CN111643447A

CN111643447A - Drug-loaded microneedle, drug-loaded microneedle patch, electrically controlled drug release microneedle system and preparation method of drug-loaded microneedle

Info

Publication number: CN111643447A
Application number: CN202010524703.XA
Authority: CN
Inventors: 胥玲玲; 杨圆; 赵超超
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-06-10
Filing date: 2020-06-10
Publication date: 2020-09-11
Anticipated expiration: 2040-06-10
Also published as: CN111643447B

Abstract

The invention discloses a drug-loaded microneedle, a drug-loaded microneedle patch, an electric control drug release microneedle system and a preparation method of the drug-loaded microneedle, belonging to the technical field of microneedle drug-loaded release, wherein the drug-loaded microneedle comprises: a microneedle substrate; at least one microneedle body formed on the microneedle substrate; the conductive polymer nano-doped body is doped in the microneedle body; and a microneedle drug doped in the conductive polymer nano-dopant; wherein at least one of the microneedle bodies is adapted to pierce the skin to deliver the conductive polymer nano-dopes into the skin, the conductive polymer nano-dopes being configured to release the microneedle drugs in response to an electrical stimulus emitted by the driving power supply means. The drug-loaded microneedle disclosed by the invention solves a plurality of technical problems of easy shedding of a coating, unsatisfactory drug release controllability, complex preparation, difficult control of microneedle size, poor skin adhesion and the like existing in a coating microneedle in the prior art.

Description

Drug-loaded microneedle, drug-loaded microneedle patch, electrically controlled drug release microneedle system and preparation method of drug-loaded microneedle

Technical Field

The invention relates to the technical field of microneedle drug-loaded release, in particular to a drug-loaded microneedle, a drug-loaded microneedle patch, an electric control drug-loaded release microneedle system and a preparation method of the drug-loaded microneedle.

Background

The micro-needle is a novel transdermal drug delivery system, when the drug is delivered, the micro-needle can pierce the stratum corneum of the skin, so that a micro-channel from the stratum corneum to the epidermis layer or the dermis shallow layer is opened for the delivery of the drug, and then the drug is absorbed by capillary vessels, and the drug active molecules reach the focus part of the human body along with the blood circulation to play a role in treatment. Compared with the traditional transdermal drug delivery system, the microneedle has the advantages of no pain feeling, autonomous drug application, accurate and rapid drug delivery, convenient carrying and use and the like because the microneedle can not touch the nerve endings of the dermis. The microneedle administration combines the advantages of both transdermal patch and subcutaneous injection, and avoids the disadvantages of both.

However, the release of the drug in the common microneedle drug delivery system is not controllable and cannot be adapted to the controlled release of the drug. In order to solve the problem, scientific research workers control the micro-needles to release the drugs in an electrical stimulation mode, namely, a metal layer is formed on the surface of the needle body of the micro-needle, and then a drug-loading conductive thin film layer is formed on the metal layer, so that the coating micro-needle is formed, and the drug-loading conductive thin film layer can release the drugs when being electrically stimulated.

In the process of implementing the embodiment of the invention, the inventor finds that at least the following defects exist in the background art:

1. the drug-carrying conductive film layer is formed on the surface of the needle body of the microneedle and is easy to peel off, so that part of the drug cannot be delivered into the skin, or the drug can be remained in the body after penetrating into the skin, and the drug administration effect is seriously influenced;

2. because the medicine-carrying conductive film layer is a medicine-carrying coating formed on the surface of the needle body of the microneedle, the medicine is easy to release in a large area at one time when receiving electric stimulation, the long-time multiple release of the medicine is difficult to be really and accurately controlled, the medicine-carrying conductive film layer cannot be suitable for a scene needing multiple times of medicine administration, and the controllability of the medicine release is not ideal;

3. when a microneedle body with a drug-carrying conductive thin film layer formed on the surface is prepared, a microneedle is usually prepared, then a metal layer is plated on the surface of the microneedle, and then electrochemical reaction is carried out to form the drug-carrying conductive thin film layer on the surface of the metal layer, so that the preparation method is complex and is not suitable for large-scale preparation;

4. because a plating layer needs to be formed on the surface of the prepared microneedle for many times, the size of the final microneedle is difficult to adjust and control;

5. because medicine carrying conducting film layer forms in the micropin outermost layer, and the secondary skin is the inert metal layer for the micropin needle body is complete stereoplasm, and skin laminating nature is not good enough.

Disclosure of Invention

The embodiment of the invention mainly aims to provide a drug-loaded microneedle, a drug-loaded microneedle patch, an electric control drug release microneedle system and a drug-loaded microneedle preparation method (a drug-loaded microneedle, a drug-loaded microneedle preparation method, a device using the drug-loaded microneedle, a device using the drug-loaded microneedle and a preparation method thereof) so as to solve at least one technical problem of the prior art that a coating of a coating microneedle is easy to fall off, the drug release controllability is not ideal, the preparation is complex, the microneedle size is not easy to control, and the skin adhesiveness is not good.

In order to achieve the above object, according to a first aspect of the present invention, there is provided a drug-loaded microneedle applied to an electrically controlled drug release microneedle system having a driving power supply device for supplying electric energy and controlling the electrically controlled drug release microneedle system to release a drug, the drug-loaded microneedle comprising: a microneedle substrate; at least one microneedle body formed on the microneedle substrate; a conductive polymer nano-dopant doped in the microneedle body; and a microneedle drug doped in the conductive polymer nano-dopant; wherein at least one of the microneedle bodies is adapted to pierce the skin to deliver the conductive polymer nano-dopant into the skin, the conductive polymer nano-dopant being configured to release the microneedle drug in response to an electrical stimulus from the driving power supply device.

According to a second aspect of the present invention, there is provided a drug-loaded microneedle patch comprising: a substrate; at least one of the drug-carrying microneedle, the microneedle substrate of at least one drug-carrying microneedle is arranged on the substrate.

According to a third aspect of the present invention, there is provided an electrically controlled drug-releasing microneedle system comprising: the drug-loaded microneedle or the drug-loaded microneedle patch described above; and the driving power supply device is configured to provide electric energy for the drug-carrying microneedle and control the drug-carrying microneedle to release microneedle drugs.

According to a fourth aspect of the present invention, there is provided a method for using an electrically controlled drug release microneedle system, which is suitable for the electrically controlled drug release microneedle system, the method comprising:

enabling at least one microneedle body of the drug-carrying microneedle to penetrate into the skin so as to send the conductive polymer nano-doped body doped with the microneedle body into the skin;

and a driving power supply device is used for supplying power to the drug-loaded micro-needle and controlling the conductive polymer nano-doped body doped with the micro-needle body to release the micro-needle drug into the skin.

According to a fifth aspect of the present invention, there is provided a method of preparing a drug-loaded microneedle, the method comprising:

preparing a conductive polymer nano-dopant doped with a microneedle drug;

mixing the conductive polymer nano-doped body with a liquid microneedle body material and then forming the mixture in a microneedle mould to form a microneedle body doped with the conductive polymer nano-doped body;

forming a microneedle substrate connected with the microneedle body on the microneedle mould;

drying and demoulding to obtain the solid drug-loaded microneedle.

According to a sixth aspect of the present invention, there is provided another method of preparing a drug-loaded microneedle, the method comprising:

preparing a high-molecular gel microneedle, wherein the high-molecular gel microneedle comprises a high-molecular gel microneedle substrate and at least one high-molecular gel microneedle needle body formed on the high-molecular gel microneedle substrate;

mixing the microneedle drug with the monomer solution of the conductive polymer to obtain a third mixed solution;

filling the third mixed solution into pores of the polymer gel microneedle body, and polymerizing the monomer of the conductive polymer in situ to form a conductive polymer nano-doped body doped with the microneedle drugs in the polymer gel microneedle body;

and drying the polymer gel microneedle doped with the conductive polymer nano-doped body to obtain the solid drug-loaded microneedle.

One or more technical solutions provided in the embodiments of the present invention have at least the following technical effects or advantages:

1. the drug-loaded microneedle provided by the application comprises a microneedle substrate, a microneedle body formed on the microneedle substrate, a conductive polymer nano-doped body doped in the microneedle body, and microneedle drugs doped in the conductive polymer nano-doped body, because the micro-needle medicament is doped in the conductive polymer nano-dopant, the conductive polymer nano-dopant doped with the micro-needle medicament is doped in the micro-needle body, namely, the nano-conductive polymer nano-dopant is embedded with the material of the micro-needle body in a melting way, thereby forming a complete micro-needle, but not only existing on the surface of the micro-needle body, and having no problem of plating layer peeling, when the micro-needle body is penetrated into the skin, the nano-conductive polymer nano-dopant doped in the micro-needle body can be completely carried into the skin, therefore, microneedle medicines doped in the conducting polymer nano-doped body are all released into the skin, the waste of the microneedle medicines does not exist, and the administration effect is effectively ensured. Thereby solving the technical problem that the plating layer of the plating layer micro-needle in the prior art is easy to fall off.

2. Because the micro-needle drugs are doped in the conductive polymer nano-dopant, the conductive polymer nano-dopant is doped in the micro-needle body, namely is uniformly embedded in the micro-needle body, when the driving power supply device provides electric energy when the drugs need to be released after the micro-needle body penetrates into the skin, the conductive polymer nano-dopant receives electrical stimulation, the conductive polymer nano-dopant close to the surface of the micro-needle body firstly releases the micro-needle drugs, the conductive polymer nano-dopant close to the middle part of the micro-needle body gradually migrates to the surface of the micro-needle body through the internal structure of the micro-needle body macromolecules after receiving the electrical stimulation to release the micro-needle drugs and then releases the micro-needle drugs, the hierarchical release of the micro-needle drugs is facilitated, the controllability of the micro-needle drugs released by the electrical stimulation is effectively improved, and because the plurality of conductive polymer nano-dopants are doped in the interior of the micro-needle body, the micro And part of the microneedle medicines can be rewrapped by the conductive polymer nano-doped body during the non-electric stimulation, so that the microneedle medicines can be more favorably controlled to be released for multiple times. Therefore, the drug-loaded microneedle provided by the embodiment of the application effectively solves the technical problem that the existing drug-loaded microneedle is difficult to control the release of the drug for a plurality of times for a long time, and is suitable for the situation that the drug needs to be administered for a plurality of times.

3. The conductive polymer nano-doped body doped with the microneedle drugs and the microneedle needle body material can be directly mixed and injected into a microneedle mould for forming or directly polymerized in situ in the macromolecular gel microneedle needle body to form the conductive polymer nano-doped body doped with the microneedle drugs, and the preparation method is simple and is easy for large-scale preparation. Thereby solving the technical problem that the preparation method of the coated microneedle in the prior art is complex and fussy.

4. Because the microneedle medicines are doped in the conductive polymer nano-doping body, and the conductive polymer nano-doping body is doped in the microneedle body and is embedded with the microneedle body in a melting way to form the complete microneedle body together, the size of the finally formed microneedle body can be adjusted by adjusting the size of the microneedle array groove of the microneedle mould, and the size is easier to control and adjust. Thereby solving the technical problem that the plated microneedle is difficult to adjust and control the size of the final microneedle due to the need of forming a metal layer and a conductive film layer in the prior art.

5. Because the microneedle medicines are doped in the conductive polymer nano-doped body, the conductive polymer nano-doped body is doped in the microneedle body, and the material of the microneedle body is selected from biocompatible materials, the microneedle body has good biocompatibility, and is favorable for being pierced into the skin to deliver the drugs to the skin. Meanwhile, the microneedle body does not need to be provided with an inert metal layer, a drug-loaded conductive thin film layer and other coating layers, and the high polymer material directly adopted by the microneedle body can absorb the body fluid swelling, so that the hardness is reduced, and the microneedle can be better attached to the surface of the skin. Effectively solves the technical problems of high hardness and poor attachment of the plated microneedle in the prior art.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention.

In the drawings:

fig. 1 is a schematic structural view of a drug-loaded microneedle according to some embodiments;

fig. 2 is a schematic structural diagram of a drug-loaded microneedle with a micro-pair electrode according to some embodiments;

fig. 3 is a schematic structural diagram of a drug-loaded microneedle patch according to some embodiments;

fig. 4 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system according to some embodiments;

fig. 5 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system having a first independent microneedle pair electrode and a second independent microneedle pair electrode, according to some embodiments;

fig. 6 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system with a first independent microneedle counter electrode, according to some embodiments;

fig. 7 is a functional block schematic diagram of an electrically controlled drug-releasing microneedle system according to some embodiments;

fig. 8 is a schematic flow diagram of a method of using an electrically controlled drug-releasing microneedle system, according to some embodiments;

fig. 9 is a schematic flow diagram of a method of drug-loaded microneedle preparation according to some embodiments;

FIG. 10 is a schematic flow chart diagram of some embodiments of step S10 in FIG. 9;

FIG. 11 is a schematic flow chart diagram of some embodiments of step S10 in FIG. 9;

fig. 12 is a flow diagram of a method of drug-loaded microneedle preparation according to some embodiments.

Detailed Description

It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.

It is noted that, unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

In the present invention, unless stated to the contrary, use of the directional terms "upper and lower" are generally directed to the orientation shown in the drawings, or to the vertical, or gravitational direction; likewise, for ease of understanding and description, "left and right" are generally to the left and right as shown in the drawings; "inner and outer" refer to the inner and outer relative to the profile of the respective member itself, but the above directional terms are not intended to limit the present invention.

In addition, the descriptions related to "first", "second", etc. in the present invention are only for descriptive purposes and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless specifically limited otherwise.

As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items. At least one of the expressions such as "when preceding a column of elements modifies the entire column of elements rather than modifying individual elements in the column.

In order to solve at least one technical problem of easy falling of a coating, unsatisfactory drug release controllability, complex preparation, difficult control of microneedle size and poor skin fit existing in a coated microneedle in the prior art, the application provides a drug-loaded microneedle, a drug-loaded microneedle patch, an electric control drug release microneedle system and a drug-loaded microneedle preparation method (a drug-loaded microneedle, a drug-loaded microneedle preparation method, a device using the drug-loaded microneedle, a device using the drug-loaded microneedle and a preparation method thereof).

The invention is further described below with reference to the accompanying drawings.

Example 1

The embodiment of the application provides a drug-carrying microneedle 100, the drug-carrying microneedle 100 is applied to an electrically controlled drug release microneedle system 300, and the electrically controlled drug release microneedle system 300 is provided with a driving power supply device 301 for providing electric energy and controlling the electrically controlled drug release microneedle system 300 to release drugs.

Fig. 1 is a schematic structural view of a drug-loaded microneedle according to some embodiments. Fig. 4 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system according to some embodiments.

Referring to fig. 1 and 4, the drug-loaded microneedle 100 includes a microneedle substrate 10, at least one microneedle body 20, a conductive polymer nano-dopant 30, and a microneedle drug.

The microneedle substrate 10 is mainly used for supporting a plurality of microneedle bodies 20, so that the microneedle bodies 20 are formed on the same surface of the microneedle substrate 10, and after the microneedle bodies 20 penetrate into the skin, the microneedle substrate 10 is usually located on the outer surface of the skin. The microneedle substrate 10 may also serve as a conductive medium for electrically communicating several microneedle bodies 20. The microneedle substrate 10 may be integrally formed with the microneedle body 20, or the microneedle body 20 and the microneedle substrate 10 may be sequentially formed.

At least one microneedle body 20 is formed on the microneedle substrate 10, and the microneedle body 20 may have a needle-like structure having a size of a micrometer scale. The same surface of the microneedle substrate 10 may be formed with a plurality of microneedle bodies 20 to form a microneedle array. The microneedle body 20 can overcome the stratum corneum barrier of the skin at a specific area of the skin and enter the active epidermis to a specific depth.

The conductive polymer nano-dopant 30 is doped in the microneedle body 20, that is, the conductive polymer nano-dopant 30 is embedded in the microneedle body 20 or formed in the microneedle body 20, which can also be understood as the conductive polymer nano-dopant 30 mixed in the microneedle body 20 to form a complete microneedle body together with the material of the microneedle body 20. The microneedle drug is doped in the conductive polymer nano-dopant 30, that is, the microneedle drug is embedded in the conductive polymer nano-dopant 30 or is encapsulated in the conductive polymer nano-dopant 30, which can also be understood as the microneedle drug mixed in the conductive polymer nano-dopant 30 and forming the complete conductive polymer nano-dopant 30 together with the conductive polymer material of the conductive polymer nano-dopant 30. Therefore, the conductive polymer nano-doped body 30 doped with the micro-needle drugs and the material of the micro-needle body 20 form the complete micro-needle body 20 together, the problem that the plating layer of the micro-needle body 20 is peeled off does not exist, the conductive polymer nano-doped body doped in the micro-needle body can be completely brought into the skin when the micro-needle body is pierced into the skin, so that the micro-needle drugs doped in the conductive polymer nano-doped body are completely released into the skin, the waste of the micro-needle drugs does not exist, the drug administration effect is effectively ensured, the situation that the conductive polymer is peeled off and remained in the skin does not exist, and the drug. Thereby solving the technical problem that the plating layer of the plating layer micro-needle in the prior art is easy to fall off.

The conductive polymer nano-dopant 30 mainly plays a role in supporting or encapsulating the microneedle drugs and releasing the microneedle drugs when being electrically stimulated. In the working mode, the microneedle body 20 pierces the skin to bring or deliver the conductive polymer nano-dopant 30 into the skin, and the conductive polymer nano-dopant 30 is configured to release the microneedle drug in response to an electrical stimulus from the driving power supply device 301. The conductive polymer nano-dopant 30 has good response to an electrical signal due to the conductive polymer material, which can be called a conductive polymer material, and the change of the oxidation-reduction state can be driven by using a lower voltage (less than or equal to 1V), that is, the oxidation-reduction state of the conductive polymer nano-dopant 30 can be changed by applying external electrical stimulation, so that the change of the polymer charge amount, the doping level, the electrical conductivity and the volume is caused, and the microneedle drug doped in the conductive polymer nano-dopant 30 is released, so that the microneedle drug enters the skin and can be absorbed by blood vessels and lymph glands to be introduced into the body circulation system. Because the micro-needle drugs are doped in the conductive polymer nano-dopant 30, and the conductive polymer nano-dopant 30 is doped in the micro-needle body 20, that is, is uniformly embedded in the micro-needle body 20, when the driving power supply device 301 supplies electric energy when the drugs need to be released after the micro-needle body 20 is pierced into the skin, the conductive polymer nano-dopant receives electrical stimulation, the conductive polymer nano-dopant close to the surface of the micro-needle body firstly releases the micro-needle drugs, the conductive polymer nano-dopant close to the middle of the micro-needle body gradually migrates to the surface of the micro-needle body through the inner structure of the micro-needle body macromolecules after receiving the electrical stimulation to release the micro-needle drugs, thereby facilitating the hierarchical release of the micro-needle drugs, effectively improving the drug release controllability, and because a plurality of conductive polymer nano-dopants 30 are doped in the micro-needle body 20, the drugs released by the electrical stimulation are not the same as the plated micro-needle In the body fluid, the micro-needle medicine gradually enters the skin body fluid from the micro-needle body, and part of the micro-needle medicine can be rewrapped by the conductive polymer nano-doped body when no electric stimulation is carried out, so that the micro-needle medicine is more favorably controlled to be released for many times. Therefore, the drug-loaded microneedle provided by the embodiment of the application effectively solves the technical problem that the existing drug-loaded microneedle is difficult to control the release of the drug for a plurality of times for a long time, is adaptable to a scene needing multiple drug administration, and is adaptable to the requirement that certain diseases repeatedly attack and need pulse type drug administration.

The conductive polymer nano-dopant 30 includes at least one of conductive polymer nanoparticles, conductive polymer nanorods, and conductive polymer nanofibers, but is not limited thereto, and the conductive polymer nano-dopant 30 may also have other shapes, and any one of the conductive polymer nanoparticles, the conductive polymer nanorods, and the conductive polymer nanofibers is doped with the microneedle drug.

The microneedle medicine is doped in the conductive polymer nano-doped body 30, and the microneedle medicine may include at least one of an anticancer drug, an analgesic, a contraceptive, a vaccine, a protein, a peptide, a polysaccharide gene, an antibody, a local anesthetic, and insulin, but is not limited thereto, and the microneedle medicine may also be other medicines or substances.

The material of the microneedle substrate 10 may include a polymer material. Preferably, the material of the microneedle substrate 10 may include at least one of hyaluronic acid, polyvinyl alcohol, polylactic acid, levopolylactic acid, polyglycolic acid, and polycaprolactone, but is not limited thereto. The material of the microneedle substrate 10 may also be a polymer gel.

The material of the microneedle body 20 may include a polymer material. Preferably, the material of the microneedle body 20 may include at least one of hyaluronic acid, polyvinyl alcohol, polylactic acid, l-polylactic acid, polyglycolic acid, and polycaprolactone, but is not limited thereto. The high molecular material is adopted as the material of the microneedle body 20, so that the high molecular material not only has excellent biocompatibility, but also can absorb body fluid in the skin to swell after the microneedle body 20 is penetrated into the skin, so that a plurality of conductive polymer nano-doped bodies 30 are in conductive communication with the body fluid, all the conductive polymer nano-doped bodies 30 can receive electric stimulation, and the conductive polymer nano-doped bodies 30 are prevented from being completely wrapped by the material of the microneedle body 20 and cannot receive electric stimulation, so that the medicine release effect is ensured.

The material of the microneedle body 20 may include a polymer gel. When the material of the microneedle body 20 is a polymer gel, the conductive polymer nano-dopant 30 may be formed in the polymer gel by in-situ polymerization, wherein in the in-situ polymerization process of the conductive polymer nano-dopant 30, the microneedle drug is doped in the conductive polymer nano-dopant 30.

The microneedle body 20 and/or the microneedle substrate 10 may be doped with at least one of gold nanorods, carbon nanotubes, silver nanowires, conductive polymers, and piezoelectric materials. By adopting the arrangement, the electric conductivity of the microneedle body 20 and/or the microneedle substrate 10 can be enhanced, so that the conductive polymer nano-doped body 30 can release the drug by receiving electric stimulation, and the drug release effect is ensured.

Preferably, the conductive polymer may include at least one of polypyrrole, polyaniline, polyacetylene, poly-p-phenylene sulfide, poly-p-phenylene, polythiophene, polypropylene, zinc oxide, polyvinylidene fluoride, but is not limited thereto; the piezoelectric material may include at least one of graphene, graphite, zinc oxide, piezoelectric ceramics, and piezoelectric crystals, but is not limited thereto.

The material of the conductive polymer nano-dopant 30 may include at least one of polypyrrole, polyaniline, polyacetylene, poly-p-phenylene sulfide, poly-p-phenylene, polythiophene, and polypropylene, and derivatives thereof, but is not limited thereto. Preferably, the material of the conductive polymer nano-dopant 30 may include polypyrrole, which has high conductivity and is easily prepared.

The mass ratio of the conductive polymer nano-dopant 30 to the microneedle body may be 0.01-1: 1.

fig. 2 is a schematic structural view of a drug-loaded microneedle with a micro-pair electrode according to some embodiments.

Referring to fig. 2, the drug-loaded microneedle 100 may further include at least one microneedle counter electrode 40, where the at least one microneedle counter electrode 40 is disposed on the microneedle substrate 10 and is located on the same side as the microneedle needle body 20; the microneedle body 20 is a working electrode, and the microneedle counter electrode 40 is used for piercing the skin, so that the driving power supply device 301, the microneedle body 20, the skin, and the microneedle counter electrode 40 form a loop. It should be noted that the microneedle is not essential to the electrode 40.

The microneedle counter electrode 40 may include a counter electrode microneedle body 41 and an inert metal layer 42, among others.

The counter electrode microneedle body 41 may be disposed on the microneedle substrate 10 or formed on the microneedle substrate 10, and the counter electrode microneedle body 41 and the microneedle body 20 are on the same surface of the microneedle substrate 10. The material of the counter electrode microneedle body 41 may be the same as that of the microneedle substrate 10 or the same as that of the microneedle body 20, and the counter electrode microneedle body 41 may be molded simultaneously with the microneedle substrate 10 or with the microneedle body 20. Preferably, the material of the counter electrode microneedle body 41 is the same as that of the microneedle body 20, facilitating simultaneous molding with the microneedle body 20.

The inert metal layer 42 is provided on the surface of the counter electrode microneedle body 41. The inert metal layer 42 may include at least one of gold, silver, and platinum, and the inert metal layer 42 may be applied to the surface of the counter electrode microneedle body 41 by at least one of sputtering, spraying, dipping, and deposition.

Preferably, the part of the microneedle substrate where the microneedle counter electrode is located is a first microneedle substrate part 101, and the part of the microneedle substrate where the microneedle body is located is a second microneedle substrate part 102, wherein the first microneedle substrate part 101 and the second microneedle substrate part 102 are connected in an insulated manner. Set up more than adopting, be convenient for all pierce the skin with micropin counter electrode and micropin body after, when drive power supply unit 301 provided the electro photoluminescence, the electric current was by the micropin counter electrode and flow through in the skin body fluid and the conductive polymer nanometer doping body of doping in the micropin body and return to drive power supply unit, thereby do benefit to the micropin medicine and release into in the skin body fluid, when can preventing that drive power supply unit 301 from providing the electro photoluminescence, partial electric current is direct through first micropin basilar part and second micropin basilar part return to drive power supply unit 301 and influence the medicine effect of releasing. In the case of preparing the microneedle substrate, an insulating material portion may be formed between the material of the first microneedle substrate portion and the material of the second microneedle substrate portion, for example, the material of the first microneedle substrate portion and the material of the second microneedle substrate portion may be doped with the conductive synergistic material, and the material between the first microneedle substrate portion and the second microneedle substrate portion may be formed into an integrated microneedle substrate without being doped with the conductive synergistic material. Also can mould first micropin base part and second micropin base part respectively, then adopt insulating material to connect first micropin base part and second micropin base part.

The configuration of the microneedle base is not limited to this, and alternatively, the first microneedle base portion and the second microneedle base portion may be integrally molded to be in conductive communication with each other.

From the above, the drug-loaded microneedle provided by the embodiment of the application has the following advantages:

1. by arranging the microneedle substrate, the microneedle body formed on the microneedle substrate, the conducting polymer nano-doped body doped in the microneedle body and the microneedle medicament doped in the conducting polymer nano-doped body, because the microneedle medicament is doped in the conducting polymer nano-doped body, the conducting polymer nano-doped body doped with the microneedle medicament is doped in the microneedle body and is melted and embedded with the material of the microneedle body, a complete microneedle is formed, but the microneedle medicament is not only present on the surface of the microneedle body, and the problem of coating peeling does not exist, the microneedle body is punctured into the skin, so that the conducting polymer nano-doped body doped in the microneedle can be completely brought into the skin, the microneedle medicament doped in the conducting polymer nano-doped body is completely released into the skin, the waste of the microneedle medicament does not exist, and the administration effect is effectively ensured. Thereby solving the technical problem that the plating layer of the plating layer micro-needle in the prior art is easy to fall off.

2. Because the micro-needle drugs are doped in the conductive polymer nano-doping bodies, the conductive polymer nano-doping bodies are doped in the micro-needle bodies, namely are uniformly embedded in the micro-needle bodies, when the driving power supply device supplies electric energy when the drugs need to be released along with the penetration of the micro-needle bodies into the skin, a plurality of conductive polymer nano-doping bodies receive electrical stimulation, the conductive polymer nano-doping bodies close to the surfaces of the micro-needle bodies firstly release the micro-needle drugs, the conductive polymer nano-doping bodies close to the middle parts of the micro-needle bodies receive the electrical stimulation to release the micro-needle drugs and then gradually migrate to the surfaces of the micro-needle bodies through the macromolecular internal structures of the micro-needle bodies to release the drugs, the hierarchical release of the micro-needle drugs is facilitated, the drugs released by the electrical stimulation on the micro-needle bodies are not the same as the plated micro-needles and are rapidly released in a large amount in the body, but gradually enters skin body fluid from the microneedle body, and part of microneedle drugs can be rewrapped by the conductive polymer nano-doped body during the non-electrical stimulation, thereby being more beneficial to controlling the repeated release of the microneedle drugs. Therefore, the drug-loaded microneedle provided by the embodiment of the application effectively solves the technical problem that the existing drug-loaded microneedle is difficult to control the release of the drug for a plurality of times for a long time, and is suitable for the situation that the drug needs to be administered for a plurality of times.

Therefore, the drug-loaded microneedle provided by the embodiment of the application solves a plurality of technical problems of easy shedding of a coating, unsatisfactory drug release controllability, complex preparation, difficult control of microneedle size, poor skin adhesiveness and the like of a coating microneedle in the prior art, and has a good market application prospect.

Example 2

Fig. 3 is a schematic structural view of a drug-loaded microneedle patch according to some embodiments.

Referring to fig. 3, the present embodiment provides a drug-loaded microneedle patch 200, where the drug-loaded microneedle 100 is applied to an electrically controlled drug release microneedle system 300, the electrically controlled drug release microneedle system 300 has a driving power supply device 301 for providing electric energy and controlling the electrically controlled drug release microneedle system 300 to release drugs, and the drug-loaded microneedle patch 200 includes a substrate 201 and at least one drug-loaded microneedle according to any one of the embodiments of the present invention described in the above embodiment 1.

The substrate 201 primarily serves to support and/or secure the drug-loaded microneedle 100. The substrate 201 may be a flexible material. The substrate 201 can also be an adhesive material, so that the drug-loaded microneedle 100 can be conveniently fixed on the skin, and the drug-loaded microneedle 100 can be attached to the skin to enable the microneedle needle body 20 to penetrate into the skin. The material of the substrate 201 may include at least one of the following materials: polyethylene terephthalate (PET), Polydimethylsiloxane (PDMS), polyimide (Kapton), Polytetrafluoroethylene (PTFE), Polycarbonate (PC), Polyamide (PA), polyethylene, polypropylene, polystyrene, natural rubber, butyl rubber, styrene-butadiene rubber, silicone rubber, epoxy resin, phenolic resin, polylactic acid, polyvinyl alcohol, polylactic acid-polyglycolic acid copolymer, collagen, hyaluronic acid, polylactide-co-glycolide, polycaprolactone, polyanhydride, polyesteramide, polybutyrate, chitosan, alginic acid, pectin, chondroitin, dextran, polylysine, fibrin, agarose, cellulose, polyethylene pyrrolidone, polyethylene glycol, polyvinyl alcohol, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethyl cellulose, polyhydric alcohols, alginates, cyclodextrins, dextrin, fructose, starch, trehalose, maltose, lactose, lactulose, raffinose, melezitose, dextran, xylitol, polylactic acid, polyglycolic acid, polyethylene oxide, polyacrylic acid, polyacrylamide, polymethacrylic acid, polymaleic acid and the like.

The microneedle substrate 10 of at least one drug-carrying microneedle 100 is arranged on the substrate 201, and when the drug-carrying microneedle 100 receives an electric signal sent by the driving power supply device 301, the conductive polymer nano-dopant 30 doped in the microneedle needle body 20 releases microneedle drugs.

Since the drug-loaded microneedle 100 in example 1 is used in this embodiment, the drug-loaded microneedle 100 also has the advantages or benefits of the drug-loaded microneedle 100 in example 1, and is not described herein again.

Example 3

Fig. 4 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system according to some embodiments. Fig. 7 is a functional block schematic diagram of an electrically controlled drug-releasing microneedle system according to some embodiments.

Referring to fig. 4 and 7, an electrically controlled drug release microneedle system 300 is provided in an embodiment of the present application, where the electrically controlled drug release microneedle system 300 includes a driving power supply device 301, a drug-loaded microneedle 100 in any one of the embodiments 1 or the drug-loaded microneedle patch 200 in the embodiment 2.

The driving power supply device 301 is configured to supply electric energy to the drug-loaded microneedle 100 of any one of the above-described embodiments 1 or the drug-loaded microneedle patch 200 of the above-described embodiment 2 and control the drug-loaded microneedle 100 to release a microneedle drug. The driving power supply device 301 may include a device for supplying power using a battery, and a self-driving power supply device for converting mechanical energy or chemical energy of a living body into electric energy.

The microneedle substrate 10 of the drug-carrying microneedle 100 can be provided with a microneedle counter electrode 40, at this time, one output end of the driving power supply device 301 is electrically connected with the microneedle body 20 or the microneedle substrate 10, and the other output end of the driving power supply device 301 is electrically connected with the microneedle counter electrode 40 of the drug-carrying microneedle. When the micro-needle substrate is in a working mode, the micro-needle body 20 and the micro-needle counter electrode 40 of the drug-carrying micro-needle 100 are both inserted into the skin, the driving power supply device 301 outputs electric energy, so that a loop is formed among the driving power supply device 301, the micro-needle body 20 or the micro-needle substrate 10, the skin and the micro-needle counter electrode 40, and the conductive polymer nano-dopant 30 doped in the micro-needle body 20 releases micro-needle drugs in response to electrical stimulation.

Fig. 5 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system having a first independent microneedle pair electrode and a second independent microneedle pair electrode, according to some embodiments.

Referring to fig. 5, the electrically controlled drug release microneedle system 300 may further include a first independent micro-pair electrode 302 and a second independent micro-pair electrode 303.

First independent little to electrode 302 is connected with an output of drive power supply unit 301, and first independent micropin is to electrode and medicine carrying micropin components of a whole that can function independently setting, and first independent little is to electrode 302 and medicine carrying micropin 100 or medicine carrying micropin paster 200 relatively independent and not continuous promptly.

The second independent is little to electrode 303 and another output electricity of drive power supply unit 301 are connected, and the second is independent is little to electrode and medicine carrying micropin components of a whole that can function independently setting, and the second is independent is little to electrode 303 and medicine carrying micropin 100 or medicine carrying micropin paster 200 relatively independent and not continuous promptly.

The first independent micro-pair electrode 302 and the second independent micro-pair electrode 303 are both used for penetrating into the skin, so that the driving power supply device 301, the first independent micro-pair electrode 302, the skin 400, the microneedle needle body 20 of the drug-carrying microneedle and the second independent micro-pair electrode 303 form a loop, current can flow through the first independent micro-pair electrode 302, body fluid in the skin 400, a conductive polymer nano-doped body doped in the microneedle needle body 20, the second independent micro-pair electrode 303 and the driving power supply device 301, the electric communication between the body fluid in the skin and the conductive polymer nano-doped body is facilitated, and the drug release effect is ensured.

The first individual microneedle counter electrode 302 can include a first individual microneedle substrate 3021, at least one first individual microneedle body 3022, and a first inert metal layer 3023.

The material of the first individual microneedle substrate 3021 may be the material that can be used for the microneedle body 20 in the above-described embodiment 1 or the material that can be used for the microneedle substrate 10, but is not limited thereto, and the material of the first individual microneedle substrate 3021 may also be other metal or nonmetal conductive and biocompatible material.

At least one first independent microneedle body 3022 is formed on the first independent microneedle substrate 3021, and the first independent microneedle body 3022 may be integrally formed with the first independent microneedle substrate 3021, or the first independent microneedle body 3022 and the first independent microneedle substrate 3021 may be sequentially formed, respectively. The material of the first individual microneedle body 3022 may be the material that can be used for the microneedle body 20 in the above-described embodiment 1 or the material that can be used for the microneedle substrate 10, but is not limited thereto, and the material of the first individual microneedle body 3022 may also be other metal or nonmetal conductive and biocompatible material.

The first inert metal layer 3023 is disposed on a surface of the first individual microneedle body 3022 and/or a surface of the first individual microneedle substrate 3021, a material of the first inert metal layer 3023 may include at least one of gold, silver, and platinum, and the first inert metal layer 3023 may be applied to the surface of the first individual microneedle body 3022 and/or the surface of the first individual microneedle substrate 3021 by at least one of sputtering, spraying, dipping, and deposition. The first inert metal layer 3023 is electrically connected to an output terminal of the driving power supply device 301.

The second individual microneedle electrode 303 may include a second individual microneedle substrate 3031, at least one second individual microneedle body 3032, and a second inert metal layer 3033.

The material of the second individual microneedle base 3031 may be the material that can be used for the microneedle body 20 in example 1 or the material that can be used for the microneedle base 10, but is not limited thereto, and the material of the second individual microneedle base 3031 may also be other metal or nonmetal conductive and biocompatible material.

At least one second independent microneedle body 3032 is formed on the second independent microneedle substrate 3031, the second independent microneedle body 3032 may be integrally formed with the second independent microneedle substrate 3031, or the second independent microneedle body 3032 may be sequentially formed with the second independent microneedle substrate 3031. The material of the second individual microneedle body 3032 may be the material that can be used for the microneedle body 20 in the above embodiment 1 or the material that can be used for the microneedle substrate 10, but is not limited thereto, and the material of the second individual microneedle body 3032 may also be other metal or nonmetal conductive and biocompatible material.

The second inert metal layer 3033 is disposed on a surface of the second individual microneedle body 3032 and/or a surface of the second individual microneedle substrate 3031. The material of the second inert metal layer 3033 may include at least one of gold, silver, and platinum, and the second inert metal layer 3033 may be applied to the surface of the second independent microneedle body 3032 and/or the surface of the second independent microneedle substrate 3031 by at least one of sputtering, spraying, dipping, and deposition. The second inert metal layer 3033 is electrically connected to an output terminal of the driving power supply device 301.

Fig. 6 is a schematic structural diagram of an electrically controlled drug-releasing microneedle system with a first independent microneedle counter electrode, according to some embodiments.

Referring to fig. 6, it should be noted that the first independent microneedle body 3022 and the second independent microneedle body 3032 do not need to exist at the same time, and optionally, only the first independent microneedle body 3022 or the second independent microneedle body 3032 may be needed, at this time, one output end of the driving power supply device 301 may be electrically connected to the first independent microneedle body 3022 or the second independent microneedle body 3032, and another output end of the driving power supply device 301 may be electrically connected to the microneedle substrate 10 or the microneedle body 20.

Referring to fig. 5 and 7, the driving power supply device 301 may include a self-driven energy unit 3011, where the self-driven energy unit 3011 is configured to convert mechanical energy or chemical energy of a living body into electric energy. Optionally, the self-powered energy unit 3011 may comprise at least one of a biofuel cell, a triboelectric nanogenerator, a piezoelectric generator, but is not limited thereto, and optionally, the self-powered energy unit 3011 may comprise a solar generator. The biofuel cell, the friction nano generator and the piezoelectric generator can be any one of the prior art, and are not limited and described herein. Due to the above arrangement, the self-driven energy unit 3011 can solve the problem of power supply limitation. The self-driven energy unit 3011 may be disposed on a surface of the microneedle substrate 10 of the drug-carrying microneedle 100 away from the microneedle body 20 or disposed on a surface of the substrate 201 of the drug-carrying microneedle patch 200 away from the drug-carrying microneedle 100, and the self-driven energy unit 3011 may also be disposed near the drug-carrying microneedle 100.

The driving power supply device 301 may further include an energy management unit 3012, an input end of the energy management unit 3012 is electrically connected to an output end of the self-driven energy unit 3011, and the energy management unit 3012 is configured to manage the electric energy output by the self-driven energy unit 3011 and is configured to provide electric energy to the drug-carrying microneedle and control the drug-carrying microneedle to release the microneedle drug. It should be noted that the driving power supply device 301 may directly output an electrical signal to the drug-carrying microneedle 100 through the self-driving energy unit 3011 without the energy management unit 3012, or output an electrical signal to the drug-carrying microneedle 100 through a PN junction or a diode from the self-driving energy unit 3011.

The energy management unit 3012 may include a rectification module 30121 and an energy storage module 30122.

The rectifying module 30121 is configured to convert an ac current output from the driving energy unit 3011 into a dc current, for example, convert an ac current output from the friction nano-generator into a dc current. The rectifying module 30121 may include a rectifying unit and a filtering unit, the rectifying unit converts the ac current output by the friction nano-generator into a dc current, for example, a rectifying bridge may be used, and the filtering unit converts the pulsating dc current output by the rectifying unit into a relatively stable dc current and provides the relatively stable dc current to the energy storage module 30122 for storage, for example, the energy storage module 30122 may be a rechargeable lithium battery or an energy storage capacitor.

The energy storage module 30122 is configured to store a direct current output by the rectifying module 30121, and the energy storage module 30122 is configured to provide electrical energy to the medicated microneedle and control the medicated microneedle to release microneedle drugs.

The electrically controlled drug release microneedle system 300 provided by the embodiment of the application provides electric energy to the drug carrying microneedle 100 through the driving power supply device 301, controls the drug carrying microneedle 100 to release microneedle drugs for a plurality of times for a long time, can realize the controlled release of the microneedle drugs, and can be adapted to the requirement that certain diseases repeatedly attack and need pulse type drug delivery. Because the electrically controlled drug release microneedle system 300 provided in the embodiment of the present application employs the drug-loaded microneedle 100 in embodiment 1 or the drug-loaded microneedle patch in embodiment 2, the electrically controlled drug release microneedle system also has the advantages or beneficial effects of the drug-loaded microneedle in embodiment 1, and is not described herein again.

Example 4

Fig. 8 is a flow diagram of a method of using an electrically controlled drug-releasing microneedle system, according to some embodiments.

Referring to fig. 8, an embodiment of the present application provides a method for using an electrically controlled drug release microneedle system, which is suitable for the electrically controlled drug release microneedle system 300 of any of the embodiments 3, and the method includes:

s100: causing at least one microneedle body 20 of the drug-loaded microneedle 100 to penetrate into the skin, so as to deliver the conductive polymer nano-dopant 30 doped in the at least one microneedle body 20 into the skin;

s200: the driving power supply device 301 supplies power to the drug-loaded microneedle and controls the conductive polymer nano-dopant 30 doped in the microneedle body 20 to release microneedle drugs into the skin.

Since the electrically controlled drug release microneedle system 300 in example 3 is used in the method for using an electrically controlled drug release microneedle system according to the embodiment of the present application, the electrically controlled drug release microneedle system also has the advantages or beneficial effects of the drug-loaded microneedles in example 1, and details are not repeated herein.

Example 5

Fig. 9 is a flow diagram of a method of drug-loaded microneedle preparation according to some embodiments.

Referring to fig. 9, an embodiment of the present application provides a method for preparing a drug-loaded microneedle 100 according to any one of embodiments 1, where the method includes:

s10: preparing a conductive polymer nano-dopant 30 doped with a microneedle drug;

s20: mixing the conductive polymer nano-doped body 30 with the liquid microneedle body 20 material and then molding the mixture in a microneedle mould to form the microneedle body 20 doped with the conductive polymer nano-doped body 30;

s30: forming a microneedle substrate 10 connected to a microneedle body 20 on a microneedle mold;

s40: drying and demoulding to obtain the solid drug-loaded microneedle.

Fig. 10 is a schematic flow chart of some embodiments of step S10 in fig. 9.

Referring to fig. 10, in an embodiment, S10: the preparation of the conductive polymer nano-dope 30 doped with the microneedle drug may include the steps of:

s101: providing a template solution containing a template;

s102: mixing the pyrrole monomer solution with the template solution to obtain a mixed solution;

s103: mixing a microneedle drug with the mixed solution or mixing the microneedle drug and a dopant of counter ions with the mixed solution to obtain a microneedle drug mixed solution;

s104: mixing an oxidant and the microneedle drug mixed solution to polymerize a pyrrole monomer into polypyrrole doped with the microneedle drug;

s105: and centrifuging and collecting to obtain the polypyrrole nano-doped body doped with the microneedle medicines.

The polypyrrole nano-doped body prepared by the method has high drug encapsulation rate of the microneedle, can effectively improve the doping amount of the drug in the polypyrrole, and further ensures the drug release effect of the drug-loaded microneedle.

Wherein, in providing the template solution containing the template, the template may include at least one of a surfactant, a biological macromolecule, cyclodextrin, a functional macromolecule, and an azo compound, but is not limited thereto. Alternatively, the template may further include at least one of cetyltrimethylammonium bromide (CTAB), acid red, Sodium Dodecyl Sulfate (SDS), Sodium Dodecylbenzenesulfonate (SDBS), Sodium Alkylsulfonate (SAS), gelatin, methyl orange, cyclodextrin, polyvinyl alcohol, N-methylene phosphorylated chitosan, but is not limited thereto. The template can form micelles in an aqueous solution and is used as a soft template, the pyrrole monomer can synthesize polypyrrole (PPy) with a specific structure in a structure limited by the micelles, the polypyrrole doped with microneedle drugs is formed after polymerization is completed, and the template is removed by adopting a proper solvent, so that the separation of the polypyrrole nano-doped body and the template is realized. Other similar agents that achieve the above-described effects may also serve as templates.

Wherein, after the pyrrole monomer solution is mixed with the template solution, the mixture is stirred for 10 to 60 minutes to fully mix the pyrrole monomer solution with the template solution, and then the mixed solution is obtained. Wherein the pyrrole monomer solution may be added in a state of stirring the template solution.

After the microneedle medicine is mixed with the mixed solution or the microneedle medicine and the dopant of counter ions are mixed with the mixed solution, stirring is carried out for 10-60 minutes, so that the microneedle medicine is fully dispersed in the mixed solution, and the microneedle medicine mixed solution is obtained.

In step S103, the polypyrrole is oxidized, loses electrons and has a positive charge, and if the microneedle drug is an anion, the polypyrrole can be automatically doped into the conductive polymer, and if the microneedle drug includes a cation, the polypyrrole can be doped into the conductive polymer together with the anion. The counter ion dopant in step S103 may be an anionic dopant, and the anionic dopant may include various inorganic anions (such as hydrochloride), organic anions (such as sulfonate, salicylate, and the like), and the doping of the counter ion dopant may also improve the conductivity of the conductive polymer, thereby improving the conductivity of the conductive polymer nano-dopant.

Wherein, after the oxidant is mixed with the microneedle drug mixed solution, the reaction can be continued for 12-36 hours, preferably 24 hours, so that the pyrrole monomer is fully polymerized into the polypyrrole doped with the microneedle drug. The oxidant may be FeCl₃Hydrogen peroxide, tetrachloro-alloying acid (HAuCl4), and the like.

Wherein, the centrifugal collection can be carried out by adopting an ultrafiltration tube to obtain the polypyrrole nanometer adulterated body doped with the microneedle medicines.

A method for preparing a conductive polymer nano-dopant 30 doped with a microneedle drug, such as sodium fluorescein, is described in a specific embodiment below:

5ml of a 0.1M Sodium Dodecyl Sulfate (SDS) solution containing 40mM HCl was prepared, and 25. mu.L of a pyrrole monomer solution was added with stirring. Stirring for thirty minutes, 62.5. mu.L of sodium fluorescein solution was added, stirring was continued for 30 minutes, and then 400. mu.L of 625mg/mL FeCl was added₃The reaction was continued for 24 h. And finally, centrifugally collecting the polypyrrole nano-doped body doped with the microneedle medicament (sodium fluorescein) by adopting a 3000KDa ultrafiltration tube, wherein the polypyrrole nano-doped body is usually granular.

In addition to the specific contents of the substances in the above examples, the contents may be other contents, and the proportion relationship of the substances is as follows according to the amount of the substances (n: n):

pyrrole monomer (Py): FeCl₃＝1：(1-5)

SDS：Py＝(500-3000：1)

Py: FL (fluorescein) ═ 1: (1-50)

Fig. 11 is a schematic flow chart of some embodiments of step S10 in fig. 9.

Referring to fig. 11, in an embodiment, S10: the preparation of the conductive polymer nano-dope 30 doped with the microneedle drug may include the steps of:

s110: providing an aqueous stabilizer solution containing a stabilizer;

s120: mixing an aniline monomer with a stabilizer aqueous solution to disperse the aniline monomer in the stabilizer aqueous solution to obtain a first mixed solution;

s130: mixing a microneedle drug with a first mixed solution or mixing the microneedle drug and a dopant of counter ions with the first mixed solution to obtain a second mixed solution;

s140: mixing an oxidant and the second mixed solution to polymerize aniline monomers into polyaniline doped with microneedle drugs; wherein, the oxidant can be hydrogen peroxide;

s150: and centrifuging and collecting to obtain the polyaniline nano-doped body doped with the microneedle medicines.

The polyaniline nano-doped body prepared by the method has high drug encapsulation rate of the microneedle, can effectively improve the doping amount of the drug in the polyaniline, and further ensures the drug release effect of the drug-loaded microneedle.

Wherein, in the stabilizer aqueous solution containing the stabilizer, the stabilizer can be polyvinylpyrrolidone (PVP) or other stabilizers.

A method for preparing the conductive polymer nano-dopant 30 doped with the microneedle drug, such as dexamethasone, is described in a specific embodiment below:

preparing 10mL of 10mg/mL polyvinylpyrrolidone (PVP) aqueous solution, adding 2mmol of aniline monomer into the PVP aqueous solution, stirring and dispersing, then adding 1mmol of dexamethasone hydrochloride, stirring for thirty minutes, adding 7mL of 0.3mol/L hydrogen peroxide and 0.15mol/L sulfuric acid aqueous solution, continuously stirring and reacting for 24 hours to obtain a solution containing the polyaniline nano-doped body doped with the microneedle drug (dexamethasone), and finally centrifuging and collecting the polyaniline nano-doped body, wherein the polyaniline nano-doped body is usually granular.

PVP 0.5-10mg/mL

PVP: aniline: dexamethasone: hydrogen peroxide ═ 1: (1-5): (1-5): (0.001-0.1)

The conductive polymer nano-dopant 30 and the liquid material of the microneedle body 20 are mixed and then molded in a microneedle mold to form the microneedle body 20 doped with the conductive polymer nano-dopant 30, wherein the liquid material of the microneedle body 20 may include at least one of hyaluronic acid, polyvinyl alcohol, polylactic acid, levorotatory polylactic acid, polyglycolic acid, and polycaprolactone, but is not limited thereto.

In one embodiment, when the conductive polymer nano-dopant 30 is mixed with the material of the microneedle body 20 in a liquid state, the conductive synergistic material may be mixed at the same time, and then molded in a microneedle mold to form the microneedle body 20 doped with the conductive polymer nano-dopant 30 and the conductive synergistic material. Wherein the conductive synergistic material may include at least one of gold nanorods, carbon nanotubes, silver nanowires, conductive polymers, and piezoelectric materials.

In one embodiment, forming a microneedle substrate attached to a microneedle body 20 on a microneedle mold may include: the microneedle substrate 10 material in a liquid state is molded on a microneedle mold to form the microneedle substrate 10 connected to the microneedle body 20. The microneedle substrate 10 material in the liquid state may be a material that can be used for the microneedle substrate 10 in example 1.

In one embodiment, forming a microneedle substrate attached to a microneedle body 20 on a microneedle mold may include: the conductive synergistic material and the liquid microneedle substrate 10 material are mixed and then molded on a microneedle mould to form the microneedle substrate 10 connected with the microneedle body 20. The microneedle substrate 10 material in the liquid state may be a material that can be used for the microneedle substrate 10 in example 1.

In one embodiment, the microneedle body 20 and the microneedle substrate 10 may be integrally formed. That is, the conductive polymer nano-dopant 30 and the liquid material of the microneedle body 20 may be mixed and then molded in the microneedle mold, and the microneedle substrate connected to the microneedle body 20 is formed on the microneedle mold in the same step, that is, step S20 and step S30 are simultaneously completed in step S20.

Wherein, before drying and demoulding to obtain the drug-loaded microneedle, the method can also comprise the following steps: the microneedle mold carrying the microneedle body 20 and the microneedle substrate 10 is first subjected to a freezing process and then to a vacuum process. Wherein the time of the vacuum treatment is 0.5-24 hours. Wherein the temperature of the freezing treatment is-80 ℃ to-20 ℃.

Before forming the microneedle substrate 10 connected to the microneedle body 20 on the microneedle mold, the method may further include: the liquid material of the counter electrode microneedle body 41 is molded in a microneedle mold to form the counter electrode microneedle body 41 attached to the microneedle substrate 10. As a material of the counter electrode microneedle body 41, a material that can be used for the counter electrode microneedle body 41 in embodiment 1 described above can be used.

Wherein, after obtaining the solid drug-loaded microneedle after drying and demoulding, the method can also comprise the following steps: an inert metal layer 42 is formed on the surface of the counter electrode microneedle body 41. The inert metal layer 42 may include at least one of gold, silver, and platinum, and the inert metal layer 42 may be applied to the surface of the counter electrode microneedle body 41 by at least one of sputtering, spraying, dipping, and deposition.

The method for preparing the drug-loaded microneedle by using the prepared conductive polymer nano-dopant 30 is described as follows in a specific embodiment:

preparing 25% PVA solution, adding 1% of dried polypyrrole nano-doped bodies and/or polyaniline nano-doped bodies according to the mass ratio, uniformly mixing, adding the mixture to the surface of a PDMS microneedle mould, putting the PDMS microneedle mould into the PDMS microneedle mould, freezing the PDMS microneedle mould overnight at the temperature of-20 ℃, then carrying out vacuum pumping treatment for about 30 minutes, thawing, drying and demoulding to obtain the drug-loaded microneedle doped with the conductive polymer nano-doped bodies;

then, a mask with a certain circuit pattern is covered on the drug-loaded microneedle, and then, gold is sprayed on the surface of the counter electrode microneedle body 41 by sputtering to form an inert metal layer 42, so that the drug-loaded microneedle with the surface of the counter electrode microneedle body 41 plated with the inert metal layer 42 is obtained.

The PDMS microneedle mould with different sizes can be manufactured according to requirements, and the prior art can be adopted for manufacturing the PDMS microneedle mould.

From the above, in the method for preparing the drug-loaded microneedle provided by the embodiment of the application, the conductive polymer nano-doped body 30 is prepared firstly, and then the conductive polymer nano-doped body 30 and a microneedle body material (a high polymer material) are physically mixed and then prepared by using a mold to obtain the drug-loaded microneedle, the preparation method is simple, the microneedle drug encapsulation rate is high and can reach more than 50%, the microneedle drug-loaded microneedle is easy to prepare on a large scale, and meanwhile, the prepared drug-loaded microneedle has sensitive electrical response and good microneedle drug controllable release performance. Because the drug-loaded microneedle prepared by the method of the present application in the embodiment is the drug-loaded microneedle in the embodiment 1, the prepared drug-loaded microneedle also has the advantages or beneficial effects of the drug-loaded microneedle in the embodiment 1, and details are not repeated herein.

Example 6

Referring to fig. 12, an embodiment of the present application provides a method for preparing a drug-loaded microneedle 100 according to any one of embodiments 1, where the method includes:

s1: preparing a high-molecular gel microneedle, wherein the high-molecular gel microneedle comprises a high-molecular gel microneedle substrate and at least one high-molecular gel microneedle body formed on the high-molecular gel microneedle substrate;

s2: mixing the microneedle drug with the monomer solution of the conductive polymer to obtain a third mixed solution;

s3: filling the third mixed solution into the pores of the polymer gel microneedle body, and polymerizing the monomer of the conductive polymer in situ to form a conductive polymer nano-doped body doped with the microneedle drugs in the polymer gel microneedle body;

s4: and drying the polymer gel microneedle doped with the conductive polymer nano-doped body to obtain the solid drug-loaded microneedle.

Wherein, S1: preparing a polymeric gel microneedle, comprising:

providing an aqueous chitosan solution;

mixing acrylamide, N' -methylene bisacrylamide, ammonium persulfate and a chitosan aqueous solution to obtain a mixture;

injecting the mixture into a microneedle mould, and forming under ultraviolet irradiation;

and demolding to obtain the polymer gel microneedle.

Wherein, the mixture is injected into a microneedle mould and is protected by nitrogen in the process of forming under the irradiation of ultraviolet rays.

Wherein the monomer solution of the conductive polymer is pyrrole monomer solution.

Wherein, S3: filling the third mixed solution into the pores of the polymer gel microneedle body, and polymerizing the monomer of the conductive polymer in situ to form a conductive polymer nano-dopant doped with the microneedle drug in the polymer gel microneedle body, comprising:

soaking a high molecular gel microneedle body of the high molecular gel microneedle in the third mixed solution so as to fill the third mixed solution into pores of the high molecular gel microneedle body, thereby obtaining a filled high molecular gel microneedle;

providing an aqueous oxidant solution containing an oxidant;

soaking the high molecular gel micro-needle body filled with the high molecular gel micro-needle into an oxidant aqueous solution to polymerize a monomer of the conductive polymer in situ, thereby forming a conductive polymer nano-doped body doped with the micro-needle medicament in the high molecular gel micro-needle body.

Wherein, the high molecular gel microneedle body of the high molecular gel microneedle is soaked in the third mixed solution for 4 to 72 hours at the temperature of 4 to 40 ℃.

Wherein, before soaking the polymer gel microneedle body of filling polymer gel microneedle in oxidant aqueous solution, still include: placing the microneedle filled with the polymer gel in a closed container for 1-10 hours; preferably, the temperature in the closed vessel is from 2 ℃ to 25 ℃.

Wherein, the polymer gel microneedle body filled with the polymer gel microneedle is soaked in an oxidant aqueous solution and then soaked for 5 to 20 hours at the temperature of 2 to 25 ℃.

Wherein, carry out drying process to the polymer gel micropin that is doped with conducting polymer nanometer adulterant, include: and (3) carrying out freeze drying on the high-molecular gel microneedle doped with the conductive polymer nano-doped body for 12-48 hours until the high-molecular gel microneedle is completely dried.

A method for preparing a drug-loaded microneedle is described in a specific embodiment, wherein the microneedle drug is lidocaine as an example:

(1) preparing the high molecular gel microneedle by adopting an ultraviolet polymerization method. First, 0.5g of Chitosan (CS) was dissolved in 10mL of deionized water, and then acrylamide (2.6g), N' -methylenebisacrylamide (1 wt.%), and ammonium persulfate (1.5 wt.%) were added to the CS solution under continuous magnetic stirring. The resulting mixture was injected into a microneedle mould and exposed to ultraviolet light (365nm, 2.8mW/cm2) and moulded under nitrogen. After 5 minutes, the polymer gel microneedle was prepared.

(2) Preparing solid drug-loaded micro-needles. And (2) soaking the polymer gel microneedle (IPN hydrogel) prepared in the step (1) in a pyrrole monomer solution containing lidocaine serving as a medicine, and standing at room temperature for 24 hours. Then storing the polymer gel microneedle (IPN hydrogel) in a sealed container at 4 ℃, and soaking the polymer gel microneedle (IPN hydrogel) in FeCl after 3 hours₃And storing in water solution at 4 deg.c for 12 hr to polymerize pyrrole monomer in the polymer gel micro needle to form nanometer doped conducting polymer body (mainly rod or fiber) with micro needle medicine. Wherein the mass ratio of Py to FeCl3 is 1: 3. and taking out the polymer gel microneedle (IPN hydrogel) and freeze-drying for 24 hours to obtain the solid drug-loaded microneedle.

In addition to the specific contents of the substances in the above examples, the contents of the substances may be other contents, and the mixture ratio of the substances is as follows by mass:

and (3) chitosan: 0.1-2g/mL

Acrylamide: methylene bisacrylamide: ammonium persulfate 1: (0.1% -0.5%): (0.1-0.5%)

According to the preparation method of the drug-loaded microneedle, the polymer gel microneedle is prepared firstly, and then the polymer gel microneedle is polymerized in situ in the polymer gel microneedle to form the conductive polymer nano-dopant doped with the microneedle drug, so that the drug-loaded microneedle is prepared. Because the drug-loaded microneedle prepared by the method of the present application in the embodiment is the drug-loaded microneedle in the embodiment 1, the prepared drug-loaded microneedle also has the advantages or beneficial effects of the drug-loaded microneedle in the embodiment 1, and details are not repeated herein.

The above description is only an embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that are not thought of through the inventive work should be included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope defined by the claims.

Claims

1. The utility model provides a medicine carrying microneedle, its characterized in that, medicine carrying microneedle is applied to electricity regulation and control drug release microneedle system, electricity regulation and control drug release microneedle system has and is used for providing the electric energy and controls the drive power supply unit of electricity regulation and control drug release microneedle system release medicine, medicine carrying microneedle includes:

a microneedle substrate;

at least one microneedle body formed on the microneedle substrate;

a conductive polymer nano-dopant doped in the microneedle body; and

a microneedle drug doped in the conductive polymer nano-dopant;

wherein at least one of the microneedle bodies is adapted to pierce the skin to deliver the conductive polymer nano-dopes into the skin, the conductive polymer nano-dopes being configured to release the microneedle drugs in response to an electrical stimulus emitted by the driving power supply device;

preferably, the same surface of the microneedle substrate is formed with a plurality of microneedle bodies to form a microneedle array;

preferably, the material of the microneedle substrate comprises a polymeric material;

preferably, the material of the microneedle substrate comprises at least one of hyaluronic acid, polyvinyl alcohol, polylactic acid, levopolylactic acid, polyglycolic acid, chitosan and polycaprolactone;

preferably, the material of the microneedle substrate comprises a polymeric gel;

preferably, the material of the microneedle body comprises a polymer material;

preferably, the material of the microneedle body comprises a polymer gel;

preferably, the conductive polymer nano-dopant is formed in the polymer gel by in-situ polymerization; wherein the microneedle drug is doped in the conductive polymer nano-dopant during the in-situ polymerization of the conductive polymer nano-dopant;

preferably, the material of the microneedle body includes at least one of hyaluronic acid, polyvinyl alcohol, polylactic acid, levorotatory polylactic acid, polyglycolic acid, chitosan, and polycaprolactone;

preferably, the microneedle body can absorb body fluid in the skin to swell after penetrating into the skin, so that the conductive polymer nano-doped body is in conductive communication with the body fluid;

preferably, the microneedle body and/or the microneedle substrate is doped with at least one of gold nanorods, carbon nanotubes, silver nanowires, conductive polymers and piezoelectric materials;

preferably, the conductive polymer comprises at least one of polypyrrole, polyaniline, polyacetylene, poly-p-phenylene sulfide, poly-p-phenylene, polythiophene, polypropylene, zinc oxide and polyvinylidene fluoride; the piezoelectric material comprises at least one of graphene, graphite, zinc oxide, piezoelectric ceramics and piezoelectric crystals;

preferably, the conductive polymer nano-dopant includes at least one of conductive polymer nanoparticles, conductive polymer nanorods, and conductive polymer nanofibers; any one of the conductive polymer nanoparticles, the conductive polymer nanorods, and the conductive polymer nanofibers is doped with the microneedle drug;

preferably, the material of the conductive polymer nano-dopant comprises at least one of polypyrrole, polyaniline, polyacetylene, poly-p-phenylene sulfide, poly-p-phenylene, polythiophene and polypropylene and derivatives thereof;

preferably, the material of the conductive polymer nano-dopant comprises polypyrrole;

preferably, the microneedle drugs include at least one of an anticancer drug, an analgesic, a contraceptive, a vaccine, a protein, a peptide, a polysaccharide gene, an antibody, a local anesthetic, insulin;

preferably, the drug-loaded microneedle further comprises:

at least one micro-needle counter electrode arranged on the micro-needle substrate and positioned on the same side with the micro-needle body;

the micro-needle body is a working electrode, and the micro-needle counter electrode is used for puncturing the skin so as to enable the driving power supply device, the micro-needle body, the skin and the micro-needle counter electrode to form a loop;

preferably, the part of the microneedle substrate where the microneedle counter electrode is located is a first microneedle base part, and the part of the microneedle substrate where the microneedle body is located is a second microneedle base part, wherein the first microneedle base part and the second microneedle base part are in insulation connection with each other;

preferably, the micro-pair electrode includes:

a counter electrode microneedle body disposed on the microneedle substrate;

the inert metal layer is arranged on the surface of the counter electrode microneedle body;

preferably, the material of the counter electrode microneedle body is the same as the material of the microneedle body.

2. A drug-loaded microneedle patch, comprising:

a substrate;

at least one drug-loaded microneedle of claim 1, the microneedle substrate of at least one drug-loaded microneedle being disposed on the substrate.

3. An electrically controlled drug-releasing microneedle system comprising:

the drug-loaded microneedle of claim 1 or the drug-loaded microneedle patch of claim 2;

the driving power supply device is configured to provide electric energy for the drug-loaded microneedle and control the drug-loaded microneedle to release microneedle drugs;

preferably, a microneedle counter electrode is arranged on the microneedle substrate of the drug-carrying microneedle; wherein, an output end of the driving power supply device is electrically connected with the microneedle body or the microneedle substrate, and the other output end of the driving power supply device is electrically connected with the microneedle counter electrode of the drug-loaded microneedle.

4. The electrically regulated drug release microneedle system of claim 3, further comprising:

the first independent micro-needle counter electrode is electrically connected with one output end of the driving power supply device;

the first independent micro-needle counter electrode and the drug-loaded micro-needle are arranged in a split mode, and the first independent micro-needle counter electrode is used for penetrating into the skin, so that the driving power supply device, the first independent micro-needle counter electrode, the skin and the micro-needle body of the drug-loaded micro-needle form a loop;

preferably, the first individual microneedle counter electrode comprises:

a first freestanding microneedle substrate;

a first individual microneedle body formed on the first individual microneedle substrate;

a first inert metal layer disposed on a surface of the first individual microneedle needle body and/or a surface of the first individual microneedle substrate;

the first inert metal layer is electrically connected with an output end of the driving power supply device;

preferably, the electrically regulated drug release microneedle system further comprises:

the second independent micro-counter electrode is electrically connected with the other output end of the driving power supply device;

the second independent micro-pair electrode and the drug-loaded micro-needle are arranged separately, and the second independent micro-pair electrode is used for penetrating into the skin so that the driving power supply device, the first independent micro-pair electrode, the skin, the micro-needle body of the drug-loaded micro-needle and the second independent micro-pair electrode form a loop;

preferably, the second independent micro-pair electrode includes:

a second freestanding microneedle substrate;

a second individual microneedle body formed on the second individual microneedle substrate;

a second inert metal layer disposed on a surface of the second individual microneedle body and/or a surface of the second individual microneedle substrate;

the second inert metal layer is electrically connected with an output end of the driving power supply device.

5. The electrically controlled drug-releasing microneedle system according to claim 3 or 4, wherein said driving power supply means comprises:

a self-driven energy unit configured to convert mechanical energy or chemical energy of a living body into electric energy;

preferably, the self-powered energy unit comprises at least one of a biofuel cell, a triboelectric nanogenerator, a piezoelectric generator;

preferably, the driving power supply device further includes:

the input end of the energy management unit is electrically connected with the output end of the self-driven energy unit, the energy management unit is configured to manage the electric energy output by the self-driven energy unit and provide the electric energy for the drug-carrying microneedle and control the drug-carrying microneedle to release microneedle drugs;

preferably, the energy management unit includes:

a rectification module configured to convert the alternating current output from the self-driven energy unit into direct current;

and the energy storage module is used for storing the direct current output by the rectifying module.

6. A method of using an electrically controlled drug-releasing microneedle system, which is suitable for use in the electrically controlled drug-releasing microneedle system of any one of claims 3 to 5, the method comprising:

enabling at least one microneedle body of the drug-carrying microneedle to penetrate into the skin so as to deliver the conductive polymer nano-doped body doped in the microneedle body into the skin;

and a driving power supply device is used for supplying power to the drug-loaded micro-needle and controlling the conductive polymer nano-doped body doped in the micro-needle body to release the micro-needle drug into the skin.

7. A method for preparing a drug-loaded microneedle is characterized by comprising the following steps:

preparing a conductive polymer nano-dopant doped with a microneedle drug;

drying and demoulding to obtain solid drug-loaded microneedle;

preferably, the material of the microneedle body in a liquid state includes at least one of hyaluronic acid, polyvinyl alcohol, polylactic acid, levorotatory polylactic acid, polyglycolic acid, chitosan, and polycaprolactone;

preferably, when the conductive polymer nano-dopant is mixed with the microneedle body material in a liquid state, a conductive synergistic material is simultaneously mixed, and then molded in a microneedle mold to form a microneedle body doped with the conductive polymer nano-dopant and the conductive synergistic material;

preferably, the conductive synergistic material comprises at least one of gold nanorods, carbon nanotubes, silver nanowires, conductive polymers and piezoelectric materials;

preferably, the forming of the microneedle substrate connected with the microneedle body on the microneedle mold includes:

forming a microneedle substrate material in a liquid state on the microneedle mould to form a microneedle substrate connected with the microneedle body;

mixing a conductive synergistic material with a liquid microneedle substrate material and then molding the mixture on the microneedle mould to form a microneedle substrate connected with the microneedle body;

preferably, the microneedle body is integrally formed with the microneedle substrate;

preferably, before drying and demolding to obtain the drug-loaded microneedle, the method further comprises the following steps:

freezing the microneedle mould carrying the microneedle needle body and the microneedle substrate, and then vacuumizing;

preferably, the time for the vacuumizing treatment is 0.5 to 24 hours;

preferably, the temperature of the freezing treatment is-80 ℃ to-20 ℃;

preferably, before forming the microneedle substrate connected to the microneedle body on the microneedle mould, the method further comprises:

forming a liquid counter electrode microneedle body material in the microneedle mould to form a counter electrode microneedle body connected with the microneedle substrate;

preferably, after drying and demolding to obtain the solid drug-loaded microneedle, the method further comprises the following steps:

and forming an inert metal layer on the surface of the microneedle body of the counter electrode.

8. The method for preparing a drug-loaded microneedle according to claim 7, wherein the preparing of the conductive polymer nano-dope doped with the microneedle drug comprises:

providing a template solution containing a template;

mixing a pyrrole monomer solution with the template solution to obtain a mixed solution;

mixing a microneedle drug with the mixed solution or mixing the microneedle drug and a dopant of counter ions with the mixed solution to obtain a microneedle drug mixed solution;

mixing an oxidant with the microneedle drug mixed solution to polymerize the pyrrole monomers into polypyrrole doped with the microneedle drug;

centrifuging and collecting to obtain a polypyrrole nano-doped body doped with the microneedle medicines;

preferably, the template includes at least one of a surfactant, a biomacromolecule, a cyclodextrin, a functional macromolecule, and an azo compound;

preferably, the template comprises at least one of cetyltrimethylammonium bromide (CTAB), acid red, Sodium Dodecyl Sulfate (SDS), sodium dodecylbenzene sulfonate (SDBS), Sodium Alkyl Sulfonate (SAS), gelatin, methyl orange, cyclodextrin, polyvinyl alcohol, N-methylene phosphorylated chitosan;

preferably, after the pyrrole monomer solution is mixed with the template solution, stirring is carried out for 10-60 minutes to obtain a mixed solution;

preferably, after the microneedle drug is mixed with the mixed solution or after the microneedle drug and the counter ion dopant are mixed with the mixed solution, stirring is performed for 10-60 minutes to obtain the microneedle drug mixed solution.

9. The method for preparing a drug-loaded microneedle according to claim 7, wherein the preparing of the conductive polymer nano-dope doped with the microneedle drug comprises:

providing an aqueous stabilizer solution containing a stabilizer;

mixing an aniline monomer with the stabilizer aqueous solution to disperse the aniline monomer in the stabilizer aqueous solution to obtain a first mixed solution;

mixing a microneedle drug with the first mixed solution or mixing the microneedle drug and a dopant of counter ions with the first mixed solution to obtain a second mixed solution;

mixing an oxidant with the second mixed solution to polymerize the aniline monomer into polyaniline doped with the microneedle drug;

and centrifuging and collecting to obtain the polyaniline nano-doped body doped with the microneedle medicines.

10. A method for preparing a drug-loaded microneedle is characterized by comprising the following steps:

drying the polymer gel microneedle doped with the conductive polymer nano-doped body to obtain a solid drug-loaded microneedle;

preferably, the preparing of the polymer gel microneedle comprises:

providing an aqueous chitosan solution;

mixing acrylamide, N' -methylene bisacrylamide and ammonium persulfate with the chitosan aqueous solution to obtain a mixture;

injecting the mixture into a microneedle mould and forming under ultraviolet irradiation;

obtaining the polymer gel microneedle after demoulding;

preferably, the mixture is injected into a microneedle mould and protected by nitrogen during the process of forming under ultraviolet irradiation;

preferably, the monomer solution of the conductive polymer is pyrrole monomer solution;

preferably, the filling the third mixed solution into the pores of the polymer gel microneedle body and in-situ polymerizing the monomer of the conductive polymer to form a conductive polymer nano-dopant doped with the microneedle drug in the polymer gel microneedle body includes:

soaking a high-molecular gel microneedle body of the high-molecular gel microneedle into the third mixed solution so as to fill the third mixed solution into pores of the high-molecular gel microneedle body, thereby obtaining a filled high-molecular gel microneedle;

providing an aqueous oxidant solution containing an oxidant;

soaking the polymer gel microneedle body filled with the polymer gel microneedle into the oxidant aqueous solution so as to polymerize the monomer of the conductive polymer in situ, thereby forming a conductive polymer nano-dopant doped with the microneedle drug in the polymer gel microneedle body;

preferably, a polymer gel microneedle body of the polymer gel microneedle is soaked in the third mixed solution, and is soaked for 4-72 hours at the temperature of 4-40 ℃;

preferably, before the polymer gel microneedle body filled with the polymer gel microneedle is soaked in the oxidant aqueous solution, the method further includes:

placing the filled polymer gel microneedle in a closed container for 1-10 hours;

preferably, the temperature in the closed vessel is from 2 ℃ to 25 ℃;

preferably, after the polymer gel microneedle body filled with the polymer gel microneedle is soaked in the oxidant aqueous solution, the polymer gel microneedle body is soaked for 5 to 20 hours at the temperature of 2 to 25 ℃;

preferably, the drying treatment of the polymer gel microneedle doped with the conductive polymer nano-dopant includes:

and (3) carrying out freeze drying on the high-molecular gel microneedle doped with the conductive polymer nano-doped body for 12-48 hours.