KR20230095488A - micro-needle - Google Patents

Abstract

The present invention relates to a microneedle including a first layer containing a material that selectively reacts with glucose in the body and a second layer including a material that removes or inhibits reactive oxygen species (ROS) in the body, and a method for manufacturing the same. By including a double layer of a glucose sensor layer and a reactive oxygen species removal layer, stable sensor sensitivity to glucose in the body and excellent durability can be provided.

Description

Micro-needle {micro-needle}

The present invention relates to a microneedle, and more particularly, to a microneedle for continuous glucose monitoring.

As the population ages worldwide, the burden of diabetes among members of society is increasing. Diabetes mellitus is a disease in which high blood sugar levels persist for a long period of time and is caused by insufficient production of insulin or inability of body cells to respond appropriately to the produced insulin. This leads to complications such as blindness and myocardial infarction, which lead to a decrease in quality of life. Diabetes requires continuous management, and proper blood sugar measurement is necessary accordingly.

As a conventional blood glucose measurement method, there is a method of measuring blood sugar by directly drawing blood 6 to 10 times a day. This method can accurately measure blood sugar, but has disadvantages in that it is less convenient and gives patients pain and fear because they have to injure their fingers every time. In addition, since intermittent blood sampling can only know blood glucose at the moment of measurement, hyperglycemia and hypoglycemia between measurements may be missed, and thus do not accurately reflect changes in blood glucose. Therefore, for intensive blood glucose management, a continuous glucose monitoring system (CGMS) is required.

For example, commercial CGMS include needle-type and fully implantable glucose sensors. Needle-type sensors are unreasonable for patients suffering from needle phobia to be inserted with a large needle. In addition, fully implantable sensors require implantation and removal surgery every 3 months. Accordingly, there is a need for a technique capable of maintaining blood glucose within a normal range through continuous glucose measurement without direct blood collection using an injection needle or surgery.

Korean Patent Publication No. 10-2021-0049864

An object of the present invention is to provide a microneedle that exhibits stable sensor sensitivity to glucose in the body and has excellent durability.

In order to solve the above problems, the microneedle of the present invention includes a first layer including a material that selectively reacts with glucose in the body; and a second layer including a material that removes or inhibits reactive oxygen species (ROS) in the body.

The material that selectively reacts with glucose in the body may include at least one of boronic acid and boronic acid derivatives.

The boronic acid derivative includes a structural unit derived from bis-phenylboronate; structural units derived from polyethylene glycol; and a structural unit derived from acrylamide.

Substances that remove or inhibit reactive oxygen species (ROS) in the body include polyphenol, astaxanthin, beta-carotene, glutathione (GSH), L-ascorbic acid (L- Ascorbic acid), Ubiquinone (Q, CoQ), Fisetin, α-lipoic acid (ALA), Lycopene, Tocopherol, Epigallocatechin gallate, EGCG) and dexamethasone may include at least one selected from the group consisting of.

The second layer may be coated on an outer surface of the first layer.

The first layer may further include polyacrylamide.

The polyacrylamide may be formed by polymerization of acrylamide, sodium persulfate, and tetramethylethylenediamine (N, N, N', N'-Tetramethylethylenediamine).

The polyacrylamide is acrylamide at a concentration of 15 w / v% to 30 w / v%, the sodium persulfate at a concentration of 1 w / v% to 10 w / v%, and the tetmethylethylene It may be formed by reacting diamine (N, N, N', N'-Tetramethylethylenediamine) at a concentration of 0.1 w/v% to 2 w/v%.

The second layer may further include carboxymethyl cellulose.

The second layer is carboxymethyl cellulose (carboxymethyl cellulose) concentration of 2 w / v% to 12 w / v%; and ascorbic acid may be included at a concentration of 0.4 w/v% to 0.8 w/v%.

The second layer coated on the first layer may have a thickness of 2 μm to 10 μm.

The microneedle of the present invention includes a double layer of a glucose sensor layer and a reactive oxygen species removal layer, thereby exhibiting stable sensor sensitivity to glucose in the body and providing excellent durability. In addition, the microneedle of the present invention can provide an effect of continuously monitoring glucose without causing pain to the user.

1A and 1B are perspective views of microneedles according to an exemplary embodiment.
2A and 2B are enlarged perspective views of microneedles according to an exemplary embodiment.
3 is a cross-sectional view of a microneedle according to an exemplary embodiment.
4 to 8 are diagrams showing evaluation results of microneedles according to Examples and Comparative Examples.

Since the present invention may have various changes and various forms, specific embodiments are illustrated in the drawings and described in detail in the text. However, it should be understood that this is not intended to limit the present invention to the specific disclosed form, and includes all modifications, equivalents, and substitutes included in the spirit and scope of the present invention.

In this specification, when an element (or region, layer, section, etc.) is referred to as being “on,” “connected to,” or “coupled to” another element, it is directly placed/placed on the other element. It means that they can be connected/combined or a third component may be placed between them.

Meanwhile, in the present specification, "directly disposed" may mean that there is no layer, film, region, plate, etc. added between a part of a layer, film, region, plate, etc. and another part. For example, being “directly disposed” may mean disposing without using an additional member such as an adhesive member between two layers or two members.

Like reference numerals designate like components. Also, in the drawings, the thickness, ratio, and dimensions of components are exaggerated for effective description of technical content. “And/or” includes any combination of one or more that the associated elements may define.

Terms such as first and second may be used to describe various components, but the components should not be limited by the terms. These terms are only used for the purpose of distinguishing one component from another. For example, a first element may be termed a second element, and similarly, a second element may be termed a first element, without departing from the scope of the present invention. Singular expressions include plural expressions unless the context clearly dictates otherwise.

In addition, terms such as “below”, “lower side”, “lower side”, “above”, “upper side”, and “upper side” are used to describe the relationship between components shown in the drawings. The above terms are relative concepts and will be described based on the directions shown in the drawings. In this specification, "disposed on" may indicate a case of disposing not only on top of any one member but also on the bottom.

Terms such as "include" or "have" are intended to indicate that a feature, number, step, operation, component, part, or combination thereof described in the specification exists, but that one or more other features, numbers, or steps are present. However, it should be understood that it does not preclude the possibility of existence or addition of operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms (including technical terms and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In addition, terms such as terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and unless explicitly defined herein, interpreted as too idealistic or too formal. It shouldn't be.

Hereinafter, a microneedle and a manufacturing method thereof according to an embodiment of the present invention will be described with reference to the drawings.

1A and 1B are perspective views of microneedles according to an embodiment of the present invention. 2a and 2b are enlarged perspective views of microneedles according to an embodiment of the present invention. Specifically, FIG. 2A is an enlarged perspective view of an area (A) corresponding to one microneedle shown in FIG. 1A, and FIG. 2B is an enlarged view of an area (B) corresponding to one microneedle shown in FIG. 1B. It is a perspective view shown by 3 is a cross-sectional view of a microneedle according to an embodiment. 3 is a cross-sectional view showing a portion corresponding to the line II′ of FIG. 2A.

Referring to FIGS. 1A and 1B , the microneedle 100 of one embodiment may be provided in a bonded form to the base layer 130 .

As shown in FIGS. 1A and 1B , the microneedle 100 is orthogonal to the plane defined by the first directional axis DR1 and the second directional axis DR2 . The thickness direction of the microneedle 100 is indicated by the third direction axis DR3. However, the first to third directional axes DR1 , DR2 , and DR3 shown in this embodiment are merely examples. Hereinafter, first to third directions are defined as directions indicated by each of the first to third direction axes DR1 , DR2 , and DR3 , and refer to the same reference numerals.

In one embodiment, the microneedles 100 may be provided by being bonded to the base layer 130 . The microneedles 100 have a shape protruding from the base layer 130 in the third direction, and may be disposed on the base layer 130 in plurality. Each of the plurality of microneedles 100 may be spaced apart from each other by a predetermined distance along the first and second directions DR1 and DR2 .

Referring to FIGS. 2A and 2B , of both ends of the microneedle 100, the lower end 111 is defined as the part bonded to the base layer 130, and the other end opposite to the lower end 111 is defined as the upper end 112. can do. In one embodiment, the area of the microneedle 100 when viewed on a plane defined by the first and second directions DR1 and DR2 may decrease from the lower end 111 to the upper end 112. For example, the upper end 112 may include a tip, and the lower end 111 may have a flat surface.

In one embodiment, the microneedle 100 includes a first layer 110 and a second layer 120 . The first layer 110 may be a glucose sensor layer. The first layer 110 may include a material that can be used as a sensor for continuous glucose monitoring. For example, the first layer 110 may include a material that selectively reacts with glucose in the body. In the microneedle 100 of one embodiment, the material that selectively reacts with glucose in the body included in the first layer 110 may be a material that can react reversibly to glucose without an enzyme or reagent. In one embodiment, the substance that selectively reacts with glucose in the body may include at least one of boronic acid and boronic acid derivatives. For example, the first layer 110 may include at least one of boronic acid and boronic acid derivatives as a material that selectively reacts with glucose in the body. Boronic acid and boronic acid derivatives have a glucose selectivity that is 10 times higher in reactivity with glucose than other sugars, and can be used for a long period of time, so they can be suitably used for the first layer 110, which is a glucose sensor layer.

Specifically, the boronic acid derivative includes a structural unit derived from bis-phenylboronate; Structural units derived from polyethylene glycol (PEG); and a structural unit derived from acrylamide. For example, the boronic acid derivative may be a compound in which polyethylene glycol and acrylamide are chemically bonded to bis-phenylboronate.

In the present invention, a functional group capable of exhibiting fluorescence may be bound to the boronic acid or boronic acid derivative. For example, the functional group capable of exhibiting fluorescence may be substituted or unsubstituted anthracene. However, embodiments of the present invention are not limited thereto.

The microneedle 100 of one embodiment includes a boronic acid and/or a boronic acid derivative to which anthracene capable of exhibiting fluorescence is bound to the first layer 110, and exhibits high sensitivity to glucose in the body, thereby efficiently detecting glucose in the body. ability can be demonstrated. At this time, anthracene may act as a fluorescence generating site, and boronic acid and/or boronic acid derivatives may act as a glucose recognition site. For example, anthracene, which is a fluorescent part, may be combined with a boronic acid derivative, which is a glucose recognition part, to function as a fluorescent sensor. When the microneedle 100 of one embodiment is inserted into the body, when there is no glucose in the body, the fluorescence of anthracene is captured by light-induced electron transfer (PET) generated from an unshared electron pair of a nitrogen atom, and the fluorescence is suppressed. It becomes. In addition, when glucose is present in the body, when glucose molecules are combined with boronic acid derivatives, light-induced electron transfer caused by strong reactions between nitrogen atoms and boron atoms is suppressed, and as a result, the fluorescence of anthracene becomes stronger. According to this principle, a difference in intensity of fluorescence occurs according to the concentration of glucose present in the body, and the changing intensity of fluorescence can be expressed as a blood glucose level through a calibration process and used as a sensor. Accordingly, the microneedle 100 of one embodiment includes boronic acid and/or a boronic acid derivative to which anthracene is bound to the first layer 110, which is a glucose sensor layer, so that continuous glucose monitoring is possible. However, the embodiment is not limited thereto.

As shown in FIG. 2A , the lower end 111 of the microneedle 100 according to one embodiment may have a circular shape. In this case, the microneedle 100 may have a cone shape. In addition, as shown in FIG. 2B , in the microneedle 100 of one embodiment, the lower end 111 may have a quadrangular shape having four sides of the same length or different lengths. In this case, the microneedle 100 may have a quadrangular pyramid shape. However, the embodiment of the present invention is not limited thereto, and unlike the illustration, the lower end 111 of the microneedle 100 may be a polygon such as a triangle or a pentagon, or a combination thereof, and the overall shape thereof may be a triangular pyramid or a pentagonal pyramid. It may have a polygonal pyramid such as, or a combination thereof.

Meanwhile, although not shown, the microneedle 110 may have a columnar shape having a constant diameter from the lower end 111 to the upper end 112 like a conventional injection needle, and may have a cross section of the uppermost end obliquely cut.

In the embodiment of the present invention, when the upper end 112 has a pointed tip, when the microneedle 100 provided in the form of a patch is attached to the target area, the tip penetrates the epidermis and the microneedle 110 is easily applied. It can be inserted into the epidermis.

In one embodiment, the first layer 110 contains a substance that selectively reacts with glucose in the body, for example, at least one of boronic acid and boronic acid derivatives at a concentration of about 1 w/v% to about 10 w/v%. can When at least one of boronic acid and boronic acid derivatives is included in the above content range in the first layer 110, the reaction with glucose in the body is smooth, and the microneedle 100 of one embodiment inserted into the body is used for a long time. can do.

In one embodiment, the first layer 110 may include a biocompatible material together with a material that selectively reacts with glucose in the body. The biocompatible material may be polyacrylamide.

Polyacrylamide is a high-molecular polymer formed by polymerization of acrylamide, sodium persulfate (SPS) and tetramethylethylenediamine (N, N, N', N'-Tetramethylethylenediamine, TEMED). can be material. As an example, the first layer 110 may include polyacrylamide to which the above-described boronic acid and/or boronic acid derivative are bonded. However, the embodiment is not limited thereto.

In one embodiment, the polyacrylamide included in the first layer 110 is acrylamide at a concentration of about 15 w / v% to about 30 w / v%, the sodium persulfate (1.5M) about 1 w / v% to about 10 It may be formed by reacting the concentration of w / v%, and the tetmethylethylenediamine (0.86 M) at a concentration of about 0.1 w / v% to about 2 w / v%. When polyacrylamide included in the first layer 110 is manufactured, when acrylamide is included in the above content range, microneedles can be inserted into the body with a level of hardness and at the same time absorb a sufficient amount of body fluid. . In addition, when sodium persulfate and tetmethylethylenediamine are included in the above content range, polymerization of polyacrylamide can be effectively induced.

As an example, the first layer 110 includes acrylamide having a concentration of 20 w*?*v%, bis-acrylamide having a concentration of 0.4 w*?*v%, and 5 w/v%. boronic acid and/or boronic acid derivatives having a concentration of 6 w/v%, 1.5 M sodium persulfate (SPS) having a concentration of 6 w/v%, and 0.86 M tetramethylethylenediamine having a concentration of 0.6 w/v% ( TEMED) may be included. However, the embodiment is not limited thereto.

In the microneedle 100 of one embodiment, the vertical length from the tip of the upper end 112 to the lower end 111 of the first layer 110 is not particularly limited, but is inserted into the epidermis to smoothly detect glucose in the body. To do so, it may be, for example, 650 μm to 800 μm.

On the other hand, substances that selectively react with glucose in the body, such as boronic acid and/or boronic acid derivatives, may have reduced glucose sensing sensitivity due to reactive oxygen species (ROS) in the body caused by inflammation. Accordingly, the microneedle 100 of one embodiment is a layer that removes or inhibits reactive oxygen species (ROS) so that the substance that selectively reacts with glucose in the body contained in the first layer 110 does not lose its function as a glucose sensor. It includes the second floor (120).

Referring to FIGS. 1 to 3 , the second layer 120 may be coated on the outer surface of the first layer 110 . For example, the second layer 120 may wrap around the outer surface of the first layer 110 along the third direction axis DR3 from the tip of the uppermost end of the first layer 110, that is, the upper end 112. can When the microneedle 100 of one embodiment penetrates the skin of the second layer 120, the boronic acid contained in the first layer 110 reacts smoothly with glucose in the body to sense the glucose concentration from 2 μm to 2 μm. It may be formed to a thickness of 10 μm.

In one embodiment, the second layer 120 may include a material that removes or suppresses reactive oxygen species (ROS) in the body so that the microneedle 100 provides stable sensor sensitivity.

For example, the second layer 120 is a material that removes or inhibits the reactive oxygen species (ROS) in the body, and includes polyphenol, astaxanthin, beta-carotene, and glutathione. , GSH), L-Ascorbic acid, Ubiquinone (Q, CoQ), Fisetin, α-lipoic acid (ALA), Lycopene, Tocopherol ( Tocopherol), epigallocatechin gallate (Epigallocatechin gallate, EGCG), and dexamethasone.

The substance that removes or inhibits reactive oxygen species (ROS) in the body may be included at an appropriate concentration capable of removing or suppressing reactive oxygen species, for example, at a concentration of about 0.4 w/v% to about 0.8 w/v%. can For example, as at least one of the substances that remove or inhibit active oxygen species in the body, ascorbic acid may be included in the second layer 120 at 50 mM. When the second layer 120 contains a substance that removes reactive oxygen species (ROS) within the above content range, the microneedle 100 may exhibit stable glucose sensor sensitivity.

For example, the microneedle 100 of one embodiment includes ascorbic acid in the second layer 120, thereby containing boronic acid and/or It is possible to stably maintain the sensitivity of the glucose sensor by preventing the boronic acid derivative from being oxidized by reactive oxygen species in the body and losing its function.

In one embodiment, the second layer 120 may include carboxymethyl cellulose (CMC) so that the microneedles 100 may have appropriate mechanical strength to penetrate the skin. The carboxymethylcellulose (CMC) may be included in the second layer 120 at a concentration of about 2 w/v% to about 12 w/v%. For example, carboxymethylcellulose (CMC) may be included in the second layer 120 at 4 w/v%, but the embodiment is not limited thereto. When carboxymethylcellulose (CMC) is included in the above content range in the second layer 120, the second layer 120 may be thinly and uniformly coated on the front end of the first layer 110, and the microneedle 100 ) may have excellent mechanical strength.

In the microneedle 100 according to the present invention, the vertical length from the tip of the uppermost end to the lower end is not particularly limited, but may be, for example, 700 μm to 1 mm.

In one embodiment, the base layer 130 may be a kind of patch adhered to the skin while supporting the microneedles 100 . The base layer 130 may include the same material as or a different material from the material forming the first layer 110 . For example, when the base layer 130 includes the same material as the material forming the first layer 110, it may include a material that selectively reacts with glucose in the body and the biocompatible material.

Hereinafter, a microneedle according to an embodiment of the present invention will be described in detail with reference to Examples and Comparative Examples. In addition, the examples shown below are examples for helping understanding of the present invention, and the scope of the present invention is not limited thereto.

1. Fabrication of microneedles

Example 1

1) Phosphate buffer of 60 mM NaPi, 1 mM EDTA, pH 7.4 was prepared.

2) After diluting the solution of 1) to 70% with DI water, 50 w*?*v% acrylamide and 1 w*?*v% bis-acrylamide were mixed and dissolved.

3) Dilute the solution of 2) once again to 20 w/v% using DI water to prepare a solution containing 20 w/v% acrylamide and 0.4 w/v% bis-acrylamide After that, 5 w/v% of a boronic acid derivative (F-PEG-AAM (fluorescent sensor powder) was prepared by referring to US 8,822,722 B2) was dissolved.

4) Mold PDMS mold was fabricated on the master mold by replica molding technique, and O ₂ plasma was treated for 1 minute.

5) A 6 w/v% 1.5 M SPS solution was mixed with the solution of 3) above, and loaded into a PDMS mold in an amount of 200 μl. After loading the PDMS mold, the remaining solution was stored in a refrigerator to prevent polymerization.

6) The PDMS mold loaded with the solution of 5) was treated in a sonicator for 15 minutes to remove residual bubbles, and then bubbles were removed in a desiccator for 15 minutes.

7) Take out the solution stored in the refrigerator, mix it with 0.6 w/v% 0.86 M TEMED solution, pour it into the PDMS mold, fill it up to the end, put a cover glass on it, and polymerize it on a hot plate at 80 ℃ for 30 minutes.

8) After the polymerization was completed, it was removed from the PDMS mold, washed three times with Phosphate buffer, and washed for 2 days in Phosphate buffer.

9) The washed microneedles on which the first layer was formed were dried at room temperature for one day.

10) Carboxymethylcellulose (CMC) was dissolved in Di water at 4 w/v% at 100°C.

11) Since ascorbic acid (AA) is easily oxidized at a high temperature of more than 60 ° C, the temperature of the solution of 10) was lowered to 60 ° C and ascorbic acid (AA) was dissolved at 50 mM.

12) The dried microneedles on which the first layer of 9) was formed were placed in the prepared solution of 11) to coat the surface and dried for one day.

2. Measurement of physical properties of Examples and Comparative Examples

The microneedle of Example was manufactured according to the above 1. Microneedle manufacturing method, and the comparative example microneedle was manufactured by omitting steps 10) to 12) in the above 1. Microneedle manufacturing method.

The microneedles of Examples and Comparative Examples were manufactured three times each, and the physical properties of the microneedles of each Example and Comparative Example were measured, and the average values are shown in Table 1.

division Height (μm) Width (μm) Radius of curvature (μm) Tip angle (˚) Example 730±14 286±19 23±2 16±9 comparative example 669±13 327±5 26±8 23±2

3. Evaluation of Examples and Comparative Examples and result

1) Microneedle strength test and results

To check the strength of the microneedle, the strength of the needle was checked using a tensile compressor. Figure 4 (a) is a force-displacement graph comparing the strength of a microneedle made only of polyacrylamide (microneedle, single layer of comparative example) and a microneedle coated with CMC on polyacrylamide (microneedle, double layer of example).

Specifically, the microneedles of Examples used in the microneedle strength test were manufactured according to the above 1. Microneedle manufacturing method. The microneedle of Comparative Example was manufactured by omitting steps 10) to 12) in the above 1. Microneedle Manufacturing Method.

Referring to (a) of FIG. 4, the part where the force-displacement curve rises and is greatly bent is the breakage point. It was confirmed that the strength of (the microneedle of the example) was stronger.

2) Microneedle penetration test and results

Penetration was tested using pig skin in order to confirm whether the microneedles of the examples were stably inserted into the skin.

The microneedle of the example used in the penetrability test was prepared according to the above 1. Microneedle manufacturing method, and additionally Rhodamine B was added in step 10) of the above 1. Microneedle manufacturing method, and Rhodamine B and CMC were mixed. used

The microneedle of the manufactured example was penetrated by pressing the microneedle into pig skin using a thumb. Thereafter, after removing the microneedle of the example from the pig skin, immediately after applying tripan blue to the pig skin, it was photographed and shown in FIG. 4 (b). Thereafter, after 3 to 5 minutes had elapsed, the pig skin was photographed again and shown in FIG. 4 (c).

Referring to (b) of 4, it can be visually confirmed that the microneedle penetrates the pig skin, and from this it can be confirmed that the microneedle of the embodiment has the strength to be inserted into the body.

3) Microneedle drug delivery test and result

Referring to (c) of FIG. 4, when the pig skin was pierced with a needle coated with CMC containing Rhodamine B, Rhodamine B was spread on the pig skin, and when the microneedle of the example was used, the second layer contained It was confirmed that the drug, namely ascorbic acid, could be well delivered.

4) Microneedle fluorescence intensity test and results according to glucose concentration

In order to confirm that the fluorescence-based glucose sensor in the microneedle of the example works properly, glucose monitoring was performed. The microneedles of Examples used in the fluorescence intensity test were prepared according to the above 1. Manufacturing method of microneedles.

First, glucose solutions having different concentrations were prepared. Glucose solutions with different concentrations were prepared by diluting the D-(+)Glucose solution with DI water to 0 - 500 mg/dl. As a fluorescence microscope, Zeiss' AXIO Zoom V.16 was used. The fluorescence filter is 49026 - ET - Tetracycline, which is an Excitation filter (ET405/40x), Beamsplitter (T470lpxr), and Emission filter (ET550/60m).

The fluorescence was measured at each glucose concentration with the microneedle portion upward using an upright microscope, and the results are shown in FIG. 5 . In (a)-(c) of FIG. 5, the fluorescence intensity of each glucose concentration of 0, 200, and 500 mg/dl can be visually confirmed. In (d) of Figure 5, it can be seen that the fluorescence intensity of the fluorescence sensor immobilized on the microneedle changes at the emission wavelength of 488 nm according to various glucose concentrations (0-500 mg/dl).

5) confocal assay

Confocal analysis was conducted to prove that the microneedle structure made of double layers properly constitutes the double layer. For the core body of the microneedle, a fluorescence sensor that emits blue fluorescence under 422 nm excitation light was used, and for the outer part, congo red, which emits red fluorescence under 532 nm excitation light, was used to confirm the double layer structure. In FIG. 6, it can be confirmed that the double layer structure is configured by accurately distinguishing the double layer.

6) Real-time PRET monitoring results related to CMC-film containing AA

It was confirmed whether ROS could be scavenged using CMC-film containing AA. It was demonstrated in real time that PRET can be used to scavenge hydrogen peroxide, a representative ROS in the body. As can be seen in FIG. 7 , it can be confirmed that cyt C is reduced over time. Through this, it was confirmed that AA has a reducing power sufficient to reduce hydrogen peroxide.

7) Results of drug release over time

In order to confirm that the solution contained in the coating layer is released as the coating layer dissolves over time, a drug release experiment was conducted using a Franz cell. Rhodamine B was used as a loading drug so that it could be visually confirmed. In Figure 8a, the fluorescence intensity according to the concentration of Rhodamine B was measured and fitting was performed, and based on this data, the drug concentration of Rhodamine B according to the fluorescence intensity of the drug released from the Franz cell was calculated by reverse calculation. It can be seen from b of FIG. 8 that the amount of released drug increased over time.

Although the above has been described with reference to preferred embodiments of the present invention, those skilled in the art or those having ordinary knowledge in the art do not depart from the spirit and technical scope of the present invention described in the claims to be described later. It will be understood that various modifications and changes can be made to the present invention within the scope.

Therefore, the technical scope of the present invention should not be limited to the contents described in the detailed description of the specification, but should be defined by the claims.

100: micro needle
110: first layer
111: lower part
112: upper part
120: second layer
130: base layer

Claims (11)

A first layer containing a material that selectively reacts with glucose in the body; and
A second layer comprising a material that removes or inhibits reactive oxygen species (ROS) in the body; that includes, the microneedle. According to claim 1,
The material that selectively reacts with glucose in the body includes at least one of boronic acid and boronic acid derivatives, the microneedle. According to claim 1,
The boronic acid derivative includes a structural unit derived from bis-phenylboronate; structural units derived from polyethylene glycol; And a structural unit derived from acrylamide; that will include a microneedle. According to claim 1,
Substances that remove or inhibit reactive oxygen species (ROS) in the body include polyphenol, astaxanthin, beta-carotene, glutathione (GSH), L-ascorbic acid (L- Ascorbic acid), Ubiquinone (Q, CoQ), Fisetin, α-lipoic acid (ALA), Lycopene, Tocopherol, Epigallocatechin Gallate, EGCG) and dexamethasone (Dexamethasone) that will include at least one selected from the group consisting of, the microneedle. According to claim 1,
Wherein the second layer is coated on the outer surface of the first layer, microneedles. According to claim 1,
Wherein the first layer further comprises polyacrylamide, the microneedle. According to claim 6,
The polyacrylamide is formed by polymerization of acrylamide, sodium persulfate and tetramethylethylenediamine (N, N, N', N'-Tetramethylethylenediamine), microneedle. According to claim 7,
The polyacrylamide,
The acrylamide (acrylamide) concentration of 15 w / v% to 30 w / v%;
The sodium persulfate (sodium persulfate) concentration of 1 w / v% to 10 w / v%; and
A microneedle formed by reacting the tetramethylethylenediamine (N, N, N', N'-Tetramethylethylenediamine) at a concentration of 0.1 w/v% to 2 w/v%. According to claim 1,
Wherein the second layer further comprises carboxymethyl cellulose (carboxymethyl cellulose), the microneedle. According to claim 9,
The second layer is carboxymethyl cellulose at a concentration of 2 w/v% to 12 w/v%; And 0.4 w / v% to 0.8 w / v% concentration of polyphenol (Polyphenol), astaxanthin (astaxanthin), beta-carotene (β-Carotene), glutathione (Glutathione, GSH), L-ascorbic acid acid), Ubiquinone (Q, CoQ), Fisetin, α-lipoic acid (ALA), Lycopene, Tocopherol and Epigallocatechin gallate , EGCG) to include at least one selected from the group consisting of, microneedle.
According to claim 1,
The thickness of the second layer coated on the first layer is 2 μm to 10 μm, the microneedle.

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