CN114939100A - High-density random curved surface polymer microneedle array and preparation method and application thereof - Google Patents

Abstract

The invention discloses a high-density arbitrary curved polymer microneedle array and a preparation method and application thereof. The present invention prepares a high-density arbitrary curved polymer microneedle array by adopting the principle of spontaneous and compact assembly of metal microneedles under the action of magnetic field; For simplicity and efficiency, higher scalability, flexibility and economy, it can meet the needs of neural interface, drug delivery, and subcutaneous injection. The distance between the needles of the high-density arbitrary curved polymer microneedle array prepared by the invention is less than 100 microns, the number of microneedles per square millimeter reaches more than 40, the assembly density of the microneedles is significantly improved, and the shape of the needle tip surface becomes more It is easy to control and can realize the preparation of microneedle arrays with both high density and arbitrary curved surface features.

Description

A high-density arbitrarily curved polymer microneedle array and its preparation method and application

technical field

The invention belongs to the technical field of biomedical engineering, and particularly relates to a high-density arbitrary curved polymer microneedle array and a preparation method and application thereof.

Background technique

Subcutaneous injection is widely used in clinical practice to inject vaccines and injections, but pain during injection has always been an unsolvable problem, especially for some special users such as the elderly and children. In contrast, microneedle-based transdermal delivery allows for minimally invasive access to the skin that minimizes access to the cortical dermis and nerve endings, thus significantly reducing sampling pain. In recent years, the application of microneedle array technology in the fields of drug delivery, medical cosmetology, tissue fluid extraction and biosensing is attracting more and more attention. Since the target of its action is the human skin surface, the microneedle needs to be able to fit the uneven skin and have a certain mechanical strength to penetrate the stratum corneum of the skin. In applications such as neural interface and drug delivery, the ideal microneedle should also have the following characteristics. First, for more efficient performance, high-density microneedle arrays will be preferred. For example, high-density microneedle electrodes (eg, high channel count) can better discriminate complex neural signals from densely packed neurons or nerve fibers. In addition, high-density microneedles can improve drug delivery efficiency. Second, microneedles of different heights (or lengths) will enable more comprehensive detection of neurons located at different depths in complex 3D nervous systems such as laminar cortical regions and peripheral nerves. In the case of electrical stimulation, such as stimulation of nerve fibers or the retina, microneedles of different heights can stimulate different levels of the three-dimensional space of the nervous system individually or simultaneously. Therefore, it is of great practical significance and application value to prepare microneedle arrays with high-density microneedles and the tip plane can be any curved surface.

Commonly used microneedle materials include polymers, silicon, and metals. Polymer microneedles usually have high biosafety but insufficient mechanical strength, making it difficult to pierce the stratum corneum; although silicon is hard, it is brittle and easy to break; metals have the advantage of low processing costs but poor biocompatibility. The general structure of the microneedle array is composed of solid or hollow microneedle arrays of different shapes and a substrate supporting the microneedle structure. Existing microneedle array processing methods are usually based on semiconductor processes such as photolithography, machining and etching, as well as chemical etching or laser micromachining methods to make single crystal silicon microneedles or metal microneedles, or metal templates of polymer microneedles ( CN104970804A, CN101507857A, CN108325065A, etc.). However, these processes are more complicated and the processing cost is high. What's more, most fabrication processes are for planar microneedle arrays (the tips are in the same plane). However, the skin surface of the human body is not flat, but undulating and elastic. The flat microneedle array has problems such as uneven force on human skin and the inability to completely insert the microneedle into the stratum corneum of the skin, resulting in its limited application range.

More and more studies focus on making microneedles with the same height on flexible or curved substrates to fit the undulating human surface. Although such microneedles can ensure that the microneedles are relatively completely inserted into the skin stratum corneum, due to the curved substrates Often the processing process is complicated and the problem of uneven force during use still exists. For example, when the microneedle patch is torn off, the microneedles on the side will be subjected to greater shearing force, which is more likely to break and even remain on the skin. And when facing some narrow folds of the skin, the insufficient elasticity or curvature of the substrate will also cause some microneedles to not penetrate the skin completely. Therefore, developing a simpler and lower-cost fabrication method to batch fabricate curved microneedle arrays will be of great value for the practical application of microneedle technology.

The patent (CN103301092A) discloses a preparation method of polymer microneedles. The length of the microneedles can be adjusted as required, and the adjustment of the length can form a microneedle array with any curved surface. The patent (CN103908740A) discloses a preparation method of a metal microneedle array, and specifically discloses that a base device mold, which has been poured with an epoxy resin solution and has a hole mold placed on the upper surface, is placed in a magnetic field generating device, and a uniform magnetic field is used. It interacts with the metal microneedles in the pores of the porous membrane to form a stable microneedle array structure. The patent (US2019022365A1) discloses an arbitrary curved micro-microscope based on a hole die that can be assembled in rows, and the height of the needle can be adjusted according to the surface on which the microneedle is applied, making it the same (that is, the needle tip surface is flat) or different (curved surface). Needle array preparation method.

Although these methods have the ability to prepare microneedle arrays with arbitrary curved surfaces, because the fabrication of hole-mold substrate devices often uses techniques such as machining, the resulting microneedle arrays have a needle pitch of not less than 100 microns and do not have high-density technical features , can not fully meet the dual needs of high density and arbitrary curved surfaces in the practical application of microneedle arrays, so it is urgent to develop a preparation method of microneedle arrays with both high density and arbitrary curved surface characteristics.

SUMMARY OF THE INVENTION

In order to overcome the deficiencies and shortcomings of the prior art, the primary purpose of the present invention is to provide a method for preparing a high-density arbitrary curved polymer microneedle array. The preparation method does not rely on machining or assembling methods such as machining, etching or hole mold base mold, so it is simpler and more efficient, more scalable, more flexible and more economical, and can meet the requirements of neural interface, drug delivery and subcutaneous injections, etc.

The second object of the present invention is to provide a high-density arbitrary curved polymer microneedle array prepared by the above preparation method.

The third object of the present invention is to provide the application of a high-density arbitrary curved polymer microneedle array.

The primary purpose of the present invention is achieved through the following technical solutions:

A preparation method of a high-density arbitrary curved polymer microneedle array, comprising the following steps:

(1) Preparation of metal microneedle array prototype: Place two or more conical metal microneedles with a diameter of the main body of the metal microneedle ranging from 0.05 to 0.5 mm and a diameter of the tip of the metal microneedle ranging from 0.001 to 0.01 mm vertically or obliquely. On the magnet, the metal microneedles are spontaneously and closely arranged under the action of a high-intensity magnetic field, and an arbitrary curved substrate is added between the metal microneedles and the magnet, and the metal microneedles and the substrate are brought into close contact by the magnetic force to obtain the same spatial characteristics as the substrate. The prototype of metal microneedle array;

(2) Preparation of template: a template is prepared by using the metal microneedle array prototype and template material obtained in step (1);

(3) extracting the metal microneedle array prototype from the template to obtain a high-density metal microneedle array template;

(4) pouring the polymer mixture into the high-density metal microneedle array template released in step (3);

(5) vacuuming, so that the polymer mixture poured into the high-density metal microneedle array template completely fills the pores without leaving air bubbles;

(6) performing drying treatment to solidify the polymer mixture liquid material poured into the template to obtain the microneedle array part and the substrate thin layer part of the polymer microneedle array;

(7) Connect the microneedle array part of the microneedle array prepared in step (6) and the thin layer of the substrate with the main material of the substrate to obtain a high-density arbitrary curved polymer microneedle array.

Preferably, in step (1), the metal microneedles are at least one of acupuncture needles, penetrating needles, painless needles, and metal wires that are etched or not etched.

Preferably, the diameter of the metal microneedle body is preferably 0.05, 0.1, 0.2, 0.3, 0.5 mm; the diameter of the metal microneedle tip is preferably 0.002, 0.005, 0.01 mm.

Preferably, the arbitrary curved substrate in step (1) is at least one of an arbitrary curved surface obtained by machining or three-dimensional printing.

Preferably, the magnetic field strength of the magnet in step (1) is 0.3T˜0.5T.

Preferably, the template material in step (2) is at least one of polyethylene, polytetrafluoroethylene, polydimethylsiloxane and gypsum.

Preferably, when the template material in step (2) is polyethylene, polytetrafluoroethylene and gypsum, a metal microneedle array prototype is used to press and punch a thin plate made of the material to obtain a microneedle template.

Preferably, when the template material in step (2) is polydimethylsiloxane, pour the polydimethylsiloxane into the prepared container, and insert the metal microneedle array prototype into the mixture slightly Before the surface of the needle tip, vacuum for 15-30 minutes until there are no air bubbles in the container, and then put it into a 70°C oven to cure for 3-4 hours.

Preferably, in step (4), the polymer mixture is at least one of polylactic acid, lactic acid/glycolic acid copolymer, polyvinylpyrrolidone and polyvinyl alcohol, and the mass percentage of the polymer in the polymer mixture is 10% ~80%.

The second object of the present invention is achieved through the following technical solutions:

A high-density arbitrary curved polymer microneedle array, wherein the gap between the microneedles and the microneedles is less than 100 micrometers, the number of microneedles per square millimeter reaches more than 40, the height of the needles reaches more than 900 micrometers, and the microneedles The quantity and size can be adjusted as needed.

Compared with commercial microneedles, the high-density arbitrary curved microneedles prepared by the invention have the remarkable characteristics of high density, large height and one-step molding.

The third object of the present invention is achieved through the following technical solutions:

Application of a high-density arbitrarily curved polymer microneedle array.

Specifically, the high-density arbitrarily curved polymer microneedle array is used in the fields of drug delivery, medical cosmetology, tissue fluid extraction, and biosensing.

The beneficial effects of the present invention are:

(1) The present invention prepares a high-density arbitrary curved polymer microneedle array by adopting the principle of spontaneous and compact assembly of metal microneedles under the action of a magnetic field; the preparation method does not rely on machining or assembly methods such as machining, etching, or hole mold base molds. , so it is simpler and more efficient, more scalable, more flexible and more economical, and can meet the needs of neural interface, drug delivery and subcutaneous injection.

(2) The present invention breaks through the limitation of the existing machining methods such as machining or etching on the preparation of high-density microneedle arrays. The number of microneedles in a square millimeter reaches more than 40, which significantly increases the assembly density of microneedles, and the shape of the tip surface becomes easier to control, enabling the preparation of microneedle arrays with both high density and arbitrary curved surface features.

(3) The metal microneedle unit used in the present invention can be combined with etching and other processes to improve the sharpness, so as to further improve the skin penetration ability and mechanical strength of the high-density arbitrary curved polymer microneedle array.

(4) The high-density arbitrary-curved surface polymer microneedle array prepared according to the present invention fits the skin and is more uniform in force and is not easy to break; because of its high density, it has higher performance when applied to drug delivery and medical cosmetology It can extract a larger sample size when used for tissue fluid extraction; and can detect more densely in a smaller area when used for biosensing.

Description of drawings

1 is a schematic diagram of the preparation of the prototype of the high-density metal microneedle array in Example 1;

Figure 2 is a microscope image of the prototype of the high-density metal microneedle array prepared in Example 1;

3 is a schematic diagram of the preparation of a high-density arbitrary curved polymer microneedle array in Example 2;

4 is a scanning electron microscope image of a high-density arbitrary curved polymer microneedle array in Example 2;

5 is a schematic diagram of the preparation of a high-density arbitrary curved polymer microneedle array in Example 3;

6 is a microscope image of a high-density arbitrary curved polymer microneedle array in Example 3;

7 is a schematic diagram of the structure of any curved microneedle in Example 3;

8 is a schematic diagram of the structure of any curved microneedle in Example 3;

Fig. 9 is the physical figure of polyethylene template in embodiment 6;

10 is a scanning electron microscope image of a high-density arbitrary curved polymer microneedle array in Example 6;

Figure 11 is an image of commercially available microneedles A;

Figure 12 is an image B of a commercially available commercialized microneedle;

Figure 13 is an image of commercially available microneedles C;

Fig. 14 is a needle height comparison diagram of the microneedle made by the present invention and the commercially available commercial microneedle;

Figure 15 is a comparison diagram of the needle spacing between the microneedle made by the present invention and the commercially available commercial microneedle;

Among them, metal microneedles-1, magnets-2, and curved substrates-3.

Detailed ways

The present invention will be described in further detail below with reference to the embodiments and the accompanying drawings, but the embodiments of the present invention are not limited thereto.

Example 1

This embodiment provides a high-density planar polydimethylsiloxane microneedle array with a main body diameter of 0.05 mm of metal microneedles, and the preparation method includes the following steps:

FIG. 1 and FIG. 2 are a schematic diagram of the preparation of a prototype of a high-density metal microneedle array in this example and a microscope image of the prepared prototype of a high-density arbitrarily curved polymer microneedle array.

Weigh 3g of polydimethylsiloxane in a disposable cup, stir it with a fork for 10 minutes and mix it evenly, put it into a vacuum pump, and vacuum for 15 minutes to remove air bubbles; A metal wire with a length of 40 mm is fixed with a round tube and stands vertically on the magnet, so that all the needle tips are in the same plane; under the action of the magnetic field, all the needle tips spontaneously and closely contact the substrate; add a small amount of polydimethylsiloxane into the tube , put it in a 70°C oven to cure for 1 h, so that the needle and the round tube are tightly connected and fixed; after drying, a flat metal microneedle array prototype is obtained. Pour polydimethylsiloxane into the prepared container, insert the metal microneedle array prototype until the mixture is slightly below the needle tip, vacuumize for 15 to 30 minutes until no bubbles are present, and then put it in a 70°C oven to cure for 3 hours; The metal microneedle array prototype was released from the polydimethylsiloxane template, resulting in a planar polydimethylsiloxane template.

After the template was treated with a plasma cleaner for 5 to 10 minutes, a small amount of 1H,1H,2H,2H-perfluorooctyltrichlorosilane was added dropwise beside the template overnight in a chemical fume hood to make it uniformly deposited on the surface of the template. Pour polydimethylsiloxane into the template, vacuumize for 30 minutes until there are no bubbles, and then put it in a 70°C oven to cure for 1 hour; remove the microneedle array from the template to obtain a high-density planar polydimethylsiloxane Microneedle array.

Example 2

This embodiment provides a high-density planar polydimethylsiloxane microneedle array with a microneedle body diameter of 0.2 mm, and the preparation method includes the following steps:

Weigh 3g of polydimethylsiloxane in a disposable cup, stir it with a fork for 10 minutes and mix it evenly, put it in a vacuum pump, and vacuum for 15 minutes to remove air bubbles; the diameter of the prepared 100 microneedles is A stainless steel acupuncture needle with a diameter of 0.2 mm, a length of 40 mm and a microneedle tip diameter of 0.002 mm is fixed with a round tube, and the needle tip is placed vertically on the magnet so that all needle tips are in the same plane; under the action of the magnetic field, all needle tips are A small amount of polydimethylsiloxane was added to the tube and cured in a 70°C oven for 1 hour, so that the needle and the round tube were tightly connected and fixed; a flat metal microneedle array prototype was obtained after drying. Pour polydimethylsiloxane into the prepared container, insert the metal microneedle array prototype until the mixture is slightly below the needle tip, vacuumize for 15 to 30 minutes until no bubbles are present, and then put it in a 70°C oven to cure for 3 hours; The metal microneedle array prototype was released from the polydimethylsiloxane template, resulting in a planar polydimethylsiloxane template.

After the template was treated with a plasma cleaner for 5 to 10 minutes, a small amount of 1H,1H,2H,2H-perfluorooctyltrichlorosilane was added dropwise beside the template overnight in a chemical fume hood to make it uniformly deposited on the surface of the template. Pour polydimethylsiloxane into the template, vacuumize for 30 minutes until there are no bubbles, and then put it in a 70°C oven to cure for 1 hour; remove the microneedle array from the template to obtain a high-density planar polydimethylsiloxane Microneedle array.

FIG. 3 shows a schematic diagram of the preparation of the high-density arbitrary-curved polymer microneedle array of this embodiment, and the metal microneedle array prototype includes metal microneedles 1 and magnets 2; FIG. 4 shows the high-density arbitrary curved surface of this embodiment. SEM image of a polymer microneedle array.

Example 3

This embodiment provides a high-density curved polydimethylsiloxane microneedle array with a microneedle diameter of 0.2 mm, the preparation method of which includes the following steps:

FIG. 5 shows a schematic diagram of the preparation of the high-density arbitrary curved polymer microneedle array of this embodiment. The prototype of the metal microneedle array includes metal microneedles 1, magnets 2 and a curved substrate 3; FIG. 6 shows this embodiment. Microscopy image of a high-density arbitrarily curved polymer microneedle array.

Weigh 3g of polydimethylsiloxane in a disposable cup, stir it with a fork for 10 minutes and mix it evenly, put it into a vacuum pump, and vacuum for 15 minutes to remove air bubbles; A stainless steel needle with a length of 40 mm was fixed with a round tube, and its needle tip was vertically standing on the surface of the curved substrate obtained by machining or 3D printing on the magnet. Under the action of the magnetic field, all needle tips spontaneously and closely contacted the substrate; A small amount of polydimethylsiloxane was added to the tube, and it was put into a 70°C oven to cure for 1 hour, so that the needle and the round tube were tightly connected and fixed; after drying, the prototype of the curved metal microneedle array was obtained. Pour polydimethylsiloxane into the prepared container, insert the metal microneedle array prototype until the mixture is slightly below the needle tip, vacuumize for 15 to 30 minutes until no bubbles are present, and then put it in a 70°C oven to cure for 3 hours; The metal microneedle array prototype was released from the polydimethylsiloxane template to obtain a curved polydimethylsiloxane template.

After the template was treated with a plasma cleaner for 5 to 10 minutes, a small amount of 1H,1H,2H,2H-perfluorooctyltrichlorosilane was added dropwise beside the template overnight in a chemical fume hood to make it uniformly deposited on the surface of the template. Pour polydimethylsiloxane into the template, vacuumize for 30 minutes until there are no bubbles, and then put it in a 70°C oven to cure for 1 hour; remove the microneedle array from the template to obtain a high-density curved polydimethylsiloxane Microneedle array.

In the same way, the schematic diagram of the high-density polymer microneedle structure of any curved surface can be obtained by changing the curved surface substrate, as shown in FIG. 7 and FIG. 8 .

Example 4

The present embodiment provides a high-density lactic acid/glycolic acid copolymer microneedle array, the preparation method of which includes the following steps:

Same as Example 2 or 3, the microneedle material was changed to lactic acid/glycolic acid copolymer. The specific method is as follows:

0.2 g of lactic acid/glycolic acid copolymer and 0.8 g of diethylene glycol dimethyl ether were weighed, and the lactic acid/glycolic acid copolymer was dissolved in diethylene glycol dimethyl ether to obtain a 20% lactic acid/glycolic acid copolymer solution. Pour the lactic acid/glycolic acid copolymer solution into the template, vacuumize for 15 minutes until no bubbles are present, and then dry at room temperature for 24 hours; remove the microneedle array from the template to obtain a high-density curved lactic acid/glycolic acid copolymer microneedle array .

Example 5

The present embodiment provides a high-density polyvinyl alcohol microneedle array, the preparation method of which includes the following steps:

Same as Example 2 or 3, the microneedle material was changed to polyvinyl alcohol. The specific method is as follows:

Weigh 4.5 g of polyvinyl alcohol and dissolve it in 30 ml of water to obtain a 15% polyvinyl alcohol solution. The polyvinyl alcohol solution was poured into the template, vacuumed for 15 minutes until no bubbles were present, and then dried at room temperature for 48 hours; the microneedle array was removed from the template to obtain a high-density polyvinyl alcohol microneedle array.

Example 6

This embodiment provides a high-density microneedle array polyethylene plate template, and the preparation method includes the following steps:

As in Example 2 or 3, the template material polydimethylsiloxane was changed to polyethylene board (FIG. 9 and FIG. 10). The specific method is as follows:

After the polyethylene plate was placed on a heating plate and heated to 50 degrees Celsius to soften slightly, the metal microneedle array prototype was pressed on it and cooled to form a high-density polyethylene template.

Fig. 9 is a physical view of the polyethylene template in this embodiment; Fig. 10 is a scanning electron microscope image of a high-density arbitrary curved polymer microneedle array in this embodiment.

Example 7

This example provides a comparison of the effects of the high-density microneedle arrays prepared in Examples 1-5 and commercial microneedle products.

Fig. 11, Fig. 12 and Fig. 13 are SEM images of different commercialized microneedle products A, B and C; it can be seen from Fig. 14 and Fig. 15 that the microneedle array needles prepared in Examples 1-5 of the present invention The pitch reaches the diameter of a single needle, the height of the needle reaches 950 microns, and the number of needles per square millimeter reaches more than 40. However, the needle spacing of commercial microneedles is greater than 250 microns, the height of microneedles is less than 400 microns, and the number of needles per square millimeter is less than 25. It can be seen that, compared with the commercial microneedle products A, B, and C, the microneedle arrays prepared in Examples 1-5 of the present invention have smaller spacing between the microneedles and higher height of the microneedles than the current commercially available microneedles. .

Example 8

This example provides a comparison of the drug loading between the high-density microneedle array prepared by the present invention and the commercial microneedle product, which specifically includes the following steps:

The drug carried by the microneedles is insulin (Novolin, 300IU/3mL).

Dilute the insulin solution to 5IU and soak one high-density microneedle patch in every 200 microliters of insulin solution for 30 minutes. After 30 minutes, the high-density microneedle patch was taken out, and the concentration of insulin in the soaked solution was measured by high performance liquid chromatography. In the same way, the insulin solution soaked with the commercial microneedle patch and the insulin solution not soaked with the microneedle patch were tested. After testing, the content of insulin in the solution soaked in the high-density microneedle patch<the insulin content in the solution soaked in the commercial microneedle patch<the insulin content of the unsoaked microneedle patch, that is, the high-density microneedle patch prepared by the present invention. The drug loading of the density microneedles is greater than that of commercial microneedles.

The above-mentioned embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above-mentioned embodiments, and any other changes, modifications, substitutions, combinations, The simplification should be equivalent replacement manners, which are all included in the protection scope of the present invention.

Claims (9)

1. a preparation method of high-density arbitrary curved polymer microneedle array, is characterized in that, comprises the following steps: (1) Preparation of metal microneedle array prototype: Place two or more conical metal microneedles with a diameter of the main body of the metal microneedle ranging from 0.05 to 0.5 mm and a diameter of the tip of the metal microneedle ranging from 0.001 to 0.01 mm vertically or obliquely. On the magnet, the metal microneedles are spontaneously and closely arranged under the action of a high-intensity magnetic field, and an arbitrary curved substrate is added between the metal microneedles and the magnet, and the metal microneedles and the substrate are brought into close contact by the magnetic force to obtain the same spatial characteristics as the substrate. The prototype of metal microneedle array; (2) Preparation of template: a template is prepared by using the metal microneedle array prototype and template material obtained in step (1); (3) extracting the metal microneedle array prototype from the template to obtain a high-density metal microneedle array template; (4) pouring the polymer mixture into the high-density metal microneedle array template released in step (3); (5) vacuuming, so that the polymer mixture poured into the high-density metal microneedle array template completely fills the pores without leaving air bubbles; (6) performing drying treatment to solidify the polymer mixture liquid material poured into the template to obtain the microneedle array part and the substrate thin layer part of the polymer microneedle array; (7) Connect the microneedle array part of the microneedle array prepared in step (6) and the thin layer of the substrate with the main material of the substrate to obtain a high-density arbitrary curved polymer microneedle array. 2. The method for preparing a high-density arbitrary curved polymer microneedle array according to claim 1, wherein the metal microneedles in step (1) are acupuncture needles with or without etching, acupuncture needles, At least one of painless needles and wires. 3. The method for preparing a high-density arbitrary curved polymer microneedle array according to claim 1, wherein the diameter of the metal microneedle body is 0.05, 0.1, 0.2, 0.3, 0.5 mm; the diameter of the metal microneedle tip 0.002, 0.005, 0.01 mm. 4 . The method for preparing a high-density arbitrary curved polymer microneedle array according to claim 1 , wherein the arbitrary curved substrate in step (1) is at least one of any curved surfaces obtained by machining or three-dimensional printing. 5 . kind. 5 . The method for preparing a high-density arbitrarily curved polymer microneedle array according to claim 1 , wherein the magnetic field strength of the magnet in step (1) is 0.3T˜0.5T. 6 . 6. The method for preparing a high-density arbitrary curved polymer microneedle array according to claim 1, wherein the template material in step (2) is polyethylene, polytetrafluoroethylene, polydimethylsiloxane At least one of alkane and gypsum. 7. The preparation method of high-density arbitrarily curved polymer microneedle array according to claim 1, characterized in that, in step (4), the polymer mixture is polylactic acid, lactic acid/glycolic acid copolymer, polyvinylpyrrolidone and For at least one of the polyvinyl alcohols, the mass percentage of the polymer in the polymer mixture is 10% to 80%. 8. A high-density arbitrarily curved polymer microneedle array, characterized in that, the gap between the microneedle and the microneedle of the high-density arbitrarily curved polymer microneedle array is less than 100 microns, and the root of the microneedle in every square millimeter is less than 100 microns. The number of micro-needles is more than 40, and the height of needles is more than 900 microns. The number and size of micro-needles can be adjusted according to needs. 9. An application of the high-density arbitrarily curved polymer microneedle array of claim 9 in the fields of drug delivery, medical cosmetology, tissue fluid extraction and biosensing.

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