KR102592223B1 - A micro-needle array and manufacturing method thereof - Google Patents

Abstract

One embodiment of the present invention includes the steps of (a) molding a thermoplastic substrate to manufacture a release sheet including one or more concave portions; and (b) forming microneedles by injecting microneedle raw material into the concave portion.
In addition, one embodiment of the present invention includes a release sheet of a thermoplastic substrate including one or more engraved portions; And, a microneedle array is provided in which microneedle raw material is injected into the concave portion.

Description

Microneedle array and manufacturing method thereof {A MICRO-NEEDLE ARRAY AND MANUFACTURING METHOD THEREOF}

The present invention relates to a microneedle array and a manufacturing method thereof. More specifically, a release sheet manufactured through a certain process is used as a mold required for manufacturing a microneedle array, and in the final product, the release sheet is separated from the microneedle. About a microneedle array that can prevent deformation, loss, contamination, etc. of the microneedle by leaving it in an unremoved state and removing it before application by the user or, if necessary, during the manufacturing process, and a method of manufacturing the same. will be.

In general, microneedle formulations are aimed at delivering ingredients to achieve the desired effect through the skin. Microneedle formulations use microneedles with a diameter and height of only tens to thousands of micrometers to pierce the stratum corneum, which is the main barrier layer for ingredient delivery through the skin. Using the microneedles, the target ingredient reaches the epidermal layer or dermis layer and exerts efficacy throughout the body through the area where the microneedles are applied or through the body's circulatory system.

The material of microneedles can be largely divided into metal microneedles and biodegradable material microneedles.

Metal microneedles are hollow microneedles that have a hollow like a regular injection needle with a path through which the ingredients to be delivered can move, and solid microneedles that deliver the ingredients by coating them on the surface of the microneedle. There is a form.

Meanwhile, biodegradable microneedles are mainly in the form of solid microneedles, and are applied to the skin by coating the surface of the microneedle with ingredients or forming microneedles with biodegradable polymers to deliver the ingredients as the applied microneedles decompose. .

The microneedle is generally manufactured by injecting the material constituting the needle into a metal (iron, silicon, etc.) mold in which the shape of the microneedle is engraved.

This method of forming microneedles in a metal mold necessarily involves the process of separating the microneedle from the mold to cycle the manufacturing process after forming the microneedle because the metal mold is an accessory to the microneedle manufacturing equipment or is heavier than non-metallic molds. .

Due to this manufacturing method, the external shape of the microneedle may be deformed or lost when the microneedle is separated from the metal mold, or during additional manufacturing or distribution processes after the mold is separated. Such deformation or loss may result in non-uniformity in the content of each microneedle and, consequently, in the overall content of the drug loaded into the microneedle array. In addition, since the metal mold is an accessory to the manufacturing equipment, for mass production, the manufacturing equipment must be enlarged as the metal mold becomes larger, and the manufacturing cost also increases. In addition, for continuous production, complete cleaning of the metal mold is required, which takes a lot of time and reduces manufacturing efficiency. There is a problem that the manufacturing cost is increasing due to this.

In addition, packaging material that can protect each microneedle is desperately needed after the microneedles are separated from the mold, but there is no packaging material that surrounds each microneedle.

Republic of Korea Patent Publication No. 10-1694317 (2017.01.03)

The present invention is intended to solve the problems of the prior art described above, and the purpose of the present invention is to prevent deformation, loss, and contamination of the microneedle caused by the process of forming the conventional microneedle and then separating it from the mold. The aim is to provide a microneedle array and a manufacturing method thereof that can optimize the use of microneedles as cosmetic, pharmaceutical, and medical products and improve the manufacturing efficiency of microneedles.

In addition, the present invention provides a microneedle array that is a mold of microneedles and includes a thermoplastic release sheet that can protect each microneedle.

One aspect of the present invention includes the steps of (a) molding a thermoplastic substrate to manufacture a release sheet including one or more concave portions; and (b) forming microneedles by injecting microneedle raw material into the concave portion.

In one embodiment, in step (a), the thermoplastic substrate sandwiched between a first mold including one or more first tip embossed portions and a second mold opposing the first mold may be pressed.

In one embodiment, the second mold may include one or more cutting edge engravings.

In one embodiment, the first tip embossed portion may be formed on the upper surface of one or more flat embossed portions.

In one embodiment, the second mold may include one or more flat engraved portions and one or more tipped engraved portions formed on a lower surface of the flat engraved portion.

In one embodiment, in step (a), one surface of the thermoplastic substrate may be irradiated with heat, a laser, or a combination thereof.

In one embodiment, in step (a), the thermoplastic substrate may be molded using an injection molding or extrusion molding method.

In one embodiment, in step (a), the thermoplastic substrate may be applied by spraying the thermoplastic substrate onto a first mold including one or more first tip embossed portions and then dried.

In one embodiment, in step (a), the first mold including one or more first tip embossed portions may be dipped into a solution or viscous liquid containing the thermoplastic substrate and then dried.

In one embodiment, in step (a), one or more engraved portions may be manufactured from the thermoplastic substrate using a blade or processing machine.

In one embodiment, in step (a), one or more engraved portions may be manufactured from the thermoplastic substrate using 3D printing.

In one embodiment, after step (b), (c1) laminating an adhesive sheet to a flat surface including an upper surface of the microneedle and one surface of the release sheet may be further included.

In one embodiment, after step (b), (c2) the upper surface of the microneedle is pressed with a third mold including at least one second tip embossed portion having a smaller diameter than the first tip embossed portion, thereby forming the upper surface of the microneedle. It may further include forming a channel penetrating the microneedle from the microneedle to the tip of the microneedle.

In one embodiment, after step (c1), (c2) the upper surface of the microneedle is pressed with a third mold including at least one second tip embossed portion having a smaller diameter than the first tip embossed portion, thereby forming the upper surface of the microneedle. It may further include forming a channel penetrating the microneedle from the microneedle to the tip of the microneedle.

In one embodiment, after step (b), (c3) heat, laser, or a combination thereof is irradiated to the upper surface of the microneedle to create a channel penetrating the microneedle from the upper surface to the tip of the microneedle. It may further include forming a.

In one embodiment, the channel includes a first opening formed on the upper surface of the microneedle, and a second opening formed on the tip of the microneedle, and the second opening may be closed by the release sheet. You can.

In one embodiment, after step (c2) or (c3), the method may further include (d) connecting a container containing one or more pharmaceutical ingredients to the first opening.

In one embodiment, the puncture strength of the release sheet may be greater than that of the microneedle.

In one embodiment, in step (b), after injection of the microneedle raw material, the pressure is reduced to 0.5 atm or less and then filled with a concave portion of the release sheet by using a blade or by pressing to 2 atm or more. You can.

In one embodiment, in step (b), the microneedle raw material containing the active ingredient to be delivered is filled into the concave part of the release sheet, first dried, and then the upper part is filled with the base raw material, and then secondly dried. It can be dried to form microneedles.

One aspect of the present invention is a release sheet of a thermoplastic substrate including one or more engraved portions; And, a microneedle array is provided in which microneedle raw material is injected into the concave portion.

In one embodiment, the engraved portion may be a cutting edge engraved portion.

In one embodiment, the thermoplastic substrate including the engraved portion may be a mold of the microneedle.

In one embodiment, the thermoplastic substrate may be either a metal or a non-metal.

In one embodiment, the thermoplastic substrate may be at least one selected from the group consisting of polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), polypropylene (PP), and aluminum.

In one embodiment, the thermoplastic substrate may be in the form of a sheet or sheet having a thickness of 50 μm to 10,000 μm.

In one embodiment, the release sheet may surround each of the microneedles injected into the concave portion.

In one embodiment, the release sheet may be removed immediately before applying the microneedle array to the human body.

In one embodiment, the microneedle raw material may be one or more selected from the group consisting of metals, non-metals, biodegradable polymers, and pharmaceutical ingredients.

In one embodiment, a channel penetrating the microneedle may be formed with a diameter smaller than the concave portion into which the microneedle raw material is injected.

In one embodiment, the puncture strength of the release sheet may be greater than that of the microneedle.

In one embodiment, the channel may be closed by the release sheet.

In one embodiment, the upper surface of the microneedle may further include a base.

In one embodiment, the base is made of carboxymethylcellulose (CMC), hyaluronic acid (HA), polyvinyl alcohol (PVA), polylactic acid (PLA), polylactic glycolic acid (PLGA), and polyvinylpyrrolidone. (PVP) may be at least one selected from the group consisting of

In one embodiment, an adhesive sheet may be laminated to one surface of the microneedle array.

In one embodiment, the adhesive sheet may be a sheet made of a flexible material or an adhesive may be applied and coated on one surface of the sheet.

In one embodiment, the microneedle raw material may not be a pharmacological ingredient.

In one embodiment, the channel may be a path for movement and injection of pharmacological ingredients.

In one embodiment, a container containing one or more pharmacological ingredients may be further included on the lower surface of the microneedle.

The microneedle array and its manufacturing method according to one aspect of the present invention use a release sheet manufactured through a certain process as a mold required for manufacturing the microneedle array, and the release sheet is not removed from the microneedle in the final product. It is possible to prevent deformation, loss, contamination, etc. of the microneedle by allowing it to exist in an unused state and be removed by the user before application to the human body, or, if necessary, removed during the manufacturing process.

In addition, according to the microneedle array and its manufacturing method, various shapes, specifically, hollow microneedles as well as solid microneedles, can be easily manufactured depending on the shape of the mold and whether or not a certain process is added.

In addition, according to the microneedle array and its manufacturing method, a release sheet that has the function of protecting the microneedle in the final product is used as a mold necessary for forming the microneedle, so the maximum manufacturing quantity is raw material regardless of the size of the manufacturing device. It can be adjusted according to the input amount, and thus microneedles can be produced in large quantities in a short time.

In addition, according to the microneedle array and its manufacturing method, microneedles with an elaborate shape and uniform content can be manufactured by applying a microneedle filling method using vacuum blading.

In addition, according to the microneedle array and its manufacturing method, by molding the microneedle using a two-stage molding method, the active ingredient is present only at the lower end of the microneedle, so that only an accurately controlled amount can be delivered to the user.

The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

Figure 1 schematically illustrates the steps of manufacturing a release sheet according to an embodiment of the present invention.
Figure 2 schematically illustrates the steps of forming a microneedle according to an embodiment of the present invention.
Figure 3 schematically illustrates the steps of forming microneedles using a two-stage molding method according to an embodiment of the present invention.
Figure 4 schematically illustrates the steps of laminating adhesive sheets according to an embodiment of the present invention.
Figure 5 schematically illustrates a method of applying a solid microneedle array manufactured by a method according to an embodiment of the present invention.
Figure 6 schematically illustrates the steps of manufacturing a hollow microneedle array according to an embodiment of the present invention.
Figure 7 schematically illustrates the steps of connecting a container containing a pharmacological ingredient to a hollow microneedle array according to an embodiment of the present invention.
Figure 8 schematically illustrates a method of applying a hollow microneedle array manufactured by a method according to an embodiment of the present invention.
Figure 9 shows a perspective view and a partially enlarged view of a release sheet manufactured according to an embodiment of the present invention.
Figure 10 shows a comparative photograph of a microneedle array manufactured by vacuum and atmospheric pressure blading filling methods according to an embodiment of the present invention.
Figure 11 shows an optical microscope photograph of a microneedle array manufactured by a two-stage molding method according to an embodiment of the present invention.
Figure 12 shows a photograph of a microneedle array according to an embodiment of the present invention.
Figure 13 shows a photograph in which the release sheet, which is a mold for a microneedle array according to an embodiment of the present invention, has been removed from the microneedle array.

Hereinafter, the present invention will be described with reference to the attached drawings. However, the present invention may be implemented in various different forms and, therefore, is not limited to the embodiments described herein. In order to clearly explain the present invention in the drawings, parts that are not related to the description are omitted, and similar parts are given similar reference numerals throughout the specification.

Throughout the specification, when a part is said to be “connected” to another part, this includes not only cases where it is “directly connected,” but also cases where it is “indirectly connected” with another member in between. . Additionally, when a part is said to “include” a certain component, this does not mean that other components are excluded, but that other components can be added, unless specifically stated to the contrary.

Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings.

One aspect of the present invention includes the steps of (a) molding a thermoplastic substrate to manufacture a release sheet including one or more concave portions; and (b) forming microneedles by injecting microneedle raw material into the concave portion.

In step (a), the thermoplastic substrate is pressed using a mold of a certain shape and/or one surface of the thermoplastic substrate is irradiated with heat, a laser, or a combination thereof to form a release sheet 10 including an engraved portion 11. can be manufactured.

Figure 1 schematically illustrates the steps of manufacturing a release sheet according to an embodiment of the present invention. Figures 1(a) to 1(d) show a method of manufacturing a release sheet using a mold of a certain shape, and Figure 1(e) shows a method of manufacturing a release sheet by irradiating one side of a thermoplastic substrate with heat, a laser, or a combination thereof. Indicates the method.

Figure 9 shows a perspective view and a partially enlarged view of a release sheet manufactured according to an embodiment of the present invention.

Referring to FIG. 1(a), in step (a), a first mold 100 including one or more first tip embossed portions 110 and a second mold opposing the first mold 100 ( 200) The thermoplastic substrate sandwiched therebetween may be pressed. As used herein, the term “tip embossing portion” refers to a relief protruding from the lower surface with a cross-sectional area reduced from the flat lower surface to the upper surface forming the tip to have the shape of a typical microneedle 21. Additionally, the terms “upper surface” and/or “lower surface” used in this specification are intended to specify the relative positional relationship of each component, and do not specify their absolute positions. Also, 'sheet' refers to a flat plate and does not limit a specific shape.

One side of the thermoplastic substrate is placed on the flat surface of the second mold 200, and the other side of the thermoplastic substrate is opposed to the first tip embossed portion 110 of the first mold 100. 1 After pressing with the mold 100, when the first mold 100 is removed, the thermoplastic substrate can be molded into a release sheet 10 including one or more concave portions 11. At this time, one side of the molded release sheet 10 may include one or more engraved portions 11, and the other side may be flat.

The engraved portion 11 acts as a mold for the microneedle 21 formed in a subsequent step, and may have the same shape as the microneedle 21, but may have an inverse shape in the vertical direction.

When the tip of the first tip embossed portion 110 and the second mold 200 contact, unnecessary perforations occur at the tip of the release sheet 10, and the release sheet 10 is formed in a subsequent step. 21), preferably, the vertical movement distance of the first mold 100 and/or the second mold 200 is adjusted to a certain range, or the first tip embossed portion 110 The height can be adjusted to be smaller than the thickness of the thermoplastic substrate.

Referring to FIG. 1(b), in step (a), the second mold 200 may include one or more cutting edge engraved portions 210. That is, in step (a), a first mold 100 including one or more first cutting edge embossed portions 110 and a first mold 100 facing the first mold 100 and including one or more cutting edge engraved portions 210. The thermoplastic substrate sandwiched between the second mold 200 may be pressed. As used herein, the term “tip concave portion” refers to a concave recess from the top surface in which the cross-sectional area is reduced from the flat upper surface to the lower surface forming the tip to have the shape of a typical microneedle 21.

The thermoplastic substrate is placed in the first mold such that both sides of the thermoplastic substrate face the first embossed portion 110 of the first mold 100 and the engraved portion 210 of the second mold 200, respectively. 1 After placing between the mold 100 and the second mold 200 and pressing both sides of the thermoplastic substrate with the first mold 100 and the second mold 200, the first mold 100 and When the second mold 200 is removed, the thermoplastic substrate can be molded into a release sheet 10 including one or more concave portions 11. At this time, one side of the molded release sheet 10 may include one or more engraved portions 11, and the other side may include one or more embossed portions 13 corresponding to the engraved portions 11. .

When the first tip embossed portion 110 and the tip engraved portion 210 come into contact, the thermoplastic substrate is damaged or broken, and the release sheet 10 cannot protect the microneedles 21 formed in the subsequent step. , Preferably, the vertical movement distance of the first mold 100 and/or the second mold 200 may be adjusted within a certain range so that the first mold 100 and/or the second mold 200 do not contact each other when the pressure is applied.

Referring to FIG. 1(c), the first tip embossed portion 110 may be formed on the upper surface of one or more flat embossed portions 120. That is, in step (a), a first mold 100 including one or more first tip embossed portions 110 formed on the upper surface of one or more flat embossed portions 120 and a mold facing the first mold 100. The thermoplastic substrate sandwiched between the second mold 200 may be pressed. As used herein, the term “flat embossment” refers to an embossment that protrudes at a certain height and has a cross-sectional area that is substantially the same from the flat lower surface to the upper surface. The upper surface of the flat embossed part 120 may be substantially flat, and the first tip embossed part 110 may be formed on the upper surface of the flat embossed part 120.

One side of the thermoplastic substrate is positioned on the flat surface of the second mold 200, and the other side of the thermoplastic substrate is positioned on the flat embossed portion 120 and the first tip embossed portion of the first mold 100 ( 110), pressing the other side of the thermoplastic substrate with the first mold 100, and then removing the first mold 100, the thermoplastic substrate becomes a release sheet 10 including one or more engraved portions. It can be molded. At this time, one side of the molded release sheet 10 is on the flat engraved portion 12 formed by the flat embossed portion 120 of the first mold 100 and the lower surface of the flat engraved portion 12. It may include one or more engraved portions 11 formed by the first tip embossed portion 110. As used herein, the term “flat concave portion” refers to a concave concave portion with substantially the same cross-sectional area and a certain depth from the flat upper surface to the lower surface. The lower surface of the flat engraved portion 12 may be substantially flat.

When the tip of the first tip embossed portion 110 and the second mold 200 contact, unnecessary perforations occur at the tip of the release sheet 10, and the release sheet 10 is formed in a subsequent step. 21), it is preferable to adjust the vertical movement distance of the first mold 100 and/or the second mold 200 to a certain range, or to adjust the flat embossed portion 120 and the second mold 200 to a certain range. 1 The total height of the cutting edge embossing portion 110 can be adjusted to be smaller than the thickness of the thermoplastic substrate.

Referring to FIG. 1(d), the second mold 200 may include one or more flat engraved portions 220 and one or more cutting edge engraved portions 210 formed on the lower surface of the flat engraved portion 220. . That is, in step (a), a first mold 100 including one or more first tip embossed portions 110 formed on the upper surface of one or more flat embossed portions 120 and a mold facing the first mold 100. And the thermoplastic substrate sandwiched between the second mold 200 including one or more flat engraved portions 220 and one or more tip engraved portions 210 formed on the lower surface of the flat engraved portion 220 can be pressed. .

Both sides of the thermoplastic substrate have a flat embossed portion 120 and a first tip embossed portion 110 of the first mold 100, and a flat embossed portion 220 and a tip embossed portion of the second mold 200. The thermoplastic substrate is positioned between the first mold 100 and the second mold 200 to face (210), and both sides of the thermoplastic substrate are formed with the first mold 100 and the second mold 200. After pressing, the first mold 100 and the second mold 200 are removed, and the thermoplastic substrate can be molded into a release sheet 10 including one or more engraved portions. At this time, one side of the molded release sheet 10 is on the flat engraved portion 12 formed by the flat embossed portion 120 of the first mold 100 and the lower surface of the flat engraved portion 12. It may include one or more concave portions 11 formed by the first tip embossed portion 110, and a flat embossed portion 14 and an embossed portion corresponding to the flat concave portion 12 and the concave portion 11, respectively. (13) may be included.

When the first mold 100 and the second mold 200 come into contact, the thermoplastic substrate is damaged or broken and the release sheet 10 cannot protect the microneedles 21 formed in the subsequent step. Therefore, preferably The vertical movement distance of the first mold 100 and/or the second mold 200 may be adjusted within a certain range so that the first mold 100 and/or the second mold 200 do not contact each other during the pressing.

The engraved portions 11 of the release sheet 10 molded by the method of FIGS. 1(a) and 1(b) are not connected to each other and exist independently. When manufacturing microneedles 21 using this release sheet 10 as a mold, the manufactured microneedles 21 are also not connected to each other and exist independently, so that in the subsequent step, the microneedles 21 are attached to the adhesive sheet ( 30), there is a problem that it is difficult to adhere evenly. For example, when 100 microneedles 21, which exist independently of each other in 10*10 (width*height), are combined with the adhesive sheet 30 in a subsequent step, a single microneedle attached to the adhesive sheet 30 Since the cross-sectional area of the lower surface of the microneedle 21 is insufficient, it may easily fall off from the adhesive sheet 30, causing inconvenience to the user.

In contrast, the release sheet 10 molded by the method of FIGS. 1(c) and 1(d) includes a flat engraved portion 12 and one or more engraved portions 11 formed on the lower surface of the flat engraved portion 12. It includes, and in the subsequent step, the microneedle raw material 20 is filled not only in the engraved part 11 but also in the flat engraved part 12 to form microneedles 21 formed by the engraved part 11 and the flat engraved part. Since the support 22 formed by the portion 12 is formed integrally, it is possible to prevent the single microneedle 21 from randomly falling from the adhesive sheet 30 as described above.

Referring to FIG. 1(e), in step (a), one surface of the thermoplastic substrate may be irradiated with heat, a laser, or a combination thereof. That is, the release sheet 10 can be mechanically and physically formed using a mold of a certain shape as shown in FIGS. 1(a) to 1(d), and one surface of the thermoplastic substrate is applied with heat, laser, or They can also be formed chemically or physicochemically by investigating their combinations. The heat source and/or light source for irradiating the heat and/or laser may be arranged to correspond to the number of microneedles 21 included in the microneedle 21 array and their spacing.

When manufacturing a release sheet 10 including an engraved portion 11 in the shape of a microneedle 21 using heat and/or a laser, the engraved portion 11 has a shape in which the cross-sectional area decreases from the upper surface to the lower surface. Therefore, it is necessary to control the irradiation area and intensity of heat and/or laser. For example, when irradiating heat and/or laser with the same intensity, the irradiation area can be gradually reduced.

In addition, as necessary, before irradiating heat and/or laser to the thermoplastic substrate, pretreatment is performed using methods such as masking or photoresist to expose only the cross-sectional shape of the microneedle 21 array among one surface of the thermoplastic substrate, or heat treatment. And/or by interposing a filter in the cross-sectional shape of the microneedle 21 array between the heat source and/or light source for irradiating the laser and the thermoplastic substrate, process efficiency and energy efficiency are improved by using a single heat source and/or light source. It can be improved.

Furthermore, in step (a), the thermoplastic substrate may be formed by injection molding or extrusion molding. In addition, the thermoplastic substrate may be sprayed on the first mold 100 including one or more first tip embossed portions 110, the thermoplastic substrate may be applied, and then dried and molded. Additionally, the first mold 100 including one or more first tip embossed portions 110 may be dipped into a solution or viscous liquid containing a thermoplastic substrate and then dried to form the molding. Additionally, one or more engraved portions 11 can be manufactured on a thermoplastic substrate using a blade or processing machine. Additionally, one or more engraved portions 11 can be manufactured using 3D printing on a thermoplastic substrate.

In this way, the release sheet 10 can be manufactured not only by the molding method described in FIGS. 1 (a) to 1 (e), but also by injection molding or extrusion molding, spraying, dipping, blade or processing machine, 3D printing, etc. It can also be produced in various ways using the method.

The thermoplastic substrate is a sheet or sheet-shaped substrate that has thermoplasticity at a certain thickness, and may be made of a metal or non-metal, preferably a non-metal, and more preferably a polymer. For example, the thermoplastic substrate may be a sheet made of polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), polypropylene (PP), aluminum, a PVC/PE/PVDC sheet, It may be a sheet made of multiple layers of polymer such as PVC/Aclar or PVC/ecozen, or it may be a sheet coated with a metal material (Alu) such as a PVC/Alu-Alu sheet, but is not limited thereto. Meanwhile, the thermoplastic substrate is preferably in the form of a sheet or sheet with a thickness of 50 to 10,000 μm.

Referring to FIG. 9, according to one embodiment, a release sheet 10 including 100 engraved portions 11 that exist independently of each other in 10*10 (width*height) manufactured as shown in FIG. 1(b) is shown. You can check it. The engraved portion 11 acts as a mold for the microneedle 21 formed in the subsequent step, and allows the release sheet 10 to remain in the final product without being removed from the microneedle 21, thereby providing user convenience. It is possible to prevent deformation, loss, contamination, etc. of the microneedle 21 by removing it before application to the human body or, if necessary, during the manufacturing process.

In step (b), the microneedle 21 may be formed by injecting the microneedle raw material 20 into the concave portion 11. The microneedle raw material 20 may include one or more selected from the group consisting of metals, non-metals, biodegradable polymers, and active pharmaceutical ingredients, depending on the shape of the microneedle 21. For example, the microneedle raw material 20 may be a composition containing a pharmacological ingredient when the microneedle 21 is a solid microneedle, and when the microneedle 21 is a hollow microneedle, That is, when the microneedle 21 provides a path for injection of a pharmacological ingredient, it may be a composition containing metal, non-metal, biodegradable polymer, or a combination of two or more of these, but is not limited thereto.

Figure 2 schematically illustrates the steps of forming a microneedle according to an embodiment of the present invention. FIGS. 2(a) to 2(d) show steps for forming microneedles using each release sheet molded through the method of FIGS. 1(a) (or 1(e)) to 1(d), respectively. represents.

Figure 10 shows a comparative photograph of a microneedle array manufactured by vacuum and atmospheric pressure blading filling methods according to an embodiment of the present invention.

Referring to FIG. 2, the microneedle raw material 20 may be supplied from the storage tank to the release sheet 10 through a single discharge port and injected into the engraved portion 11 and/or the flat engraved portion 12. The method of supplying and injecting the microneedle raw material 20 is not limited to this, and if necessary, the microneedle raw material 20 is placed in each of the plurality of engraved portions 11 and/or the flat engraved portions 12. The microneedle raw material (20) is directly injected into the engraved portion 11 and/or the flat engraved portion 12 through a plurality of discharge holes located adjacent to each other, or is applied using a coating method such as roll coating, bar coating, or spray coating. ) can also be injected into the concave portion 11 and/or the flat concave portion 12.

At this time, after depressurizing the pressure to 0.5 atm or less, preferably 0.1 atm or less, in the decompression chamber, the microneedle raw material 20 is introduced into the flat surface of the release sheet 10, and then the release sheet is cut using a blade. It can be filled in the concave part 11 and/or the flat engraved part 12 of (10). In this way, the filling method using a blade after decompressing the inside of the decompression chamber to a close to vacuum state suppresses the generation of bubbles in the concave portion 11 of the release sheet 10, giving the microneedle 21 an elaborate shape for pharmaceutical use. By having an equal content, it is possible to overcome the limitations of application to general cosmetics. Meanwhile, after injecting the raw material 20 of the microneedle, the microneedle may be filled by pressurizing it to 2 atmospheres or more, preferably 2 atmospheres or more and 50 atmospheres or less. It is possible to suppress the generation of bubbles in the concave portion 11 of the release sheet 10 by high pressure pressurizing the liquid material and pushing out air.

Referring to FIG. 10, in the case of the microneedle array manufactured by filling using the vacuum blading method as described above, loss of microneedles or the tips of the microneedles was rarely observed, but the microneedle array manufactured by filling using the general atmospheric pressure blading method was rarely observed. In the case of microneedle arrays, many cases of loss of microneedles or the ends of microneedles were observed. Through this, it can be confirmed that when filling using the vacuum blading method, it is possible to manufacture a microneedle array of more precise and homogeneous quality.

In addition, when the microneedle raw material 20 is supplied beyond the depth of the engraved portion 11 and/or the flat engraved portion 12, the engraved portion 11 and/or the flat engraved portion 12 of the release sheet 10 The microneedle raw material 20 remains in the area excluding the engraved portion 12, so that the adhesive sheet 30 cannot be smoothly laminated in the subsequent step and/or to form a channel penetrating the microneedle 21. When pressurizing using the third mold 300, the remaining amount of microneedle raw material 20 may escape to the outside of the mold, causing contamination of the mold, and it is economically disadvantageous as an excessive amount of microneedle raw material 20 is used. do.

In this regard, after supplying the microneedle raw material 20, the area excluding the concave portion 11 and/or the flat engraved portion 12 of the release sheet 10 is used using a method such as squeezing. The remaining microneedle raw material 20 can be removed, and any area between the area of the release sheet 10 excluding the engraved portion 11 and/or the flat engraved portion 12 and the lower surface of the microneedle 21 By removing the steps to form a substantially flat surface, problems that may occur in subsequent steps as described above can be prevented.

In the method of manufacturing the microneedle 21 array, the release sheet 10 manufactured in step (a) is used as a mold required for manufacturing the microneedle 21 array in step (b), and the final product is Modification of the microneedle 21 by allowing the release sheet 10 to exist in a state without being removed from the microneedle 21 and to be removed before application to the human body by the user or, if necessary, to be removed during the manufacturing process. , loss, pollution, etc. can be prevented.

Figure 3 schematically illustrates the steps of forming microneedles using a two-stage molding method according to an embodiment of the present invention. 3(a) to 3(d) show two-stage microneedle molding using each release sheet molded through the method of FIGS. 1(a) (or 1(e)) to 1(d), respectively. Indicates the molding steps by method.

Figure 11 shows an optical microscope photograph of a microneedle array manufactured by a two-stage molding method according to an embodiment of the present invention.

Referring to FIGS. 3(a) to 3(d), according to one embodiment, forming the microneedle 21 may proceed in the following two steps. First, the microneedle raw material 20 containing the active ingredient such as the pharmacological ingredient to be delivered is filled into the concave portion 11 of the release sheet 10 as described above and then first dried. Then, the dried microneedles 21 are reduced in volume and exist only at the lower end of the concave portion 11. Next, the base raw material 23 is filled into the upper part of the dried microneedle 21 as described above and then dried a second time.

Through this, it is possible to form a microneedle array in which the microneedles 21 and the base 24 are manufactured separately. At this time, the microneedle 21 and the base 24 can be made of different materials. Preferably, the microneedle 21 and the base 24 are made of carboxymethyl cellulose (CMC) and hyaluronic acid (HA), respectively. ), polyvinyl alcohol (PVA), polylactic acid (PLA), polylactic glycolic acid (PLGA), polyvinylpyrrolidone (PVP), etc., but is not limited thereto.

In this way, a microneedle array manufactured by a two-stage molding method can be manufactured so that active ingredients such as pharmacological ingredients are present only at the lower part of the microneedle 21, if necessary, so that only an accurately controlled amount can be delivered to the user.

Referring to FIG. 11, the microneedle 21 and the base 24 manufactured by the two-stage molding method as described above were examined under a general light-field microscope, a dark-field microscope, and a rhoda, respectively. It shows an OM image (Optical Microscope image) taken with a rhodamine filter installed. At this time, for visual confirmation, rhodamine, a light-emitting material, was used instead of active ingredients such as pharmacological ingredients, and through this, it was confirmed that rhodamine exists only at the lower end of the microneedle 21 and emits light.

After step (b), (c1) may further include laminating an adhesive sheet to one surface of the microneedle array.

Figure 4 schematically illustrates the steps of laminating adhesive sheets according to an embodiment of the present invention. FIGS. 4(a) and 4(b) show the step of laminating an adhesive sheet to one side, that is, a flat surface, of the microneedle array manufactured in FIGS. 2(b) and 2(d), respectively.

The flat surface may include a lower surface of the microneedle 21 and one surface of the release sheet 10 (FIG. 4(a)), and a lower surface of the support 22 formed integrally with the microneedle 21. and one side of the release sheet 10 (FIG. 4(b)).

The adhesive sheet 30 may be a sheet made of a thermoplastic substrate such as metal, polymer, or fabric, or an adhesive applied or coated on one side of the sheet. The adhesive may be a release adhesive that can be attached and peeled off more than once.

One side of the adhesive sheet 30 to which the adhesive is applied is laminated to one side of the microneedle 21 array, that is, a flat surface, so that the lower surface of the microneedle 21 can be attached and fixed, and the release sheet ( The area attached to one side of 10) maintains adhesiveness even after the release sheet 10 is removed for application to the skin, so that it can be attached to the skin for the period necessary to deliver the pharmacological ingredient contained in the microneedle 21.

In the microneedle 21 array in which the adhesive sheet 30 is laminated, the bonding force between the side of the microneedle 21 and the release sheet 10 is such that the adhesive sheet 30 and the lower surface of the microneedle 21 If the bonding force is greater than the required amount, when removing the release sheet 10 for application to the skin, the microneedles 21 are peeled off from the adhesive sheet 30 while coupled to the release sheet 10. drugs cannot be administered. Therefore, the composition of the adhesive and the resulting adhesion force are adjusted so that the bonding force between the adhesive sheet 30 and the lower surface of the microneedle 21 is greater than the bonding force between the side of the microneedle 21 and the release sheet 10. and/or coating one side of the release sheet 10 in contact with the microneedle raw material 20 with a certain material and/or surface treating it to give a certain level of roughness to the microneedle 21. By lowering the bonding force between the side and the release sheet 10, the release sheet 10 can be easily removed.

Figure 5 schematically illustrates a method of applying a solid microneedle array manufactured by a method according to an embodiment of the present invention. Figures 5(a) and 5(b) show a method of applying the solid microneedle array manufactured in Figures 4(a) and 4(b), respectively.

Referring to FIG. 5, when applied to the skin, only the release sheet 10 can be removed from the solid microneedle array, and a plurality of microneedles 21 attached to the adhesive sheet 30 penetrate into the skin and The pharmacological ingredient contained in the needle 21 can be delivered into the body, and the portion of the adhesive sheet 30 to which the microneedle 21 is not attached can be attached to the skin for the period necessary for the pharmacological ingredient to be delivered. .

Meanwhile, a certain process is added to the solid microneedle array manufactured after steps (b) and/or (c1), for example, by pressing the solid microneedle array using a mold of a certain shape and/or A hollow microneedle array can be manufactured by irradiating one surface of the solid microneedle array with heat, a laser, or a combination thereof.

Figure 6 schematically illustrates the steps of manufacturing a hollow microneedle array according to an embodiment of the present invention. Figures 6(a) (or Figure 6(d)) to Figure 6(c) show additional processing of the microneedle array manufactured in Figures 2(b), Figure 2(d), and Figure 4(a), respectively. The steps for manufacturing a hollow microneedle array are shown.

Referring to FIGS. 6(a) and 6(b), after step (b), (c2) one or more second tip embossed portions 310 with a smaller diameter than the first tip embossed portion 110 are formed. The lower surface of the microneedle 21 may be pressed with the third mold 300, thereby forming a channel 40 penetrating the microneedle 21 from the lower surface to the tip of the microneedle 21. .

Referring to FIG. 6(c), after step (c1), (c2) a third mold including one or more second tip embossed parts 310 with a smaller diameter than the first tip embossed part 110 ( By pressing the lower surface of the microneedle 21 with 300), a channel 40 passing through the microneedle 21 from the lower surface to the tip of the microneedle 21 can be formed.

Referring to FIG. 6(d), after step (b), (c3) heat, laser, or a combination thereof is irradiated to the lower surface of the microneedle 21 to remove the microneedle 21 from the lower surface. A channel 40 can be formed that penetrates the microneedle 21 up to the tip.

The channel 40 is a path for movement and injection of a pharmacological component and includes a first opening formed on the lower surface of the microneedle 21 and a second opening formed on the tip of the microneedle 21. And, the second opening may be closed by the release sheet 10. If the second opening is not closed by the release sheet 10 and is exposed to the air, the microneedle 21 may be deformed, lost, or contaminated during further manufacturing or distribution.

In order to maintain the second opening portion closed by the release sheet 10 before application to the skin, preferably, the height of the second tip embossed portion 310 is adjusted to the concave portion formed on the release sheet 10. (11) and/or the depth of the flat engraved portion 12 or more, but less than the depth of the combined depth of the engraved portion 11 and/or the flat engraved portion 12 and the thickness of the release sheet 10, Alternatively, the depth of the engraved portion 11 and/or the flat engraved portion 12, the thickness of the release sheet 10, and the thickness of the adhesive sheet 30 may be adjusted to be less than the combined depth. When forming the channel 40 by irradiating heat and/or laser, the irradiation intensity and/or time can be adjusted within a certain range.

In addition to adjusting the length of the second tip embossed portion 310, the release sheet 10 may be used as the release sheet 10, which has a puncture strength greater than that of the microneedle 21. The puncture strength is the force required to puncture a test sample and can be measured based on methods such as ASTM D3763. When the puncture strength of the release sheet 10 is greater than that of the microneedle 21, even if the length of the second tip embossed portion 310 exceeds the above range, when applied at a certain pressure and/or irradiated at a certain intensity A channel 40 may be formed that penetrates the microneedle 21 but does not penetrate the release sheet 10.

The hollow microneedle array manufactured through the method of FIG. 6 generally does not itself contain a pharmacological ingredient, but has the function of providing a path for movement and injection of the pharmacological ingredient. Accordingly, after step (c2) or (c3), (d) a container 50 containing one or more pharmacological ingredients 60 may be connected to the first opening.

Figure 7 schematically illustrates the steps of connecting a container containing a pharmacological ingredient to a hollow microneedle array according to an embodiment of the present invention. 7(a) to 7(c) show the first hollow microneedles manufactured in FIG. 6(a) (or FIG. 6(d)), FIG. 6(c), and FIG. 6(b), respectively. It represents the step of connecting a container containing one or more pharmaceutical ingredients to the opening.

Figure 8 schematically illustrates a method of applying a hollow microneedle array manufactured by a method according to an embodiment of the present invention. Figure 8 shows a method of applying the hollow microneedle array manufactured in Figure 7(b).

Referring to Figures 7 and 8, when applied to the skin, only the release sheet 10 can be removed from the hollow microneedle array, and a plurality of hollow microneedles 21 attached to the adhesive sheet 30 are It penetrates into the skin and provides a path through which the pharmacological ingredient 60 carried in the container 50 can move, and when the user presses the container 50, the pharmacological ingredient carried in the container 50 moves into the hollow type. It can be delivered into the body through the channel 40 of the microneedle 21. The portion of the adhesive sheet 30 to which the microneedle 21 is not attached may be attached to the skin for the period necessary to deliver the pharmacological ingredient 60.

FIG. 12 is a perspective view of the release sheet 10 without being removed from the microneedle arrays 21 and 22, and FIG. 13 is a photograph of the release sheet 10 being removed from the microneedle array.

Referring to Figures 12 and 13, the release sheet 10 is a mold of the microneedle array and exists as a packaging material that surrounds and protects each microneedle. Before application to the human body, individual microneedles 21 are protected by the release sheet 10 in the form of a microneedle array as shown in FIG. 12, and immediately before application to the human body, the release sheet 10 is removed from the microneedle array and applied to the human body.

The description of the present invention described above is for illustrative purposes, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive. For example, each component described as unitary may be implemented in a distributed manner, and similarly, components described as distributed may also be implemented in a combined form.

The scope of the present invention is indicated by the claims described below, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present invention.

100 first mold
110 1st cutting edge relief
120 flat embossed part
200 second mold
210 cutting edge engraving
220 flat engraved part
300 third mold
310 2nd tip embossed part
10 release sheet
11 Engraved portion
12 Flat engraved portion
13 Embossed part
14 Flat embossing
20 Microneedle Raw Materials
21 Microneedles
22 support
23 Base raw material
24 basal
30 adhesive sheets
40 channels
50 containers
60 Pharmacological ingredients

Claims (39)

A mold including a concave portion corresponding to the shape of the microneedle, a flat engraved portion corresponding to the shape of the base of the microneedle, and a flat peripheral portion that extends horizontally from the upper side of the flat engraved portion toward the periphery to provide an adhesive surface of the adhesive sheet. Steps provided by injection molding of thermoplastic materials,
Injecting microneedle raw material into the concave portion and flat concave portion of the mold, followed by pressure filling and drying;
Adhering a single-layer adhesive sheet to the dried base and the flat periphery of the mold;
A method of manufacturing a microneedle array product comprising the step of packaging the product so that the mold functions as a packaging material surrounding the microneedle while the adhesive sheet is adhered to the base and the flat periphery of the mold. delete delete delete delete delete delete delete delete delete delete According to paragraph 1,
The mold is a method of manufacturing a microneedle array product by surrounding and protecting each microneedle formed in the concave portion. According to clause 12,
A method of manufacturing a microneedle array product in which the mold is removed immediately before application of the microneedle array to the human body. According to clause 13,
The adhesive sheet is a sheet made of a flexible material or a method of manufacturing a microneedle array product in which an adhesive is applied and coated on one side of the sheet. According to clause 14,
In the injection, pressure filling, and drying steps of the microneedle raw material, the microneedle raw material containing the active ingredient to be delivered is injected into the concave portion of the mold, and after first pressure filling and drying, the base raw material is placed on top of the microneedle raw material. Forming a microneedle array by injection, secondary pressure filling, and drying.
Method for manufacturing microneedle array products. delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete