KR20230089977A - Microneedle patch and manufacturing method of microneedle patch - Google Patents

Abstract

A microneedle patch of the present invention includes an adhesive sheet in close contact with the skin, a needle support body disposed on the adhesive sheet, and a needle body disposed on the needle support body and having a tip part, and at least one of the needle support and the needle body includes a swellable polymer material that expands when in contact with a body fluid.

Description

Microneedle patch and manufacturing method of microneedle patch {Microneedle patch and manufacturing method of microneedle patch}

The present invention relates to a microneedle patch and a method for manufacturing the microneedle patch.

Numerous drugs and physiologically active substances for the treatment of diseases have been developed, but in delivering drugs and physiologically active substances into the body, there is a problem in passing through biological barriers (eg, skin, oral mucosa, brain-vascular barrier, etc.) and drug delivery efficiency issues still remain to be improved.

Drugs and physiologically active substances are generally administered orally in the form of tablets or capsules, but many drugs cannot be effectively delivered only by the above administration method for reasons such as digestion or absorption in the gastrointestinal tract or loss by liver mechanisms. Additionally, some drugs cannot effectively diffuse through the intestinal mucosa. Patient compliance is also an issue (for example, patients who need to take medications at specific intervals, critically ill patients who cannot take medications, etc.).

Another common technique for the delivery of drugs and bioactive substances is the use of conventional needles. While this method is more effective than oral administration, it has problems such as pain at the injection site, local skin damage, bleeding, and disease infection at the injection site.

In order to solve the above problems, various microneedle patches including microneedles have been developed. Microneedle patches developed to date have been mainly used for in vivo drug delivery, blood collection, and in vivo analyte detection.

Unlike conventional needles, microneedles are characterized by painless skin penetration and no trauma. At this time, since the microneedle must have penetrability to penetrate the skin and penetrate the stratum corneum of 10-20 μm, which is the strongest obstacle in the skin, it is required to have sufficient physical hardness. In addition, an appropriate length to increase the efficiency of drug delivery by reaching capillaries should also be considered.

Conventional microneedles were limited to materials such as silicon, polymer, metal, and glass due to limitations in the manufacturing method, and by using a manufacturing method through molding technology, drug denaturation due to complicated and long manufacturing time, insufficient hardness, and drug It has disadvantages such as loss. Therefore, there is a need for a microneedle that has a diameter small enough to realize painlessness when penetrating the skin and a length sufficient to penetrate deep into the skin, implement sufficient hardness without any particular limitation on the material, and minimize drug loss. The demand persists.

In order to solve the above problems, an object of the present invention is to provide a microneedle patch including microneedles formed of a swellable polymer material that expands upon contact with a body fluid and a method for manufacturing the same.

In addition, an object of the present invention is to provide a microneedle patch having acuity, sufficient hardness, and increased adhesiveness, and a method for manufacturing the same, so as to effectively inject drugs.

An object of the present invention as described above is to include a pressure-sensitive adhesive sheet in close contact with the skin, a needle support disposed on the pressure-sensitive adhesive sheet, and a needle body disposed on the needle support and having a tip, among the needle support and the needle body. At least one is achieved by a microneedle patch comprising a swellable polymer material that expands upon contact with body fluids.

Here, at least one of the needle supporter and the needle body may contain a drug, and at least one of the needle supporter and the needle body may expand upon contact with a body fluid and supply the drug.

In addition, at least one of the needle support and the needle body may be formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved.

Furthermore, the needle body includes a swellable polymer material and has a base diameter (D) corresponding to the diameter of the bottom in contact with the needle support, a needle height (H) corresponding to the orthogonal distance from the bottom to the top, and the diameter of the tip It is provided in a shape having a corresponding needle diameter (N), and the needle body may expand while maintaining the shape such that at least one of the base diameter, the needle height, and the needle diameter increases upon contact with body fluid.

Meanwhile, the base diameter and the needle diameter may increase 1.1 times or more and less than 2 times upon contact with body fluid.

Furthermore, the needle body includes a swellable polymer material and has a base diameter (D) corresponding to the diameter of the bottom in contact with the needle support, a needle height (H) corresponding to the orthogonal distance from the bottom to the top, and the diameter of the tip It is provided in a shape having a corresponding needle diameter (N), and when the needle body comes into contact with body fluid, one of the base diameter, the needle height, and the needle diameter may increase and another may decrease.

In addition, the adhesive sheet and the needle supporter form one adhesive surface, the needle supporter is inserted into the adhesive sheet from the adhesive surface, and the needle body extends outward from the adhesive surface. It can be.

Furthermore, the needle supporter may be inserted into the adhesive sheet and disposed in a plurality of concave shapes spaced apart from each other, and the needle body may be respectively disposed on the plurality of needle supporters.

In addition, the needle supporter may be inserted into the adhesive sheet and disposed in the form of a layer extending in parallel, and a plurality of needle bodies spaced apart from each other may be disposed on the needle supporter.

Meanwhile, an object of the present invention as described above is to form a needle support on a base resin, form an adhesive sheet on the base sheet to cover the needle support, and form a cover resin on the adhesive sheet. and disposing the needle supporter and the adhesive sheet upside down so that the base resin is disposed thereon, removing the base resin, and forming a needle body on the needle supporter, And at least one of the needle bodies is achieved by a method for manufacturing a microneedle patch, characterized in that it comprises a swellable polymer material that expands upon contact with bodily fluid.

Here, at least one of the needle support and the needle body may be formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved.

Furthermore, in the step of forming the needle body, a pair of structures in which base needles are formed on the needle supporter are provided, and the pair of structures are formed so that the pair of base needles formed on the pair of structures are in contact with each other. The pair of structures are relatively moved to be closer to each other, and the pair of structures are moved away from each other so that the pair of base needles are adhered to each other and stretched, and the shape is deformed, and the deformed base needles may form the needle body.

Meanwhile, the needle supporter may include a plurality of supporters spaced apart from each other on the base resin, the adhesive sheet may cover each of the plurality of supports, and the needle body may be formed on each of the plurality of supports.

In addition, the needle body may be spaced apart from each other on the needle support body to form a plurality of them.

According to the microneedle patch and the manufacturing method of the present invention having the above configuration, there is an advantage in that the drug can be effectively injected by expanding to increase the surface area and volume upon contact with bodily fluid.

1 is a view schematically showing a process of manufacturing a sheet of a microneedle patch according to an embodiment of the present invention;
Figure 2 is a plane photograph of the sheet produced according to Figure 1,
3 schematically illustrates a process of manufacturing a microneedle patch according to an embodiment of the present invention using the sheet according to FIG. 1;
4 is a side view of the microneedle patch manufactured according to the process of FIG. 3;
5 schematically illustrates a process of manufacturing a sheet of a microneedle patch according to another embodiment of the present invention;
Figure 6 is a plane photograph of the sheet produced according to Figure 5,
7 schematically illustrates a process of manufacturing a microneedle patch according to another embodiment of the present invention using the sheet according to FIG. 5;
8 is a side view of the microneedle patch manufactured according to the process of FIG. 7;
9 is a view schematically showing changes in a needle body in a microneedle patch according to an embodiment of the present invention;
10 to 13 are photographs of experimental changes in the needle body in the microneedle patch according to an embodiment of the present invention;
14 is a diagram schematically showing changes in a needle body in a microneedle patch according to another embodiment of the present invention.

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

1 is a view schematically illustrating a process of manufacturing a sheet 190 of a microneedle patch according to an embodiment of the present invention, and FIG. 3 is an embodiment of the present invention using the sheet 190 according to FIG. 1 It is a diagram schematically illustrating a process of manufacturing the microneedle patch according to the example.

A microneedle patch according to an embodiment of the present invention may be formed through the process of FIGS. 1 and 3 . That is, FIGS. 1 and 3 are views showing the process of manufacturing the microneedle patch of the present invention, and the shape shown in (c) of FIG. 3 corresponding to the last step is the microneedle patch 170, 170a. can be understood as indicated.

First, as shown in (a) of FIG. 1 , the needle support 110 may be formed by spotting the first base resin 100 . The first base resin 100 corresponds to a sheet temporarily prepared to form the needle support 110 . That is, the first base resin 100 is omitted from the final patch sheet 190 .

The first base resin 100 may be provided in the shape of a flat plate, and may be provided in the form of, for example, a synthetic resin or a transparent PET film.

The needle support 110 may be formed by spotting a plurality of pieces on top of the first base resin 100 . For example, the needle supporter 110 may be configured in plurality, including a first supporter 1101, a second supporter 1102, and a third supporter 1103 spaced apart from each other. Each of the supports 1101, 1102, and 1103 may have the same shape as each other and may be sequentially disposed.

At this time, the needle support 110 may be formed by spotting and solidifying the first viscous composition by being spaced apart from each other by a predetermined interval on the upper surface of the first base resin 100. Accordingly, each of the supports 1101, 1102, and 1103 is the same as a whole, but may be formed in slightly different shapes due to the influence of adhesion or draft. The first viscous composition forming the needle support 110 will be described later in detail.

In addition, the needle support 110 may be formed in various shapes on the first base resin 100 through various methods. In addition, each of the supports 1101, 1102, and 1103 forms a substantially circular, elliptical, or curved surface by surface tension, and has a hemispherical shape (hereinafter referred to as 'hemispheric') on the first base resin 100. can be formed as

At this time, the arrangement, interval or number of each support body 1101, 1102, 1103 may be formed differently as needed. For example, each of the supports 1101, 1102, and 1103 may form a lattice and be regularly arranged.

Meanwhile, as shown in (b) of FIG. 1 , an adhesive sheet 120 may be formed on the first base resin 100 and the upper portion of the needle support 110 . That is, the adhesive sheet 120 may be formed on top of the first base resin 100 to cover the needle support 110 . Accordingly, the needle support 110 is disposed between the adhesive sheet 120 and the first base resin 100 .

The adhesive sheet 120 is formed above the needle supporter 110 to completely cover the needle supporter 110 .

Subsequently, in the state of FIG. 1 (b), a first cover resin 130 is attached to the top of the adhesive sheet 120 and provided. Then, as shown in (c) of FIG. 1, the needle support 110 and the adhesive sheet 120 are turned upside down so that the first base resin 100 is disposed on the top. That is, the shape shown in FIG. 1(b) is reversed so that the first cover resin 130 is located at the bottom and the first base resin 100 is located at the top.

At this time, the first cover resin 130 corresponds to the bottom surface and the first base resin 100 corresponds to the top surface. Like the first base resin 100, the first cover resin 130 may be provided in the shape of a flat plate, and may be provided in the form of, for example, a synthetic resin or a transparent PET film. That is, the first cover resin 130 and the first base resin 100 may be provided with the same configuration or different configurations, and may be named by different names for convenience of explanation.

As shown in (d) of FIG. 1, the first base resin 100 is removed, and the needle support 110 and the adhesive sheet 120 are placed on top of the first cover resin 130. It is provided in a shape and constitutes the sheet 190 of the microneedle patch.

FIG. 2 is a plane photograph of the sheet 190 manufactured according to the process of FIG. 1 .

Referring to FIGS. 1 and 2 , the needle support 110 is inserted into the adhesive sheet 120 and disposed therein. For example, it can be said that the needle supporter 110 is inserted into the adhesive sheet 120 in an engraved pattern recessed inwardly. In this case, the intaglio shape may be formed in a substantially hemispherical, curved or semi-elliptical shape, for example.

Here, the fact that the needle supporter 110 has a hemispherical shape is described as an example, and the needle supporter 110 may be formed in various shapes such as a curved shape and a semi-elliptical shape in addition to a hemispherical shape.

Also, the needle supporter 110 may be inserted into the adhesive sheet 120 to form one surface of the adhesive sheet 120 . As described above, since the first base resin 100 is provided flat, the needle support 110 and the adhesive sheet 120 formed by being adhered thereto may form a flat surface. And, when the first base resin 100 is removed, one surface formed by the needle support 110 and the adhesive sheet 120 is exposed. Hereinafter, such one side is referred to as an adhesive side. For example, the adhesive surface may mean a surface in contact with the skin.

In addition, as described above, the respective supports 1101, 1102, and 1103 are spaced apart from each other, and the adhesive sheet 120 is exposed and disposed between the respective supports 1101, 1102, and 1103. Accordingly, when the adhesive surface is in contact with the skin, adhesive strength may be increased through the adhesive sheet 120 disposed between the supports 1101, 1102, and 1103. In addition, since each of the supports 1101, 1102, and 1103 can be more effectively adhered, the dosage efficiency can be increased.

FIG. 3 is a diagram schematically illustrating a process of manufacturing microneedle patches 170 and 170a according to an embodiment of the present invention using the sheet according to FIG. 1 . Below, we look at them in order.

First, as shown in (a) of FIG. 3 , a second viscous composition for forming the base needle 140 may be spotted on the needle support 110 . The second viscous composition may be made of the same material as or a different material from the first viscous composition for the needle support 110 described above. This will be described in detail later.

The number of base needles 140 corresponding to those of the needle supporter 110 may be formed. For example, the base needle 140 may be formed in plurality, including a first base 1401, a second base 1402, and a third base 1403 formed on each of the supports 1101, 1102, and 1103. there is. In detail, the first base 1401 is formed on the upper portion of the first support body 1101, the second base 1402 is formed on the upper portion of the second support body 1102, and the third base ( 1403) is formed on top of the third support 1103.

Although not shown in the drawing, it is also possible that a plurality of base needles 140 are spotted on the upper surface of the one needle supporter 110 . In this case, the base needle 140 may be spaced apart and spotted on the upper surface of the one needle supporter 100 .

Meanwhile, each of the supports 1101, 1102, and 1103 or each of the bases 1401, 1402, and 1403 are separately named for convenience of explanation, and correspond to the same configuration. In addition, each of the supports 1101, 1102, and 1103 and each of the bases 1401, 1402, and 1403 are formed of a viscous composition and may be formed in slightly different shapes, but this is irrelevant to the characteristics of the present invention.

In summary, the base needles 140 are spotted on the upper surfaces of the plurality of supports 1101, 1102, and 1103 spaced apart from each other, and the base needles 140 are composed of the needle supports 110 and the adhesive sheet 120. It may protrude upward from the formed adhesive surface. Hereinafter, the shape shown in (a) of FIG. 3 is referred to as a structure 150.

Subsequently, as shown in (b) of FIG. 3, a pair of structures 150 and 150a are disposed facing each other. At this time, each of the structures 150 and 150a is formed in the same manner as in (a) of FIG. 3 described above, and corresponds to the same configuration.

Accordingly, the first structure 150 includes the first needle support 110, the first adhesive sheet 120 and the first base needle 140, and the second structure 150a includes the second needle support 110a , a second adhesive sheet 120a and a second base needle 140a.

Specifically, the first structure 150 and the second structure 150a are disposed such that the first base needle 140 and the second base needle 140a face each other. That is, the adhesive surface of the first structure 150 and the adhesive surface of the second structure 150a are disposed to face each other. Then, the first structure 150 and the second structure 150a move relative to each other, so that the first base needle 140 and the second base needle 140a come into contact.

For example, the second structure 150a is disposed so that the adhesive surface faces upward. Then, the first structure 150 is placed on top of the second structure 150a so that the adhesive surface faces the bottom surface. Then, the first structure 150 is lowered so that the first base needle 140 and the second base needle 140a come into contact with each other.

At this time, the first needle supporter 110, the second needle supporter 110a, the first adhesive sheet 120, and the second adhesive sheet 120a are disposed so as not to come into contact with each other. In addition, each of the needle supports 110 and 110a and the adhesive sheets 120 and 120a are completely solidified and do not deform even when in contact with each other.

On the other hand, the first base needle 140 and the second base needle 140a correspond to a state in which the viscous composition is not solidified, and may be deformed in shape by contacting each other. That is, the structures 150 and 150a are disposed in contact with each other in a state in which the base needles 140 and 140a are not completely solidified.

Subsequently, as shown in (c) of FIG. 3, the structures 150 and 150a are relatively moved in directions away from each other. As a result, the base needles 140 and 140a are tensioned and solidified.

The base needles 140 and 140a adhered to each other form needle bodies 160 and 160a through a tensioning and solidifying step. Accordingly, the microneedle patches 170 and 170a of the present invention can be manufactured. That is, the microneedle patches 170 and 170a include the needle supports 110 and 110a, the adhesive sheets 120 and 120a, and the needle bodies 160 and 160a.

A more detailed look at the process of forming the needle bodies 160 and 160a is as follows.

As described above, the first base needle 140 and the second base needle 140a are disposed in a state of being adhered to each other. Also, the first needle supporter 110 and the first adhesive sheet 120 are relatively moved in a direction away from the second needle supporter 110a and the second adhesive sheet 120a.

Accordingly, the attached base needles 140 and 140a move away from each other, and their ends are stretched and their radii are reduced by the adhesive force. Eventually separated into a pair, needle bodies 160 and 160a having cutting edges may be formed, respectively.

For example, as shown in FIG. 3 , the ends to which the substantially hemispherical base needles 140 and 140a are attached are stretched and transformed into substantially conical needle bodies 160 and 160a.

That is, the needle bodies 160 and 160a may be formed by pulling the base needles 140 and 140a adhered to each other at a predetermined speed and by a desired length. For example, the base needles 140 and 140a adhered to each other are 1) first stretched at a first speed as much as a first length (primary tension), 2) after waiting for a predetermined time in a state where the tension is stopped (standby), 3) secondarily stretched as much as the second length at the second speed (secondary tension), and 4) separated from each other (cutting). In addition, in the separation or cutting step, it may be cut by moving quickly in a completely solidified state or cut using a cutting tool such as a laser.

For example, the base needles 140 and 140a attached to each other are stretched by 10 to 5000 μm at 0.8 to 600,000 μm/s without blowing, and after waiting for 1 to 100 seconds in a state where the tension is stopped, 1 In the state of blowing with the viscous composition at a wind speed of ~100 m/s, secondarily stretched by 10 to 5000 μm at 0.8 to 600,000 μm/s, then solidified and cut the viscous composition while blowing at a wind speed of 5 to 100 m/s do.

At this time, the first speed, the first length, the waiting time, the second speed, the second length, and whether or not to blow can be set differently as needed, which can be determined according to the required result value. In particular, as the waiting time in the state in which the tension is stopped after the first tension increases, the diameter of the middle portion increases, and thus the strength may be relatively strong. The above method is described in detail in Korean Patent Registration No. 10-1254240 of the present applicant.

In summary, the microneedle patches 170 and 170a are formed as follows. 1) forming the needle supporter 110 on top of the first base resin 100, 2) forming the adhesive sheet 120 on the top of the first base resin 100 to cover the needle supporter 110 ) to form 3) The first cover resin 130 is formed on the upper surface of the adhesive sheet 120, turned over and placed, and 4) the first base resin 100 is removed to expose the adhesive surface. 5) A pair of structures 150 in which the base needles 140 are formed on the adhesive surface corresponding to the position of the needle supporter 110 are provided. 6) The pair of structures 150 and 150a are moved relative to each other so that the base needles 140 and 140a are attached to each other, and 7) the base needles 140 and 140a that are attached to each other are moved relative to each other so that they are further apart. It is stretched to form the needle bodies 160 and 160a.

Meanwhile, in the embodiment of FIG. 3 described above, the base needles 140 and 140a are spotted and formed on both the upper and lower structures 150 and 150a, but are not limited thereto.

For example, although not shown in the drawing, the second base needle 140a may be spotted only on the lower second structure 150a. That is, the base needle may not be spotted on the first needle support 110 of the upper first structure 150 . In this case, when the first structure 150 and the second structure 150a move relative to each other in a direction closer to each other, the surface of the first needle supporter 110 of the first structure 150 is the second structure ( 150a) may move to come into contact with the second base needle 140a. After the surface of the first needle supporter 110 of the first structure 150 comes into contact with the second base needle 140a of the second structure 150a, the first structure 150 and the second structure 150a Since a method of tensioning the second base needle 140a by relatively moving ) in a direction away from each other is similar to the above-described embodiment, repetitive description will be omitted.

4 is a side view of the microneedle patch manufactured according to the process of FIG. 3 .

As shown in Figure 4, it can be seen that the needle body 160 is formed. Meanwhile, in FIG. 4 , the needle body 160 is formed by a viscous composition containing chitosan as a swelling polymer material to be described later. This swellable polymer material will be described in detail later.

Meanwhile, the shapes of the aforementioned microneedle patches 170 and 170a are exemplary, and the microneedle of the present invention may be manufactured in various shapes. Hereinafter, microneedles having needle structures of different shapes will be described. However, the following microneedle patches 270 and 270a may be manufactured through the same process as the previously described microneedle patches 170 and 170a. Therefore, for the same process, the above description is cited and detailed description is omitted, and the same name is used for the corresponding configuration and is distinguished through reference numerals.

5 is a view schematically illustrating a process of forming a sheet 290 of a microneedle patch according to another embodiment of the present invention, and FIG. 7 is another embodiment of the present invention using the sheet 290 according to FIG. It is a diagram schematically illustrating a process of manufacturing the microneedle patches 270 and 270a according to the example.

Microneedle patches 270 and 270a according to another embodiment of the present invention may be formed through the processes of FIGS. 5 and 7 . That is, FIGS. 5 and 7 are diagrams showing the process of manufacturing the microneedle patches 270 and 270a of the present invention, and the shape shown in (c) of FIG. 7 corresponding to the last step is the microneedle patch ( 270, 270a).

As shown in (a) of FIG. 5, a third needle support 210 may be formed on the second base resin 200. The third needle support 210 may be formed to extend along the top of the second base resin 200 . At this time, the third needle support 210 may be formed by coating the above-described first viscous composition on top of the second base resin 200.

Subsequently, as shown in (b) of FIG. 5 , an adhesive sheet 220 may be formed on the second base resin 200 and the third needle support 210 . That is, the adhesive sheet 220 may be formed on top of the second base resin 200 to cover the third needle supporter 210 . Accordingly, the third needle supporter 210 is disposed between the adhesive sheet 220 and the second base resin 200 .

Thereafter, in the state of FIG. 5(b), a second cover resin 230 is provided on the top of the adhesive sheet 220, and then, as shown in FIG. 5(c), the second base resin 200 ) is placed on top. That is, the third needle supporter 210 and the adhesive sheet 220 are disposed upside down.

Subsequently, as shown in (d) of FIG. 5, the upper third resin 200 is removed, and the third needle support 210 and the adhesive sheet 220 are provided in a predetermined shape.

FIG. 6 is a plan view of a sheet 290 fabricated according to FIG. 5 .

Referring to FIGS. 5 and 6 , the third needle supporter 210 is inserted into the adhesive sheet 220 and disposed in the form of a single layer, that is, a layer extending in parallel. In other words, the third needle supporter 210 is provided in a state of being entirely inserted into the adhesive sheet 220 . For example, the third needle supporter 210 may be recessed into the adhesive sheet 220 in a flat plate shape. In this case, the adhesive sheet 220 may be exposed along the edge of the third needle supporter 210 .

In addition, the third needle supporter 210 is inserted into the adhesive sheet 220 to form one surface of the adhesive sheet 220 . As described above, since the second base resin 200 is provided flat, the third needle supporter 210 and the adhesive sheet 220 formed by being adhered thereto may form one flat surface. Hereinafter, such one side is referred to as an adhesive side. For example, the adhesive surface means a surface in contact with the affected area.

FIG. 7 is a diagram schematically illustrating a process of manufacturing microneedle patches 270 and 270a according to an embodiment of the present invention using the sheet 290 shown in FIG. 5 . Below, we look at them in order.

First, as shown in (a) of FIG. 7 , a second viscous composition for forming the base needle 240 may be spotted on the upper portion of the third needle supporter 210 . The second viscous composition may be made of the same material as or a different material from the first viscous composition for the third needle support 210 described above. This will be described in detail later.

A plurality of base needles 240 may be formed in the third needle supporter 210 . For example, the base needle 240 may include a first base 2401, a second base 2402, and a third base 2403 spaced apart from each other. Each base 2401, 2402, 2403 may be formed in a slightly different shape, but this is irrelevant to the characteristics of the present invention.

Unlike the needle supporter 110 described above, the third needle supporter 210 is formed to extend in the form of a flat sheet. Accordingly, a plurality of base needles 240 may be formed on one third needle supporter 210 . Such a shape has the advantage of being more convenient to manufacture and more effectively supporting the needle bodies 260 and 260a, which will be described later.

In summary, a plurality of base needles 240 are spotted on the upper surface of the third needle supporter 210 at a distance from each other, and the base needles 240 are connected to the third needle supporter 210 and the adhesive sheet 220. ) may be formed by protruding upward from the formed adhesive surface. Hereinafter, the shape shown in (a) of FIG. 7 is referred to as a structure 250.

Subsequently, as shown in (b) of FIG. 7, a pair of structures 250 and 250a are disposed facing each other. At this time, each of the structures 250 and 250a is formed in the same manner as in (a) of FIG. 7 described above, and corresponds to the same configuration.

Accordingly, the third structure 250 includes the third needle support 210, the third adhesive sheet 220, and the third base needle 240, and the fourth structure 250a is the fourth needle support 210a , a fourth adhesive sheet 220a and a fourth base needle 240a.

Specifically, the third structure 250 and the fourth structure 250a are disposed such that the third base needle 240 and the fourth base needle 240a face each other. That is, the adhesive surface of the third structure 250 and the adhesive surface of the fourth structure 250a are disposed to face each other. Also, the third and fourth base needles 250 and 250a are moved relative to each other, so that the third base needle 240 and the fourth base needle 240a come into contact with each other.

For example, the fourth structure 250a is disposed such that the adhesive surface faces upward. Then, the third structure 250 is disposed above the fourth structure 250a so that the adhesive surface faces the bottom surface. Then, the third structure 250 is lowered so that the third base needle 240 and the fourth base needle 240a come into contact with each other.

At this time, the third needle supporter 210, the second needle supporter 210a, the first adhesive sheet 220, and the second adhesive sheet 220a are disposed so as not to come into contact with each other. In addition, each of the needle supports 210 and 210a and the adhesive sheets 220 and 220a are completely solidified so that their shapes are not deformed even when in contact with each other.

On the other hand, the third base needle 240 and the fourth base needle 240a correspond to a state in which the viscous composition is not solidified, so that the shape may be deformed by coming into contact with each other. That is, the structures 250 and 250a are disposed in contact with each other in a state in which the base needles 240 and 240a are not completely solidified.

Subsequently, as shown in (c) of FIG. 7, the structures 250 and 250a are moved relative to each other in a direction away from each other. As a result, the base needles 240 and 240a are tensioned and solidified.

The base needles 240 and 240a adhered to each other form the needle bodies 260 and 260a through a tensioning and solidifying step. Accordingly, the microneedle patches 270 and 270a of the present invention can be manufactured. That is, the microneedle patches 270 and 270a include the needle supports 210 and 210a, the adhesive sheets 220 and 220a, and the needle bodies 260 and 260a.

Since the process of forming the needle bodies 260 and 260a has been described in the foregoing embodiment, repetitive description will be omitted.

In this way, the microneedle patches 270 and 270a may form needle supports 210 and 210a having different shapes from those of the previously described microneedle patches 260 and 260a. In addition, the microneedle patches 270 and 270a may form needle bodies 260 and 260a having the same shape as the previously described microneedle patches 170 and 170a. Hereinafter, the needle bodies 160, 160a, 260, and 260a will be described in detail.

8 is a side view of the microneedle patch manufactured according to the process of FIG. 7 .

As shown in Figure 8, it can be seen that the needle body 260 is formed. Meanwhile, in (a) of FIG. 8, the needle body 260 is formed by a viscous composition containing chitosan as a swelling polymer material, and in (b) of FIG. 8, the needle body 260 is It is formed by a viscous composition containing PVA (Polyvinyl alcohol) as a swelling polymer material. This swellable polymer material will be described in detail later.

9 is a diagram schematically illustrating changes in a needle body of a microneedle patch according to an embodiment of the present invention. 9 (a) and (b) show only the needle bodies 160, 160a, 260, and 260a of the microneedle patches 170, 170a, 270, and 270a described above. Hereinafter, one needle body 160 will be described in detail and the description will be cited.

Referring to FIG. 9 , the needle body 160 may have a substantially circular cone shape. That is, the needle body 160 may be provided with a shape in which a lower surface is formed in a substantially circular shape and a diameter gradually narrows toward the upper side to form a tip. Hereinafter, the diameter of the bottom surface of the needle body 160 is referred to as the base diameter (D), and the orthogonal distance from the bottom surface to the top surface is referred to as the needle height (H). At this time, the base diameter (D) may be understood as a cross-sectional diameter of a portion in contact with the needle supporter 110, and the needle height (H) may be understood as a perpendicular distance from the needle supporter 110 or the adhesive surface. there is.

At this time, as described above, the needle body 160 corresponds to a configuration formed by solidifying the viscous composition. Accordingly, the bottom surface of the needle body 160 may not form a perfect circle, and the base diameter D may be obtained as an approximate value. The height of the needle (H) may be formed to a set value as needed, but may have a predetermined error in the separation or cutting step.

On the other hand, the needle body 160 corresponds to a shape formed by being cut by tension. Accordingly, the upper end forms a predetermined tensile fracture surface rather than a point, and a generatix is formed as a curve. At this time, the curvature of the generatrix may be determined by a tensile speed or the like in the process of forming the needle body 160 described above.

As described above, the needle body 160 may be formed by being stretched at a first rate and then stretched again at a second rate. In this case, the second speed may be faster than the first speed. Accordingly, as shown in FIG. 9 , the needle body 160 may form a thinner and longer tip toward the top. At this time, the diameter of the part stretched at the second speed is referred to as the needle diameter (N). In detail, the needle diameter (N) corresponds to the tip diameter of the needle body 160, and may be calculated as an average value or a median value thereof.

In addition, since the upper end of the needle body 160 forms a fractured surface, a complete shape may not be formed up to a predetermined portion. Accordingly, the upper diameter of the needle body 160 may be replaced by the needle diameter N.

Meanwhile, at least one of the aforementioned needle body 160 and needle support 110 may contain a drug administered to the human body. That is, when the microneedle patch 170 according to the present invention is attached to the human body, the drug included in at least one of the needle body 160 and the needle support 110 can be injected into the human body and delivered.

To this end, at least one of the needle body 160 and the needle support 110 may include swellable hydrophilic polymers that expand when in contact with bodily fluids.

When the microneedle patch 170 according to the present invention is attached to a human body and the needle body 160 or the needle support 110 expands in contact with body fluid, the inside of the needle body 160 or the needle support 110 The contained drug can be delivered into the human body. In this case, the needle body 160 or the needle support 110 can maintain its shape or form without being decomposed even after contacting bodily fluid. That is, even when the needle body 160 or the needle support 110 expands, the basic shape or shape can be maintained.

Specifically, at least one of the needle body 160 and the needle support 110 may include a swellable polymer material such as polyvinyl alcohol (PVA) or chitosan. PVA and chitosan are merely examples of swellable polymer materials, and the swellable polymer materials are not limited thereto.

As a result, at least one of the first viscous composition for the needle support 110 and the second viscous composition for the needle body 160 may include a drug and a swellable polymer material. In this case, the first viscous composition and the second viscous composition may include the same swellable polymer material or different swellable polymer materials.

Hereinafter, a viscous composition containing a drug forming the needle body 160 or the needle support 110 will be described.

First, a case in which distilled water is used as a solvent and PVA is used as a polymer material will be described. 1) Add distilled water (Di water 50 to 80% by weight) to a stirrer and heat to 50 to 100 ° C, 2) Add PVA (5 to 30% by weight) and stir at a speed of 200 to 800RPM until completely dissolved do. 3) After completely dissolved, a water-soluble polymer such as HPMC (hydroxypropyl methylcellulose) (2 to 20% by weight) or CMC (carboxymethyl cellulose) (2 to 20% by weight) is added and heated to 50 to 100 ° C. to 200 to 200 Stir at a speed of 800 RPM. 4) Subsequently, a drug (API: Active Pharmaceutical Ingredient), for example, Donepezil (5 to 30% by weight) is added while maintaining the temperature of 50 to 100 ° C., and stirred at a speed of 200 to 800 RPM. 5) After complete dissolution, glycerin (0.3 to 10% by weight) is added at 30 to 80° C. and stirred at a speed of 100 to 600 RPM until completely dissolved.

In addition, a case in which an aqueous solution of acetic acid is used as a solvent and chitosan is used as a polymer material will be described. 1) Add an aqueous solution of acetic acid (50 to 80% by weight) to a stirrer and heat to 30 to 80 ° C, 2) Add chitosan (5 to 30% by weight) and stir at 200 to 800 RPM until completely dissolved Stir at speed. 3) After completely dissolved, a water-soluble polymer such as HPMC (hydroxypropyl methylcellulose) (2 to 20% by weight) or CMC (carboxymethyl cellulose) (2 to 20% by weight) is added and heated to 30 to 80 ° C. to 200 to 200 Stir at a speed of 800 RPM. 4) Subsequently, a drug (API: Active Pharmaceutical Ingredient), for example, Donepezil (5 to 30% by weight) is added while maintaining the temperature of 50 to 100 ° C., and stirred at a speed of 200 to 800 RPM. 5) After complete dissolution, glycerin (0.3 to 10% by weight) is added at 30 to 80° C. and stirred at 100 to 600 RPM until completely dissolved.

Donepezil corresponding to the aforementioned drug is only a drug used to test the microneedle patch 170 according to the present invention, and the present invention is not limited to the above drug. For example, the type of drug that can be contained in the needle body 160 or the needle support 110 is not particularly limited.

Meanwhile, the needle body 160 may be formed by forming the needle support 110 or the base needle through the above-described process using the viscous composition formed as described above and deforming it. At least one of the needle support body 110 and the needle body 160 thus formed has a property of expanding or swelling by combining with bodily fluid.

For example, the needle support 110 and the needle body 160 may be formed through the same viscous composition or different viscous compositions. Here, the same viscous composition may be defined as having the same swellable polymer material included in the composition, and furthermore, all containing drugs.

In addition, in the different viscous compositions, only one of the compositions for the needle support 110 and the needle body 160 contains a swellable polymer material, or the swellable polymer material included in the composition is different from each other, or whether or not a drug is contained may be defined differently.

For example, the needle support 110 may include PVA, and the needle body 160 may include chitosan, or vice versa. Furthermore, at least one of the needle support 110 and the needle body 160 may contain a drug.

Hereinafter, the case where the needle body 160 includes a swellable polymer material will be described in detail. 9(a) shows the original state of the needle body 160, and FIG. 9(b) shows a state where the needle body 160 expands due to contact with bodily fluid.

The needle body 160 is combined with bodily fluid so that the base diameter D, the needle height H, and the needle radius N can be changed. In particular, at least one of the base diameter (D), the needle height (H) and the needle radius (N) may be increased in a range of 1 to 200%. As a result, the surface area and volume of the needle body 160 may be increased.

For example, the needle body 160 may have a base diameter (D) of about 807 μm, a needle length (H) of about 413 μm, and a needle diameter (N) of about 90 μm. And, when combined with body fluid, the needle body 160 has a base diameter (D') of about 1048 μm, a needle length (H') of about 426 μm, and a needle diameter (N) of about 158 μm. Accordingly, the base diameter (D) increased by about 30%, and the needle diameter (N) increased by about 76%. Although the needle length (H) has little change, it can be seen that as a result, the volume and surface area of the needle body 160 are increased.

10 to 13 are photographs of changes in the needle body of the microneedle patch according to an embodiment of the present invention.

10 and 11 correspond to cases in which the needle body 160 includes Chitosan among swelling polymer materials. FIG. 10 shows the original state of the needle body 160, and FIG. 11 shows the state after contact with the body fluid simulation solution (PBS, Phosphate Buffer Saline).

In the case of the needle body shown on the left in FIGS. 10 and 11, the base diameter was changed from 809.15 μm to 1029.4 μm, the needle length (H) was changed from 404.91 μm to 407.84 μm, and the needle diameter (N) was changed from 96.13 μm to 407.84 μm. changed to 171.90 μm. In addition, in the case of the needle body shown on the right in FIGS. 10 and 11, the base diameter was changed from 806.33 μm to 1068.94 μm, the needle length (H) was changed from 423.85 μm to 445.7 μm, and the needle diameter (N) was 84.53 μm to 145.65 μm.

12 and 13 correspond to the case where the needle body 160 includes PVA among the swellable polymer materials. FIG. 12 shows the original state of the needle body 160, and FIG. 13 shows the state after contact with body fluid simulation solution (PBS, Phosphate Buffer Saline).

In the case of the needle body shown on the left in FIGS. 12 and 13, the base diameter was changed from 873.61 μm to 1002.10 μm, the needle length (H) was changed from 614.74 μm to 614.67 μm, and the needle diameter (N) was changed from 123.8 μm to 614.67 μm. changed to 155.85 μm. In addition, in the case of the needle body shown on the right in FIGS. 12 and 13, the base diameter was changed from 888.55 μm to 1044.70 μm, the needle length (H) was changed from 611.85 μm to 607.46 μm, and the needle diameter (N) was 123.84 μm to 167.5 μm.

Through these experimental values, it can be confirmed that the surface area and volume increase when the needle body comes into contact with body fluid. At this time, it can be seen that the needle length (H) is slightly unchanged, but the base diameter (D) and the needle diameter (N) are increased in the lateral direction of the needle body. In summary, upon body fluid contact, the base diameter (D) and the needle diameter (N) increase 1.1 times or more and less than 2 times, and the needle length (H) has relatively little change.

In addition, at least one of the needle supporter 110 and the needle body 160 may contain a drug as described above. That is, in the microneedle patch 170 of the present invention, 1) the needle body 160 contains a drug, 2) the needle support 110 contains a drug, or 3) the needle body 160 and the needle support ( 110) may all contain drugs.

Table 1 attached below describes experimental values obtained by measuring the value of actually containing a drug when the needle support or needle body contains the drug.

A B C D E F Measures 3.88mg 3.97mg 3.95mg 3.96mg 4.68mg 4.68mg

In the case of A and B, 4 mg of the drug was included only in the viscous composition for forming the needle support, and the amount of the drug was measured again after actually forming the needle support. In addition, the experiment was conducted in the case where A included chitosan and B included PVA. As a result, in the case of A, 3.88mg was measured and 97.0% of the drug was measured compared to the theoretical value, and in the case of B, 3.97mg was measured and 99.2% of the drug was measured compared to the theoretical value. That is, it can be seen that the drug is effectively contained even when the drug is included only in the needle support.

In the case of C and D, 4 mg of the drug was included only in the viscous composition for forming the needle body, and the amount of the drug was measured again after actually forming the needle body. In addition, the experiment was conducted in the case where C included chitosan and D included PVA. As a result, in the case of C, 3.95mg was measured and 98.7% of the drug was measured compared to the theoretical value, and in the case of D, 3.96mg was measured and 99.0% of the drug was measured compared to the theoretical value. That is, it can be seen that the drug is effectively contained even when only the needle body contains the drug.

In the case of E and F, 4.75 mg of the drug was included in the viscous composition for forming the needle support and the needle body, and the amount of the drug was measured again after actually forming the needle support and the needle body. In addition, the experiment was conducted in the case where E included chitosan and F included PVA. As a result, in the case of E, 4.68mg was measured and 98.5% of the drug was measured compared to the theoretical value, and in the case of F, 4.68mg was measured and 98.6% of the drug was measured compared to the theoretical value. That is, it can be seen that the drug is effectively contained even when the drug is included in both the needle support and the needle body.

Meanwhile, FIG. 14 is a diagram schematically showing changes in a needle body in a microneedle patch according to another embodiment of the present invention.

Referring to FIG. 14, according to the experiment of the present applicant, when the needle body comes into contact with body fluid, one of the aforementioned base diameter (D), the needle height (H), and the needle diameter (N) increases and the other decreases. can be modified to

For example, in the form of FIG. 14 (a), upon body fluid contact, it may be deformed as shown in FIG. 14 (b). It can be seen that the needle body shown in FIG. 14 (b) has a relatively increased base diameter (D") compared to the shape of FIG. 14 (a), and a reduced needle height (H"). In this case, the needle diameter (N") may be about the same or larger.

In addition, in the form of FIG. 14 (a), upon body fluid contact, it may be deformed as shown in FIG. 14 (c). In the needle body shown in (c) of FIG. 14, it can be seen that the base diameter (D''') is relatively decreased compared to the shape of (a) of FIG. 14, and the needle height (H''') is increased. can In this case, the needle diameter (N''') may be approximately the same or smaller.

Even in the needle body according to (b) and (c) of FIG. 14, when the body fluid contacts, any one of the above-described base diameter (D), the needle height (H), and the needle diameter (N) increases and expands, so the needle body The drug contained in can be injected into the human body.

In summary, at least one of the needle support and the needle body of the present invention may include a swellable polymer material or a drug. At this time, the needle support and the needle body can be understood as one 'microneedle'. The microneedle means a configuration in which at least a part is inserted into the skin to inject a drug.

For example, when the needle support and the needle body are formed of the same viscous composition, they are each formed through the manufacturing process described above. Also, the needle supporter and the needle body may form an integrated microneedle.

Although the above has been described with reference to preferred embodiments of the present invention, those skilled in the art variously modify and change the present invention within the scope not departing from the spirit and scope of the present invention described in the claims described below. You will be able to. Therefore, if the modified implementation basically includes the elements of the claims of the present invention, all of them should be considered to be included in the technical scope of the present invention.

100, 200: base sheet
110, 210: needle support
120, 220: adhesive sheet
130, 230: cover sheet
140, 240: base needle
150, 250: structure
160, 260: needle body
170, 270: microneedle patch

Claims (14)

A pressure-sensitive adhesive sheet that adheres to the skin;
a needle support disposed on the adhesive sheet; and
It is disposed on the needle support and includes a needle body having a tip,
The microneedle patch, characterized in that at least one of the needle support body and the needle body comprises a swellable polymer material that expands upon contact with body fluid. According to claim 1,
At least one of the needle support and the needle body contains a drug,
The microneedle patch, characterized in that at least one of the needle supporter and the needle body expands upon contact with body fluid and supplies the drug. According to claim 1,
At least one of the needle support and the needle body is formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved. According to claim 1,
The needle body includes a swellable polymer material and has a base diameter (D) corresponding to the diameter of the bottom in contact with the needle support, a needle height (H) corresponding to the orthogonal distance from the bottom to the top, and a diameter corresponding to the tip It is provided in a shape having a needle diameter (N),
The microneedle patch, characterized in that at least one of the base diameter, the needle height, and the needle diameter increases when the needle body contacts the body fluid. According to claim 4,
The microneedle patch, characterized in that the base diameter and the needle diameter increase 1.1 times or more and less than 2 times when the body fluid contacts. According to claim 1,
The needle body includes a swellable polymer material and has a base diameter (D) corresponding to the diameter of the bottom in contact with the needle support, a needle height (H) corresponding to the orthogonal distance from the bottom to the top, and a diameter corresponding to the tip It is provided in a shape having a needle diameter (N),
The microneedle patch, wherein one of the base diameter, the needle height, and the needle diameter of the needle body increases and the other decreases when the body fluid contacts. According to claim 1,
The adhesive sheet and the needle support form one adhesive surface,
The microneedle patch of claim 1, wherein the needle support is inserted into the adhesive sheet from the adhesive surface and the needle body extends outward from the adhesive surface. According to claim 7,
The needle support is inserted into the adhesive sheet and disposed in a plurality of intaglio shapes spaced apart from each other,
The microneedle patch, characterized in that the needle body is disposed on each of the plurality of needle supports. According to claim 7,
The needle support is inserted into the pressure-sensitive adhesive sheet and is disposed in the form of a layer extending in parallel,
The microneedle patch, characterized in that a plurality of needle bodies are disposed spaced apart from each other on the needle support. Forming a needle support on a base resin;
forming an adhesive sheet on the base sheet to cover the needle support;
forming a cover resin on the upper portion of the adhesive sheet and disposing the needle supporter and the adhesive sheet upside down so that the base resin is disposed thereon;
removing the base resin; and
Forming a needle body on the needle support,
The method of manufacturing a microneedle patch, characterized in that at least one of the needle support and the needle body comprises a swellable polymer material that expands upon contact with body fluid. According to claim 10,
At least one of the needle support and the needle body is formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved. According to claim 10,
Forming the needle body,
A pair of structures in which base needles are formed on the needle support body,
Relatively moving the pair of structures so that the pair of structures are brought closer to each other so that the pair of base needles respectively formed on the pair of structures come into contact with each other,
Relatively moving the pair of structures away from each other so that the pair of base needles are attached to each other, stretched, and deformed in shape,
The method of manufacturing a microneedle patch, characterized in that the deformed base needle forms the needle body. According to claim 10,
The needle support includes a plurality of supports formed spaced apart on the base resin,
The adhesive sheet covers each of the plurality of supports,
The method of manufacturing a microneedle patch, characterized in that the needle body is formed on each of the plurality of supports. According to claim 10,
The needle body
A method of manufacturing a microneedle patch, characterized in that a plurality is formed by being spaced apart on the needle support.

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