KR102845321B1 - Apparatus for Manufacturing Microneedle and Method for Manufacturing Microneedle Using the Same - Google Patents

Abstract

The present invention relates to a microneedle manufacturing device and a microneedle manufacturing method using the same. According to one aspect of the present invention, a microneedle manufacturing device is disclosed, which includes: a mold having one or more notch grooves on one surface for forming a tip of the microneedle; a nozzle for filling a material into each of the one or more notch grooves; a substrate lifting/lowering unit for lowering or raising the substrate so that the substrate can come into contact with the upper side of each of the materials filled in the one or more notch grooves; and a control unit for controlling the nozzle and the substrate lifting/lowering unit.

Description

Apparatus for Manufacturing Microneedle and Method for Manufacturing Microneedle Using the Same

The present invention relates to a microneedle manufacturing device and a microneedle manufacturing method using the same.

Dissolving microneedles (DMNs) are a promising alternative to subcutaneous injections and oral administration, the most widely used delivery systems in the medical field. Microneedles enhance therapeutic drug delivery rates by directly directing substances into the epidermis or dermis, while also providing less pain than subcutaneous injections, improving patient convenience.

These microneedles can be formed by filling a material (20) containing a pharmaceutical ingredient into a mold (10) having a plurality of V-shaped grooves (12) formed therein, as shown in (a) and (b) of FIG. 1, by dropping or the like, and then covering one surface of the mold (10) with a patch (30), as shown in (c) of FIG. 1, and then applying centrifugal force as shown in (d) of FIG. 1, and then detaching the patch to form a microneedle (1).

Alternatively, as shown in (a) to (e) of FIG. 2, a material (20) may be applied to a surface of a mold (10) where a groove (12) is formed, a centrifugal force may be applied to the mold (10) so that the material (20) is uniformly filled in the groove (12), and then a patch (30) may be covered and integrated after squeezing to remove any residue of the material on the surface of the mold (10) by pushing it out with a spatula or the like, and then detached to form a microneedle (1).

Meanwhile, this type of microneedle manufacturing method has the disadvantage of manufacturing equipment becoming larger, more complex, and more precise because it manufactures by tensioning the material (20) using centrifugal force, and when a patch (30) is covered on one side of the mold (10), the patch (30), the mold (10), and the material (20) come into surface contact, thereby applying pressure to the material (20), and a part of the material (20) may leak out of the mold (10).

In addition, as shown in FIG. 3, since the patch (30) and the drug (20) come into direct contact through surface contact, there is a problem that the drug component of the material (20) diffuses toward the patch (30), resulting in loss of material content, as shown in (b) of FIG. 3.

Figure 4 is a fluorescence microscope photograph of a micro patch formed by a conventional method, and it can be confirmed that the material component (red color) that should be distributed at the tip of the micro needle has diffused to the patch side, which means that the material component applied to the human body is lost.

The present invention is intended to solve the above-mentioned problems, and aims to provide a microneedle manufacturing device capable of manufacturing microneedles with a simpler structure and process while minimizing material loss, and a microneedle manufacturing method using the same.

The purpose of the present invention is not limited to the purposes mentioned above, and other purposes not mentioned will be clearly understood by those skilled in the art from the description below.

In order to solve the above object, according to one aspect of the present invention, a device for manufacturing a microneedle is disclosed, comprising: a mold having one or more notch grooves for forming a tip of the microneedle on one surface; a nozzle for filling a material into each of the one or more notch grooves; a substrate lifting/lowering unit capable of lowering or raising the substrate so that the substrate can come into contact with the upper side of each of the materials filled in the one or more notch grooves; and a control unit for controlling the nozzle and the substrate lifting/lowering unit.

When the substrate is brought into contact with the material, one surface of the substrate and the mold can be maintained spaced apart from each other.

It may further include a spacer that is placed on one side of the mold and maintains a gap between the one side of the mold and the substrate.

The height of the spacer may be lower than the height formed by the uppermost part of the material from one surface of the mold.

Each of the one or more notch grooves may be filled with a first material and a second material, wherein the second material may be filled on an upper side than the first material.

The above first material can be filled only in a portion of the notch groove in the height direction.

The amount of the first material filled in the notch groove may be 10 to 100% of the depth of the notch groove.

The second material may be filled into the notch groove so that the upper end is positioned higher than one surface of the mold in which the notch groove is formed.

The upper end of the second material may be positioned 10 to 1000 μm higher than one surface of the mold.

When the substrate is in contact with the second material, the gap between the substrate and one surface of the mold may be smaller than the height of the uppermost part of the second material from one surface of the mold.

The second material may have the same or different components as the first material.

The above second material may be a component having a shrinkage ratio in the range of 0 to 80% when dried.

It may further include a drying unit for drying the material filled in the above notch groove.

The above mold may be made of polydimethylsiloxane (PDMS) material.

The above spacer may have a height of 250 μm.

The nozzle used when filling the first material and the nozzle used when filling the second material may have different diameters.

According to another aspect of the present invention, a method for manufacturing a microneedle using the above-described microneedle manufacturing device is provided, comprising: a first material filling step of filling a portion of the volume of each notch groove of a mold with a first material; a second material filling step of filling a second material on an upper side of the first material filled in the notch groove; a substrate contact step of bringing a substrate close to the mold so that the substrate and one surface of the mold are spaced apart from each other so that the substrate and the second material are in contact with each other; a second material drying step of drying the second material while the substrate and the second material are in contact with each other; and a microneedle separation step of separating microneedles manufactured by the first material and the second material from the notch groove of the mold after the second material is dried.

The method may further include a first material drying step of drying the first material after the first material is filled into the notch groove.

The first material filling step may include a first material applying step of applying a first material to a surface of the mold where the notch grooves are formed; a rotating step of applying centrifugal force to the mold so that the first material is uniformly filled in each of the notch grooves; and a squeezing step of pushing out and removing any remaining first material remaining on one surface of the mold after the rotating step.

The above first material filling step can fill the first material by dropping the first material into the notch groove of the mold.

The above first material filling step and second material filling step may be a step of applying a pressure of 400 kPa to the first material or the second material for 0.100 seconds.

The above rotation step may be a step of applying a gravity of 3511g for 1 hour.

According to the microneedle manufacturing equipment of the present invention and the microneedle manufacturing method using the same, the manufacturing device and process are simplified by manufacturing microneedles without applying centrifugal force to the mold and the material filled in the mold.

In addition, since the substrate makes point contact rather than surface contact when it comes into contact with the material filled in the mold, no pressure is applied to the material, so the material does not leak out of the mold, making it easier to quantify microneedles.

In addition, since the second material is positioned between the first material containing the active pharmaceutical ingredient and the substrate, the diffusion of the first material's ingredients into the substrate can be blocked, thereby minimizing the loss of the material ingredients.

Additionally, since centrifugal force is applied for filling rather than tensioning the material, the equipment can be more simplified.

The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description of the claims.

The above summary, as well as the detailed description of preferred embodiments of the present application described below, will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the present invention, preferred embodiments are depicted in the drawings. However, it should be understood that the present application is not limited to the precise arrangements and means illustrated.
Figure 1 is a drawing illustrating a conventional microneedle manufacturing process;
Figure 2 is a drawing showing another example of a conventional microneedle manufacturing process;
Figure 3 is a drawing showing how the material of a microneedle is diffused into a patch during a conventional microneedle manufacturing process;
Figure 4 is a drawing showing a conventional microneedle in which a material has been diffused into a patch, taken using a fluorescence microscope;
FIG. 5 is a drawing showing an example of a microneedle manufactured by a microneedle manufacturing device according to one embodiment of the present invention;
FIG. 6 is a drawing illustrating a microneedle manufacturing device according to one embodiment of the present invention;
FIG. 7 is a drawing sequentially illustrating a process for manufacturing a microneedle using a microneedle manufacturing device according to one embodiment of the present invention;
FIG. 8 is a drawing sequentially illustrating another type of process for manufacturing microneedles using a microneedle manufacturing device according to one embodiment of the present invention;
FIG. 9 is a drawing comparing the heights of a first material and a second material filled in a notch groove of a mold of a microneedle manufacturing device according to one embodiment of the present invention;
FIG. 10 is a drawing showing the gap between the substrate and the mold and the height of the spacer of a microneedle manufacturing device according to one embodiment of the present invention;
FIGS. 11 and 12 are drawings showing various shapes of microneedles manufactured using a microneedle manufacturing device according to one embodiment of the present invention;
FIG. 13 is a drawing showing the appearance of a pharmaceutical component of a first material in a microneedle manufactured by a microneedle manufacturing device according to one embodiment of the present invention being diffused;
Figure 14 is a flowchart illustrating a method for manufacturing microneedles according to one embodiment of the present invention.
Figure 15 is a flowchart illustrating another embodiment of the first material filling step of the microneedle manufacturing method of the present invention.
Figure 16 is a photograph of a master mold manufactured using a centrifugal forming method.
Figure 17 is a drawing of a single microneedle core of a master mold.
Figure 18 is a drawing taken from above of a PDMS material mold manufactured using a master mold.
Figure 19 is a side view of a PDMS material mold manufactured using a master mold.
Figure 20 is a drawing of a notch groove in a PDMS material mold manufactured using a master mold.
Figure 21 is a photograph of a microneedle manufactured as a mold made of PDMS material.

Hereinafter, preferred embodiments of the present invention, which can specifically realize the objectives of the present invention, will be described with reference to the attached drawings. In describing the present embodiments, identical names and symbols will be used for identical components, and additional explanations thereof will be omitted.

Hereinafter, one embodiment of the microneedle manufacturing device of the present invention will be described.

Meanwhile, the material forming the microneedles used in this embodiment comprises a biocompatible or biodegradable material. As used herein, the term "biocompatible material" refers to a material that is substantially non-toxic to the human body, chemically inert, and non-immunogenic. As used herein, the term "biodegradable material" refers to a material that can be decomposed in a living body by bodily fluids or microorganisms.

Specifically, biocompatible and/or biodegradable materials that can be used in the present embodiment include, for example, polyesters, polyhydroxyalkanoates (PHAs), poly(α-hydroxyacids), poly(β-hydroxyacids), poly(3-hydroxybutyrate-co-valerate; PHBV), poly(3-hydroxyproprionate; PHP), poly(3-hydroxyhexanoate; PHH), poly(4-hydroxyacids), poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), poly(4-hydroxyhexanoate), poly(esteramide), polycaprolactone, polylactide, polyglycolide, poly(lactide-co-glycolide; PLGA), polydioxanone, polyorthoester, polyetherester, polyanhydride, poly(glycolic acid-co-trimethylene carbonate), Polyphosphoesters, polyphosphoester urethanes, poly(amino acids), polycyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), poly(tyrosine carbonate), polycarbonates, poly(tyrosine arylate), polyalkylene oxalates, polyphosphazenes, PHA-PEG, ethylene vinyl alcohol copolymer (EVOH), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, styrene-isobutylene-styrene triblock copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, polyvinyl chloride, polyvinyl ether, polyvinyl methyl ether, polyvinylidene halides, polyvinylidene fluoride, polyvinylidene chloride, polyfluoroalkenes, polyperfluoroalkenes, polyacrylonitrile, Polyvinyl ketone, polyvinyl aromatics, polystyrene, polyvinyl ester, polyvinyl acetate, ethylene-methyl methacrylate copolymer, acrylonitrile-styrene copolymer, ABS resin and ethylene-vinyl acetate copolymer, polyamide, alkyd resin, polyoxymethylene, polyimide, polyether, polyacrylate, polymethacrylate, polyacrylic acid-co-maleic acid, chitosan, dextran, cellulose, heparin, hyaluronic acid, alginate, inulin, starch or glycogen, preferably polyester, polyhydroxyalkanoates (PHAs), poly(α-hydroxyacid), poly(β-hydroxyacid), poly(3-hydroxybutyrate-co-valerate; PHBV), poly(3-hydroxyproprionate; PHP), Poly(3-hydroxyhexanoate; PHH), poly(4-hydroxyacid), poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), poly(4-hydroxyhexanoate), poly(esteramide), polycaprolactone, polylactide, polyglycolide, poly(lactide-co-glycolide; PLGA), polydioxanone, polyorthoester, polyetherester, polyanhydride, poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acid), polycyanoacrylate, poly(trimethylene carbonate), poly(iminocarbonate), poly(tyrosine carbonate), polycarbonate, poly(tyrosine arylate), polyalkylene oxalate, polyphosphazenes, PHA-PEG, chitosan, dextran, cellulose, Heparin, hyaluronic acid, alginate, inulin, starch or glycogen.

The above micro needle (100) may include a tip (112), a neck (122), and a substrate (130), as shown in FIG. 5.

The above-mentioned tip (112) is formed with a sharp end so that it can penetrate human skin. The above-mentioned tip (112) is formed so that it melts after penetrating human skin, allowing the active ingredient of the drug to penetrate the human body.

In addition, the neck portion (122) is formed on the opposite side of the portion where the sharp tip of the tip portion (112) is formed, and serves to fix the tip portion (112) to the substrate (130). The neck portion (122) may be broken, cut, or melted by a physical or chemical action after the micro needle is applied to human skin. At this time, the neck portion (122) may have an inflection point formed so that the diameter becomes narrower and then larger as it goes toward the substrate (130), or may be formed into a cone shape by widening, or may be formed in a straight line without a change in diameter.

The above substrate (130) is intended to apply the tip portion (112) and the neck portion (122) to human skin, and the tip portion (112) and the neck portion (122) are arranged and may be formed of a flexible or elastic material so as to come into close contact with the curve of human skin. In addition, the substrate (130) may be formed to have adhesive properties so as to adhere to the skin.

The microneedle manufacturing device according to the present embodiment may include a mold (210), a nozzle (220), a substrate lifting/lowering unit (230), a control unit (250), and a spacer (260), as illustrated in FIG. 6.

The above mold (210) may have a plurality of notch grooves (212) formed on one surface. The notch grooves (212) may be formed in a V-shaped cross-section in the shape of a cone with a sharp tip at the upper end.

At this time, the cross-section of the notch groove (212) can be formed so that it becomes wider as it goes upward and there is no narrow part.

The above nozzle (220) is a component that fills the first material (110) and the second material (120) into each of the notch grooves (212). One or more nozzles (220) may be provided to fill the first material (110) and the second material (120) while moving through each notch groove (212), or a nozzle (220) may be provided for each notch groove (212). Alternatively, the nozzle (220) that discharges the first material (110) and the nozzle (220) that discharges the second material (120) may be provided differently from each other.

The first material (110) above contains an effective pharmaceutical ingredient and can be formed into a material that hardens through a process such as drying. After hardening, the first material (110) forms a tip (112) that forms a pointed tip along the shape of the notch groove (212), and can penetrate human skin or melt inside the skin to deliver the pharmaceutical ingredient to the human body.

The above second material (120) can be applied to the upper side of the first material (110) filled in the notch groove (212) by a dropping method or the like.

The above second material (120) can form the neck portion (122) after being hardened.

The second material (120) may be formed of the same components or materials as the first material (110), or may be formed of different components or materials from the first material (110). The second material (120) may contain the same active pharmaceutical ingredient as the first material (110), or may contain a different active pharmaceutical ingredient from the first material (110). Of course, the second material (120) may not contain any active pharmaceutical ingredient.

In addition, the second material (120) may have a shrinkage rate of 0 to 80%. In this case, the shrinkage rate is a shrinkage rate compared to when it is not dried and when it is dried. For example, when the shrinkage rate of the second material (120) is 0%, when it is dried, the volume or cross-sectional area does not decrease compared to when it is not dried, and when it is 80%, when it is dried, it shrinks by 80% compared to when it is not dried.

Additionally, the second material (120) may be made of a component or material that does not diffuse or absorb the active ingredient contained in the first material (110).

The substrate lifting/lowering part (230) may be provided to lower the substrate (130) so that the substrate (130) comes into point contact with the upper side of the second material (120) filled in the notch groove (212), or to raise the upper side of the second material (120) and the substrate (130) so that the first material (110) and the second material (120) arranged on the substrate (130) are separated from the mold (210).

Such a substrate lifting/lowering unit (230) may include a gripping unit (232) that grips or supports the substrate (130) and an arm unit (234) that raises/lowers the gripping unit (232).

The control unit (250) can control the nozzle (220) and the substrate lifting/lowering unit (230).

The above control unit (250) can control the nozzle (220) to fill the lower portion of the notch groove (212) of the mold (210) with the first material (110) and to drop and fill the second material (120) into the notch groove (212) filled with the first material (110).

In addition, the control unit (250) can dry the first material (110) filled in the notch groove (212) before the second material (120) is filled, and dry the second material (120) filled on the upper side of the first material (110). At this time, the first material (110) or the second material (120) can wait for a predetermined time until it is dried.

Alternatively, a drying unit (240) may be provided to dry or harden the first material (110) and the second material (120) filled in the mold (210). The drying unit (240) may dry the first material (110) and the second material (120) using light, dry air, heat, or the like.

In addition, the control unit (250) can control the substrate lifting/lowering unit (230) so that the substrate (130) comes into point contact with the upper end of the second material (120) filled in the notch groove (212). In addition, when the drying unit (240) is provided, the control unit can control the drying unit (240).

At this time, when the substrate (130) comes into contact with the second material (120), it is possible to control the substrate (130) and one surface of the mold (210) to not come into contact and to maintain a spaced state.

As illustrated in (a) and (b) of FIG. 7, the control unit (250) can control the nozzle (220) so that, when the nozzle (220) injects the first material (110) into the notch groove (212), only a portion of the notch groove (212) is filled. At this time, as illustrated in FIG. 9, the amount of the first material (110) filled can be controlled to be 10 to 100% of the depth of the notch groove (212). That is, the depth (L1) of the notch groove (212) to the depth (L2) of the first material (110) filled inside the notch groove (212) can be in the range of 1:0.1 to 1:1.

That is, the first material (110) can be filled only in a portion of the volume, not the entire volume, of the notch groove (212).

In addition, the control unit (250) can dry the first material (110) after the first material (110) is applied within the notch groove (212). At this time, the control unit (250) can wait for a predetermined time for the first material (110) to dry, or can operate the drying unit (240) to dry the first material (110).

The control unit (250) can control the nozzle (220) so that the second material (120) is applied to the notch groove (212), as shown in (c) of FIG. 7, after the first material (110) is dried. At this time, as shown in FIG. 9, the second material (120) can protrude further upward than the top of the notch groove (212) (one surface of the mold (210)), and the height at which the second material (120) protrudes further than the mold (210) can be 10 to 1000 μm.

After the second material (120) is applied, the control unit (250) can control the substrate lifting/lowering unit (230) so that the substrate (130) comes into contact with the upper end of the second material (120), as shown in (d) of FIG. 7.

At this time, as illustrated in FIG. 10, when the substrate (130) comes into contact with the second material (120), the gap (L4) between the substrate (130) and one surface of the mold (210) may be smaller than the height (L3) formed by the uppermost part of the second material (120) from one surface of the mold (210).

The above spacer (260) is placed on one side of the mold (210) and can maintain a gap between one side of the mold (210) and the substrate (130).

That is, since the spacer (260) is placed on one side of the mold (210), the height to which the substrate (130) descends is limited, thereby maintaining the gap between the substrate (130) and the mold (210). The thickness (L5) of the spacer (260) may be thinner than the height (L3) formed by the uppermost part of the second material (120) from one side of the mold (210).

Additionally, the thickness (L5) of the spacer (260) may be equal to the gap (L4) between the substrate (130) and one surface of the mold (210) when the substrate (130) is in point contact with the second material (120).

In addition, the control unit (250) can form microneedles of different shapes by controlling the filling amount of the second material (120) or the type of the second material (120) being filled.

That is, as shown in (a) of FIG. 11, when the filling amount of the second material (120) is increased further, the second material (120) may shrink when cured as shown in (b) of FIG. 11, and a neck portion (122) having a shape in which the diameter becomes wider as it goes upward as shown in (c) of FIG. 11 may be formed.

Alternatively, as shown in (a) of FIG. 12, if a material having a low shrinkage rate and a component that does not reduce in volume or cross-sectional area even when dried is used as the material of the second material (120), as shown in (b) of FIG. 12, there is no change in cross-sectional area or shape in the dried state compared to when it was first applied ((a) of FIG. 11), so that the shape of the neck portion (122) in the initially applied shape can be formed as shown in (c) of FIG. 12.

In addition, when the second material (120) is a material or component that does not diffuse or absorb the active ingredient contained in the first material (110), as shown in (a) and (b) of FIG. 13, the neck portion (122) made of the second material (120) is positioned between the tip portion (112) made of the first material (110) and the substrate (130), so that the active ingredient contained in the first material (110) is blocked from diffusing to the substrate (130) and remains on the tip portion (112), thereby preventing the active ingredient from being wasted, and thus enabling the application of a more accurate amount of material.

In addition, since the substrate (130) and the second material (120) are in point contact rather than surface contact, the pressure applied to the first material (110) and the second material (120) applied to the notch groove (212) is minimized, thereby preventing the first material (110) and the second material (120) from overflowing from the mold (210).

In addition, since centrifugal force is not applied to the first material (110) and the second material (120) applied to the notch groove (212), the structure and manufacturing process of the microneedle manufacturing device can be simplified.

Meanwhile, in the above-described embodiment, when the nozzle (220) injects the first material (110) into the notch groove (212), the first material is dropped so that only a portion of the notch groove (212) is filled. However, as shown in (a) and (b) of FIG. 8, after applying the first material (110) to one surface of the mold (210), centrifugal force is applied so that the material is uniformly filled in the notch groove (212), and squeezing can be performed by pushing out one surface of the mold (210) with a spatula (270) or the like.

By squeezing in this way, as shown in (c) of Fig. 8, the first material (110) can be filled into a portion of the inside of the notch groove (212) due to surface tension, etc. Thereafter, similar to the above-described embodiment, the second material (120) can be applied on top of the first material (110) to continue the subsequent process.

Hereinafter, a method for manufacturing a microneedle according to one embodiment of the present invention will be described.

The microneedle manufacturing method according to the present embodiment may include a first material filling step (S110), a first material drying step (S120), a second material filling step (S130), a substrate contact step (S140), a second material drying step (S150), and a microneedle separation step (S160), as illustrated in FIG. 14.

The first material filling step (S110) is a step of filling the first material into the notch groove (212) of the mold (210), as shown in (a) of FIG. 7, as shown in (b) of FIG. 7. At this time, the first material may be filled to fill a portion of the volume of the notch groove (212). At this time, the first material may be filled into the notch groove (212) by dropping or applying.

At this time, as illustrated in FIG. 9, the first material (110) may be filled so that the amount filled is 10 to 100% of the depth of the notch groove (212). That is, the depth (L1) of the notch groove (212) to the depth (L2) of the first material (110) filled inside the notch groove (212) may be in the range of 1:0.1 to 1:1.

The above first material drying step (S120) is a step of drying and hardening the first material (110) filled in the notch groove (212). In the first drying step, the first material (110) may be dried to form a tip portion (112). The first material drying step (S120) may not be performed if necessary, and the second filling step (S130) may be performed immediately.

The second material filling step (S130) is a step of filling the second material (120) on the upper side of the first material (110) filled in the notch groove (212) after the first material (110) is dried, as shown in (c) of FIG. 7.

At this time, as shown in FIG. 9, the second material (120) can be filled so as to protrude upwards more than the upper end of the notch groove (212) (one side of the mold (210)), and the height (L3) at which the second material (120) protrudes more than the mold (210) can be 10 to 1000 μm.

And the substrate contact step (S140) is a step in which the substrate (130) approaches one surface of the mold (210) so that the substrate (130) and one surface of the mold (210) are spaced apart from each other, and the substrate (130) and the second material (120) come into point contact.

At this time, as illustrated in FIG. 10, when the substrate (130) comes into contact with the second material (120), the gap (L4) between the substrate (130) and one surface of the mold (210) may be smaller than the height (L3) formed by the uppermost part of the second material (120) from one surface of the mold (210).

Accordingly, the substrate (130) does not come into contact with the mold (210) and comes into point contact with the upper end of the second material (120).

The second material drying step (S150) is a step in which the second material (120) is dried while the substrate (130) and the second material (120) are in contact, as illustrated in (d) of Fig. 7. In the second material drying step (S150), the second material (120) may shrink to form a neck portion (122) depending on the physical properties of the second material (120).

After the second material (120) is dried in the second material drying step (S150), the micro needle separation step (S160) is performed as shown in (e) of FIG. 7.

The above microneedle separation step (S160) is a step in which the substrate (130) is moved away from the mold (210) so that the second material (120) in contact with the substrate (130) and the first material (110) in contact with the second material (120) are separated from the notch groove (212) of the mold (210).

In the above micro needle separation step (S160), the substrate (130) on which the tip (112) and the neck (122) are arranged is separated from the mold (210) so that a micro needle can be manufactured.

Meanwhile, the first material filling step (S110), as described above, is a step of filling the first material to fill a portion of the volume of the notch groove (212). At this time, if the size of the notch groove (212) is narrow, the first material may not be uniformly filled within the notch groove (212). In this case, the first material filling step (S110) may optionally include a first material application step (S112), a rotation step (S114), and a squeezing step (S216), as illustrated in FIG. 15.

The above first material application step (S112) is a step of applying the first material (110) to one surface of the mold (210) where each notch groove (212) is formed, as shown in (a) of FIG. 8.

After the first material application step (S112), a rotation step (S114) may be performed. The rotation step (S114) is a step of applying centrifugal force to the mold (210) so that the first material (110) is uniformly filled into each of the notch grooves (212). The first material dropped in the first material application step (S112) can be uniformly filled into the notch grooves (212) by the centrifugal force applied in the rotation step (S114).

After the above-described rotating step (S114), a squeezing step (S116) may be performed to remove the first material (210) remaining on one surface of the mold (210) by pushing it out using a spatula (270), etc. In the squeezing step (S116), the first material (210) remaining on one surface of the mold (210) is pushed out, and after being pushed out, the first material (210) may remain only inside the notch groove (212). In addition, the first material (210) inside the notch groove (212) may fill up to a portion below the upper end of the notch groove (212) due to surface tension, etc. Thereafter, the above-described first material drying step (S120) or second material filling step (S130) may be performed.

Of course, the first material application step (S112), the rotation step (S114), and the squeezing step (S216) may or may not be performed as needed.

Meanwhile, when filling the first material, the first material can be filled into each notch groove using dropping.

Hereinafter, an example of manufacturing a microneedle using the microneedle manufacturing device of the present invention will be described.

First, as illustrated in Fig. 16, a master mold (300) is manufactured in which a plurality of cores (310) are arranged in a manner that matches the size and shape of the micro needle to be produced. At this time, the master mold (300) can be manufactured using a centrifugal molding method.

Each core (310) of the above master mold (300) is formed to a height of approximately 635 μm, as shown in FIG. 17, and the width of the end is approximately 30 μm, so that a sharp tip can be formed.

And, using the above master mold (300), a process for manufacturing a mold (210) for manufacturing micro needles is introduced.

Mix the first solution and the second solution in a mass ratio of 1:10, then homogenize by stirring for more than 5 minutes.

Afterwards, the solution is poured into a 30 mm diameter petri dish with a master mold containing a microneedle array shape manufactured using a centrifugal molding method, and then defoaming is performed in a vacuum environment.

After the solution has been de-foamed, it is cured at 80°C for 6 hours and then separated from the petri dish, thereby manufacturing a mold (210) having a microneedle array shape as a template, as shown in FIGS. 18 and 19.

At this time, the first solution may be Sylgard 184 B, the second solution may be Sylgard 184 A, and the mold (210) is made of polydimethylsiloxane (PDMS), a silicone material having a predetermined elasticity and porosity, so that breakage is prevented during the manufacture of the microneedle, and the drying of the first material (110) and the second material (120) filled in the mold (210) can be assisted.

A plurality of notch grooves (212) can be formed in the above mold (210), and each notch groove (212) can have a depth (L1) of approximately 618 μm, as shown in FIG. 20, and the end can have a tip of approximately 31 μm.

In addition, a process of forming a micro needle (100) by injecting a first material (110) and a second material (120) into the mold (210) is described.

First, the first material (110) is filled into the notch groove (212).

The above first material (110) is a 40% (w/v) solution of hyaluronic acid (32 kDa) containing 0.1% (w/v) of red fluorescent Rhodamine B, which can be injected through a nozzle (220) having a diameter of 200 μm by applying a pressure of 400 kPa for 0.100 seconds to each notch groove (212) in the previously manufactured mold (210) using a dispenser (Musashi, ML-5000X-mini).

After the injection of the hyaluronic acid solution containing Rhodamine B into all the notch grooves (210) of the mold (210) is completed, it is placed in a tabletop centrifuge (Hanil Scientific Inc., T05R), and then dried for 1 hour after applying a gravity of 3511 g.

At this time, the centrifugal force applied using the centrifuge is to fill the first material (110) injected into the notch groove (212) without any gaps by applying pressure with centrifugal force into the notch groove (212).

Then, the second material (120) is filled on the upper side of the first material (110) filled in the notch groove (212).

The second solution (120) is a 70% (w/v) hyaluronic acid solution containing 0.1% (w/v) of green fluorescent Calcein. Using a dispenser, the second solution (120) is applied to the first material (110), which is a solid hyaluronic acid solution containing Rhodamine B, by applying a pressure of 400 kPa for 0.100 seconds, and is discharged through a nozzle (220) having a diameter of 400 μm.

Afterwards, a spacer (260) having a height of 250 μm is placed around the mold (210), and a substrate (130) made of poly-styrene material is placed on the spacer (260) so that it comes into point contact with the hyaluronic acid solution containing Calcein of the discharged second material (120).

After drying for 3 hours in this state, when poly-styrene is separated from the mold (210), a candle micro needle (100) having a shape similar to that of Fig. 21 can be confirmed.

As described above, preferred embodiments of the present invention have been described. It will be apparent to those skilled in the art that the present invention may be embodied in other specific forms, in addition to the embodiments described above, without departing from the spirit or scope thereof. Therefore, the above-described embodiments should be considered illustrative rather than restrictive, and accordingly, the present invention is not limited to the above description, but may be modified within the scope of the appended claims and their equivalents.

110 First material 112 Cutting edge
120 Secondary Material 122 Neck
130 substrate 210 mold
212 Notch Home 220 Nozzle
230 Lifting and lowering section 232 Grabbing section
234 Arm section 240 Dry section
250 Control Unit 260 Spacer
S110 1st filling stage S120 1st material drying stage
S130 Secondary filling stage S140 Point contact stage
S150 Second material drying step S160 Micro needle separation step

Claims (22)

As a device for manufacturing microneedles,
A mold having one or more notch grooves on one side for forming the tip of the micro needle;
A nozzle for filling a material into each of the one or more notch grooves;
A substrate lifting/lowering unit capable of lowering or raising the substrate so that the substrate can come into contact with the upper side of each of the materials filled in the one or more notch grooves;
A spacer placed on one side of the mold and maintaining a gap between the one side of the mold and the substrate; and
A microneedle manufacturing device including a control unit that controls the nozzle and the substrate lifting and lowering unit. In the first paragraph,
A microneedle manufacturing device in which, when the substrate is brought into contact with the material, one surface of the substrate and the mold are maintained spaced apart from each other. delete In the first paragraph,
A microneedle manufacturing device wherein the height of the spacer is lower than the height formed by the uppermost part of the material from one surface of the mold. In the first paragraph,
A microneedle manufacturing device, wherein each of the one or more notch grooves is filled with a first material and a second material, wherein the second material is filled on an upper side than the first material. In paragraph 5,
A microneedle manufacturing device in which the first material is filled only in a portion of the notch groove in the height direction. In paragraph 6,
A microneedle manufacturing device, wherein the amount of the first material filled in the notch groove is 10 to 100% of the depth of the notch groove. In paragraph 5,
A microneedle manufacturing device in which the second material is filled into the notch groove so that the upper end is positioned higher than one surface of the mold in which the notch groove is formed. In paragraph 8,
A microneedle manufacturing device in which the upper end of the second material is positioned 10 to 1000 ㎛ higher than one surface of the mold. In paragraph 8,
A microneedle manufacturing device, wherein when the substrate is in contact with the second material, the gap between the substrate and one surface of the mold is smaller than the height formed by the uppermost end of the second material from one surface of the mold. In paragraph 5,
A microneedle manufacturing device wherein the second material is the same as or different from the first material. In paragraph 5,
A microneedle manufacturing device, wherein the second material is a component having a shrinkage rate in the range of 0 to 80% when dried. In the first paragraph,
A microneedle manufacturing device further comprising a drying unit for drying a material filled in the notch groove. In the first paragraph,
The above mold is a microneedle manufacturing device made of polydimethylsiloxane (PDMS) material. In the first paragraph,
The above spacer is a microneedle manufacturing device having a height of 250 μm. In paragraph 5,
A microneedle manufacturing device in which the nozzle used when filling the first material and the nozzle used when filling the second material have different diameters. In a microneedle manufacturing method for manufacturing a microneedle using a microneedle manufacturing device according to any one of claims 1 to 2 and claims 4 to 16,
A first material filling step of filling a portion of the volume of each notch groove of the mold with a first material;
A second material filling step of filling a second material on top of the first material filled in the notch groove;
A substrate contact step of bringing the substrate close to the mold so that one surface of the substrate and the mold are spaced apart from each other so that the substrate and the second material come into contact with each other;
A second material drying step of drying the second material while the substrate and the second material are in contact with each other, and
A microneedle separation step for separating microneedles manufactured by the first material and the second material from the notch groove of the mold after the second material is dried;
A method for manufacturing microneedles, comprising: In paragraph 17,
A method for manufacturing a microneedle, further comprising a first material drying step of drying the first material after the first material is filled into the notch groove. In Article 17,
The above first material filling step is,
A first material application step of applying a first material to the surface of the mold where the notch groove is formed;
A rotation step of applying centrifugal force to the mold so that the first material is uniformly filled into each of the above notch grooves;
After the above rotation step, a squeezing step for pushing out and removing the remaining first material remaining on one surface of the mold;
A method for manufacturing microneedles, comprising: In Article 17,
The above first material filling step is,
A method for manufacturing a microneedle, wherein the first material is dropped into the notch groove of the mold to fill the first material. In Article 17,
A method for manufacturing a microneedle, wherein the first material filling step and the second material filling step are steps of applying a pressure of 400 kPa to the first material or the second material for 0.100 seconds. In Article 19,
The above rotation step is a method for manufacturing microneedles, wherein a gravity of 3511 g is applied for 1 hour.