Microneedle patch and manufacturing method thereof

Abstract

One embodiment of the present invention provides a micro needle patch having excellent adhesive and hemostatic properties, characterized by comprising a base and a plurality of micro needles formed on the base, the micro needles comprising GelMA, polydopamine, and a hemostatic material, wherein the hemostatic material comprises powdered cuttlefish bone or silicate.

Description

Technology Field

[0001] The present invention relates to a micro-needle patch, and more specifically, to a micro-needle patch having adhesive and hemostatic properties and a method for manufacturing the same. Background Technology

[0003] Bleeding can occur externally, such as from trauma, explosions, or gunshot wounds, or internally, such as from internal bleeding or the rupture of an aneurysm. In particular, excessive bleeding requires immediate hemostasis as it can lead to hemorrhagic shock, organ failure, and, in severe cases, death.

[0004] Sutures and staples are commonly and simply used in this situation. This method involves piercing the tissue to stitch the wound, but it results in the formation of permanent scars accompanied by severe pain and requires additional treatment. While bandages, hemostatic agents, and sealants rapidly absorb moisture to induce blood clot formation, they rely on chemical adhesion, making them difficult to use in cases of excessive bleeding or on flexible and active areas.

[0005] Therefore, there is a need for research on products that adhere well even to areas of excessive bleeding and enable blood coagulation. Prior art literature

[0007] Republic of Korea Registered Patent No. 10-2222704 The problem to be solved

[0008] The technical problem that the present invention aims to solve is to resolve the problems of the aforementioned prior art by providing a micro-needle patch and a method for manufacturing the same.

[0009] The technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned technical problems will be clearly understood by those skilled in the art to which the present invention belongs from the description below. means of solving the problem

[0011] To achieve the above technical problem, one embodiment of the present invention provides a micro-needle patch.

[0012] In one embodiment of the present invention, the micro needle patch comprises a base; and a plurality of micro needles formed on the base, the micro needles comprising GelMA, polydopamine, and a hemostatic agent, wherein the hemostatic agent may be powdered cuttlefish bone or silicate.

[0013] In addition, in one embodiment of the present invention, the powdered cuttlefish bone may contain hydroxyapatite.

[0014] In addition, in one embodiment of the present invention, the silicate may include laponite.

[0015] In addition, in one embodiment of the present invention, the polydopamine is 1% to 10% by weight and the hemostatic material is 0.5% to 10% by weight relative to 100% by weight of the total micro needle, and the remainder may include GelMA and other inevitably added impurities.

[0016] In addition, in one embodiment of the present invention, the height of the micro needle may be 100 μm to 1000 μm.

[0017] In addition, in one embodiment of the present invention, the diameter of the micro needle may be 100 μm to 1000 μm.

[0018] To achieve the above technical problem, one embodiment of the present invention provides a method for manufacturing a micro-needle patch.

[0019] In one embodiment of the present invention, the method for manufacturing a micro-needle patch comprises the steps of: preparing a mixed solution by mixing GelMA, a photoinitiator, polydopamine, and a hemostatic agent in distilled water; applying the mixed solution onto a mold having an intaglio formed corresponding to the shape of a micro-needle; and curing the mixed solution applied onto the mold to manufacture a micro-needle patch, wherein the hemostatic agent may be powdered cuttlefish bone or silicate.

[0020] In addition, in one embodiment of the present invention, the powdered cuttlefish bone may contain hydroxyapatite.

[0021] In addition, in one embodiment of the present invention, the polydopamine is 1% to 10% by weight and the hemostatic material is 0.5% to 10% by weight relative to 100% by weight of the total micro needle, and the remainder may include GelMA and other inevitably added impurities.

[0022] In addition, in one embodiment of the present invention, in the step of manufacturing the micro-needle patch, UV light may be irradiated to cure the mixed solution. Effects of the invention

[0024] A micro-needle patch according to one embodiment of the present invention is provided with an adhesive hemostatic agent comprising marine biologically derived and natural materials, which enables adhesion to wound sites wet from bleeding, which was lacking in conventional adhesives and hemostatic agents, and can provide biocompatibility and biodegradability.

[0025] In addition, the present invention includes polydopamine inspired by the adhesive protein of mussels that can adhere well to wet surfaces, thereby providing an effect that enables adhesion to wounds caused by bleeding, as well as to curved and active areas.

[0026] In addition, the present invention includes powdered cuttlefish bone or silicate, which are marine biological and natural materials, and can provide the effect of promoting blood coagulation factors for rapid blood clot formation.

[0027] In addition, the present invention can provide the effect of producing a microneedle patch that causes less pain due to a minimally invasive method, is effectively fixed by being directly inserted into the skin, and exhibits a more rapid hemostatic ability by coming into direct contact with blood.

[0028] 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 of the invention or the claims. Brief explanation of the drawing

[0030] FIG. 1 is a flowchart showing the steps of a method for manufacturing a micro-needle patch according to one embodiment of the present invention. FIG. 2 is a schematic diagram showing the process of a method for manufacturing a micro-needle patch according to one embodiment of the present invention. FIG. 3 is an actual and cross-sectional image of a micro-needle patch according to one embodiment of the present invention, observed with an optical microscope. Fig. 4. This is an image showing the mechanical strength of the patch after inserting it into pig skin using a thumb. Figure 5 is an image confirming the adhesiveness of the adhesive hemostatic microneedle patch by slicing porcine heart tissue. Figure 6 is a graph showing that it can withstand pressure sufficiently through a burst pressure test. Figure 7 is an image showing the blood coagulation time of an adhesive hemostatic microneedle patch using sheep's blood. Specific details for implementing the invention

[0031] The present invention will be described below with reference to the attached drawings. However, the present invention may be implemented in various different forms and is therefore not limited to the embodiments described herein. Furthermore, in order to clearly explain the present invention in the drawings, parts unrelated to the explanation have been omitted, and similar parts throughout the specification have been given similar reference numerals.

[0032] Throughout the specification, when it is stated that a part is "connected (connected, in contact, combined)" with another part, this includes not only cases where they are "directly connected," but also cases where they are "indirectly connected" with other members interposed between them. Furthermore, when it is stated that a part "includes" a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but rather allows for the inclusion of additional components.

[0033] The terms used herein are merely for describing specific embodiments and are not intended to limit the invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as “comprising” or “having” are intended to indicate the presence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0034] Embodiments of the present invention will be described in detail below with reference to the attached drawings.

[0035] Conventional hemostatic agents had the problem of being difficult to use on wounds that were wet due to bleeding or on curved wounds.

[0036] To solve these problems, the present invention provides a micro-needle patch that promotes blood coagulation and has excellent adhesion to wet wound sites, as well as to curved and active areas, and a method for manufacturing the same.

[0037] Hereinafter, the present invention will be described with reference to the drawings presented in this specification. For reference, the drawings may be partially exaggerated to illustrate the features of the present invention. In such cases, it is preferable to interpret them in light of the entire intent of this specification.

[0039] A micro-needle patch according to one embodiment of the present invention is described.

[0040] The micro-needle patch of the present invention is an adhesive hemostatic micro-needle patch comprising polydopamine and powdered cuttlefish bone or silicate, based on the idea that biocompatible marine biological-derived and natural materials can simultaneously perform adhesion and hemostasis.

[0041] In addition, the micro-needle patch of the present invention allows for less pain due to its minimal invasiveness, enables direct insertion into the skin, and can facilitate faster blood coagulation by coming into contact with blood.

[0042] At this time, to specifically describe the present invention having the aforementioned characteristics, a micro-needle patch according to one embodiment of the present invention comprises a base; and a plurality of micro-needles formed on the base, comprising GelMA, polydopamine, and a hemostatic substance; wherein the hemostatic substance may be powdered cuttlefish bone or silicate.

[0043] At this time, the powdered cuttlefish bone may contain hydroxyapatite.

[0044] At this time, the main component of cuttlefish bone is aragonite, and hydroxyapatite can be produced by performing hot water extraction at high temperatures.

[0045] For example, to remove the remaining salt in the cuttlefish bone, it may be soaked in distilled water for 60 to 84 hours, then soaked in industrial methanol (90%) for 60 to 84 hours to remove oily components, then washed with distilled water, then air-dried at room temperature for 24 hours, and then dried in an oven (60 to 100°C) for 4 to 7 hours. Next, the completely dried cuttlefish bone may be first crushed using a spatula and then secondarily crushed using a grinder to produce powdered cuttlefish bone.

[0046] At this time, hydroxyapatite is produced from the manufactured powdered cuttlefish bone through hot water extraction.

[0047] At this time, the above hydroxyapatite is similar to natural hard tissue and mineral components and also has higher porosity characteristics, which can maximize the function of water absorption and has the effect of promoting blood coagulation due to the calcium carbonate (blood coagulation factor) component, which is a component of bone.

[0048] Therefore, the hemostatic properties of the micro-needle patch of the present invention can be improved by using powdered cuttlefish bone that has undergone hot water extraction.

[0049] Meanwhile, the above silicate may preferably include laponite.

[0050] At this time, Laponite is a synthetic clay mineral, a smectite-based clay in the form of magnesium-lithium silicate-based nanoparticles, and Laponite has the characteristic of forming a transparent gel when dispersed in water.

[0051] In addition, the form of the laponite can be, for example, a disc-shaped nanoparticle with a diameter of about 25 to 35 nm and a thickness of about 1 to 5 nm.

[0052] At this time, highly charged nanoparticles such as laponite can induce blood coagulation through the aggregation of platelets in the blood and the activation of coagulation factors.

[0053] This allows for the enhancement of the hemostatic properties of the micro-needle patch by inducing blood coagulation.

[0054] In particular, since the raponite is included inside the micro-needles of the micro-needle patch of the present invention, the contact area with blood can be improved, thereby further accelerating the coagulation time.

[0055] Meanwhile, the aforementioned polydopamine is a compound inspired by mussel-derived adhesive proteins, intended to enhance the adhesive properties of the wound site through adhesive proteins rather than relying solely on microneedles to adhere to surfaces wet by bleeding at the wound site.

[0056] The characteristics of the micro-needle patch may vary depending on the content ratio in which each of the substances having the aforementioned characteristics exist inside the micro-needle.

[0057] Accordingly, preferably, with respect to 100% by weight of the total micro needle, the polydopamine is 1% to 10% by weight, the hemostatic agent is 0.5% to 10% by weight, and the remainder may include GelMA and other inevitably added impurities.

[0058] At this time, if the above polydopamine is less than 1%, a problem of insufficient adhesive ability may occur, and if it exceeds 10%, the viscosity may become too strong, causing a problem in making the patch.

[0059] In addition, if the hemostatic material containing the powdered cuttlefish bone or silicate is only 0.5% by weight, a problem may arise where the hemostatic effect is negligible, and if it exceeds 10% by weight, the viscosity becomes too strong, which may cause problems in making the patch.

[0060] Accordingly, it is desirable to satisfy the aforementioned content range.

[0061] Meanwhile, in the micro-needle patch manufactured with the aforementioned content range, the height of the micro-needle may be 100 μm to 1000 μm.

[0062] This is because if the height of the micro needle is less than 100 μm, it cannot penetrate the epidermal layer of the skin, so drug delivery is not properly carried out, and the needle may not be fully inserted, which may cause problems with physical fixation, and if it exceeds 1000 μm, it may cause pain and leave wounds and scars on the tissue.

[0063] In addition, the diameter of the micro needle may be 1000 μm to 1000 μm.

[0064] In this case, the radius of the micro-needle refers to the diameter of the circular cross-section obtained as a vertical cross-section when the part of the micro-needle in contact with the base is cut.

[0065] The reason the aforementioned radius range is desirable is that if the diameter of the micro-needle is less than 100 μm, a problem may arise where the micro-needle breaks easily when inserted, and if it exceeds 1000 μm, a problem may arise where pain is involved when the micro-needle is inserted and scarring may occur in the tissue.

[0067] Through this, the micro-needle patch, which is an embodiment of the present invention, can simultaneously perform adhesion and hemostasis by manufacturing micro-needles using biocompatible marine biological-derived and natural materials, and can rapidly heal wounds by reducing pain through minimal invasiveness using micro-needles and increasing the surface area in direct contact with blood by being directly inserted into the skin, thereby promoting faster blood coagulation.

[0068] Below, we intend to explain in detail a method for manufacturing a micro-needle patch that achieves the aforementioned effects.

[0070] A method for manufacturing a micro-needle patch according to one embodiment of the present invention is described.

[0071] The method for manufacturing a micro-needle patch according to the present invention can apply all the contents described above regarding the micro-needle patch, and although detailed descriptions of overlapping parts have been omitted, they can be applied in the same way even if such descriptions are omitted.

[0073] FIG. 1 is a flowchart showing the steps of a method for manufacturing a micro-needle patch according to one embodiment of the present invention.

[0074] Referring to FIG. 1, a method for manufacturing a micro-needle patch comprises the steps of: preparing a mixed solution by mixing GelMA, a photoinitiator, polydopamine, and a hemostatic agent in distilled water (S100); applying the mixed solution onto a mold having an intaglio formed corresponding to the shape of a micro-needle (S200); and curing the mixed solution applied onto the mold to manufacture a micro-needle patch (S300), wherein the hemostatic agent may be powdered cuttlefish bone or silicate.

[0076] The first step describes the preparation of a mixed solution by mixing GelMA, a photoinitiator, polydopamine, and a hemostatic agent in distilled water. (S100)

[0077] At this time, the hemostatic material may be powdered cuttlefish bone or silicate.

[0078] At this time, the GelMA can be dissolved by adding it to the distilled water in a freeze-dried state.

[0079] For example, freeze-dried GelMA can be dissolved in DI-water at a temperature of 30°C to 40°C for 2 to 4 hours to first prepare a solution with a final concentration of 15% w / v to 25% w / v.

[0080] Afterwards, the concentrations of the photoinitiator and polydopamine can be adjusted and added to the solution in which GelMA is dissolved.

[0081] For example, a photoinitiator (PI) (0.3% w / v to 0.7% w / v) and PDA (1% to 10% w / v) can be added, the photoinitiator can be exposed to light to cause a curing reaction, and then mixed using a vibrating mixer.

[0082] Next, a mixed solution can be prepared by adding various concentrations of laponite dispersion or powdered cuttlefish bone to a solution mixed with GelMA and polydopamine and mixing it again using a mixer.

[0083] At this time, the powdered cuttlefish bone may contain hydroxyapatite.

[0084] At this time, the prepared mixed solution preferably comprises, based on 100% by weight of the mixed solution, 15% to 25% by weight of the GelMA, 1% to 10% by weight of the polydopamine, 0.5% to 10% by weight of the hemostatic agent, and the remainder may include the photoinitiator and other inevitably added impurities.

[0086] The second step describes applying the above-mentioned mixed solution onto a mold having an intaglio formed corresponding to the shape of a micro-needle. (S200)

[0087] The above mold may be, for example, a mold having a plurality of intaglio formed corresponding to the shape of micro-needles manufactured from PDMS.

[0088] At this time, the size of the micro-needle engraving formed in the mold may vary depending on the size of the micro-needle to be manufactured.

[0089] Meanwhile, after applying the mixed solution onto the mold, the empty space of the intaglio can be completely filled with the mixed solution through a vacuum process.

[0090] In addition, to manufacture the base area together, the above-mentioned mixed solution can be applied to the mold in an amount greater than the amount filling the intaglio.

[0092] The third step describes the step of manufacturing a micro-needle patch by curing the mixed solution applied to the mold. (S300)

[0093] At this time, the above mixed solution contains a photoinitiator, so the above mixed solution can be cured through light irradiation.

[0094] UV light can be irradiated to cure the above mixed solution.

[0095] Through this, a patch with micro-needles formed according to the intaglio shape of the above mold can be manufactured.

[0096] After that, a micro-needle patch can be manufactured by removing the mold.

[0098] The present invention will be explained in more detail below through examples and experimental examples. These examples and experimental examples are solely for the purpose of illustrating the present invention, and the scope of the present invention is not limited by these examples and experimental examples.

[0100] Example 1: Preparation of powdered cuttlefish bone

[0101] First, to remove the remaining salt in the cuttlefish bone, it was immersed in distilled water for 72 hours, and then to remove the oily components, it was immersed in industrial methanol (90%) for 72 hours.

[0102] After that, the precipitated cuttlefish bone was washed with distilled water, air-dried at room temperature for 24 hours, and dried in an oven (80°C) for 5 hours.

[0103] Next, the completely dried cuttlefish bone was first crushed using a spatula and then secondarily crushed using a grinder to produce powdered cuttlefish bone.

[0104] At this time, the powdered cuttlefish bone was stored in a -20℃ freezer to prevent the denaturation of organic matter contained within the bone structure.

[0106] Example 2: Preparation of a micro-needle patch

[0107] FIG. 2 is a schematic diagram showing the process of a method for manufacturing a micro-needle patch according to one embodiment of the present invention.

[0108] Referring to Fig. 2, first, freeze-dried GelMA foam was dissolved in DI-water at 37°C for 24 hours to prepare a solution with a final concentration of 20% w / v, to which a photoinitiator (hereinafter PI) (0.5% w / v), PDA (1% to 10% w / v), and laponite or powdered cuttlefish bone (0.5% to 10%) were added. At this time, when the PI is exposed to light, a curing reaction occurs.

[0109] At this time, 1 g of GelMA, 10 ml of DI-water, 0.5% (0.005 g) of PI of GelMA, 2% (0.02 g) of polydopamine of GelMA, and 2% (0.2 g) of laponite or powdered cuttlefish bone of DI-water were added.

[0110] Afterwards, the solution containing GelMA, PI, polydopamine, raponite, or powdered cuttlefish bone was mixed using a vibrating mixer.

[0111] After that, the mixture was filled into the mold cavity through a vacuum process.

[0112] Additionally, after applying the solution onto the mold, the mixture was cured by irradiating it with UV light at an intensity of 300 mW / cm² for 5 minutes.

[0113] Afterwards, a micro-needle patch was manufactured by drying it at room temperature overnight and removing the mold.

[0115] Experimental Example 1: Observation of the surface of the manufactured micro-needle patch

[0116] FIG. 3 is an actual and cross-sectional image of a micro-needle patch according to one embodiment of the present invention, observed with an optical microscope.

[0117] Referring to Fig. 3, it can be seen that micro-needles are formed on the surface of the patch.

[0119] Experimental Example 2: Observation of Physical Properties of Manufactured Microneedles

[0120] Fig. 4. This is an image showing the mechanical strength of the patch after inserting it into pig skin using a thumb.

[0121] Referring to Fig. 4, it can be seen that the microneedles of the microneedle patch have penetrated the pig skin.

[0123] Figure 5 is an image confirming the adhesiveness of the adhesive hemostatic microneedle patch by slicing porcine heart tissue.

[0124] Referring to Figure 5, it can be seen that the micro-needle patch remains attached without falling off even when strong external pressure is applied and the shape of the pig heart tissue is deformed, which can be inferred to indicate excellent adhesion.

[0126] Figure 6 is a graph showing that it can withstand pressure sufficiently through a burst pressure test.

[0127] Looking at this, the horizontal axis represents the concentration of polydopamine (GelMa = polydopamine content 0%, P1L1 = polydopamine content 1%, P3L1 = polydopamine content 3%, and P5L1 = polydopamine content 5%), and it can be seen that the microneedle patch containing polydopamine adheres well to the collagen tissue even under external pressure, whereas the flat patch made without microneedles easily detaches under pressure.

[0128] In addition, the present invention can be seen to show that the adhesive ability improves as the concentration of polydopamine increases, whereas in the case of a flat patch, it can be seen that the adhesive ability does not improve beyond a certain level even if the polydopamine content increases.

[0130] Figure 7 is an image showing the blood coagulation time of an adhesive hemostatic microneedle patch using sheep's blood.

[0131] Looking at Figure 7, the horizontal axis represents the concentration of polydopamine, and it can be seen that blood coagulation improves as the concentration of polydopamine increases.

[0132] In addition, it can be observed that blood coagulation occurs more effectively than when only laponite or powdered cuttlefish bone is used, which can be inferred to be because the adhesive ability of polydopamine causes blood to clot, thereby causing hemostasis more quickly.

[0133]

[0134] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0135] The scope of the present invention is defined by the claims set forth below, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts thereof should be interpreted as being included within the scope of the present invention.

Claims

Claim 1 A micro-needle patch comprising: a base; and a plurality of micro-needles formed on the base, each comprising GelMA, polydopamine, and a hemostatic agent; wherein the hemostatic agent is powdered cuttlefish bone containing porous hydroxyapatite, and wherein, based on 100% by weight of the total micro-needles, the polydopamine is 1% to 10% by weight, the hemostatic agent is 0.5% to 10% by weight, and the remainder comprises GelMA and other inevitably added impurities. Claim 2 delete Claim 3 delete Claim 4 delete Claim 5 A micro-needle patch according to claim 1, characterized in that the height of the micro-needles is 100 μm to 1000 μm. Claim 6 A micro-needle patch according to claim 1, characterized in that the diameter of the micro-needles is 100 μm to 1000 μm. Claim 7 A method for manufacturing a micro-needle patch comprising: a step of preparing a mixed solution by mixing GelMA, a photoinitiator, polydopamine, and a hemostatic agent in distilled water; a step of applying the mixed solution onto a mold having an intaglio formed corresponding to the shape of a micro-needle; and a step of curing the mixed solution applied onto the mold to manufacture a micro-needle patch; wherein the hemostatic agent is powdered cuttlefish bone containing porous hydroxyapatite, and relative to 100% by weight of the total micro-needle, the polydopamine is 1% to 10% by weight, the hemostatic agent is 0.5% to 10% by weight, and the remainder comprises GelMA and other inevitably added impurities. Claim 8 delete Claim 9 A method for manufacturing a micro-needle patch according to claim 7, wherein, based on 100% by weight of the mixed solution, the GelMA is 15% to 25% by weight, the polydopamine is 1% to 10% by weight, the hemostatic agent is 0.5% to 10% by weight, and the remainder comprises the photoinitiator and other inevitably added impurities. Claim 10 A method for manufacturing a micro-needle patch according to claim 7, characterized in that, in the step of manufacturing the micro-needle patch, UV light is irradiated to cure the mixed solution.

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