Iontophoresis drug delivery method and device

Abstract

The invention relates to the technical field of transdermal iontophoresis drug delivery, and discloses an iontophoresis drug delivery method, which is realized by the following steps: under the action of current, an active agent of a second dielectric layer is electrically permeated into a drug delivery area through a first dielectric layer, and the active agent of the second dielectric layer is limited to diffuse to the first dielectric layer, so that the drug delivery area is enlarged; the efficiency of directionally penetrating the active agent into the administrated area is improved; the iontophoresis dosing device which can be repeatedly used, can be used for medicinal separation and is convenient to popularize in the market is invented by the method.

Description

Technical Field

[0001] The present application relates to the technical field of transdermal iontophoresis drug delivery, and more specifically to an iontophoresis drug delivery method and device thereof. Background Art

[0002] Ion electropermeation drug delivery technology is a non-invasive method that uses electromotive force to pass active substances with certain polarity through the skin at a certain rate and enter the systemic circulation to produce systemic or local therapeutic effects. Since this drug delivery method avoids the first-pass effect (the phenomenon that some drugs are administered through the gastrointestinal tract and are metabolized in the intestinal mucosa and liver before being absorbed into the blood circulation, which ultimately leads to a decrease in the amount of the original drug entering the blood circulation), it has the advantages of stable plasma drug concentration and has broad application prospects.

[0003] The existing ion permeation drug delivery methods usually use electrically driven single-point electrodes or multiple drug delivery carriers with electrodes for drug delivery. The above methods either have low transdermal efficiency or are prone to safety issues such as skin burns. Although the current ion permeation drug delivery technology route further balances transdermal efficiency and safety issues, due to the shunting effect of the electromotive force energy of the drug to be permeated by the integrated medium, the transdermal efficiency will be lost to a certain extent.

[0004] In addition, iontophoresis drug delivery devices have always been related to drug safety, and related devices cannot be widely mass-produced, which greatly limits the extensive application of the market, and many iontophoresis drug delivery devices often lack the basis for reuse, especially in the field of beauty, resulting in a large amount of waste of consumables. Therefore, it is very necessary to study a new iontophoresis drug delivery device and method that can be reused, separated from medicine, and easy to market. Summary of the invention

[0005] The purpose of the present application is to provide an iontophoresis drug delivery method and device thereof, so as to achieve efficient and safe iontophoresis drug delivery and improve the permeability.

[0006] The present application discloses an iontophoresis drug delivery method, wherein an active agent in a second medium layer is electrically infiltrated into a drug delivery area through a first medium layer under the action of an electric current, and the active agent in the second medium layer is restricted from diffusing toward the first medium layer, thereby improving the efficiency of the active agent directional penetration into the drug delivery area.

[0007] In a preferred embodiment, the first dielectric layer and the second dielectric layer have resistances respectively, and can divert the current intensity passing through the drug-administered area.

[0008] In a preferred embodiment, the implementation method steps include:

[0009] S1. Covering the drug-administered area with at least one second medium layer and a first medium layer in sequence;

[0010] S2. energizing the first dielectric layer through a power source so that the first dielectric layer obtains electric potential energy under the action of the current;

[0011] S3. The active agent in the second medium layer moves in a directional manner under the action of the electric potential energy and electrically penetrates into the drug-administered area.

[0012] In a preferred example, the first dielectric layer covers the second dielectric layer, and the first dielectric layer and the second dielectric layer are electrically conductive.

[0013] In a preferred embodiment, at least one spacer is disposed in the second medium layer, and the spacer can increase the content of the active agent in the second medium layer that is electrically permeated into the drug-administered region.

[0014] In a preferred embodiment, it further comprises: a conductive layer, a drug-carrying layer;

[0015] The conductive layer includes a conductive electrode area and a first dielectric layer; the drug-carrying layer includes a second dielectric layer;

[0016] The drug-carrying layer is disposed below the conductive layer;

[0017] The conductive electrode region is disposed above the first dielectric layer;

[0018] The second dielectric layer is disposed below the first dielectric layer.

[0019] In a preferred example, the conductive electrode region and the first dielectric layer are formed integrally.

[0020] In a preferred embodiment, a protective layer is provided between the conductive layer and the drug-carrying layer.

[0021] In a preferred embodiment, the drug-carrying layer can be independent of the conductive layer.

[0022] In a preferred embodiment, the conductive layer can be electrically connected to M independent drug-carrying layers, wherein M≥1.

[0023] Compared with the prior art, the main differences and effects of the embodiments of the present application are:

[0024] Achieve efficient and safe iontophoresis drug delivery and improve permeability and penetration efficiency;

[0025] Furthermore, the adaptability and application range of the iontophoresis drug delivery device is expanded to meet the need to reduce consumables;

[0026] Furthermore, it can be efficiently mass-produced to meet the needs of extensive market promotion and application.

[0027] The specification of the present application records a large number of technical features, which are distributed in various technical solutions. If all possible combinations of technical features of the present application (i.e., technical solutions) are to be listed, the specification will be too long. In order to avoid this problem, the various technical features disclosed in the above-mentioned invention content of the present application, the various technical features disclosed in the various embodiments and examples below, and the various technical features disclosed in the accompanying drawings can be freely combined with each other to form various new technical solutions (these technical solutions should all be regarded as having been recorded in this specification), unless the combination of such technical features is technically infeasible. For example, in one example, feature A+B+C is disclosed, and in another example, feature A+B+D+E is disclosed, and features C and D are equivalent technical means that play the same role. Technically, only one can be used, and it is impossible to use them at the same time. Feature E can be combined with feature C technically. Then, the solution of A+B+C+D should not be regarded as having been recorded because it is technically infeasible, and the solution of A+B+C+E should be regarded as having been recorded. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0029] Figure 1 is a schematic structural diagram of an iontophoresis drug delivery device according to one embodiment of the present application;

[0030] Figure 2 This is a schematic structural diagram of a first medium layer and a second medium layer of an iontophoresis drug delivery device according to an embodiment of the present application being separated from each other;

[0031] Figure 3 is a schematic diagram of a forward current drug delivery process of an iontophoresis drug delivery device according to one embodiment of the present application;

[0032] Figure 4 is a schematic diagram of a negative current drug delivery process of an iontophoresis drug delivery device according to an embodiment of the present application;

[0033] Figure 5 It is a schematic diagram of the implementation steps of the iontophoresis drug delivery method in one embodiment of the present application.

[0034] In the accompanying drawings, the symbols are as follows:

[0035] 1- Power supply;

[0036] 2-conductive layer;

[0037] 201-conductive electrode area;

[0038] 202-electrode spacing area;

[0039] 203-first dielectric layer;

[0040] 204- third peeling film;

[0041] 3-drug loading layer;

[0042] 301- second dielectric layer;

[0043] 302-interval area;

[0044] 303-first peeling film;

[0045] 304- second peeling film;

[0046] 4- backing layer;

[0047] 5-Connectors;

[0048] 601-603-steps of the method; DETAILED DESCRIPTION

[0049] In the following description, many technical details are provided to help readers better understand the present application. However, those skilled in the art can understand that the technical solution claimed in the present application can be implemented even without these technical details and various changes and modifications based on the following embodiments.

[0050] Description of some concepts:

[0051] Ion electrophoresis: Ion electrophoresis is a physical process in which ions diffuse in a medium under the drive of an electric field. The principle of direct current ion introduction is to introduce drug ions into the human body through intact skin or mucous membranes based on the principle that like charges repel each other and opposite charges attract each other in a direct current electric field. Ions of different charges can be introduced into the body, with cations introduced from the anode and anions from the cathode.

[0052] In order to make the objectives, technical solutions and advantages of the present application clearer, the implementation methods of the present application will be further described in detail below in conjunction with the accompanying drawings.

[0053] In one embodiment of the present application, an iontophoresis drug delivery device is provided, the structure of which is as follows: Figure 1 and Figure 2 As shown, the structure includes a power source 1, a conductive layer 2 and a drug-carrying layer 3.

[0054] The power source 1 is used to generate the electricity required to infiltrate the drug to be infiltrated into the area to be administered. The drug to be infiltrated can also be called an active agent. The electricity can be direct current, alternating current, or pulse current, and the direct current, alternating current, or pulse current intensity ranges from 0.1 mA to 5 mA. In some embodiments, a voltage / current control device can be provided so that the present embodiment can adjust the voltage / current output according to the real-time state of the area to be administered to achieve adaptive ion electropermeation.

[0055] The drug-carrying layer 3 includes a second medium layer 301, which covers the drug-administered area, wherein the second medium layer 301 includes a filling material and a drug to be permeated, and each second medium layer 301 is provided with at least one spacer 302 that divides the second medium layer 301 into independent areas. The resistance of the spacer 302 is greater than the resistance of the second medium layer 301.

[0056] The thickness of the second dielectric layer is 0.01 mm to 50 mm, preferably 0.2 mm to 0.8 mm. The gap of the spacer 302 in the second dielectric layer 301 is 1 mm to 10 mm, preferably 2 mm to 6 mm. The spacer 302 can be made of gap materials such as air, polymer materials (such as plastics, rubber, etc.). The spacer 302 is made of high impedance material, which can block the drug to be infiltrated from moving left and right in the second dielectric layer 301, and increase the content of the drug to be infiltrated in the second dielectric layer 301 that is electrically infiltrated into the administered area. In some embodiments, the spacer 302 can be designed as a variable resistor, and the resistance value is adjusted according to the voltage difference between the adjacent second dielectric layers 301 and the setting requirements of the target penetration depth of the drug to be infiltrated.

[0057] The conductive layer 2 includes a first dielectric layer 203 and a conductive electrode area 201 located above the first dielectric layer 203. During the ion electropermeation process, the first dielectric layer 203 is located above the second dielectric layer 301 and is electrically connected to the second dielectric layer 301. The first dielectric layer 203 includes a filling material, and the resistance of the first dielectric layer 203 is greater than the resistance of the second dielectric layer 301. The conductive electrode area 201 is used to electrically connect the power supply 1 and the first dielectric layer 203, respectively, and after power is turned on, the drug to be permeated in the second dielectric layer 301 is electropermeated into the drug administration area.

[0058] The conductive electrode area 201 and the first dielectric layer 203 can be integrally formed. Specifically, the thickness of the first dielectric layer is 0.01 mm to 50 mm, preferably 0.2 mm to 0.8 mm. In addition, the conductive electrode area 201 and the first dielectric layer 203 can also be independent of each other to meet market application requirements.

[0059] In one embodiment, the conductive electrode area 201 includes a first electrode 205, a second electrode 206, and an electrode spacing area 202 that separates the first electrode 205 from the second electrode 206, the first electrode 205 is electrically connected to the first end of the power source 1, and the second electrode 206 is electrically connected to the second end of the power source 1, wherein the spacing area 302 and the electrode spacing area 202 are arranged at corresponding positions. In other words, the positions of the spacing area 302 and the electrode spacing area 202 overlap in a direction perpendicular to the drug-administered area. It can be understood that the second dielectric layer 301 in the figure is divided into two independent areas by the spacing area 302, and the two independent areas correspond to the two electrodes respectively. In another embodiment, the number of electrodes in the conductive electrode area 201 can be greater than 2, for example, including 3 or 4 electrodes.

[0060] The electrodes separated by the electrode spacing area 202 can make the positive and negative ions in the first dielectric layer 203 move in a directional manner after power is turned on, reducing the disordered movement of ions in the first dielectric layer 203, thereby greatly improving the effect of electric potential energy. When the spacing area 302 is set to correspond to the electrode spacing area 202 in the conductive electrode of the first dielectric layer 203, the spacing area 302 can prevent the left and right parts of the second dielectric layer 301 from interfering with each other, thereby improving the electro-permeation efficiency of the drug to be permeated, and achieving the best skin permeation effect. Figure 3 and Figure 4 As shown, the main flow direction of the permeated agent can be changed by changing the direction of the current.

[0061] In one embodiment, Figure 1 and Figure 2 As shown, the conductive layer 2 further includes a backing layer 4 and a plurality of connectors 5. The backing layer 4 is used to cover the plurality of electrodes, and the backing layer 4 is an insulating material, which can effectively prevent the conductive electrode area 201 from being exposed to the outside. The plurality of connectors 5 are used to electrically connect the power source 1 and the plurality of electrodes, respectively, and each of the plurality of connectors 5 is at least partially disposed in the backing layer 4.

[0062] In one embodiment, the resistance of the first dielectric layer 203 is between 1KΩ and 20KΩ, and the resistance of the second dielectric layer 301 is 10% to 80% of the resistance of the first dielectric layer 203. The first dielectric layer 203 and the second dielectric layer 301 can divide the current intensity passing through the drug delivery area.

[0063] The first dielectric layer 203 and the second dielectric layer 301 can be an integral structure or a split structure. That is, the conductive layer 2 and the drug-carrying layer 3 can be integrally formed or independent of each other. In one embodiment, the first dielectric layer 203 and the second dielectric layer 301 are split structures, and the iontophoresis drug delivery device includes a plurality of drug-carrying layers 3 (e.g., M), and each second dielectric layer 301 in the plurality of drug-carrying layers 3 can cover the drug delivery area in the form of vertical stacking, or horizontal arrangement, or a combination of vertical stacking and horizontal arrangement. Among them, each second dielectric layer 301 can include the same or different drugs to be infiltrated, so that in the same drug delivery procedure, it is possible to achieve simultaneous electro-permeation of different drug delivery areas (when vertically stacked); or simultaneous electro-permeation of different drugs to be infiltrated in a certain drug delivery area (when horizontally arranged).

[0064] In one embodiment, the pharmaceutical agent to be infiltrated has polarity and a molecular weight of less than 5000 Daltons, and may include a combination of one or more of β-nicotinamide mononucleotide, glutathione, tranexamic acid, nicotine, analgesics, anesthetics, antibiotics, insulin, and trace elements required by the human body (such as vitamins, calcium, iron, etc.).

[0065] In one embodiment, the filling material may include a combination of one or more of a gel material, a paste material, and a liquid material. The gel material may include a combination of one or more of polyethylene glycol, polyvinyl alcohol, polyhydroxyethyl methacrylate, polyacrylic acid, polymethacrylic acid, gelatin, and alginic acid, etc., which have a porous network structure. The paste material may be grease, etc., and the liquid material may be water or alcohol, etc. In particular, the pores in the porous network structure contain a material that can dissolve a solvent for the drug to be infiltrated.

[0066] In one embodiment, Figure 5 As shown, the implementation method steps include:

[0067] Step 601, sequentially covering the drug-administered area with at least one second medium layer 301 and a first medium layer 203;

[0068] Step 602, energizing the first dielectric layer 203 through a power source, so that the first dielectric layer 203 obtains electric potential energy under the action of the current;

[0069] Step 603: The active agent in the second dielectric layer 301 moves in a directional manner under the action of the electric potential energy and electro-permeates into the drug-administered area.

[0070] In one embodiment, a protective layer is provided between the conductive layer 2 and the drug-carrying layer 3; preferably, the flat surface of the protective layer can cover the horizontal planes of the first dielectric layer 203 and the second dielectric layer 301, so that the first dielectric layer 203 and the second dielectric layer 301 do not penetrate each other before use. The conductive layer 2 and the drug-carrying layer 3 can be formed as one piece, and before formal use, the protective layer between the two is removed in a specific manner, so that conductivity can be generated between the first dielectric layer 203 and the second dielectric layer 301. Note: The specific method here can be physical (such as manually removing the isolation film, etc.), or other methods such as chemical separation using a material with separation properties; in particular, the conductive layer 2 and the drug-carrying layer 3 can be split structures. In other words, the drug-carrying layer 3 can be independent of the conductive layer 2, and when in use, they can be connected to each other by adhesion, magnetism or other methods. Specifically, as Figure 3 As shown, a peeling film is provided between the first medium layer 203 and the second medium layer 301 as a protective layer. The two peeling films are torn off separately before use and overlapped for use; another peeling film is provided on the side of the second medium layer 301 that contacts the medicated area. The peeling film is torn off before use so that the second medium layer 301 covers and fits the medicated area.

[0071] The following describes in detail a method for using the device of the present application by removing physical protection, the method comprising the following steps:

[0072] Step 701, providing a drug-carrying layer 3, the drug-carrying layer 3 comprising a second dielectric layer 301, wherein the top and bottom of each second dielectric layer 301 are respectively covered with a first stripping film 303 and a second stripping film 304, wherein each second dielectric layer 301 comprises a filling material and a drug to be infiltrated, and each second dielectric layer 301 is provided with at least one spacer 302 for dividing the second dielectric layer 301 into independent areas, and the resistance of the spacer 302 is greater than the resistance of the second dielectric layer 301;

[0073] Next, the first peeling film 303 and the second peeling film 304 at the top and bottom of one or more second medium layers 301 are removed, and each second medium layer 301 covers the drug-administered area.

[0074] Step 702, providing a conductive layer 2, the conductive layer 2 comprising a first dielectric layer 203, a conductive electrode region 201 located on the top of the first dielectric layer 203 and a third peeling film 204 located on the bottom of the first dielectric layer 203, wherein each first dielectric layer 203 comprises a filling material, and the resistance of the first dielectric layer 203 is greater than the resistance of the second dielectric layer 301.

[0075] Then, the third release film 204 in the conductive layer 2 is removed, and the first dielectric layer 203 is attached to the second dielectric layer 301 .

[0076] Step 703, electrically connecting the conductive electrode area 201 to the power source 1, and the power source 1 generates the electricity required to penetrate the drug to be penetrated into the administration area.

[0077] The market application scenarios of the conductive layer 2 and the drug-carrying layer 3 being used independently are huge, because the second dielectric layer can contain different drugs to be infiltrated to achieve different cosmetic, medical or other application needs. The first dielectric layer 203 can be reused in different scenarios, which greatly reduces consumables and is more convenient for market promotion.

[0078] The present application divides the dielectric layer in the general iontophoresis drug delivery into an upper and lower two-layer structure; the first dielectric layer 203: a dielectric layer with a certain resistance range covers the bottom of multiple conductive electrodes separated by the electrode spacing area 202, and uses the resistance difference between the dielectric layer and the skin organ to shunt the current intensity passing through the skin. Specifically, stratifying the current means that when the output current is constant, the current will actively distribute the current intensity passing through the skin according to the skin resistance, so as to achieve the effect of active safety. The second dielectric layer 301: a dielectric layer with a certain resistance range containing the drug to be penetrated and the spacing area 302, which is electrically connected to the first dielectric layer 203. It can reduce the shunting effect of the electromotive force energy of the drug to be penetrated and improve the transdermal efficiency. The first dielectric layer 203 and the second dielectric layer 301 can be an integrated structure or a split structure. In practical applications, the split structure is more conducive to commercialization.

[0079] Generally speaking, most of the medium layers on the market contain the drug to be infiltrated in an integrated manner, which is essentially different from the separate application of the second medium layer 301 containing the drug to be infiltrated independently and the first medium layer 203 without medicinal effect in the present invention.

[0080] The following experimental data will show the difference in the effects of the two. Both use vitamin C (VC) as the drug to be infiltrated, and the medium layer is filled with gel material. The existing technical solution adopts the technical solution of the integrated medium layer, and the new technical solution adopts the technical solution of the present invention. Under the premise of ensuring safety, the comparison of the effects of the two is shown in the following table:

[0081]

[0082] It can be seen that the skin penetration amount of the new technology solution is significantly higher than that of the existing technology solution and the efficiency is also higher. Within the same penetration time setting, the skin penetration amount of VC of the new technology solution is about 3 times that of the existing technology solution, and the penetration rate is about 3.8 times that of the existing technology solution. This has a very significant technical effect in the field of transdermal drug delivery.

[0083] It should be noted that in the claims and description of this patent, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, the elements defined by the sentence "including one" do not exclude the existence of other identical elements in the process, method, article or device including the elements.

[0084] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference individually. In addition, it should be understood that after reading the above teaching content of this application, those skilled in the art can make various changes or modifications to this application, and these equivalent forms also fall within the scope defined by the claims attached to this application.

[0085] In some cases, the actions or steps described in the claims may be performed in a different order than in the embodiments and still achieve the desired results. In addition, the processes depicted in the drawings do not necessarily require the specific order or sequential order shown to achieve the desired results. In some embodiments, multitasking and parallel processing are also possible or may be advantageous.

Claims

1. An iontophoresis drug delivery method, characterized in that: Under the action of electric current, the active agent in the second medium layer is electrically infiltrated into the drug-administered area through the first medium layer, and the active agent in the second medium layer is restricted from diffusing toward the first medium layer, thereby improving the efficiency of the active agent directional penetration into the drug-administered area.

2. The iontophoresis drug delivery method according to claim 1, characterized in that: The first medium layer and the second medium layer have resistances respectively, and can divide the current intensity passing through the drug-administered area.

3. The iontophoresis drug delivery method according to claim 1, characterized in that: The implementation steps include: S1. Covering the drug-administered area with at least one second medium layer and a first medium layer in sequence; S2. energizing the first dielectric layer through a power source so that the first dielectric layer obtains electric potential energy under the action of the current; S3. The active agent in the second medium layer moves in a directional manner under the action of the electric potential energy and electrically penetrates into the drug-administered area.

4. The iontophoresis drug delivery method according to claim 1, characterized in that: The first dielectric layer covers the second dielectric layer, and the first dielectric layer and the second dielectric layer are electrically conductive.

5. The iontophoresis drug delivery method according to claim 1, characterized in that: At least one spacer is arranged in the second medium layer, and the spacer can increase the content of the active agent in the second medium layer that electrically permeates into the drug-administered region.

6. An iontophoresis drug delivery device, characterized in that: The iontophoresis drug delivery method according to any one of claims 1 to 5 is adopted, further comprising: a conductive layer, a drug-carrying layer; The conductive layer includes a conductive electrode area and a first dielectric layer; the drug-carrying layer includes a second dielectric layer; The drug-carrying layer is disposed below the conductive layer; The conductive electrode region is disposed above the first dielectric layer; The second dielectric layer is disposed below the first dielectric layer.

7. The iontophoresis drug delivery device according to claim 6, characterized in that: The conductive electrode region and the first dielectric layer are formed integrally.

8. The iontophoresis drug delivery device according to claim 6, characterized in that: A protective layer is provided between the conductive layer and the drug-carrying layer.

9. The iontophoresis drug delivery device according to claim 6, characterized in that: The drug loading layer can be independent of the electronically conductive layer.

10. The iontophoresis drug delivery device according to claim 6, characterized in that: The conductive layer can be electrically connected to M mutually independent drug-carrying layers, wherein M≥1.

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