CN106063971A - Percutaneous electric osmose doser based on metal porous microneedle array and medication - Google Patents

Abstract

The present invention relates to a percutaneous electroosmosis drug delivery device and drug delivery method based on a metal porous microneedle array. It is connected with the cathode of the medical physiological electrode by welding, the metal porous microneedle array 1 is not connected with the metal porous microneedle array 2, and the anode and cathode of the medical physiological electrode are respectively connected with the controllable pulse power supply. The present invention utilizes the microneedle array Penetrate the skin to destroy the tissue structure of the stratum corneum, then provide drug delivery channels for liquid drugs through the pores of the metal porous microneedle array, and finally electrify both ends of the microneedle array, and use the electric field and electroosmotic flow to make the drug penetrate into the human body.

Description

Transdermal electroosmotic drug delivery device and drug delivery method based on metal porous microneedle array

technical field

The invention relates to the technical field of biomedical engineering, and more specifically, to a transdermal electroosmotic drug delivery device based on a metal porous microneedle array and a transdermal electroosmotic drug delivery method based on a metal porous microneedle array.

Background technique

With the development of society and the improvement of science and technology, more and more people pay attention to medical and health issues. Among the treatment methods at this stage, drug therapy is the most common treatment method. Its therapeutic principle is to transfer the drug from the outside of the body to the human body through a certain transport method to produce the drug effect.

Injection is the most direct way of drug delivery in drug therapy, but the pain brought by injection to patients will affect the progress of treatment, and injection cannot achieve the effect of sustained release, which will cause blood drug concentration to rise rapidly in a short time High, low drug utilization, which requires doctors to frequently administer medication, which not only affects the efficiency of treatment but also causes greater pain to patients.

Transdermal drug delivery has outstanding advantages, not only can avoid complicated drug delivery process, but also the drug has a high drug utilization rate in the body. Because transdermal administration is absorbed through the skin through capillaries and enters the human body's circulation, it avoids its enzymatic hydrolysis by enzymes in the gastrointestinal tract and the "first-pass effect" of the liver, and releases the drug through the control of transdermal administration. The speed can make the drug exist in the blood at a constant concentration for a long time, which reduces the side effects of the drug to a certain extent and enhances the drug effect. Therefore, transdermal drug delivery is now attracting the attention of many domestic and foreign pharmacists.

In the process of transdermal administration, due to the barrier effect of the stratum corneum, it is difficult for most drugs to penetrate directly into the skin. Therefore, overcoming the barrier function of cutin is the key to improving the rate of transdermal drug delivery. Techniques used to overcome the barrier function of the stratum corneum are known as transdermal enhancement techniques. At present, common permeation-enhancing technologies mainly include iontophoresis, ultrasonic induction, magnetic field and electrophoresis, and pore-forming techniques, such as electroporation, thermal poration, microneedle pore-forming, and laser-introduction techniques. Microneedle pore-forming technology belongs to physical pore-making technology. It penetrates the stratum corneum of the epidermis and destroys its structure through the puncture effect of micro-needles, but it does not penetrate the tissues and nerves of the dermis. Therefore, it has the advantages of slight pain, good wound healing, and small damage. At the same time, the manufacturing process is relatively simple, and there is potential for low-cost mass production, so the development prospect of microneedle hole-making technology is very promising.

Although the microneedle array transdermal drug delivery technology has a good prospect, the microneedle array transdermal drug delivery technology is still immature, which is determined by the manufacturing process and structure of the microneedle array itself. Common microneedle arrays can be divided into solid needles and hollow needles. Solid needles have good mechanical properties and can puncture the skin. However, due to their structural limitations, drugs need to be smeared after puncture during the administration process. Not only the operation is complicated but also the rate of administration is uncontrollable. Hollow needles can be used for microneedle injection, but their mechanical properties are slightly insufficient. In recent years, the introduction of the concept of degradable microneedles has brought new ideas for transdermal drug delivery. Degradable microneedles can degrade autonomously during the drug delivery process and can load more drugs, but the mechanical properties are insufficient and cannot be achieved. Controlled drug release rate is still a difficult problem that researchers need to overcome at this stage.

Contents of the invention

The purpose of the present invention is to overcome the deficiencies of the prior art, and provide a transdermal electroosmotic drug delivery device and a transdermal electroosmotic drug delivery method based on metal porous microneedle arrays. The metal porous microneedle array adopted in the present invention has a porous structure, which provides storage space and drug delivery channel for liquid medicine; at the same time, the metal porous microneedle array has good mechanical properties and mechanical strength, ensuring that the shape of the metal porous microneedle array is There is no obvious change during the administration process; since the selected material is a metal material with good biocompatibility, it will not cause immune rejection to the human body during the skin puncture process; The two ends of the array are energized, and the rate of drug administration is controlled by adjusting the magnitude of the current to achieve the effect of controlled release.

In order to solve the problems of the technologies described above, the technical solution adopted in the present invention is:

A transdermal electroosmotic drug delivery device based on a metal porous microneedle array, including two metal porous microneedle arrays, a medical physiological electrode and a controllable pulse power supply, the metal porous microneedle array-and the anode of the medical physiological electrode by welding The metal porous microneedle array 2 is connected to the cathode of the medical physiological electrode by welding, the metal porous microneedle array 1 is not connected to the metal porous microneedle array 2, and the anode and cathode of the medical physiological electrode respectively connected with the controllable pulse power supply correspondingly.

The present invention utilizes the pores and conductive properties of the metal microneedle array to simultaneously conduct microneedle array percutaneous electroosmosis administration of drugs, which is simple to operate and simplifies the administration steps, and the administration rate can be adjusted by adjusting the current parameters of the controllable pulse power supply. Regulation is carried out to make transdermal electroosmotic administration controllable. At the same time, the pores of the microneedle array can provide drug storage for liquid drugs, and the larger pore size can allow macromolecular drugs to pass through smoothly, making the microneedle array transdermal drug delivery more efficient. Finally, the whole device has good biocompatibility, will not cause too much harm to the human body during the administration process, and the puncture site can heal itself in a short time.

The metal porous microneedle array is formed by metal sintering, and the metal with good biocompatibility is selected as the raw material of the microneedle array, so as to avoid the immune rejection reaction of the microneedle array in the contact process of the skin. Preferably, the metal porous microneedle array The material can be titanium alloy.

The shape and size of the metal porous microneedle array are determined by the size of the inverted mold microneedle array. In order to ensure that the metal porous microneedle array can penetrate into the skin tissue without causing more harm to people, and at the same time the porous structure provides a drug delivery route, the substrate thickness of the metal porous microneedle array is 3-15mm. The height of the microneedle is 300-600um, the height of the needle tip is 30-80um, and the distance between the needles is 2-5mm.

The material of the medical physiological electrode is silver or silver chloride, and the shape of the medical physiological electrode is square or circular.

The current signal of the controllable pulse power supply is a pulse signal, the current intensity is 0.5mA, the waveform is a square wave, the frequency is 50HZ, and the power-on time is 10min.

The present invention also provides a transdermal electroosmosis drug delivery method based on the metal porous microneedle array, the first metal porous microneedle array is connected to the anode of the medical physiological electrode by welding, the second metal porous microneedle array is connected to the cathode of the medical physiological electrode Connected by welding, the metal porous microneedle array 1 is not connected to the metal porous microneedle array 2, the anode and cathode of the medical physiological electrode are respectively connected to the controllable pulse power supply, the metal porous microneedle The needle tip of the array is pre-stored with liquid medicine, and during the process of dripping the liquid medicine into the back of the substrate of the metal porous microneedle array drop by drop with a syringe, the controllable pulse power supply is activated for electroosmotic drug delivery. Adjusting the current parameters of the controllable pulse power supply regulates the drug delivery rate.

The present invention is based on the percutaneous electroosmotic drug delivery method of the metal porous microneedle array, which uses the pores of the metal porous microneedle array to store liquid medicine, and provides a drug delivery channel for it during the drug delivery process, ensuring stable and sustainable drug delivery throughout the process into the body. At the same time, the controllable pulse power supply is used to control the voltage of the tip of the microneedle array, thereby controlling the rate of drug delivery, so that the treatment process becomes more efficient. The administration rate of the method is controllable, and the administration amount can be adjusted according to the treatment demand, without causing too much harm to the human body.

In order to make the process of electroosmotic drug delivery efficient, the signal generated by the controllable power supply selects the pulse signal. Since the stratum corneum of the skin will be polarized during the electroosmotic drug delivery process, the pulse signal can increase the drug delivery rate and the frequency of the signal. The waveform and duty cycle can be fine-tuned according to the specific situation of the drug.

At the same time, the needle tip is kept perpendicular to the skin surface during the puncture process, which can ensure that the microneedles will not break and embed into the skin surface during the whole process, ensuring safety.

Description of drawings

Fig. 1 is the schematic structural diagram of the transdermal electroosmotic drug delivery device based on the metal porous microneedle array in Example 1;

2 is a schematic cross-sectional view of the metal porous microneedle array in Example 1;

Fig. 3 is the top view of embodiment 1 metal porous microneedle array;

FIG. 4 is a schematic diagram of the transdermal electroosmotic drug delivery process in Example 1. FIG.

detailed description

The present invention will be further described below in combination with specific embodiments. Wherein, the accompanying drawings are only for illustrative purposes, showing only schematic diagrams, rather than physical drawings, and should not be construed as limitations on this patent; in order to better illustrate the embodiments of the present invention, some parts of the accompanying drawings will be omitted, Enlargement or reduction does not represent the size of the actual product; for those skilled in the art, it is understandable that certain known structures and their descriptions in the drawings may be omitted.

In the drawings of the embodiments of the present invention, the same or similar symbols correspond to the same or similar components; The orientation or positional relationship indicated by etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the referred device or element must have a specific orientation, use a specific Orientation structure and operation, therefore, the terms describing the positional relationship in the drawings are only for illustrative purposes, and should not be construed as limitations on this patent. Those of ordinary skill in the art can understand the specific meanings of the above terms according to specific situations.

Example 1

As shown in Figure 1, the percutaneous electroosmotic drug delivery device based on the metal porous microneedle array of the present embodiment includes a metal porous microneedle array one 1, a metal porous microneedle array two 2, a medical physiological electrode 3 and a controllable pulse power supply 4. The metal porous microneedle array 1 and the metal porous microneedle array 2 are not connected to each other, the material of the medical physiological electrode 3 is silver, and the shape is a cube whose length, width and height are 1:0.5:0.45cm, and the metal porous microneedle array 1 It is connected to the cathode of the medical physiological electrode 3 by welding, the metal porous microneedle array 2 is connected to the anode of the medical physiological electrode 3 by welding, and the anode and cathode of the medical physiological electrode 3 are connected to the controllable pulse power supply 4 respectively.

Figure 2 is a schematic cross-sectional view of the metal porous microneedle array. The metal porous microneedle array substrate 5 selected in this example has a thickness of 1.5 cm, the tip height of the microneedles 6 is 500 um, the bottom diameter of the tip is 200 um, and the distance between the needles is 1 mm. The porosity of the microneedle array is 15%, and the average pore size is 100um. The above setting is to ensure that the metal porous microneedle array can penetrate into the skin tissue without causing more harm to people, and at the same time, the porous structure provides a drug delivery route. Finally, the microneedle array is sintered from titanium alloy micron particles. Titanium alloy has good biocompatibility and will not cause immune rejection of the skin during puncture.

As shown in Figure 3 is the top view of the metal porous microneedle array, the metal porous microneedle array is a square array of 10 × 10, the distance between rows and columns is 1 mm, and the entire substrate is a square of 1.5 × 1.5 cm. The success rate of the puncture can be guaranteed, and the influence between the needles during the puncture can be avoided.

It should be noted that the metal porous microneedle array 1 and the metal porous microneedle array 2 described herein are two identical metal porous microneedle arrays, and the metal porous microneedle array described herein is the metal porous microneedle array 1 and the metal porous microneedle array A general term for metal porous microneedle array II.

FIG. 4 is a schematic diagram of a transdermal electroosmotic drug delivery method based on a metal porous microneedle array. The device used in the transdermal electroosmotic drug delivery method in this embodiment is shown in FIG. 1 , FIG. 2 and FIG. 3 .

The specific operation steps of the transdermal electroosmotic drug delivery method in this embodiment are as follows:

a. Select a certain area on the surface of the skin tissue as the transdermal administration area, and carry out disinfection treatment on it.

b. Drop the liquid medicine into the needle tip of the metal porous microneedle array, so that the liquid medicine is pre-stored in the needle tip. After the liquid medicine penetrates into the metal porous microneedle array, press the metal porous microneedle array to the surface of the skin tissue, and wait After the needle array is punctured, it is fixed with medical adhesive tape.

c. Use a syringe to absorb liquid medicine, and drop the liquid medicine into the back of the substrate of the metal porous microneedle array, turn on the controllable pulse power supply, and perform electroosmotic drug delivery, and adjust the current parameters of the power supply during the drug delivery process. The speed is regulated. In this embodiment, the current signal is set as a pulse signal, the current intensity is 0.5mA, the waveform is a square wave, the frequency is 50HZ, and the power-on time is 10min.

d. After the drug administration, the metal porous microneedle array is taken out, and the area where the drug is administered on the skin surface is disinfected with medical alcohol.

The transdermal electroosmotic drug delivery method in this embodiment includes three drug delivery processes, the first is that the drug stored in the hole diffuses into the skin tissue after the microneedle punctures the skin, and the second is that the liquid drug Titration, the drug enters the skin from the base position along the needle tip through the through-hole of the microneedle array. The third is that after the electricity is applied, the drug is subjected to the action of the magnetic field and the electroosmotic flow, and quickly enters the human body. The combination of the three methods not only has high efficiency, but also the rate of administration can be adjusted.

Embodiment two

The operation method of this embodiment is similar to that of Embodiment 1, except that the metal porous microneedle array selected in this embodiment has a porosity of 10%, and the microneedle arrays are arranged in 7 rows in total.

Apparently, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the implementation of the present invention. For those of ordinary skill in the art, other changes or changes in different forms can be made on the basis of the above description. It is not necessary and impossible to exhaustively list all the implementation manners here. All modifications, equivalent replacements and improvements made within the spirit and principles of the present invention shall be included within the protection scope of the claims of the present invention.

Claims (9)

1. The transdermal electroosmotic drug delivery device based on the metal porous microneedle array is characterized in that it comprises two metal porous microneedle arrays, medical physiological electrodes and controllable pulse power supply, and the metal porous microneedle array one and the medical physiological The anode of the electrode is connected by welding, the metal porous microneedle array 2 is connected with the cathode of the medical physiological electrode by welding, the metal porous microneedle array 1 is not connected to the metal porous microneedle array 2, the medical The anode and cathode of the physiological electrodes are respectively connected to the controllable pulse power supply. 2 . The device according to claim 1 , wherein the metal porous microneedle array is formed by metal sintering, and the shape and size of the metal porous microneedle array are determined by the size of the inverted mold microneedle array. 3. The device according to claim 1 or 2, wherein the metal porous microneedle array material is titanium alloy. 4. The device according to claim 3, wherein the base thickness of the metal porous microneedle array is 3-15mm, the height of the microneedles is 300-600um, the height of the needle tip is 30-80um, and the distance between the needles is The distance is 2 ~ 5mm. 5. The device according to claim 4, wherein the material of the medical physiological electrode is silver or silver chloride, and the shape of the medical physiological electrode is square or circular. 6. The device according to claim 5, wherein the current signal of the controllable pulse power supply is a pulse signal, the current intensity is 0.5mA, the waveform is a square wave, the frequency is 50HZ, and the power-on time is 10min. 7. A transdermal electroosmotic drug delivery method based on a metal porous microneedle array, characterized in that the metal porous microneedle array one is connected to the anode of the medical physiological electrode by welding, and the metal porous microneedle array two is connected to the medical physiological electrode The cathode of the electrode is connected by welding, the metal porous microneedle array one is not connected to the metal porous microneedle array two, the anode and cathode of the medical physiological electrode are respectively connected to the controllable pulse power supply, The needle tip of the metal porous microneedle array pre-stores liquid medicine, and during the process of dripping the liquid medicine into the back of the substrate of the metal porous microneedle array drop by drop with a syringe, the controllable pulse power supply is activated to perform electroosmotic drug delivery , adjusting the current parameters of the controllable pulse power supply during the administration process to regulate the administration rate. 8 . The drug delivery method according to claim 7 , wherein the controllable pulse power supply provides a pulse current, and the waveform, frequency and duty cycle of the pulse current are adjusted to regulate the drug delivery rate. 9. The drug delivery method according to claim 8, wherein the metal porous microneedle array is as described in claims 2 to 4, the medical physiological electrode is as described in claim 5, and the controllable pulse The power supply is as described in claim 6.