TWI423831B - Ion permeation drug delivery system - Google Patents

Description

Iontophoresis drug delivery system

The present invention relates generally to several therapeutic agents for transdermal delivery, and more particularly to an iontophoretic drug delivery system for packaging of such systems for long expiration and ease of assembly. The system package includes an iontophoresis patch assembly that houses a power source, electronics, electrodes, and a drug pack assembly that carries a therapeutic agent that is loaded as a separate seal assembly. The packaged system is also easy to assemble when used.

Electron iontophoresis is well known and has found significant commercial use of electrophoretic compounds through the skin at the system electrode sites of the same charge.

Several self-contained and durable iontophoresis systems have been developed in which the circuit structure and power supply have been integrated into a single skin patch. In many of these devices, drug ions are delivered to the body from an aqueous "drug" reservoir in an iontophoresis device, and oppositely charged counterions are delivered from a "reverse" reservoir. Since the drug/ion solution is often stored in a large amount at a distance, and at the time of use, a useful iontophoresis is introduced into an absorbing layer of the electrode, an additional step is required to incorporate the drug ion and the counter ion into the device. However, the electrode is liable to be overfilled or insufficiently filled, so that a skilled person skilled in the art is required in this respect. Further, since the drug solution and the electrode are separately stored, management of the two kinds of stocks is required.

In order to prevent the user from merging the aqueous drug or the ion storage tank during use, the drug solution may be pre-packaged with an electrode, or a liquid storage tank may be contacted with an electrode assembly for storage, and will be dried during use. The drug layer is inserted into the reservoir. Unfortunately, with either configuration, an electrode is still stored in a humid environment, and the assembly and other components are immune to corrosion degradation.

For these and other reasons, the penetration of iontophoresis into the transdermal drug delivery patch and the active drug remains a challenging problem. Since the iontophoret patch contains several electrodes and electronic devices, and the drug solution is usually water in nature, if there is no barrier between the aqueous environment and the electronic device, it may be within two years within the expected expiration date. Both the electronic device and the drug solution will deteriorate. A packaging solution is sought that provides a barrier between the electronic device and the drug solution and thus meets the expiration date, while still allowing the drug solution and the electronic device to be combined in a combined device during use. There is a further desire for a solution that not only provides an effective shelf life to address the issue of surrounding the co-packaged aqueous drug solution with electrodes and electronic circuitry, but also makes it easier for the operator or user to activate and apply the patch.

This application is a non-provisional application of the following patent application: Patent Application No. 61/094,442, filed on September 5, 2008, and the priority of claiming the patent application, the entire contents of which are hereby incorporated by reference. The manner is incorporated in the present application.

The present invention provides a pre-packaged complete iontophoretic drug delivery system that is easily combined by the package state. The pre-packaged complete iontophoretic drug delivery system of the present invention comprises an iontophoretic patch and a therapeutic agent, both of which are administered and which have a long expiration date. The system comprises two main components, namely: a drug pack assembly comprising one or more gel pads, at least one of which comprises an active agent; and an iontophoretic patch assembly comprising a plurality of electrodes and a power supply. The drug pack assembly and the iontophoretic patch assembly are packaged together, but are separate components during storage of the system, and are immediately combined into a combined state by use of a built-in alignment technique, the alignment technique Utilizing an alignment structure that can take any of a number of forms, one form includes an associated foldable device or a folded support structure that carries the components on separate compartments, and another form that involves a separate pair Use of a quasi-fixing or guiding element.

In one embodiment, in a configuration that is designed to fold in a different manner to accommodate both storage and use, a plurality of continuous support lattice structures are used to penetrate an iontophoresis into the patch assembly and a seal containing therapeutic ions or The active ingredient-containing drug pack assembly is loaded in a separate setting. A feature of this type of arrangement is a foldable configuration or a folded support structure.

Alternatively, an iontophoresis patch assembly and a sealed drug pack assembly can be stored as separate components in a package structure and combined using an alignment fixture or guide element prior to use, the alignment fixture or The guiding element can be a separate component or can be packaged to initially adhere to any of the iontophoresis patch or drug pack assembly.

In addition, although most drug or therapeutic ionic species will typically be packaged in a drug pack assembly in gel form, some may be placed in a therapeutic patch in a dry state, in which case the therapeutic ions are combined when the system is combined The species is combined with the gel or other solution.

The collapsible embodiment features a plurality of continuous tethers in a foldable device or a folded support structure, wherein an iontophoretic patch assembly is attached to a compartment support structure, and a clearly shaped and sealed drug pack assembly Attached to the compartment adjacent to the corresponding drug and electrode part in an alignment register with an appropriate fold line therebetween. The folded support structure or foldable device is preferably made of a paperboard or polymeric material having a selectively applied release coating or pressure sensitive tape to allow iontophoresis into the patch assembly and the drug pack assembly to adhere to the compartments . A typical iontophoretic patch assembly includes all of the required tape, liner, electronics, and circuit components.

The sealed drug pack assembly is made of a low moisture permeability material and comprises at least one permeable gel absorbent pad that inhales a desired drug solution, typically in the form of a gel, until the time of use, the gel absorption The pads are still separately protected in a sealed drug pack assembly during the expiration date.

The foldable configuration includes a cavity and a fold line to allow and guide various different compartments to be folded inwardly or folded over the other, and includes a release coating (which can be combined with the chin) applied to the back, and A printed coating is applied to the front side with a surface to which printing can be applied. The printable coating surface may comprise a conventional clay material, the iontophoretic patch assembly being adhered to the first coating of the release coating or the back side of the foldable device, the drug The package assembly is bonded to the adjacent compartment on the printable coating or on the front side of the coated clay. The collapsible device further comprises a plurality of electrode cavities formed according to the shape and position of the gel absorbing pad, which when the folding device is folded, allows the ion ions to penetrate into the patch assembly to connect and register the contents of the drug pack assembly, as described The iontophoresis patch assembly and the drug pack assembly are registered in the compartment, and when the foldable device is folded in a combined arrangement, the clear shape of the drug pack assembly and the iontophoresis into the electrode of the patch assembly are facilitated. Corresponding to the cavity alignment.

In some such embodiments, wherein there is a folded support structure associated with the drug pack assembly and the iontophoretic patch assembly, the folded support structure can further include a divider assembly configured to ionize The drug delivery system is physically separated from the drug pack assembly and the iontophoresis patch assembly when the drug delivery system is in a folded storage state. As described above, in these embodiments, the folded support structure can include a first compartment associated with the iontophoretic patch assembly, and a second compartment associated with the drug pack component, wherein the first The second compartment is connected by a fold line. The folding support structure further includes a dividing line assembly formed of one or more additional compartments, such as connecting the dividing line assembly on the other side connected to the first compartment relative to the second compartment, wherein And the additional one or more compartments are configured to physically separate the iontophoretic patch assembly from the drug pack assembly when the system is in a folded storage state, the splitter assembly separating the drug pack component from the electrical ion not only in the folded storage state The patch assembly is also inserted into the protective assembly structure of the system components.

The gel pads are stored in a generally inert sealed drug pack assembly prior to use to prevent interaction of the contents with the surrounding environment, thereby preventing the drug solution or any electronic devices or other ion ions that are protected in the vicinity of the drug pack assembly. There is any degradation in the penetration of the patch assembly. Based on maintaining the integrity of the contents, the material in direct contact with the drug solution during storage is preferably defined as a relatively inert material comprising a well-formed cuvette, a gel absorbent pad, and a barrier cover for the drug pack assembly. Low moisture permeability materials include vinyl, polyester, polyamide, including nylon, or polyalkyl such as polyethylene and polypropylene. The material may also be a material selected from the group consisting of a variety of fabrics, foils, metal films or other materials that further reduce moisture permeability. The receptacle and the barrier cover should also be formed of a material that is inert or stable when facing components such as drug solutions and gel absorbent pads.

An embodiment includes a receptacle formed by an aluminum/polymer composite material and a barrier cover, the barrier cover being provided with a release coating for easy removal during use, in this embodiment, the gel absorbent pads It consists of a laminate of a suitable polymeric layer and coating which is stable against and in contact with the drug solution. Preferably, the gel absorbent pads are of a nonwoven substrate having a known gel absorbency or rate of action, and are suitable for use in the absorbent nonwoven substrate including cotton, polypropylene, polyethylene and polyester fibers, preferably. The absorbing material is polypropylene.

A number of alternative embodiments use an alignment fixture or guide element to combine the iontophoretic drug delivery system by a plurality of separate components that can be supplied as a separate component or with an iontophoretic patch assembly Or a combination of a drug pack component, in which the combined durable iontophoresis patch assembly and the drug pack assembly are similarly separated, and the configuration and cooperation of the iontophoresis patch assembly and the drug pack assembly are similar. The same as described in the folding embodiment.

In the case of the collapsible embodiment, in use, the operator first strips the barrier cover of the sealed drug pack assembly to expose the gel pads that are still attached to a compartment of the system. The iontophoretic patch assembly is adhered to an adjacent cell. Then, the operator folds the partitions so that the gel pads are in close contact with the electrode cavities of the plasma ions penetrating into the patch assembly, and the electrodes of the plasma ions penetrating into the patch assembly are provided with an occlusion double The surface tape layer is attached to an occlusive layer of the surface of the gel pad when the electrode is in contact with both the electrode of the patch assembly and the gel pad. The fully assembled patch is then peeled off from a folded or other suitable release coating on the folded support structure, the gel pads being permanently adhered to the iontophoretic patch assembly by occluding a double sided tape layer The electrodes are, and finally, the assembled patch is applied to the patient. Many embodiments or variations are conceivable from the basic concepts and manners.

An embodiment having a separate alignment fixing assembly or guiding element, in a drug package assembly and an iontophoresis patch assembly structure having a plurality of guiding elements continuously on an alignment fixture or guiding element A number of labeled alignment openings are combined. The drug pack assembly is first assembled to its guiding element, and as in other embodiments the barrier cover is typically removed, and then the iontophoretic patch assembly is assembled over the open drug pack assembly, and the drug pack assembly is Several gel pads are placed against several corresponding electrodes, so A combined configuration is then created wherein the gel pads are permanently bonded to the electrodes by occluding a double sided tape layer, and wherein the assembly can be separated and applied to a patient. In several alternative embodiments, the guide element package can be assembled to the drug pack assembly and then combined with the iontophoretic patch assembly, or the iontophoretic patch assembly can be assembled to the guide element and then The drug pack assembly is combined.

Referring to Figures 1A through 14, the present invention provides an iontophoretic drug delivery system. In addition, the present invention provides a fully functional, self-contained, easy to use form in the form of a prepackaged iontophoretic drug delivery system. An iontophoresis device having a long stable expiration date, the system comprising: a drug pack assembly, a folded support structure, and an iontophoresis patch assembly comprising a power source, current control electronic device , and several electrodes. The device is ready for use and requires only a few simple operations to activate the iontophoresis patch assembly and apply to the treatment site. In some embodiments, the operations consist of removing a barrier cover of a drug pack assembly, folding the cells into each other, and stripping the iontophoretic patch assembly from a release coating. In other embodiments, the iontophoretic patch assembly and the drug pack assembly are first combined on an alignment fixture or guide member and the alignment fixture or guide member is removed. In the following, several preferred embodiments of the device are described to illustrate the concept of the invention, but it is not intended that the embodiments limit the scope of the inventive concept in any way.

1A, 1B, and 2 illustrate an embodiment of a foldable device 20 in an open or horizontal configuration in a cross-sectional exploded view, a combined cross-sectional view, and a top view, respectively, and FIGS. 9A and 9B illustrate the side view and the top view, respectively. The foldable device 20 is folded in a package configuration for long term storage. The foldable device 20 is comprised of three main components: a folded support structure 22, an iontophoretic patch assembly 24, and a drug pack assembly 26.

The folded support structure 22 can comprise a cardboard (or similar material) coated on one side The release coating 28 and the substrate coated with a printable coating 30 on the reverse side are illustrated in FIG. 1C in a fragmentary enlarged cross-sectional view illustrating a portion of the folded support structure 22, the release coating 28 and the printable coating 30 being illustrated. The release coating 28 can be a vaporized coating, and the printable coating 30 can be a clay coating. An alternative folded support structure 22 can be a heated polymer or the like. The folded support structure 22 can include a plurality of fold lines 32, 33, and 34 that can be created by perforations, scores, and/or creases, in the case of a heated substrate, at fold lines 32, 33, and 34. Heating forms several active hinges. Depending on the number of fold lines, the folded support structure 22 can be divided into a plurality of compartments that provide a plurality of areas to adhere to the various components of the foldable device 20, and further, can utilize printed instructions and/or provide a release The coating 28 is applied to a compartment to avoid permanent sticking to other compartments when folded up during storage.

As shown in FIG. 1A and FIG. 9A, on the side of the release coating 28 of the substrate, the iontophoretic patch assembly 24 adheres to the first compartment 36A of the folded support structure 22 with an adhesive, and the iontophoresis is applied. The sheet assembly 24 includes a foam tape layer 38, a closed double-sided tape layer 40, and an electrode sub-assembly layer 42 composed of a power source, an electronic device and a plurality of electrodes for operating the patch (not shown), and A layer of tape 44 is lining up. As shown in FIG. 1B, the adhesive face of the foam tape layer 38 and the upper tape layer 44 are adhered to the side of the release coating 28 of the folded support structure 22.

As shown in Figure 2, the folded support structure 22 has an anode cavity 46 and a cathode cavity 48 that align with the corresponding anode and cathode gel absorbent pads 72, 74 during assembly/startup. The anode cavity 46 and the cathode cavity 48 respectively expose the underlying electrodes, including the anode 50 and the cathode 52. Also shown in Figure 2 is a semi-detached liner 54 by perforating the first compartment 36A to create a semi-release liner 54. The patch 170 for completely assembling is peeled off from the folded support structure 22 after startup, as shown in FIG. 3D.

The semi-detached liner 54 serves as a support for assembling a complete patch 170 to aid in application. In addition, the operator is allowed to easily operate the assembled patch 170 so that the fully assembled patch 170 does not stick to the operator's fingers. More preferably, the half-assembled full patch 170, which is not covered by the semi-detached liner 54, is first attached to the patient's skin, and then the semi-detached lining 54 is removed by the raised block 54B in the semi-detached lining 54. The peeling is removed and, finally, the other half of the assembled patch 170 is attached to the patient's skin.

On the first compartment 36A, a double-sided tape 56 is adhered to the printable coating 30 side of the folded support structure 22, the double-sided tape 56 having a dual function, one being temporarily bonded as shown in FIG. 9A by a peeling The coating 28 faces keep the foldable device 20 closed during its long-term storage condition, and the second function is permanent when the parts are folded as shown in Figure 3C to transfer the anode gel pad 60 and the cathode gel pad 62. The ground is adhered to a second compartment 36B of the folding support structure 22 so that the first compartment 36A can no longer be opened.

As shown in FIG. 9A, the folded support structure 22 also includes an individual third compartment 36C and a fourth compartment 36D. The third compartment 36C and the fourth compartment 36D collectively form a separation line assembly for iontophoresis. The drug delivery system is configured to physically separate the drug packet assembly 26 and the iontophoretic patch assembly 24 when present in the folded storage phase. The third and fourth compartments 36C and 36D of the folded support structure 22 utilize the release coating 28 during folding to prevent the double-sided tape layer 40 from contacting the barrier cover 64 of the drug pack assembly 26 and permanently adhering during long term storage.

As shown in FIGS. 1B and 2, when the system is present in a pre-folded state prior to storage, the drug pack assembly 26 is present in the central region of the folded support structure 22, on one side of the drug pack assembly 26, the iontophoresis The patch assembly 24 is disposed in the first compartment 36A, and the drug pack assembly 26 is spaced apart from the iontophoretic patch assembly 24 on the other side of the patch assembly 36C, 36D. The divider assembly 36C, 36D provides system storage simultaneously. Structural separation and external protection.

On the printable coating 30 side of the folded support structure 22, a second double sided tape 66 is adhered to the second compartment 36B, as shown in Figures 1A, 1B and 2, for permanently holding the drug pack assembly 26 Bonding to the folded support structure 22, or, for example, without the double-sided tape 66, may be applied to the bottom of the drug pack assembly 26 or the side of the printable coating 30 of the folded support structure 22 by applying a heat seal coating. 26 is heat sealed to the folded support structure 22.

As shown in FIG. 1B and FIG. 3A, the drug pack assembly 26 is provided with a well-shaped baffle cover 64 having a low moisture permeability, a flat bottom layer 68 containing two separate gel positions, one position including one The anode gel pad 60, another location includes a cathode gel pad 62. The shape of the low moisture permeable barrier cover 64 having a well-defined shape is preferably as shown in FIG. 1B, and the flat bottom layer 68 is composed of an aluminum foil synthetic film which may include a heat seal coating on the side contacting the gel pad ( Not shown). If a heat seal coating is used, preferably an immediate strippable coating, the anode gel pad 60 and the cathode gel pad 62 are dispensed from the anode and cathode gels onto the composite or laminated nonwoven and impregnated thereto. Formed in a synthetic nonwoven material.

The clear shape of the low moisture permeable barrier cover 64 has been successfully constructed of a cold formable aluminum composite material having a sealing layer on the underside of the barrier cover and a nylon layer on the opposite side of the sealing layer. Alternatively, for example, the product contact surface may be comprised of polyvinyl chloride (PVC) without a sealing layer, and if a sealing layer is utilized, a peelable heat seal coating is preferred. The anode gel absorbent pad 72 and the cathodic gel absorbent pad 74 can each be formed using a conventional cold forming tool of a Teflon (polytetrafluoroethylene) plug or mechanically by vacuum or pressure. If an alternative material is used, including other fluoroplastics formed from sheets or films, such as those sold under the trade name Aclar, polydichloroethylene (PVDC), and other low moisture permeability barrier heating to form packaging materials, then The material can be formed by heating.

7A and 7B are respectively a top view and a side cross-sectional view showing the structure of an anode gel absorbent pad 72 or a cathode gel absorbent pad 74. As shown, the anode gel absorbent pad 72 or the cathode gel absorbent pad 74 is shown. Preferably, the material is of a non-woven structure to maintain consistency of the charge material in the structure, and may comprise a plurality of layers of material, possibly up to three layers, which may comprise a thick needle punched polypropylene layer 76, a thin permeable polyethylene mesh Layer 78, and a thin polypropylene occlusion ring 80. The layers can be thermally welded without the need for a bond, and all three layers are cut to have the same outer edge shape. The occlusive ring 80 is cut into an occluded peripheral ring shape in which the occlusion ring 80 is perforated to form a permeable region 84 therein. When the device is used in combination, the shape of the permeable region 84 conforms to the shape of the electrodes of the anode 50 (shown in Figure 2) and the cathode 52 by allowing the gel to move through the layer and contact the entire area of the electrodes. Importantly, the occlusive ring 80 provides a barrier for gel movement so that the outer surface remains relatively dry during storage, aiding in the transfer of the gel pad during startup of the device.

In one embodiment, both the anode gel absorbent pad 72 and the cathode gel absorbent pad 74 are similar in shape. Of course, the electrodes can be of any convenient shape, and the electrodes in a known patch embodiment can be Same or different shapes. 8A and 8B illustrate an alternative shape of either an anode and/or a cathode made of a nonwoven composite material 86 in a front view and a cross-sectional view. This embodiment has a peripheral ring 88 having a shape that has a permeable region. 90. 10 shows an alternative embodiment showing a device 100 having a drug pack assembly 102 having different shapes of anode and cathode receptacles, 104 and 106, respectively, in a similar manner, different However, a plurality of anode and cathode receptacles 104 and 106 having corresponding shapes are reflected in the foam layer, the folded support structure 22, and the anode 108 and cathode 110 in the occlusion rings 114 and 116. Only the corresponding components assembled together in a combined device need to have the same shape shape.

An important aspect of the present invention relates to the shelf life stability of co-packaged iontophoretic drug delivery systems. Based on the history of such devices, the primary impact in this regard is that such devices are not commercially viable due to limitations in the expiration date. success. As noted, co-packaging techniques have included efforts to package wet drug gels directly into the electrodes during long-term storage, and efforts to isolate power and electronics within the same package through low moisture permeable (high barrier) materials. The wet gel is only packaged directly in contact with the electrode and is connected to a power source and electronics by a cable or other connector during use. As described, these devices are each filled with long-term stability challenges, such as the final wet gel. It will degrade the metal in the electrode, power supply and electronic equipment, and it is the turn to deteriorate and pollute and degrade the stability of the gel.

In the present invention, a stable long-term co-packaging is achieved by providing a storage container for the anode and cathode gel so that the product does not expose the gel to react with the gel or absorb the gel. Since the gel material itself is not shaped, a carrier substrate material is used to provide the gel shape and structure, providing a stable support when assembled to use the system to facilitate removal of the gel from the long term storage container. The carrier substrate should be composed of a material that does not filter out, react or absorb the gel component. Preferably, the drug package component and the carrier substrate are made of a stable, relatively inert material such as polypropylene and polyethylene, and can be based on a gel. The nature of use and selection of any suitable material.

The effective period stability will vary depending on the construction of the patch component and the overall stability of the patch composition. The shelf life depends on the retention of the bond quality and the maintenance of the specific function of the circuit component. The device should have at least 2 The stable and effective period of the year.

Figures 5A through 5E illustrate a method of forming, filling and sealing a drug pack assembly in a step-by-step view in accordance with the present invention. Figure 6 above illustrates the situation when the drug pack assembly of Figure 5 is combined. In the method of Figures 5A through 5E, the drug pack assembly 120 is in the inverted position In the combination, a baffle cover 122 made of a low moisture permeability material is first provided, and is shaped to produce an anode receptacle 124 and a cathode receptacle 126 at a specific interval and depth, respectively, followed by an anode gel. The absorbent pad 128 is placed in a well-shaped anode receptacle 124 and a cathode gel absorbent pad 130 is placed in the cathode receptacle 126 of defined shape in the same manner. The anode gel absorbent pad 128 and the cathode gel absorbent pad 130 may have a structure similar to that shown in FIGS. 7A to 7B and 8A to 8B, and the anode gel absorbent pad 128 and the cathode gel absorbent pad 130 are oriented so that each The occlusion rings 132, 134 are placed toward the interior of the cavity and contact the bottom of the anode receptacle and the cathode receptacles 124, 126 having a defined shape. The anode gel absorbent pad 128 and the cathode gel absorbent pad 130 are set to be placed just in the shape of the bottom of the well-shaped anode receptacle and the cathode receptacles 124, 126. In this manner, the anode receptacle and the cathode receptacle are clearly shaped. 124, 126 then initially provides the anode gel absorbent pad 128 and the cathode gel absorbent pad 130 to the barrier cover 122.

The remaining steps performed in a time sequence will be as explained below, and the component can allow the opening time to be determined by the rate of pad osmosis, which is related to the viscosity of the gel used.

At time t = t0, as shown in Figure 5C, a quantity of viscous thick anode gel 136 is dispensed to uniformly cover the central permeable region 84 of the anode gel absorbent pad 128 (shown in Figure 7A), similarly A quantity of viscous cathode gel 138 is dispensed to uniformly cover a permeable region of the cathode gel absorbent pad 130. As also shown in Figure 5C, both the anode gel 136 and the cathode gel 138 are dispensed in a manner such that once a known amount of gel is dispensed, the total height of the mat plus gel height somewhat exceeds the well-defined anode receptacle. 124 or the depth of the cathode receptacle 126. The gel must be in a higher viscosity range for a period of time necessary to maintain its shape/height during device assembly. Applying a carrier substrate 140 (Fig. 5D) and heat sealing to the barrier cover at t < t0 < t1 122. As also shown in FIG. 5D, the carrier substrate 140 is contacted and pressed against the cathode gel 138A and the anode gel 136A, so that the gel wets the inner surface of the carrier substrate 140 and spreads out.

Alternatively, in another embodiment (not shown), the carrier substrate can be formed similar to a well-defined baffle cover to create a nested configuration, in this example, the gel plus pad height can be designed when combined The carrier substrate and the barrier cover are such that the gel will contact the carrier substrate in a similar manner to that of the described embodiment.

In this procedure, a period of time from t = t0 to t = t1 is defined as the dispensed anode gel 136 and cathode gel 138 being wetted through their respective anode gel absorbent pads 128, cathode gel absorbent pads 130. And the time required to begin wetting the barrier cover 122 with a clear shape of the bottom of the anode receptacle 124 and the cathode receptacle 126. Time is an element because it has been found that if the carrier substrate 140 is applied, the gel is completely wetted through the respective anode gel absorbent pad 128, the cathodic gel absorbent pad 130, and the anode of the barrier cover 122 having a well-defined shape. On the surface of the cavity 124 and the cathode cavity 126, the anode gel absorbent pad 128 and the cathode gel absorbent pad 130 are preferentially adhered to the inner side of the well-defined barrier cover 122 once filled. This is of course not desired when trying to combine the systems because the saturated anode gel absorbent pad 128 and the cathodic gel absorbent pad 130 will adhere to the barrier cover 122 instead of the carrier substrate 140. The period of time from t = t0 to t = t1 is also defined as the time during which the gel will properly maintain its height when the carrier substrate 140 is applied so that the gel will wet and adhere to the inner surface of the carrier substrate.

For the above reasons, the gel is formulated to a preferred viscosity range to provide the correct flow rate and surface tension. For example, a 100,000 centipoise gel may have a time window of about 2 to 4 minutes, which is appropriate for normal assembly.

During this process, the gel initially contacts and wets the carrier substrate 140 between the carrier substrate 140 and the anode gel absorbent pad 128 and the cathode gel absorbent pad 130. When the surface tension of the gel exceeds the gravitational force on the anode gel absorbent pad 128 and the cathode gel absorbent pad 130, the gel is allowed to act as a binder, and therefore, when the anode gel absorbent pad 128 and the cathode gel absorbent pad 130 are slowly Upon absorption of the gel, the anode gel absorbent pad 128 and the cathode gel absorbent pad 130 will adhere to the carrier substrate 140 and to the carrier substrate 140 regardless of the orientation of the device. Therefore, as shown in FIG. 5E, after the carrier substrate 140 and the barrier cover 122 are sealed, the compressed gel is absorbed (soaked) into the anode gel absorbent pad 128 and the cathode gel absorbent pad 130, respectively, resulting in a fully absorbed anode. Gel pad 128A and fully absorbed cathodic gel pad 130A. As described above, the fully absorbed anode gel pad 128A and cathode gel pad 130A continue to adhere to the carrier substrate 140, whereby as shown in Figure 5E, anode and cathode headspaces 142 and 144 are created in the package, respectively. It has been found that due to the high surface tension of the gel and the preferred high viscosity, the fully absorbed pad will remain temporarily present in the anode receptacle 124 and the cathode receptacle 126 of the individually shaped barrier cover 122, as shown The carrier substrate 140 is adhered throughout the intended life of the device.

It should be understood that in order to minimize excess gel, the amount of gel added to each of the anode receptacle 124 and the cathode receptacle 126 should match the absorbance of each gel, and the amount and viscosity of the gel are preferably absorbed. The gel does not wet the outer surfaces of the occlusive rings 146, 148 on the patch. In this manner, the outer surfaces of the occlusive rings 146, 148 should remain relatively dry, facilitating the adhesion transfer of the gel absorbent pads during startup. Adhesively adhered to the corresponding anode and cathode cavities of the iontophoretic patch assembly. In the regions of the anode and cathode headspaces 142 and 144, the inner surface of each of the well-defined barrier covers 122 should remain gel-free and It is drier.

In order for this assembly concept to work, it must be established that the gel has a preferred viscosity, preferably between 8,000 and 120,000 centipoise, but is not limited as long as the process can be successfully followed. Develop a useful gel in the system by dissolving it in water Appropriate amount of drug or physiological saline and a gel forming agent such as HPMC (hydroxypropyl methylcellulose) to produce a proper amount of conductive gel. Other gel forming agents such as PVP (polyvinylpyrrolidone) may also be used. ), PEO (polyethylene oxide) or PVA (polyvinyl alcohol), 2% by weight of HPMC powder has developed a successful gel.

The concentration of an activator in the gel can vary widely depending on the gel forming agent useful and the desired amount of tablet and the duration of the application. Typically, the concentration will range from about 0.2% to about 10% by weight.

Figures 3A through 3D illustrate, in cross-section, a preferred embodiment of how a preferred embodiment can be activated and deployed to a therapeutically usable structure. Figure 4 above illustrates the situation of Figure 3A after removal of the barrier cover 64. 9A and 9B illustrate a completely packaged device in a side view and a top view, respectively.

Starting from the packaged device of Figures 9A and 9B, an unfolding or assembly method will be described. First, the double-sided tape 56 is detached from the side of the release coating 28 of the fourth compartment 36D by tearing the projections 160. Completely unpack and unpack the complete device. Second, the barrier cover 64 with a well-defined shape is removed or stripped from the flat bottom layer 68 to expose the anode and cathode gel pads 60, 62 which are adhered to the flat bottom layer 68 via the surface tension of the gel as shown in Figure 3A. . The stripping action begins by stripping the tabs 18 (Fig. 2) on the barrier cover 64 member.

Next, as shown in FIG. 3C, the first compartment 36A is folded onto the second compartment 36B by the folding line 32, thereby occluding the occlusion ring 80 of the anode and cathode gel pads 60, 62 with the iontophoresis. The occlusive double-sided tape layer 40 of the sheet assembly 24 is permanently bonded into contact, and the double-sided tape 56 is brought into contact with the printable coating 30 of the folded support structure 22 and permanently adhered to the second compartment 36B, thereby preventing the first division The grid 36A is reopened. Figure 3B shows an intermediate motion diagram of the folding of the first compartment 36A to the second compartment 36B, preferably by pressing the iontophoresis into the outer surface of the patch assembly 24 to ensure closure. The occlusive ring 80 in which the double-sided tape layer 40 is permanently bonded to the gel pad is in good condition.

Finally, the semi-release liner 54 is stripped from the folded support structure 22 with the assembled patch 170 at the raised block 54A, and the exposed half-packed complete patch 170 adhesive can be applied to the treatment site, and then utilized. Projection block 54B (Fig. 9B) strips semi-release liner 54 from self-assembled patch 170 and adheres the remaining half of the patch to the treatment site.

11A to 11C illustrate an alternative embodiment including an alignment fixture or guiding element, and illustrating the activation of the embodiment. FIG. 12 is a view illustrating the embodiment of FIG. 11B, and the sectional views of FIGS. 11A to 11C are taken. From this embodiment. As seen in Figure 11A, the device 200, when packaged, includes three main components: a guiding member 202 having a plurality of spaced apart alignment members 204, 206; a drug pack assembly 208 disposed, and a The ions penetrate into the patch assembly 210. The primary component design components are stored in a common package and combined when the device 200 is ready for use.

The drug pack assembly 280 includes a flat card substrate layer 212 that is designed with a plurality of spaced alignment openings 214 and 216 that are aligned with the alignment members 204 and 206 during assembly. The anode and cathode gel pads 218 and 220 are respectively loaded on a bottom layer 222 and separated from the drug pack assembly 280 barrier cover 224 in the manner of the above-described embodiments of Figs. 5A through 5E, and the drug pack assembly 208 is adhered by a double-sided tape 226. Flat card substrate layer 212.

The iontophoretic patch assembly 210 is mounted on a flat card substrate layer 228 using spaced alignment openings 230 and 232 and a semi-release liner 234 as in the previous embodiment. The iontophoretic patch assembly 210 has a foam similar to that described above. The structure of the tape layers 236, 256 and the double-sided tape 238, the electrode sub-assembly layer 240, and the upper tape layer 242.

In use, the individual components are aligned and combined with each other using a component that aligns itself to adjacent components. In this manner, as shown in FIG. 11A, the guiding component 202 can be utilized. The spaced alignment members 204, 206 are positioned upwardly on a flat surface. Next, the drug pack assembly 208 is assembled to the guide element 202 by the alignment member 204 registering the alignment opening 214 in the drug pack assembly 280 and the alignment member 206 to the alignment opening 216. The barrier cover 224 can then be stripped from the drug pack assembly 208, exposing the anode and cathode gel pads 218 and 220, respectively, and then using the alignment members 204 and 206 in conjunction with the alignment openings 230 and 232 to penetrate the ions. The sheet assembly 210 is assembled to the drug pack assembly 208 whereby the gel pads are placed in alignment with the corresponding electrodes, as shown in the cross-sectional view of FIG. 11B and the top view of FIG. 12, the drug pack assembly 208 and the ion ions. The penetration patch assembly 210 is assembled on the guiding element 202 in a continuous registration manner.

In this stacking situation, the assembled patch 250 is ready to be placed apart for placement in the patient&apos;s affected area, as shown in Figure 11C, by simply peeling the semi-release liner 234 from the flat card substrate layer 212 to complete the separation. Thereby, the device 200 is separated from the flat card substrate layer 228 and carries the assembled patch 250. As explained in the above embodiment, the complete patch 250 is then assembled ready for use by the patient.

It should be understood that the drug pack assembly 208 and the iontophoresis patch assembly 210 are similar in construction except that the flat card substrate layers 212, 228 in this embodiment are a plurality of separate flat members rather than a plurality of folded joints. In the above embodiment, the flat card substrate layers 212, 228 include a plurality of alignment openings 214, 216, 230, 232 that correspond to alignment members 204 and 206 on the guiding member 202, and such layers do not require sputum or other The coating is detached so that both sides can contain a printable clay coating material or the like (as shown in Figure 12).

The flat card substrate layers 212, 228 may also be constructed of any suitable polymeric material, and the alignment members 204 and 206 of the guiding member 202 are preferably formed by heating or injection molding of a suitable polymeric material.

Figure 13 illustrates an alternate embodiment of the embodiment of Figures 11A through 11C in a cross-sectional exploded view in which a planar member layer 212 is replaced in a drug pack assembly 308 by a guiding member 302 having alignment members 304 and 306. In addition, the drug pack assembly 308 is similar to the drug pack assembly 208 described above, and a baffle cover 324. The iontophoretic patch assembly 310 is also similar to the flat card substrate layer 328 and the semi-release liner 334 having a plurality of spaced alignment openings 330 and 332 as shown in FIG. 11A, the drug package assembly 308 being double sided Tape 326 is bonded to guiding element 302.

Combining and initiating a combination and activation similar to the embodiment shown in Figures 11A through 11C, therefore, removing the baffle cover 324 of the drug pack assembly 308 and aligning the alignment members 304 and 306 using the alignment openings 330 and 332 The ion ions penetrate the patch assembly 310 and the drug pack assembly 308, and then the assembled patch is peeled off in accordance with FIG. 11C.

Figure 14 illustrates a further embodiment of the apparatus of the present invention in a cross-sectional exploded view, which represents another alternative to that shown in Figures 11A through 11C, in this embodiment, an alignment fixture 402 having alignment members 404 and 406. Instead of the flat card substrate layer 228 associated with the iontophoretic patch assembly 410. The alignment fixture 402 includes an anthrone release coating on the upper surface that is applied to the side to which the iontophoretic patch assembly 410 is attached prior to removal. This embodiment is assembled and painted in a similar manner to the above-described embodiments, thereby removing the barrier cover 424 of the drug pack assembly 408, aligning the alignment openings 414 and 416 adjacent the semi-release liner 412 with the alignment members 404 and 406. Precisely, and peel off the alignment device in the manner of Figure 11C.

It should be understood that the combination device or patch applied to a user may be of any size, such as from about 1 cm x 2 cm to about 15 cm x 20 cm, depending on the activator being treated and the condition to be treated. different.

The present invention is described in considerable detail to comply with the Patent Act and to provide the funds necessary for those skilled in the art to apply the novel principles and the exemplary embodiments required for construction and use. It is to be understood, however, that the invention may be embodied in a variety of different embodiments and various modifications can be made without departing from the scope of the invention.

18‧‧‧ protruding block

20‧‧‧Folding device

22‧‧‧Folding support structure

24, 210, 310, 410‧‧‧Electro-ion penetration patch assembly

26, 102, 120, 208, 308, 408‧‧ ‧ drug pack components

28‧‧‧Uncoating

30‧‧‧Printable coating

32, 33, 34‧‧‧ fold line

36A‧‧‧ first division

36B‧‧‧Second division

36C‧‧‧ third division

36D‧‧‧ fourth division

38, 236, 256‧‧ ‧ foam tape layer

40‧‧‧Closed double-sided tape layer

42, 240‧‧‧electrode sub-assembly layer

44, 242‧‧‧Upper tape layer

46‧‧‧Anode cavity

48‧‧‧cathode cavity

50, 108‧‧‧ anode

52, 110‧‧‧ cathode

54, 234, 334, 412‧‧‧ semi-detached lining

54A, 54B, 160‧‧‧ protruding blocks

56, 66, 226, 238, 326‧‧ ‧ double-sided tape

60, 218‧‧‧Anode gel pad

62, 220‧‧‧ Cathodic Gel Mat

64, 122, 224, 324, 424‧ ‧ barrier cover

68‧‧‧flat bottom layer

72, 128‧‧‧Anode gel absorbent pad

74,130‧‧‧Cathodic gel absorbent pad

76‧‧‧ needle punched polypropylene layer

78‧‧‧ permeable polyethylene mesh layer

80, 114, 116, 132, 134, 146, 148‧‧ ‧ occlusion rings

84, 90‧‧‧ permeable area

86‧‧‧Nonwoven synthetic materials

88‧‧‧ perimeter ring

100, 200‧‧‧ devices

104, 124‧‧‧ anode tank

106, 126‧‧‧ cathode tank

128A‧‧‧Absorbed complete anode gel pad

130A‧‧‧Absorbing a complete cathode gel pad

136, 136A‧‧‧Anode gel

138, 138A‧‧‧ cathode gel

140‧‧‧ Carrier substrate

142‧‧‧Anode head space

144‧‧‧ Cathode head space

170, 250‧‧‧Assembled complete patch

202, 302‧‧‧ guidance elements

204, 206, 304, 306, 404, 406‧ ‧ aligning members

212, 228, 328‧‧ ‧ flat card substrate layer

214, 216, 230, 232, 330, 332, 414, 416‧‧ ‧ alignment openings

222‧‧‧ bottom layer

402‧‧‧Aligning fixtures

FIG. 1A is a cross-sectional exploded view showing an embodiment of a foldable iontophoresis drug delivery system; FIG. 1B is a combination view of the device shown in FIG. 1A; FIG. 1C is a fragmentary enlarged sectional view showing FIGS. 1A and 1B. a portion of the folded support structure showing the release coating and the printable coating; FIG. 2: The above view illustrates the embodiment shown in FIGS. 1A and 1B; FIGS. 3A to 3D are cross-sectional views illustrating a stepwise activation of the device of FIG. Figure 4: The above view illustrates the embodiment of Figures 3A to 3D, showing the flow after removal of the masked cover with a clear shape from the drug pack assembly; Figures 5A to 5E: illustrating the drug and saline in a cross-sectional view Step-by-step method and design of the gel package on the gel absorbent pad; Figure 6: The above view illustrates the embodiment shown in Figures 5A to 5E as shown in combination; Figures 7A and 7B: respectively, the above view and the cross-sectional view illustrate the embodiment of Figure 6 Gel Absorbing Pad; Figures 8A and 8B: an alternate embodiment of a gel absorbent pad, respectively, in the above view and cross-sectional view; Figure 9A: A foldable view in a foldable (storage) configuration in accordance with the present invention Iontophoresis drug delivery system Figure 9B: The above view illustrates the package configuration of Figure 9A; Figure 10: The above view illustrates an alternate embodiment of the device in an open, horizontal configuration; Figure 11A is a cross-sectional exploded view showing an alternative embodiment of the apparatus of the present invention having separate iontophoretic patches and drug pack assemblies and a guiding member; Figure 11B: sectional view of the exploded components of Figure 11A Figure 11C: illustrates a separate case for the assembled iontophoretic drug delivery system of Figures 11A and 11B; Figure 12: The above view illustrates the assembly of Figure 11B; Figure 13: illustrates the Figures 11A through 11C in a cross-sectional exploded view In another alternative embodiment of the illustrated embodiment, the drug pack assembly is carried by the guiding member; and Figure 14 is a cross-sectional exploded view illustrating yet another alternative embodiment of the embodiment illustrated in Figures 11A through 11C.

22‧‧‧Folding support structure

24‧‧‧Electro-ion penetration patch assembly

36A‧‧‧ first division

54A, 54B, 160‧‧‧ protruding blocks

Claims (45)

An iontophoretic drug delivery system for pre-use assembly, comprising: (a) a drug pack assembly that is encapsulated when the ionizing agent is in a storage state, including one or more a gel pad; (b) an iontophoretic patch assembly; (c) wherein in an assembled state, the iontophoretic patch assembly is configured to align one or more of the drug pack components in a conductive relationship a gel pad; and (d) an alignment structure for assisting in assembling the components, wherein the alignment structure is selected from the group consisting of: (1) a folded support structure, and the drug pack component In association with the iontophoretic patch assembly, the folded support structure includes a divider assembly configured to physically separate and protect the iontophoretic drug delivery system when present in a folded storage phase The drug pack assembly and the ionizing agent are inserted into the patch assembly; and (2) a guiding member for separate and continuous alignment of the drug pack assembly with the iontophoresis patch assembly. The iontophoretic drug delivery system of claim 1, wherein the alignment structure comprises a multi-divided folded support structure that allows the drug pack assembly, the ion to penetrate the patch assembly, and the separation Line components are associated. The iontophoretic drug delivery system of claim 2, wherein the drug pack component and the iontophoresis patch assembly are disposed on a plurality of separate compartments of the folded support structure. The iontophoretic drug delivery system of claim 2, wherein the folded support structure presents a folded configuration for storage and a different folded configuration for assembly of the system. The iontophoretic drug delivery system of claim 2, wherein the folded support structure comprises four connected cells. The iontophoresis drug delivery system of claim 1, wherein the drug packet assembly and the iontophoresis patch assembly are disposed on the plurality of separate alignment structures, and wherein the alignment structure comprises The guiding element is associated with at least one of the alignment structures. The iontophoretic drug delivery system of claim 3, wherein the folded support structures are joined. The iontophoretic drug delivery system of claim 6, wherein the guiding element comprises a plurality of convex alignment members, and the alignment structures comprise a plurality of alignment openings for receiving the pairs Quasi-components. The iontophoretic drug delivery system of claim 5, wherein one of the folded support structures is adhered to the guiding element prior to assembly of the system. The iontophoresis drug delivery system of claim 1, wherein the drug package component comprises a plurality of gel pads comprising an anode gel pad and a cathode gel pad, one prior to assembly The barrier cover with low moisture permeability is isolated. The iontophoretic drug delivery system of claim 10, wherein the gel pad comprises one or more layers of a nonwoven polymer matrix. The iontophoretic drug delivery system of claim 10, comprising a quantity of therapeutic agent ion species in a gel associated with at least one of the gel pads. The iontophoretic drug delivery system of claim 1, wherein the iontophoret patch comprises a quantity of therapeutic agent. The iontophoretic drug delivery system of claim 10, wherein the gel pad is adhered to one of the drug pack components by adhesion of a gel material prior to assembly of the system. Carrier substrate. The iontophoretic drug delivery system of claim 12, wherein the therapeutic agent is present in the gel at a concentration of from about 0.2% to about 10%. The iontophoresis drug delivery system of claim 1, wherein the iontophoresis patch assembly comprises a plurality of electrodes including an anode and a cathode, and a power source. The iontophoresis drug delivery system of claim 16, wherein the drug package component comprises a plurality of gel pads, and the electrodes are mounted in a plurality of cavities, and the system is assembled into the assembled state. The cavities are adapted to receive the gel pads of the drug pack assembly. The iontophoretic drug delivery system of claim 1, wherein the iontophoresis patch assembly further comprises a layer of occlusive double-sided tape that adheres to the gel pad in the assembled state. Equal electrode. The iontophoretic drug delivery system of claim 10, wherein the barrier cover having a low moisture permeability comprises a material selected from the group consisting of: a metal/polymer composition And polyvinyl chloride (PVC). An iontophoretic drug delivery system for packaging for easy assembly, comprising: (a) a drug pack assembly comprising an anode gel pad and a cathode gel pad, the gel pad being configurable prior to assembly Removably mounted on a first alignment structure and isolated by a barrier cover having a low moisture permeability; (b) an iontophoretic patch assembly comprising an anode and a cathode and a a power source, the iontophoresis patch assembly is removably mounted on a second alignment structure; (c) wherein the iontophoretic patch assembly comprises a plurality of shaped cavities, The anode is associated with the cathode, and in an assembled state, the cavities are configured to receive the anode and cathode gel pads respectively in a conductive relationship; (d) wherein the first alignment structure and the second alignment The structure is selected from the group consisting of a plurality of connected folding cells comprising a plurality of dividing line assemblies for folding storage, and a plurality of separate members for assembly with a guiding member; e) a quantity of therapeutic ion species located on the anode gel pad, the cathode gel pad The iontophoretic patch of the at least one. The iontophoretic drug delivery system of claim 20, wherein the iontophoresis patch assembly further comprises a layer of occlusive double-sided tape that adheres to the gel pad in the assembled state Equal electrode. An iontophoretic drug delivery system comprising: (a) a drug pack assembly comprising one or more gel pads; (b) an iontophoresis patch assembly; (c) an alignment structure, To assist in assembling the components, the alignment structure includes a multi-divided folded support structure having a compartment associated with each of the drug pack components; (d) wherein when the alignment structure is folded in an assembled state, The iontophoresis patch assembly is configured to align with the gel pad of the drug pack component in a conductive relationship; and (e) wherein the drug pack component and the iontophoresis patch assembly and the plurality of compartments It is located inside a folded structure, and if folded in a package or storage state, a separator line assembly is inserted between the drug pack assembly and the iontophoresis patch assembly. The iontophoretic drug delivery system of claim 22, wherein the storage configuration of the folded support structure is ensured by a release coating. The iontophoretic drug delivery system of claim 16, wherein the iontophoretic patch assembly further comprises a half of the detachment liner covering a portion of the iontophoretic patch assembly. A pharmaceutical pack assembly for assembly into an iontophoresis drug delivery system, comprising: (a) a carrier substrate; (b) one or more gel absorbent pads adhered to the carrier substrate; (c) a barrier cover made of a low moisture permeable material, and the gel The absorbent pad spatially separates and encloses the gel absorbent pad; and (d) a quantity of gel material absorbed into the gel absorbent pad, at least one of the gel absorbent pads comprising a A quantity of therapeutic agent. The pharmaceutical pack assembly of claim 25, further comprising an occlusive ring located on one of the exposed surfaces of each of the one or more gel absorbent pads. The pharmaceutical pack assembly of claim 26, wherein the occlusive ring matches a periphery of a corresponding electrode. The pharmaceutical pack assembly of claim 25, wherein the gel absorbent mat comprises a plurality of laminated nonwoven polymer matrices. The pharmaceutical pack assembly of claim 28, wherein the matrix comprises a plurality of perforations. The pharmaceutical pack assembly of claim 25, wherein the gel material has a viscosity of at least 8,000 centipoise. The pharmaceutical pack assembly of claim 25, wherein the gel material comprises a material selected from the group consisting of hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone ( PVP), polyethylene oxide (PEO), and polyvinyl alcohol (PVA) and combinations thereof. The pharmaceutical pack assembly of claim 31, wherein the gel material has a viscosity of at least 8,000 centipoise. The pharmaceutical pack assembly of claim 31, wherein the gel material comprises hydroxypropyl methylcellulose (HPMC). The pharmaceutical pack assembly of claim 33, wherein the gel material has a viscosity of at least 8,000 centipoise. The pharmaceutical pack assembly of claim 25, wherein the gel absorbent pad comprises one or more materials selected from the group consisting of cotton, polypropylene, polyethylene, and a polyester. fiber. The pharmaceutical pack assembly of claim 35, wherein the gel absorbent pad comprises polypropylene. The pharmaceutical pack assembly of claim 29, wherein the gel absorbent pad comprises polypropylene. The pharmaceutical pack assembly of claim 35, wherein the gel absorbent mat comprises a plurality of laminated nonwoven materials. The pharmaceutical pack assembly of claim 25, wherein the barrier cover having a low moisture permeability comprises a material selected from the group consisting of metal/polymer composites and polyvinyl chloride. (PVC). The pharmaceutical pack assembly of claim 39, wherein the barrier cover comprises an aluminum/nylon composite material. A method of assembling a drug pack assembly for iontophoresis into a drug delivery system, comprising: (a) placing one or more gel absorbent pads into a plurality of pockets, the pockets being located in a shaped mask; (b) dispensing a gel amount onto each of the one or more gel absorbent pads, wherein the gel height extends beyond the depth of each corresponding pocket; (c) applying a substantially flat carrier substrate to the barrier cover contacting the gel, and sealing the carrier substrate to the barrier cover; and (d) allowing the gelation when the gel is drawn into each of the gel absorbent pads The glue causes each of the gel absorbent pads to adhere to the carrier substrate and is pulled away from a corresponding receiving groove to provide a clearance between the barrier cover and the gel absorbent pads. The method of claim 41, wherein the step (c) is completed before the gel is wetted through the gel absorbent pads. The iontophoresis drug delivery system of claim 1, comprising: storing the drug packet assembly and the iontophoresis patch assembly as separate entities in a common package for use prior to use; Assembly, wherein the drug pack assembly and the iontophoretic patch assembly are configured to merge when stacked to form a self-contained durable drug delivery system. A method of using a pre-packaged iontophoretic drug delivery system, the system comprising a drug pack assembly and an iontophoresis patch assembly, the method comprising: (a) removing the drug pack assembly from a storage package And the ionizing agent is inserted into the patch component, and removing one of the necessary barrier cover and the half of the detaching lining; (b) combining the drug packet component and the iontophoresis sticker by using an alignment structure a sheet assembly for assembling the system, wherein the drug pack assembly is permanently bonded to the iontophoretic patch assembly to form a fully assembled patch; wherein the alignment structure is selected from the following; (1) a folded support structure associated with the drug pack assembly and the iontophoretic patch assembly, the folded support structure comprising a separator line assembly, wherein the iontophoretic drug delivery system is present in a folded storage In the stage, the dividing line assembly is configured to physically separate and protect the drug pack component and the iontophoresis patch assembly; and (2) a guiding component for the drug pack component and the iontophoretic patch Components are separated and continuously aligned. And (c) applying the assembled patch to a patient's skin at a desired location. The method of claim 44, wherein the fully assembled patch is applied to the skin after the semi-detached liner is removed, and before the entire patch is bonded, approximately half of the fully assembled sticker is exposed. sheet.