle.

[0046] In some embodiments, the second time period corresponding to the reverse pulse includes one or more reverse scan segments. For example, in Figure 3 The first reverse scan segment shown includes multiple scan rate segments with different current amplitude, frequency, and duty cycle settings. The second scan rate segment of the first reverse scan segment includes five reverse pulses with the same current amplitude, frequency, and duty cycle. The third scan rate segment of the first reverse scan segment includes three reverse pulses with the same current amplitude, frequency, and duty cycle. In some embodiments, the current amplitude, frequency, and duty cycle values ​​preset or adjusted for each scan rate segment of the first reverse scan segment are different. For example, in the second time period corresponding to the reverse pulse, after experiencing a reverse pulse with the same current amplitude, frequency, and duty cycle as the pulsed DC current of the first reverse scan segment, another reverse pulse with the same current amplitude, frequency, and duty cycle as the pulsed DC current of the first reverse scan segment is experienced.

[0047] In some embodiments, the pulse DC current amplitude of each scan rate segment in the forward or reverse scan segment is preset or adjustable; that is, the pulse current amplitude of each scan rate segment can be different or the same. In the first scan rate segment of the first forward scan segment, the pulse DC current amplitude is less than that of the pulse DC current amplitude in the second scan rate segment and also less than that of the pulse DC current amplitude in the third scan rate segment. In other words, within the first scan rate segment, the pulse DC current amplitude is maintained at a relatively small value; within the second scan rate segment, the pulse DC current amplitude is maintained at a relatively medium value; and within the third scan rate segment, the pulse DC current amplitude is maintained at a relatively high value. It should be understood that the pulse DC current amplitude can increase progressively with each scan rate segment, decrease progressively with each scan rate segment, or can be alternately increased or decreased, or otherwise adjusted.

[0048] In some embodiments, the frequency of the pulsed DC current in each scan rate segment of the forward or reverse scan segment is preset or adjustable; that is, the frequency of the pulsed DC current in each scan rate segment can be different or the same. The duty cycle value of the pulsed DC current in each scan rate segment is also preset or adjustable. The frequency or duty cycle of the pulsed DC current can increase sequentially in each scan rate segment, decrease sequentially in each scan rate segment, or alternately increase or decrease, or be adjusted in other ways. In some embodiments, the absolute values ​​of various parameters in the first forward scan segment can be substantially the same as the absolute values ​​of various parameters in the first reverse scan segment, or they can differ, for example, within a deviation range of ±20%. It should be understood that it is necessary to ensure that the total charge of the forward and reverse pulses is substantially the same, preferably not exceeding a deviation range of ±20%.

[0049] Figure 3 This example merely illustrates how the first time period of a positive pulse can be divided into a first positive scan segment, which is further divided into a first scan rate segment, a second scan rate segment, and a third scan rate segment. This illustrative division does not necessarily mean that the first positive scan segment can only include three scan rate segments (i.e., a first scan rate segment, a second scan rate segment, and a third scan rate segment). The first time period can include more or fewer positive scan segments, and each positive scan segment can also include more or fewer scan rate segments. Similarly, the second time period can include more reverse scan segments, and each reverse scan segment can also include more or fewer scan rate segments.

[0050] The following combination Figure 4To illustrate, during at least one of the first time period and the second time period, the power supply 110 of the iontophoresis drug delivery device 100 provides a pulsed DC power supply with a predetermined duty cycle (e.g., a first duty cycle predetermined value), and the frequency of the pulsed DC power supply varies (e.g., varies between a first frequency threshold and a second frequency threshold). Figure 4 A schematic diagram of a pulsed direct current 400 according to an embodiment of the present disclosure is shown.

[0051] like Figure 4 As shown, during the first time period corresponding to the positive pulse, the frequency of the pulsed DC current increases, while the duty cycle remains at a preset value. During the second time period when the power supply provides a reverse DC pulse, the frequency of the pulsed DC current increases again, while the duty cycle remains at the preset value. Thus, the increasing frequency of the pulsed DC current means that the number of pulses applied by the iontophoresis drug delivery device 100 to the drug-treated area per unit time increases, while the increased frequency and unchanged duty cycle mean that the duration of electroosmosis of the drug-treated area by a single pulse from the iontophoresis drug delivery device 100 decreases.

[0052] Figure 4 The frequency variation of the pulsed direct current shown is merely illustrative. In some embodiments, the frequency variation of the pulsed direct current is not necessarily a regular change from small to large or from large to small; it can be other variations, such as from large to small and then back to large, or from small to large and then back to small. In some embodiments, by setting a first frequency threshold and a second frequency threshold, the range of frequency variation can be preset, and this range can be determined based on the measured individual skin characteristics or the drug-administered ingredient. In some embodiments, the fixed values ​​of the frequency variation and duty cycle of the reverse pulsed direct current in the second time period are not necessarily referenced (e.g., equal to) the fixed values ​​of the frequency variation and duty cycle of the forward pulsed direct current in the first time period. The principle is to ensure that the amount of electricity of the forward pulsed direct current in the first time period provided by the power supply 110 of the iontophoresis drug delivery device 100 is substantially the same as the amount of electricity of the reverse pulsed direct current in the second time period, or does not exceed a predetermined deviation range (e.g., ±20%).

[0053] The following combination Figure 5 To illustrate, during at least one of the first time period and the second time period, the power supply 110 of the iontophoresis drug delivery device 100 provides a pulsed direct current with a predetermined frequency (e.g., a first predetermined frequency value) and the duty cycle of the provided pulsed direct current is varied (e.g., varying between a first duty cycle threshold and a second duty cycle threshold). Figure 5 A schematic diagram of a pulsed direct current 500 according to an embodiment of the present disclosure is shown.

[0054] like Figure 5As shown, during the first time period, the frequency of the forward pulsed DC current is a preset value, and the duty cycle of the forward pulsed DC current changes from small to large and then from large to small. During the second time period, the frequency of the reverse pulsed DC current is also a preset value, and the duty cycle of the reverse pulsed DC current changes from small to large and then from large to small. Thus, if the frequency of the pulsed DC current remains unchanged, it means that the number of pulses of the iontophoresis drug delivery device 100 to the drug-treated area per unit time remains unchanged. However, if the frequency remains unchanged but the duty cycle changes, it means that the duration of the electro-osmosis of the drug-treated area by a single pulse of the iontophoresis drug delivery device 100 to the drug-treated area becomes longer (corresponding to a larger duty cycle) or shorter (corresponding to a smaller duty cycle).

[0055] It should be understood that Figure 5 The variation in the duty cycle of the pulsed DC shown is merely illustrative. In some embodiments, the variation in duty cycle is not necessarily a regular progression from small to large or from large to small; it can also vary in other irregular ways. By setting a first duty cycle threshold and a second duty cycle threshold, i.e., by setting an upper and lower limit for the duty cycle threshold, the range of duty cycle variation can be preset. This range can be determined based on the individual skin characteristics being measured (e.g., skin sensitivity) or the drug-administered ingredient. In some embodiments, the preset value of the frequency of the reverse pulsed DC in the second time period and the setting of the duty cycle variation threshold are not necessarily referenced (e.g., equal to) the preset value of the frequency of the forward pulsed DC in the first time period and the setting of the duty cycle variation threshold. The principle is to ensure that the charge in the first time period of the forward pulse is substantially the same as the charge in the second time period of the reverse pulse, or does not exceed a predetermined deviation range (e.g., ±20%).

[0056] The following combination Figure 6 To illustrate, during at least one of the first and second time periods, the frequency of the pulsed DC power supply 110 of the iontophoresis drug delivery device 100 varies (e.g., varies between a first frequency threshold and a second frequency threshold), and the duty cycle of the pulsed DC power supply also varies (e.g., varies between a first duty cycle threshold and a second duty cycle threshold). Figure 6 A schematic diagram of a pulsed direct current 600 according to an embodiment of the present disclosure is shown.

[0057] like Figure 6As shown, during the first time period, the frequency of the positive pulsed DC current decreases and then increases; the duty cycle also increases and then decreases. Similarly, after entering the second time period, the frequency of the reverse pulsed current decreases and then increases, while the duty cycle also increases and then decreases. Thus, the change in the frequency of the pulsed DC current means a change in the number of pulses that the iontophoresis drug delivery device 100 performs on the drug-treated area per unit time. The change in the duty cycle also means a change in the duration of a single pulse of the iontophoresis drug delivery device 100 on the drug-treated area.

[0058] It should be understood that Figure 6 The simultaneous changes in frequency and duty cycle of the pulsed DC power shown are merely illustrative. In some embodiments, the changes in frequency and duty cycle of the pulsed DC power are not necessarily regular changes from small to large or from large to small; they can also be irregular changes. By setting a first frequency threshold and a second frequency threshold, and a first duty cycle threshold and a second duty cycle threshold, the range of frequency and duty cycle changes can be preset. This range can be determined based on the measured individual skin characteristics (e.g., skin sensitivity) or the drugged ingredient. In some embodiments, the frequency and duty cycle changes of the reverse pulsed DC power in the second time period do not necessarily refer to (e.g., be equal to) the frequency and duty cycle changes of the forward pulsed DC power in the first time period. The principle is to ensure that the forward pulse charge provided by power supply 110 in the first time period does not exceed a predetermined deviation range (e.g., ±20%) compared to the reverse pulse charge in the second time period.

[0059] In some embodiments, one or more electrodes in the current iontophoresis drug delivery device 100 may share a single continuous dielectric layer. Alternatively, multiple discrete dielectric layers may be electrically connected separately. The power supply 110 may be configured to provide a bipolar pulsed direct current, providing a positive pulsed direct current for a first time period and switching the provided current to a reverse pulsed direct current for a second time period. To ensure a balance of total charge, the total charge delivered in the first time period must be substantially the same as, or not exceed, a predetermined deviation range (e.g., ±20%) of the total charge delivered in the second time period. In some embodiments, the duration of the positive or reverse pulsed direct current may be a few seconds or minutes, between 1 second and 1 minute, or between 1 minute and 30 minutes. In some embodiments, the duty cycle of the pulsed direct current may be 1% to 100%.

[0060] In some embodiments, in order to further improve transdermal drug delivery efficiency and efficacy, and to provide a desired number of different active agents, the amplitude, frequency and duty cycle of the pulsed direct current can be dynamically changed so that the various active agents included or attached to the medium layer can be efficiently penetrated into the skin of the drug delivery area under the drive of bidirectional pulsed direct current with matched electroosmotic parameters.

[0061] It should be understood that the scan formed by the pulsed direct current described in this disclosure may have linear, triangular, sine wave, exponential or pseudo-random characteristics, and the scan period may be set or varied between 10 milliseconds and 10 minutes.

[0062] The various embodiments of this disclosure have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles, practical application, or technical improvements to the embodiments in the market, or to enable others skilled in the art to understand the embodiments disclosed herein.

[0063] The above description is merely an optional embodiment of this disclosure and is not intended to limit this disclosure. Various modifications and variations can be made to this disclosure by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this disclosure should be included within the scope of protection of this disclosure.

Claims

1. An iontophoresis drug delivery device, comprising: A power source is used to generate pulsed direct current required to penetrate the drug into the administration area of ​​a living organism, wherein the power source generates a positive pulsed direct current in a first time period and a reverse pulsed direct current in a second time period. A medium layer for contacting the drug delivery area, wherein the medium layer includes or has an active agent attached thereto, the active agent being permeated into the drug delivery area via the pulsed direct current; as well as At least two electrodes are provided for receiving the pulsed DC current from the power supply output, so as to provide the received pulsed DC current to the dielectric layer; The at least two electrodes are detachably electrically connected to the dielectric layer, wherein the at least two electrodes are configured as at least one of the following: The at least two electrodes are detachably fixed to the dielectric layer by a snap-fit ​​structure that is coupled to each other; The at least two electrodes are detachably fixed to the dielectric layer by a magnetic attraction structure; as well as The at least two electrodes have a clamping structure, which clamps them onto the dielectric layer to achieve electrical connection between the at least two electrodes and the dielectric layer; wherein the current amplitude, frequency and duty cycle of the forward pulse DC and the reverse pulse DC are preset or adjustable; The first time period corresponding to the positive pulse DC current includes at least one positive scanning segment, wherein each positive scanning segment includes one or more positive scanning rate segments, and the current amplitude, frequency value and duty cycle value preset or adjusted for each positive scanning rate segment are different. The second time period corresponding to the reverse pulse DC current includes one or more reverse scanning segments, wherein the reverse scanning segment includes multiple scanning rate segments with different current amplitude, frequency and duty cycle setting values. The setting of at least one of the frequency, the current amplitude, and the duty cycle is associated with characteristics of the drug delivery area, which are determined by measurement, and the current amplitude, frequency, and duty cycle of the pulsed direct current depend on the active agent and medium formulation, as well as the user's skin condition.

2. The apparatus of claim 1, wherein the power source alternately generates the forward pulse DC and the reverse pulse DC, and the difference between the amount of the forward pulse DC generated by the power source in the first time period and the amount of the reverse pulse DC generated by the power source in the second time period is less than or equal to a predetermined value.

3. The apparatus of claim 1, wherein at least one of the forward pulsed DC and the reverse pulsed DC meets at least one of the following criteria: At least one of the first time period and the second time period is between 1 second and 30 minutes; The frequency is between 100 Hz and 50 kHz; and The current amplitude is between 0.1mA and 10mA.

4. The apparatus of claim 1, wherein in at least one of the first time period and the second time period, the duty cycle is a predetermined first duty cycle value, and the frequency varies between a first frequency threshold and a second frequency threshold.

5. The apparatus of claim 1, wherein in at least one of the first time period and the second time period, the frequency is a first frequency predetermined value, and the duty cycle varies between a first duty cycle threshold and a second duty cycle threshold.

6. The apparatus of claim 1, wherein in at least one of the first time period and the second time period, the frequency varies between a first frequency threshold and a second frequency threshold, and the duty cycle varies between a first duty cycle threshold and a second duty cycle threshold.

7. The apparatus according to claim 1, further comprising: A gel containing or having one or more of the active agents attached.

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