A non-contact iontophoretic transdermal drug delivery system and method

Abstract

The present invention provides a non-contact ion transdermal drug delivery system and method, belonging to the technical field of transdermal drug delivery. The system includes an extraction unit and an ion regulation unit; the extraction unit includes a high-voltage power supply, an extraction chamber, and electrodes; the electrodes are connected to the high-voltage power supply and are vertically arranged inside the extraction chamber, and the extraction chamber includes an extraction area, a conical connection area, and a microporous area with microporous channels arranged in sequence from top to bottom; the ion regulation unit includes a stepped electric field chamber, an ion regulation module, and a guiding power supply; the ion regulation module includes at least two groups of coaxial and vertically spaced annular electrodes. The method includes: placing a drug and a solvent in the extraction chamber, generating electrohydrodynamics under the action of a direct current high voltage, extracting drug active molecules and converting them into drug active ions; entering the stepped electric field chamber to generate drug active ion clusters and penetrate to the area to be administered. The present invention develops a transdermal drug delivery system and method that is contactless, free of exogenous contamination, in-situ extraction, has high utilization rate and good penetration.

Description

Technical Field

[0001] The present invention belongs to the technical field of transdermal drug delivery, and particularly relates to a non-contact iontophoresis drug delivery system and method. Background Art

[0002] Transdermal drug delivery is an important drug delivery route, which can provide continuous and stable drug release, avoid the first-pass effect, and improve the bioavailability of drugs; transdermal drug delivery is widely used in the fields of treating chronic diseases, controlling pain, and topical application. At present, the research on transdermal drug delivery mainly focuses on optimizing the transdermal absorption system, improving drug penetration, and enhancing skin biocompatibility. However, this field still faces some challenges; for example, how to effectively break through the natural barrier of the skin under non-invasive conditions to achieve efficient drug delivery.

[0003] Iontophoresis is a physical process in which ion flow diffuses directionally in a medium driven by an electric field force. The external electric field force can be used to enhance the transdermal rate of drugs through the membrane and achieve efficient drug delivery.

[0004] However, the existing iontophoresis drug delivery technology still has many limitations in practical applications. For example, it relies on high current intensity to drive drugs through the skin, which may cause adverse reactions such as skin polarization, erythema, or burns, and has low drug utilization rate, poor penetrability, and the transdermal efficiency needs to be improved. In addition, traditional iontophoresis technology usually requires the drug itself to be in ionic form and needs to be in contact with the skin for a long time, which further limits its application scope. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide a non-contact iontophoresis drug delivery system and method, aiming to solve at least one technical problem in the background art.

[0006] The present invention is implemented as follows:

[0007] In a first aspect of the present invention, a non-contact iontophoresis drug delivery system is provided, which includes an extraction unit and an ion regulation unit;

[0008] The extraction unit includes:

[0009] A high-voltage power supply for providing the electrohydrodynamic required for extracting drug active molecules;

[0010] An extraction chamber for separating the active molecules in the drug and converting the drug active molecules into drug active ions at the front end of the microporous area of the extraction chamber;

[0011] An electrode electrically connected to the high-voltage power supply and vertically disposed inside the extraction chamber;

[0012] The ion regulation unit includes:

[0013] A stepped electric field chamber, which is located below the extraction chamber and is connected to the extraction chamber;

[0014] An ion regulation module, which is built into the stepped electric field chamber and forms a stepped electric field for forming drug active ion clusters from drug active ions. The ion regulation module is non-contact with the skin of the area to be administered;

[0015] A guiding power supply, which powers the ion regulation module;

[0016] Wherein, the ion regulation module includes at least two groups of coaxial and vertically spaced annular electrodes;

[0017] Preferably, the extraction chamber includes an extraction area, a microporous area with microporous channels inside, and a conical connection area connecting the extraction area and the microporous area. The electrode is inserted from the extraction area and extends deep into the microporous area; the electrode is electrically connected to a high-voltage power supply; the pore diameter of the microporous channel is 5μm to 500μm, the length of the microporous channel is 1mm to 30mm, and the shape is cylindrical or frustum-conical;

[0018] Preferably, a heating element and a vibration device are arranged outside the extraction area;

[0019] The heating element heats the inside of the extraction area;

[0020] The vibration device provides mechanical vibration inside the extraction area.

[0021] Preferably, each group of annular electrodes is electrically connected to the guiding power supply, and the guiding power supply outputs different magnitudes of DC voltages to each group of annular electrodes. The DC voltages increase sequentially from top to bottom to form a stepped electric field, and the range of the DC voltage is 10V to 50V or -50V to -10V.

[0022] Preferably, inside the stepped electric field chamber, the annular electrodes form a through hole in the middle, and the pore diameter of the through hole gradually increases from top to bottom.

[0023] Preferably, the high-voltage power supply outputs continuous DC voltage or discontinuous DC voltage to generate electrohydrodynamics; the minimum value of the DC voltage period output by the high-voltage power supply is 1μs, the duty cycle is 1% to 100%, and the magnitude is -5kV to +5kV.

[0024] Preferably, the material of the electrode is selected from at least one of platinum, gold, graphite, glassy carbon, titanium, stainless steel, silicon nitride, titanium nitride, and ceramic;

[0025] The material of the extraction chamber is selected from at least one of polytetrafluoroethylene, polyether ether ketone, fluororubber, polyphenylene sulfide, polyethylene, and glass.

[0026] In the second aspect of the present invention, a non-contact iontophoresis transdermal drug delivery method is provided, which uses the above-mentioned non-contact iontophoresis transdermal drug delivery system; the transdermal drug delivery system is placed above the area to be administered; the transdermal drug delivery method includes the following steps:

[0027] Provide a drug and a solvent;

[0028] Place the drug and the solvent in an extraction chamber, and submerge the drug in the solvent;

[0029] A high-voltage power supply applies a DC voltage to the solvent in the extraction chamber through electrodes to generate electrohydrodynamics, and the electrohydrodynamics passes through the microscopic gaps of the drug to extract the active molecules in the drug; after flowing through the microchannel, the solvent is atomized and removed, and the drug active molecules are converted into drug active ions;

[0030] The drug active ions enter the stepped electric field chamber, and the ion regulation module outputs multiple sets of stepped DC voltages of different magnitudes, so that a stepped electric field is formed around the drug active ions to generate drug active ion clusters;

[0031] The drug active ion clusters penetrate into the skin of the area to be administered.

[0032] Preferably, the form of the drug is solid, liquid or paste; the source of the drug is traditional Chinese medicine or finished medicine in different dosage forms;

[0033] The solvent is selected from at least one of water, ethanol or propylene glycol.

[0034] Preferably, the distance between the ion regulation module and the skin of the area to be administered is 1 cm to 8 cm.

[0035] Compared with the prior art, the present invention has the following beneficial effects:

[0036] 1. The present invention uses high-voltage electrohydrodynamics to in-situ extract drug active molecules + stepped electric field to generate drug active ion clusters, so that the effective components in the drug are efficiently precipitated, and can penetrate into the area to be administered in a non-contact manner, avoiding damage to the human skin, and developing a transdermal drug delivery device and method with no contact, no exogenous pollution, in-situ extraction, higher utilization rate and better penetrability.

[0037] 2. The present invention provides a DC high voltage for the drug and the solvent through a high-voltage power supply to generate electrohydrodynamics, and the electrohydrodynamics passes through the molecular or tissue gaps, supplemented by heating and vibration, to efficiently extract the active molecules in the drug; then the electrohydrodynamics containing the drug active molecules flows through the microchannel and the solvent is atomized and removed, and the drug active molecules are converted into an ionic state; by using this soft ionization technology, the neutral molecules in the drug active components can be converted into ions without any damage to the active molecules, so as to realize transdermal drug delivery after ionization of the drug active components, which has a certain universality.

[0038] 3. The present invention provides a stepped electric field chamber below the extraction chamber. By applying a stepped DC voltage to several groups of annular electrodes, a stepped electric field is formed around the drug active ions, generating drug active ion clusters. The stepped electric field is used to control the velocity and size of the drug active ion clusters and improve their transdermal penetration rate. The drug active ions can effectively penetrate the skin and enter the blood circulation system to achieve the purpose of drug administration.

[0039] 4. The method of the present invention does not use any harmful reagents, can perform in-situ extraction of drugs, and does not require complex pretreatment or exogenous reagent assistance, ensuring that the drug active molecules maintain their natural active state during the extraction process. This in-situ extraction method not only maximally retains the effective components of the drug but also significantly improves the utilization rate of the drug, providing a more efficient and safer solution for transdermal drug delivery. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 is a schematic structural diagram of the ion transdermal drug delivery system of the present invention;

[0041] Figure 2 is a schematic structural diagram of the simulation experimental device of the ion transdermal drug delivery system in Example 2 of the present invention;

[0042] Figure 3 is the first mass spectrum of the Coptis chinensis active ions extracted in Example 2 of the present invention;

[0043] Figure 4 is the second mass spectrum of the Coptis chinensis active ions extracted in Example 2 of the present invention;

[0044] Figure 5 is the UV absorption diagram of the normal saline in the diffusion cell before and after the transdermal experiment in Example 2;

[0045] Figure 6 is the comparison diagram of the mass spectrometry signal intensity of berberine after different treatments in Example 3;

[0046] Figure 7 is the comparison diagram of the mass spectrometry signal intensity of berberine after different treatments in Example 4;

[0047] Figure 8 is the change diagram of the current magnitude with time in Example 4;

[0048] Figure 9 is the UV absorption diagram of the normal saline in the diffusion cell before and after the transdermal experiment in Example 5;

[0049] Figure 10 is the UV absorption diagram of the normal saline in the diffusion cell before and after the transdermal experiment in Example 6;

[0050] Figure 11It is the ultraviolet absorption graph of the physiological saline in the diffusion cell before and after the transdermal experiment in Example 7.

[0051] Illustration: 1 - extraction area, 2 - heating element, 3 - electrode, 4 - vibration device, 5 - conical connection area, 6 - microporous area, 7 - stepped electric field chamber, 8 - ion regulation module, 9 - through hole, 10 - high - voltage power supply, 11 - auxiliary power supply, 12 - guiding power supply, 13 - diffusion cell, 14 - magnetic stirrer, 15 - artificial skin, 16 - fixture, 17 - cover. Detailed implementation manners

[0052] In order to make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the following further elaborates on the present invention in conjunction with embodiments. It should be understood that the specific implementation cases described herein are only used to explain the present invention and are not used to limit the present invention.

[0053] Example 1

[0054] As Figure 1 shown, a non - contact ion transdermal drug delivery system, which includes an extraction unit and an ion regulation unit;

[0055] The extraction unit includes: a high - voltage power supply 10 for providing the electro - fluid required to extract drug active molecules; an extraction chamber for separating the active molecules in the drug; an electrode 3, which is electrically connected to the high - voltage power supply 10 and is vertically arranged inside the extraction chamber;

[0056] The ion regulation unit includes: a stepped electric field chamber 7, which is located below the extraction chamber and is connected to the extraction chamber; an ion regulation module 8, which is built into the stepped electric field chamber 7 and forms a stepped electric field for forming drug active ion clusters from drug active ions; a guiding power supply 12 for supplying power to the ion regulation module 8.

[0057] The extraction chamber includes an extraction area 1 with an external heating element 2 and a vibration device 4, a microporous area 6 with internal microporous channels, and a conical connection area 5 connecting the extraction area 1 and the microporous area 6; the pore diameter of the microporous channels is 5μm - 500μm, the length of the microporous channels is 1mm - 30mm, and the shape is cylindrical or truncated conical; the material of the extraction chamber is a highly chemically resistant inert material, such as polytetrafluoroethylene, polyether ether ketone, fluororubber, polyphenylene sulfide, polyethylene, glass and other materials, which can prevent contamination of the drug delivery system.

[0058] The electrode 3 is vertically arranged inside the extraction chamber, inserted from the extraction area 1 and extending into the microporous area 6; the electrode 3 is electrically connected to the high - voltage power supply 10; to ensure that no chemical reaction occurs with the extracted drug, solvent, etc. under the condition of energization, the material of the electrode 3 is adjusted according to actual needs, such as platinum, gold, graphite, glassy carbon, titanium, stainless steel, silicon nitride, titanium nitride, ceramic and other materials.

[0059] The high-voltage power supply 10 outputs continuous DC voltage or discontinuous DC voltage to generate electrofluids. To ensure efficient in-situ extraction of drugs, the minimum period of the DC voltage output by the high-voltage power supply is 1 μs, the duty cycle is 1% - 100%, and the magnitude is -5 kV to +5 kV. The electrofluids pass through the microscopic gaps of the drug through the electrode 3, and with the assistance of the heating element 2 and the vibrating device 4, the active molecules in the drug are effectively separated.

[0060] In a specific implementation, the heating element 2 and the vibrating device 4 are respectively electrically connected to the auxiliary power supply 11. The heating element 2 heats the inside of the extraction area 1, and its controllable temperature range is room temperature RT to 100 °C. The specific temperature setting can be adjusted according to the drug and the solvent. The vibrating device 4 provides high-frequency mechanical vibration inside the extraction area 1, and the vibrating device 4 can adopt a mechanical vibration device or an ultrasonic vibration device. In the present invention, the heating element 2 and the vibrating device 4 apply energy to the extraction area 1, and the drug sample in the extraction area 1 is subjected to the dual effects of heat energy and high-frequency vibration. Among them, the heat energy raises the temperature and enhances the molecular thermal motion, while the high-frequency vibration promotes the molecular motion and forms a cavitation effect. The synergistic effect of the two not only accelerates the extraction process, but also improves the extraction rate and purity of the target component, making the entire extraction process more efficient and environmentally friendly.

[0061] The stepped electric field chamber 7 is internally provided with an ion adjustment module 8. The ion adjustment module 8 includes at least two groups of coaxial and vertically spaced annular electrodes. Each group of annular electrodes is electrically connected to the guiding power supply 12. The guiding power supply 12 applies a positive voltage or a negative voltage to each group of annular electrodes respectively. Each group of annular electrodes outputs DC voltages of different magnitudes, and the DC voltage range is -50 V to +50 V, specifically 10 V to 50 V or -50 V to -10 V. Along the direction from top to bottom, the DC voltage values output by each group of annular electrodes increase to form a stepped electric field. The positive and negative of the voltage are set according to the characteristics of the active ions in the drug. If the delivered target component is a positive ion, a positive voltage is applied, and vice versa. When a negative voltage is applied, the increase in the DC voltage value means an increase in the absolute value of the output DC voltage. A through hole 9 is formed in the middle of the annular electrode, and the aperture of the through hole 9 gradually increases from top to bottom.

[0062] In a specific implementation, the active molecules of the drug are dissolved in the solvent, converted into drug active ions in the extraction chamber, and then enter the stepped electric field chamber 7, moving downward along the through hole 9. As the ion adjustment module 8 outputs multiple groups of stepped DC voltages of different magnitudes inside the stepped electric field chamber 7, a stepped electric field is formed around the drug active ions. The stepped electric field focuses the drug active ions to form drug active ion clusters, controls the speed and size of the drug active ion clusters, and improves their transdermal permeability to achieve the purpose of drug delivery.

[0063] In a specific implementation, the drug and the solvent are placed in the extraction chamber, and the solvent submerges the drug. Among them, the forms of the drug include solid, liquid, and paste. The sources of the drug are mainly traditional Chinese medicines or finished medicines in different dosage forms, all of which can be placed in the extraction chamber for drug administration. To ensure the safety of the skin at the medication site, reagents harmless to the human body are preferentially selected as solvents, such as water, ethanol, and propylene glycol.

[0064] Example 2

[0065] Based on the non-contact iontophoretic transdermal drug delivery system shown in Example 1, a transdermal experimental device is built in this example for simulation experiments, as Figure 2 shown.

[0066] The artificial skin 15 is placed below the stepped electric field chamber 7, and the artificial skin 15 is 1 cm to 8 cm away from the end of the stepped electric field chamber 7 (set to 5 cm in this example). A diffusion cell 13 is arranged below the artificial skin 15. A magnetic stir bar 14 is placed inside the diffusion cell 13. Then, the artificial skin 15 and the diffusion cell 13 are fixed through a cover body 17 arranged on the outer edge and a horseshoe-shaped fixture 16. The diffusion cell 13 is filled with physiological saline to simulate human subcutaneous tissue fluid, and the diffusion cell 13 is placed in a constant temperature device. The temperature inside the diffusion cell 13 is set to 36°C; the artificial skin completely covers the diffusion cell 13.

[0067] In this example, the electrode 3 uses a graphite electrode, the pore diameter of the microchannel is set to 200 μm, and the length of the microchannel is set to 15 mm; the ion regulation module 8 uses 6 groups of annular electrodes; the drug uses the traditional Chinese medicine Coptis chinensis, and the solvent uses ethanol. The main active ingredient in Coptis chinensis is berberine, which can be used to treat ulcers caused by bacterial infections and dengue fever.

[0068] The non-contact iontophoretic transdermal drug delivery method in this example includes the following steps:

[0069] S1. Mix the Coptis chinensis powder and ethanol and heat them to 45°C to dissolve the berberine in Coptis chinensis, and then add an equal amount of ultrapure water to form a Coptis chinensis solution with a concentration of 100 ppm, and place it in the extraction chamber;

[0070] S2. Start the high-voltage power supply, apply a DC voltage to the Coptis chinensis solution through the electrode to generate an electrohydrodynamic, and the DC voltage parameters include: the magnitude of the DC voltage is +5 kV, the period is 2 μs, and the duty cycle is 50%; at the same time, start the heating element and the vibration device. The electrohydrodynamic passes through the microscopic gaps of Coptis chinensis, and with the assistance of the heating element and the vibration device, the active molecules (such as berberine) are extracted; the electrohydrodynamic containing the active molecules moves downward through the microchannel region, atomizes and removes the solvent after flowing through the microchannel, and the active molecules are converted into active ions; the active ions generated in this step are detected by a mass spectrometer, and the first-level mass spectrum and the second-level mass spectrum are respectively as Figure 3 and Figure 4 shown;

[0071] S3. Start the guiding power supply and output DC voltages of different magnitudes to each group of annular electrodes, with the range being +10V to +50V. The voltage value increases from top to bottom, and the voltage difference between two adjacent annular electrodes is basically the same. Thus, a stepped electric field is formed around the drug active ions, and the active ions are focused by the stepped electric field to form active ion clusters.

[0072] S4. The active ion clusters penetrate into the artificial skin and enter the diffusion cell below.

[0073] Figure 5 are the ultraviolet absorption graphs of the normal saline in the diffusion cell before and after the transdermal experiment (the experimental time is 120 min). It can be seen from Figure 5 that after the transdermal experiment, the berberine of the drug effectively penetrates through the artificial skin and enters the normal saline.

[0074] Example 3

[0075] On the basis of Example 2, adjust the heating and vibration operations in step S2, set up a control group, and keep other steps the same. The grouping is as follows:

[0076] Group A has no heating and no vibration;

[0077] Group B has only heating and no vibration;

[0078] Group C has no heating and only vibration;

[0079] Group D has heating and vibration, that is, Example 2.

[0080] Test the mass spectrometry signal intensity of berberine in the normal saline in the diffusion cell under the above different treatments. As Figure 6 shown, it can be seen that Group D > Group C > Group B > Group A. From this, it can be seen that the content of berberine in the normal saline is higher after heating and vibration, indicating that heating and vibration promote the precipitation of berberine and its transdermal permeability.

[0081] Example 4

[0082] On the basis of Example 2, adjust the distribution of the electric field and through holes in step S3, and keep other steps the same. The grouping is as follows:

[0083] Group A has no stepped electric field applied;

[0084] Group B has a low-voltage electric field applied, that is, output +10V voltage to each group of annular electrodes;

[0085] Group C has a high-voltage electric field applied, that is, output +50V voltage to each group of annular electrodes;

[0086] Group D is a stepped electric field with a decreasing applied voltage, that is, a DC voltage of +10V to +50V is output to each group of annular electrodes, and the voltage value decreases from top to bottom;

[0087] Group E is a stepped electric field with an increasing applied voltage. At the same time, the aperture of the through-hole 9 in each group of annular electrodes remains unchanged, and its aperture is the same as that of the lowermost through-hole 9 in Example 2;

[0088] Group F is a stepped electric field with an increasing applied voltage. At the same time, the aperture of the through-hole 9 in each group of annular electrodes gradually decreases from top to bottom;

[0089] Group G is a stepped electric field with an increasing applied voltage. At the same time, the aperture of the through-hole 9 in each group of annular electrodes gradually increases from top to bottom, that is, Example 2.

[0090] The mass spectrometry signal intensity of berberine in normal saline in each of the above-mentioned diffusion cells was measured and compared with that before the transdermal experiment, as Figure 7 shown. It can be seen from Figure 7 that under different electric field patterns, the comparison results of the mass spectrometry signal intensity of berberine are: Group G > Group D > Group C > Group B > Group A. After applying a stepped electric field with an increasing applied voltage, the content of berberine in normal saline is the highest. After applying a stepped electric field with a decreasing applied voltage, a high-voltage electric field, a low-power electric field, and a non-stepped electric field, the content of berberine in normal saline decreases in turn, indicating that applying a stepped electric field with an increasing applied voltage improves the transdermal permeability of the drug and achieves the purpose of efficient drug delivery. In addition, it can be seen from Figure 7 that under different through-hole aperture distributions, the comparison results of the mass spectrometry signal intensity of berberine are: Group G > Group F > Group E. The influence of the through-hole aperture distribution on the transdermal permeability of the drug is as follows: as the through-hole gradually becomes larger, the distance between individual active ion clusters gradually becomes larger, and the distribution of active ion clusters gradually becomes uniform, making it difficult for active ion clusters to aggregate and increase. Moreover, due to the surface effect, the drug micro-droplets will spontaneously evaporate the residual solvent, making the active ion clusters further smaller. As the aperture gradually becomes larger, the residual solvent is removed faster, and the active ion clusters become smaller and smaller. As a result, the transdermal permeability is higher when they reach the artificial skin.

[0091] During the operation of applying the stepped electric field, the change of the current of drug ions with time during the drug delivery process was detected, as Figure 8 shown. It can be seen from Figure 8 that during the operation of the transdermal drug delivery system, the ionic current hardly changes with time, and the value does not exceed 0.15 microamps. It is safe and reliable and will not cause harm to human skin.

[0092] Example 5

[0093] On the basis of Example 2, the drug in step S1 was modified.

[0094] The non-contact iontophoresis drug delivery method in this example includes the following steps:

[0095] S1. Mix nicotinamide with a solution of ethanol and water (by volume, ethanol: water = 1:1), heat the mixture to 45 °C, and prepare a nicotinamide solution with a concentration of 100 ppm. Place the solution in the extraction chamber.

[0096] S2. Start the high-voltage power supply, apply a DC voltage to the nicotinamide solution through the electrodes to generate electrohydrodynamics. The DC voltage parameters include: the magnitude of the DC voltage is +5 kV, the period is 2 μs, and the duty cycle is 50%. At the same time, start the heating element and the vibration device. The electrohydrodynamics containing the active ingredient (nicotinamide) moves downward through the micro-porous region, atomizes and removes the solvent after flowing through the micro-porous channel, and the active ingredient is converted into active ions.

[0097] S3. Start the guiding power supply, output stepped DC voltages with different magnitudes to each group of annular electrodes, with a range of +10 V to +50 V, form a stepped electric field around the drug active ions, and use the stepped electric field to focus the active ions to form active ion clusters.

[0098] S4. The active ion clusters penetrate into the artificial skin and enter the diffusion cell below.

[0099] Figure 9 This is the UV absorption graph of the physiological saline in the diffusion cell before and after the transdermal experiment (the experiment time is 10 min) in this example. It can be seen from Figure 9 that after the transdermal experiment, nicotinamide effectively penetrates through the artificial skin and enters the physiological saline.

[0100] Example 6

[0101] In this example, hyaluronic acid is used to replace nicotinamide in Example 5, and other steps and conditions are the same as those in Example 5.

[0102] Figure 10 This is the UV absorption graph of the physiological saline in the diffusion cell before and after the transdermal experiment (the experiment time is 10 min) in this example. It can be seen from Figure 10 that after the transdermal experiment, hyaluronic acid effectively penetrates through the artificial skin and enters the physiological saline.

[0103] Example 7

[0104] In this example, collagen is used to replace nicotinamide in Example 5, and other steps and conditions are the same as those in Example 5.

[0105] Figure 11 This is the UV absorption graph of the physiological saline in the diffusion cell before and after the transdermal experiment (the experiment time is 10 min) in this example. It can be seen from Figure 11 that after the transdermal experiment, collagen effectively penetrates through the artificial skin and enters the physiological saline.

[0106] The embodiments described above merely represent several implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent for the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these all fall within the protection scope of the present invention. Therefore, the protection scope of the patent for the present invention shall be subject to the appended claims.

Claims

1. A non-contact ion transdermal drug delivery system, characterized in that: The transdermal drug delivery system comprises an extraction unit and an ion adjustment unit; The extraction unit comprises: A high voltage power supply for providing the electric fluid required to extract the active molecules of the drug; An extraction chamber is used to separate active molecules from the drug and convert the drug active molecules into drug active ions at the front end of the extraction chamber; An electrode, which is electrically connected to the high voltage power supply and vertically arranged inside the extraction chamber; The ion adjustment unit comprises: A stepped electric field chamber, which is located below the extraction chamber and connected to the extraction chamber; An ion regulating module is built into the stepped electric field chamber and forms a stepped electric field, and is used to form drug-active ions into drug-active ion clusters, and the ion regulating module is in non-contact with the skin of the drug-administered area; A pilot power source, which supplies power to the ion adjustment module; Wherein, the ion adjustment module comprises at least two groups of coaxial annular electrodes spaced apart from each other; The extraction chamber comprises an extraction zone, a microporous zone with microporous channels therein, and a conical connection zone connecting the extraction zone and the microporous zone. The electrode is inserted from the extraction zone and penetrates into the microporous zone; the electrode is electrically connected to a high voltage power supply.

2. A non-contact ion transdermal drug delivery system according to claim 1, characterized in that: The pore size of the microporous channel is 5 μm to 500 μm, the length of the microporous channel is 1 mm to 30 mm, and the shape is cylindrical or truncated conical.

3. A non-contact ion transdermal drug delivery system according to claim 1, characterized in that: The extraction zone is externally provided with a heating element and a vibrating device; The heating element heats the interior of the extraction zone; The vibration device provides mechanical vibration inside the extraction area.

4. A non-contact ion transdermal drug delivery system according to claim 1, characterized in that: Each group of annular electrodes is connected to a guiding power supply, which outputs DC voltages of different magnitudes to each group of annular electrodes. The DC voltage increases from top to bottom to form a step electric field. The DC voltage range is 10V to 50V or -50V to -10V.

5. A non-contact ion transdermal drug delivery system according to claim 1, characterized in that: The annular electrode is in the stepped electric field chamber, with a through hole formed in the middle, and the aperture of the through hole increases gradually from top to bottom.

6. The non-contact ion transdermal drug delivery system according to claim 1, characterized in that: The high-voltage power supply outputs a continuous DC voltage or a discontinuous DC voltage; the DC voltage cycle output by the high-voltage power supply has a minimum value of 1μs, a duty cycle of 1% to 100%, and a magnitude of -5kV to +5kV.

7. The non-contact ion transdermal drug delivery system according to claim 1, characterized in that: The material of the electrode is selected from at least one of platinum, gold, graphite, glassy carbon, titanium, stainless steel, silicon nitride, titanium nitride, and ceramics; The material of the extraction chamber is selected from at least one of polytetrafluoroethylene, polyetheretherketone, fluororubber, polyphenylene sulfide, polyethylene and glass.

8. The non-contact ion transdermal drug delivery system according to claim 1, characterized in that: The method for using the ion transdermal drug delivery system comprises the following steps: providing drugs and solvents; placing the drug and the solvent in an extraction chamber, with the solvent submerging the drug; The high-voltage power supply applies a DC voltage to the solvent in the extraction chamber through electrodes to generate an electric fluid, which passes through the microscopic gaps in the drug to extract the active molecules of the drug; after flowing through the microporous channels, the solvent is atomized and the active molecules of the drug are converted into active ions of the drug; The drug-active ions enter the stepped electric field chamber, and the ion regulation module outputs multiple sets of stepped DC voltages of different sizes, so that a stepped electric field is formed around the drug-active ions, generating drug-active ion clusters.

9. A non-contact ion transdermal drug delivery system according to claim 8, characterized in that: The drug is in the form of solid, liquid or paste; the drug source is medicinal materials or finished drugs in different dosage forms; The solvent is selected from at least one of water, ethanol or propylene glycol.

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