Microneedle patch and manufacturing method thereof

Abstract

The invention discloses a microneedle patch and a manufacturing method thereof. The microneedle patch includes a microneedle layer. The microneedle layer has a total area thereon, and includes a first region thereon. The first region has a first area less than or equal to the total area. The material of the microneedle layer comprises a biocompatible material and a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof.

Description

Technical Field

[0001] The present invention relates to the field of transdermal delivery, and in particular to a microneedle patch and a method for manufacturing the same. Background Art

[0002] Microneedle patches are generally found in the fields of medical treatment and medical beauty. In order to meet the requirements of the appearance and variability of microneedle patches, there is a conventional method for manufacturing microneedle patches, which uses a laser to drill microholes on a mold according to a pattern design; however, since each new pattern design requires the mold to be remade, the cost is high and not conducive to mass production. Another manufacturing method uses a plug manufactured by 3D printing technology and a common mold to form microneedles arranged according to the design pattern; however, since each new pattern design requires the production of a new plug, and the cost of manufacturing the plug is high, in addition, the fit between the plug and the mold needs to be improved, so this method is not conducive to commercial production. Summary of the invention

[0003] The present invention provides a microneedle patch, which has a changeable appearance and can be used by users to change the shape to achieve various visual effects. It can also provide marking, tracking, indicating and other functions for identity recognition and medical assistance.

[0004] The present invention also provides a method for manufacturing a microneedle patch, which can reduce manufacturing costs, help improve the microneedle yield, and facilitate mass production of the microneedle patch.

[0005] To achieve one or part or all of the above purposes or other purposes, one embodiment of the present invention provides a microneedle patch, comprising a microneedle layer having a total area. The microneedle layer also comprises a first region. The first region has a first area that is less than or equal to the total area. The material of the microneedle layer comprises a biocompatible material and a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof.

[0006] In one embodiment of the present invention, the material of the microneedle layer further includes tattoo pigment.

[0007] In one embodiment of the present invention, the amount of the aforementioned thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof accounts for 0.1-40 wt % of the microneedle layer material.

[0008] In one embodiment of the present invention, the amount of the thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof is 2-35 wt % of the microneedle layer material.

[0009] In one embodiment of the present invention, the amount of the thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof is 10-25 wt % of the microneedle layer material.

[0010] In one embodiment of the present invention, the microneedle layer material further comprises a tattoo pigment, and the amount of the thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance, the tattoo pigment or a combination thereof accounts for 0.1-40 wt % of the microneedle layer material.

[0011] To achieve one or part or all of the above-mentioned purposes or other purposes, one embodiment of the present invention also provides a method for manufacturing a microneedle patch, comprising the steps of: providing a mold, wherein the internal space of the mold includes a bottom surface, and a plurality of conical holes are formed on the bottom surface, which are spaced apart from each other and extend in a direction away from the bottom surface; providing a biocompatible material, mixing a thermochromic material, a photochromic material or a combination thereof into the biocompatible material to form a first mixture; distributing the first mixture to the mold and forming a microneedle layer, wherein the microneedle layer includes a plurality of microneedles spaced apart from each other; setting a mask above the microneedle layer, wherein the mask has a pattern area which is projected onto the microneedle layer; and providing a heat source, a cold source, a light source or a combination thereof, and applying temperature changes, light or a combination thereof to the microneedle layer through the mask so that the microneedle layer displays a pattern, wherein the pattern corresponds to the pattern area of ​​the mask.

[0012] To achieve one, part, or all of the above purposes or other purposes, one embodiment of the present invention further provides a microneedle patch, which is prepared by a method including the above steps.

[0013] Since the present invention adopts thermochromic materials, photochromic materials, thermochromic substances, photochromic substances or combinations thereof, a mask and a heat source, a cold source or a light source can be used in combination, which is beneficial to simplifying the manufacturing process.

[0014] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments, but is not intended to limit the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 FIG. 4 is a schematic flow chart of a method for manufacturing a microneedle patch according to an embodiment of the present invention.

[0016] Figures 2 to 8 Schematic diagram of the steps of a method for manufacturing a microneedle patch according to an embodiment of the present invention.

[0017] Fig. 9 FIG. 4 is a schematic top view of a microneedle patch according to a first embodiment of the present invention.

[0018] Fig.10 FIG. 4 is a schematic three-dimensional diagram of a microneedle patch according to a second embodiment of the present invention.

[0019] Fig.11 FIG. 4 is a schematic three-dimensional diagram of a microneedle patch according to a third embodiment of the present invention.

[0020] Fig.12 FIG. 4 is a schematic top view of a microneedle patch according to a third embodiment of the present invention.

[0021] Among them, the reference numerals

[0022] S110~S150: Steps

[0023] 2: Mold

[0024] 20: Bottom

[0025] 21: Cone hole

[0026] 300: First Mixture

[0027] 300': Second mixture

[0028] 40, 40a, 40b: Microneedle patches

[0029] 400, 400a, 400b: Microneedle layer

[0030] 410, 410a, 410b: Microneedle

[0031] 420, 420a, 420b: base layer

[0032] 421, 421a: Side 1

[0033] 422a: Side 2

[0034] 500, 500a: carrier layer

[0035] 6: Mask

[0036] 60: Pattern area

[0037] 7: Cold / heat / light source

[0038] P': Projection

[0039] P: Pattern

[0040] A, A1, A2: First area DETAILED DESCRIPTION

[0041] The aforementioned and other technical contents, features and effects of the present invention will be clearly presented in the following detailed description of a preferred embodiment with reference to the drawings. The directional terms mentioned in the following embodiments are only with reference to the directions of the attached drawings. Therefore, the directional terms used are used to illustrate and not to limit the present invention. In addition, the terms "first", "second", etc. mentioned in this specification or the scope of the patent application are only used to name the name of the element or to distinguish different embodiments or scopes, and are not used to limit the upper or lower limit of the number of elements.

[0042] The present invention provides a microneedle patch and a method for manufacturing the same. The microneedle patch is preferably identifiable, for example, it can display a pattern or text. Alternatively, the microneedle patch itself has a specific shape, and the shape of the microneedle patch can reflect a specific pattern or text. The microneedle patch of the present invention can also be used as a tattoo patch.

[0043] Figure 1 FIG. 1 is a schematic diagram of a process for manufacturing a microneedle patch according to an embodiment of the present invention. Figure 1 As shown, the manufacturing method may include step S110: providing a mold, wherein the internal space of the mold includes a bottom surface, and a plurality of conical holes are formed on the bottom surface, which are spaced apart from each other and extend in a direction away from the bottom surface; step S120: providing a biocompatible material, mixing a thermochromic material, a photochromic material or a combination thereof into the biocompatible material to form a first mixture; step S130: distributing the first mixture to the mold and forming a microneedle layer, wherein the microneedle layer includes a plurality of microneedles spaced apart from each other; step S140: setting a mask above the microneedle layer, wherein the mask has a pattern area projected on the microneedle layer; step S150: providing a heat source, a cold source, a light source or a combination thereof, and applying temperature change, light or a combination thereof to the microneedle layer through the mask, so that the microneedle layer shows a pattern, wherein the pattern corresponds to the pattern area of ​​the mask. Each step is further described as follows.

[0044] Step S110:

[0045] The mold of step S110 may be, for example, a mother mold, and is preferably formed of a polymer material. In some embodiments, the mother mold may be formed, for example, by using a male mold and a polymer material such as polyethylene, polypropylene, polylactic acid, polybutylene succinate, or polydimethylsiloxane. The male mold (not shown) may have a plurality of cone-shaped or needle-shaped structures, which reflect the shape of the microneedles of the microneedle patch. The cone-shaped or needle-shaped structure of the male mold may be, for example, a cone, a triangular pyramid, or a quadrangular pyramid, but is not limited thereto. The mold serving as the mother mold is formed with a hole complementary to the cone-shaped or needle-shaped structure by the male mold. Figure 2 As shown, the internal space of the mold 2 includes a bottom surface 20, and a plurality of tapered holes 21 are formed on the bottom surface 20, which are spaced apart from each other and extend in a direction away from the bottom surface 20. The shape of the tapered hole 21 corresponds to the shape of the microneedle, and the depth of the tapered hole 21 can reflect the height of the microneedle. In a preferred embodiment of the present invention, the depth of the tapered hole 21 can be 100-2000 μm, and the height of the microneedle is, for example, 100-2000 μm.

[0046] Step S120:

[0047] The microneedle patch of the present invention is in principle a patch with soluble and / or biodegradable microneedles, and the main component constituting the microneedles is a biocompatible material. The biocompatible material may include hyaluronic acid, polyvinyl pyrrolidone, polyvinyl alcohol, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, pullulan gum, collagen, xanthan gum, pectin, polyglutamic acid, short-chain polypeptides, sodium alginate, maltodextrin, cyclodextrin, propylene glycol alginate, gelatin, gum arabic, methylcellulose, and polysaccharides such as dextran, polymannan, short-chain polysaccharides, disaccharides such as trehalose, sucrose, lactose, monosaccharides such as glucose, polyols such as mannitol, sorbitol or a combination thereof, but not limited thereto, for example, other polymer materials and low molecular weight materials other than those listed may also be used. In addition, the material constituting the microneedle preferably includes a polymer material and a low molecular weight material, wherein the low molecular weight material can be used to adjust the properties. The biocompatible material is preferably in the form of a solution or a sol in the preparation stage, and can be heated or cooled to be formed after being injected into the mold 2. In a preferred embodiment of the present invention, the biocompatible material includes hyaluronic acid, for example.

[0048] The biocompatible material is uniformly mixed with a thermochromic material, a photochromic material or a combination thereof. That is, one of the thermochromic material and the photochromic material can be selected and mixed into the biocompatible material, or both can be used together to form a first mixture 300. The thermochromic material is a material that can change color under a specific temperature change. The specific temperature change can be, for example, a temperature rise to a certain degree, a temperature drop to a certain degree, or a specific temperature range, but is not limited thereto. In addition, the color change can be reversible or irreversible. Thermochromic materials include any known or yet to be developed materials that can change color or cause color change, for example, can include color-changing liquid crystal, spirolactone, fluoroline, spiropyran, fulgide, triarylmethane, bis(methyldimethylamino) tetrachloronickelate (II), bis(ethyldiethylamino) tetrachlorocuprate (II), tetraorganoarsenic, tetraorganotin, tetraorganobismuth, ammonium metavanadate, manganese violet, metal oxides, metal sulfides, iodides or combinations thereof, but not limited thereto. Metal oxides are, for example, titanium dioxide, zinc oxide, indium oxide, lead oxide, chromium oxide, aluminum oxide, vanadium dioxide, metal sulfides are, for example, zinc sulfide, and iodides are, for example, mercuric iodide, mercuric silver iodide, copper iodide, but not limited thereto. Thermochromic materials can be mixed into biocompatible materials in the form of, for example, powder, liquid, microcapsule or a combination thereof. Some embodiments of the present invention use thermochromic microcapsules with gold particles (insilico), such as Chameleon T series, Bichrom T series, Irreversibility T series, and SpyBall. The thermochromic material allows the microneedles or microneedle layer (described later) formed by the first mixture 300 to undergo, for example, color development (from originally transparent and colorless to color), color loss (from originally colored to transparent and colorless), and color conversion (from original color to another color) under temperature changes. The color change is not limited to what can be seen by the naked eye.

[0049] Photochromic materials are materials that can change color or cause color change under specific illumination. The color change is not limited to being visible to the naked eye. The specific illumination may be, for example, UV light, infrared light, visible light, but is not limited thereto. The color change may also be reversible or irreversible. Photochromic materials include any known or yet to be developed material that can change color, for example, triarylmethane, spiropyran, spiropyran, diarylethene, azobenzene, nitrone, fulgide, naphthopyran, quinone, chloride, halide, hydroxide, metal complex, coordination compound, dark color-changing mineral or a combination thereof, but is not limited thereto. Azobenzene is, for example, azovinylbenzene, chloride is, for example, silver chloride, halide is, for example, silver halide, zinc halide, hydroxide is, for example, yttrium hydroxide, and coordination compound may be, for example, sodium nitroprusside, ruthenium sulfoxide. The photochromic material can be mixed into the biocompatible material in the form of, for example, powder, liquid, microcapsule or a combination thereof. In some embodiments of the present invention, for example, photochromic microcapsules are used. The photochromic material allows the microneedles or microneedle layer (described later) formed by the first mixture 300 to undergo, for example, color development, color elimination, and color conversion under temperature changes. The amount of the thermochromic material, the photochromic material or a combination thereof can account for 0.1~40wt% of the first mixture 300, for example, 0.1%, 1wt%, 5wt%, 10wt%, 15wt%, 20wt%, 25wt%, 30wt%, 35wt% and 40wt%, wherein when the thermochromic material and the photochromic material are used in combination, the sum of the amounts of the two also accounts for 0.1~40wt% of the first mixture 300. In an embodiment of the present invention, for example, the total amount of the thermochromic material and the photochromic material accounts for 18% of the first mixture 300, wherein the thermochromic material and the photochromic material can be combined in a ratio of 5:1, for example, that is, the amounts of the thermochromic material and the photochromic material account for 15% and 3% of the first mixture 300, respectively, but not limited to this.

[0050] In principle, the amount of thermochromic material, photochromic material or their combination should not be too high. One of the reasons is that this will make the amount of biocompatible material relatively low, which will lead to insufficient microneedle strength, loss or other instability such as physical properties, affecting the efficacy of microneedle puncturing the skin. On the other hand, the amount of thermochromic material, photochromic material or their combination should not be too low, because this may make the color too light and not conducive to identification. In a preferred embodiment of the present invention, the amount of thermochromic material, photochromic material or their combination is further 2~35wt%, such as 2wt%, 4wt%, 7wt%, 11wt%, 15wt%, 19wt%, 23wt%, 27wt%, 31wt% and 35wt%. For example, hyaluronic acid and photochromic powder with a mixing ratio of 95:5 can be used as the material of the microneedle layer. In a more preferred embodiment of the present invention, the amount of the thermochromic material, the photochromic material or a combination thereof is 10-25wt%, for example, 10wt%, 12wt%, 14wt%, 16wt%, 18wt%, 20wt%, 22wt%, 24wt% and 25wt%. According to the type and content of the thermochromic material and the photochromic material, step S120 may further include making the thermochromic material, the photochromic material or a combination thereof evenly dispersed in the biocompatible material. Further, when the amount of the thermochromic material, the photochromic material or a combination thereof is, for example, greater than 10wt%, the formula of the biocompatible material may be adjusted to facilitate the average dispersion of the thermochromic material, the photochromic material or a combination thereof in the microneedle, thereby obtaining a better color change result.

[0051] In addition to the thermochromic material and the photochromic material, the embodiments of the present invention may further add other components to the biocompatible material. For example, the other components may include the aforementioned low molecular weight material, catalyst, substrate of the thermochromic or photochromic material, donor of the thermochromic or photochromic material such as a proton donor, and additives for adjusting the properties of the microneedles, but are not limited thereto.

[0052] In a preferred embodiment of the present invention, the thermochromic material, the photochromic material, or a combination thereof, or a derivative thereof (described later) preferably also has the effect of tattooing. In this case, the thermochromic material, the photochromic material, or a combination thereof, or a derivative thereof can be injected into the skin through a microneedle to achieve the effect of tattooing, and further achieve the purpose of decoration or marking. Step S120 can further include mixing a tattoo pigment into the first mixture 300 to form a second mixture 300'. Tattoo pigments include any known or yet to be developed materials that can display a specific color pattern on the skin, for example, can include mercuric sulfide (cinnabar), cadmium selenide sulfide (cadmium red), iron oxide, carmine, cochinilla, chromium oxide, hydrated chromium oxide, cupric chloride, chromium trioxide, emerald green, cobalt aluminate, indigo, phthalic acid blue, cadmium sulfide, lemon yellow, chromium zinc, hydrate of ferric oxide, logwood, carbon, iron monoxide, ferric oxide, black ink, cadmium salts, Venetian red, zinc oxide, barium sulfate, titanium dioxide, lead carbonate, manganese violet (ammonium manganese (3+) diphosphate), various aluminum salts quinacridone, dihydroxyquinoline acridine, dioxane, carbazole, naphthalenedione or a combination thereof. Tattoos are not limited to permanent or temporary tattoos.

[0053] The tattoo pigment, the thermochromic material, the photochromic material or a combination thereof may account for 0.1-40wt% of the second mixture 300', for example, 0.1wt%, 1wt%, 5wt%, 10wt%, 15wt%, 20wt%, 25wt%, 30wt%, 35wt% and 40wt%. In an embodiment of the present invention, for example, the total amount of the tattoo pigment, the thermochromic material and the photochromic material accounts for 18% of the second mixture 300', wherein the tattoo pigment, the thermochromic material and the photochromic material may be combined in a ratio of, for example, 1:3:2, that is, the amount of the tattoo pigment, the thermochromic material and the photochromic material respectively accounts for 9%, 6% and 3% of the second mixture 300', but is not limited thereto.

[0054] Step S130:

[0055] Step S130 uses the mold 2 of step S110 and the first mixture 300 or the second mixture 300' of step S120. Figure 3A As shown, during distribution, the first mixture 300 is first injected into the inner space of the mold 2, and preferably, the liquid surface of the first mixture 300 can be horizontal and parallel to the bottom surface 20. Figure 3BAs shown, the second mixture 300' is injected into the inner space of the mold 2. Figure 4 As shown, the first mixture 300 (or the second mixture 300'; hereinafter referred to as the first mixture 300) can enter the conical hole 21 from the bottom surface 20 due to the influence of gravity, for example. The conical hole 21 is filled with the first mixture 300, and preferably completely filled. As the first mixture 300 enters the conical hole 21, its liquid level above the bottom surface 20 can drop.

[0056] Whether the first mixture 300 completely fills the conical hole 21 can be checked by an instrument or by observing whether the liquid level changes. Afterwards, the first mixture 300 can be solidified and formed in the mold 2 to form a plurality of microneedles 410 and a base layer 420. The microneedles 410 and the base layer 420 constitute the microneedle layer 400, wherein the plurality of microneedles 410 are arranged on one side of the base layer 420 at intervals from each other. Generally speaking, the materials constituting the microneedles 410 and the base layer 420 are the same, for example, a mixture of hyaluronic acid and photochromic powder, but not limited thereto. In some embodiments of the present invention, the materials of the microneedles 410 and the base layer 420 may also be different. For example, the conical hole 21 can be filled with the first mixture 300 containing a thermochromic material, a photochromic material or a combination thereof and a biocompatible material, and then the bottom surface 20 can be covered with a biocompatible material to form a plurality of microneedles 410 containing a thermochromic material, a photochromic material or a combination thereof and a base layer 420 without the same. Alternatively, the conical hole 21 may be first filled with the second mixture 300 ′ containing tattoo pigments, and then the bottom surface 20 may be covered with a biocompatible material to form a plurality of microneedles 410 containing tattoo pigments and a base layer 420 not containing tattoo pigments.

[0057] The manufacturing method of the present invention may further include step S135: separating the microneedle layer 400 from the mold 2. The separated microneedle layer 400 is as follows: Figure 5 In the embodiment of the present invention, the microneedle 410 may be a cone, a triangular pyramid, or a quadrangular pyramid, but is not limited thereto, and the height may be, for example, 100 to 2000 μm. The side of the base layer 420 having the microneedle 410 may be a first side 421, and the side opposite to the first side 421 may be a second side 422. Figure 6 As shown, a carrier layer 500 may be further disposed on the second surface 422. The carrier layer 500 may be made of a relatively tough material, such as a film or a piece of cloth, and may carry the microneedle layer 400 and facilitate the user to hold the microneedle patch.

[0058] Step S140:

[0059] like Figure 7As shown, the mask 6 used in step S140 has a pattern area 60. In the embodiment of the present invention, the pattern area 60 may be a hollow area on the mask 6, but is not limited thereto. For example, the solid part of the mask 6 outside the hollow area may also present a pattern and be another pattern area. In the preferred embodiment of the present invention, the hollow area on the mask 6 is the pattern area 60. The hollow area is not limited to Figure 7 In addition to the cross shape shown, for example, other shapes such as geometric shapes, irregular shapes, and text may be used, but the present invention is not limited to this.

[0060] The mask 6 of the embodiment of the present invention preferably has heat insulation, light blocking or a combination thereof, so when there is a heat source, a cold source or a light source on one side of the mask 6, the mask 6 can partially block the heat, cold or light. In other words, the hot and cold temperatures or light are preferably transmitted from the hollow area to the other side of the mask 6, and conversely, the other side corresponding to the part outside the hollow area is preferably not affected by temperature and light. The material of the mask 6 can be, for example, metal, silicone, inorganic silicone, paper, plastic, resin, but is not limited thereto.

[0061] In the embodiment of the present invention, Figure 7 As shown, the mask 6 may be disposed on the side of the microneedle layer 400 having the microneedles 410, and the pattern area 60 is projected onto the microneedles 410 and the base layer 420. The mask 6 may not have directionality, for example, when its pattern area 60 is a completely symmetrical pattern, it makes no difference whether the mask 6 faces the microneedle layer 400 with any side. The mask 6 may also have directionality, for example, when its pattern area 60 is an asymmetrical figure such as the letter "B", in which case the mask 6 will produce different projections P' with different sides facing the microneedle layer 400. Therefore, when the mask 6 is disposed on the side of the microneedle layer 400 having the microneedles 410, step S140 may further include making the direction of the projection P' opposite to the tattoo pattern to be achieved by the microneedle patch 40, for example, opposite to the left and right. On the contrary, when the mask 6 is disposed on the base layer 420 side of the microneedle layer 400, the projection P' may be in the same direction as the tattoo pattern to be achieved by the microneedle patch 40. The number of the pattern regions 60 is not limited to one, that is, the mask 6 may have a plurality of pattern regions 60. In addition, the pattern region 60 may be a single continuous region or may be a plurality of discontinuous regions.

[0062] Step S150:

[0063] Step S150 can select a cold / hot source or light source 7 according to the aforementioned steps, and can further determine the cold source or hot source according to the specific content of the thermochromic material, or determine the wavelength of the light source according to the specific content of the photochromic material. For example, when the thermochromic material changes color when the temperature drops, a cold source is usually selected. The cold source or hot source can heat up or cool down the microneedle layer 410 through, for example, air conduction or electromagnetic waves through the mask 6. Specifically, the cold / hot source includes but is not limited to cold / hot air, liquid nitrogen, microwaves, and lasers. Because the mask 6 body preferably has heat insulation properties, the cold / hot source passes through the pattern area 60 and causes the projection range P' on the microneedle layer 400 to be heated or cooled, thereby Figure 8 As shown, the color of the microneedle layer 400 in the projection range P' changes to reveal the pattern P. In some embodiments of the present invention, the mask 6 is a stamping polydimethylsiloxane (PDMS) mask, and the heat source 7 can be, for example, a 60-350° C. hot air gun.

[0064] On the other hand, the light source 7 can be a light source of various wavelengths, including but not limited to ultraviolet light, infrared light, and visible light, which illuminates the microneedle layer 400 through the mask 6. Since the mask 6 body preferably has light blocking properties, the light passes through the pattern area 60 and illuminates the projection range P' on the microneedle layer 400, thereby causing the microneedle layer 400 to change color in the projection range P' and display the pattern P. In some embodiments of the present invention, the mask 6 is a laser engraved metal mask, and the light source 7 can be, for example, a 5W 200~380nm ultraviolet lamp. Depending on the type of photochromic material, the wavelength range of the light emitted by the light source 7 preferably includes 365nm ultraviolet light.

[0065] The aforementioned "color change of the thermochromic material / photochromic material" may be caused by changes in the thermochromic material or photochromic material itself, such as structural changes, under temperature changes or light exposure. In the present invention, the changed thermochromic material or photochromic material is referred to as a derivative. The derivative may be formed by a thermochromic or photochromic material and other components. For example, after light exposure, the photochromic material may form a bond with other components to produce a derivative, but the invention is not limited thereto. "Thermochromic material / photochromic material causes a color change" may be caused by products generated by the thermochromic material, photochromic material and other components under temperature changes or light exposure (hereinafter referred to as products after temperature changes or products after light exposure). For example, the photochromic material may catalyze its substrate under light exposure to generate products, and the photochromic material itself only acts as a catalyst to cause other components to change color, but the invention is not limited thereto. In the present invention, the derivatives of thermochromic materials and their temperature-changing products may be referred to as thermochromics, and the derivatives of photochromic materials and their products after illumination may be referred to as photochromics. However, in some embodiments of the present invention, thermochromics also refer to the totality of thermochromic materials and their derivatives or products after temperature change, and are not limited thereto. For example, thermochromics may be the totality of thermochromic materials such as spirolactone, spiropyran, fulgide and their proton donors such as bisphenol A, parabens, 1,2,3-triazole derivatives, and 4-hydroxycoumarin. In addition, photochromics also refer to the totality of photochromic materials and their derivatives or products after illumination, and are not limited thereto. The color change effective time of thermochromics and photochromics may be temporary or permanent. For example, color may be temporarily developed and maintained for a period of time. After the period, the color may be gradually lost or immediately lost.

[0066] In the embodiments of the present invention, the thermochromic material or photochromic material that can generate a product after temperature change or after light exposure can further have the effect of tattoo, and its product can also have the effect of tattoo. In addition, the thermochromic material or photochromic material that can form the above-mentioned derivative under the action of temperature change or light exposure can further have the effect of tattoo, and its derivative can also have the effect of tattoo. In this case, if Figure 8 As shown, the microneedle layer 400 has a component with the effect of tattoo pigment within the scope of its pattern P, and the pattern P preferably reflects the effect of tattooing with the microneedle patch 40 roughly like the pattern P. The component with tattoo effect can be distributed only in the microneedles 410, or can be distributed only in the base layer 420, or can be distributed in both in the pattern P. The color produced by the component with tattoo effect on the skin is not limited to the same color as the pattern P.

[0067] The manufacturing method of the present invention may further include step S155: cutting the microneedle layer 400 according to the pattern P. The cut microneedle layer 400 may have a shape corresponding to the pattern P. Fig. 9In the embodiment shown, the pattern P is a cross, and the microneedle layer 400 is also a cross. Fig.10 As shown, the carrier layer 500 disposed on the second surface 422 of the microneedle layer 400 may also have the same shape, but is not limited thereto. After completing step S150 or step S155, the microneedle patch 40 may be obtained. The microneedle patch 40 may contain a component having a tattoo effect, and thus may be used as a tattoo patch.

[0068] The present invention also provides a microneedle patch. Fig.11 In the illustrated embodiment, the microneedle patch 40a includes a microneedle layer 400a. The microneedle layer 400a includes a base layer 420a and a plurality of microneedles 410a, wherein the base layer 420a has a first surface 421a and a second surface 422a opposite to each other, and the plurality of microneedles 410a are disposed at intervals on one surface, such as the first surface 421a. The microneedle patch 40a may further include a carrier layer 500a, and the microneedle layer 400a may be disposed on the carrier layer 500a on the other surface of the base layer 420a, such as the second surface 422a.

[0069] The microneedle layer 400a may have a total area. The total area is related to the size and shape of the microneedle layer 400a. The total area may also be equivalent to the area of ​​the first surface 421a or the second surface 422a. Fig.11 In the embodiment, the microneedle layer 400a is rectangular, so the total area can be roughly the product of the length and width of the rectangle. The microneedle layer 400a includes a first area A1. The first area A1 is preferably located on the side where the microneedles 410a are located, such as the first side 421a, and can also be located on the second side 422a. The number of first areas A1 is not limited to one. For example, there are multiple first areas A1 on the first side 421a. In addition, the first area A1 can be a single continuous area or can be multiple discontinuous areas. The first area A1 has a first area. The first area can be less than or equal to the total area. Fig.11 In the embodiment of the present invention, the first area A1 of the microneedle layer 400a has a substantially cross-shaped pattern and is located within the range of the first surface 421a. In this case, the first area is substantially the area of ​​the cross, and the first area is smaller than the total area. However, in some embodiments, the first area may be equal to the total area. Fig. 9 As shown in the example, the first surface 421 is in a cross shape, the first region A is also in a cross shape, the total area is the area of ​​the cross, and the first area is also the area of ​​the cross and is equal to the total area.

[0070] The material of the microneedle layer 400a includes a biocompatible material and a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof. In other words, the microneedle layer 400a is composed of a biocompatible material and may contain any one to any three or all of the thermochromic material, the photochromic material, the thermochromic substance, and the photochromic substance. The definitions of the thermochromic material, the photochromic material, the thermochromic substance, and the photochromic substance may be as described above and are not repeated here. The method of forming the microneedle layer 400a with a biocompatible material and a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof may be as described above; furthermore, the microneedle layer 400a may also be manufactured by the method described above. It is known that the thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof may be distributed on the microneedles 410a and the base layer 420a of the microneedle layer 400a, or may be distributed only on the microneedles 410a or the base layer 420a.

[0071] In an embodiment of the present invention, the thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof accounts for 0.1-40wt% of the microneedle layer material, preferably 2-35wt%, and more preferably 10-25wt%. In a preferred embodiment of the present invention, the thermochromic material is a thermochromic microcapsule, and the photochromic material is a photochromic microcapsule. In some embodiments of the present invention, the thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof may have the effect of tattooing.

[0072] In a preferred embodiment of the present invention, the thermochromic substance, the photochromic substance or a combination thereof is further distributed on the plurality of microneedles 410a located in the first area A1, and it can have the effect of tattooing. Fig.11 As shown in the example, the microneedles 410a in the cross-shaped pattern contain thermochromic substances, photochromic substances or a combination thereof, and can be used to achieve a tattoo effect. The area outside the first area A1 preferably does not contain thermochromic substances, photochromic substances or a combination thereof, but may contain thermochromic materials, photochromic materials or a combination thereof. Fig.11 In the embodiment, the base layer 420a of the first area A1 also contains a thermochromic substance, a photochromic substance or a combination thereof, but the present invention is not limited thereto. For example, the base layer 420a may be composed only of a biocompatible material without containing a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof.

[0073] like Fig.12In the embodiment shown, the material of the microneedle layer 400b may further include tattoo pigments, that is, tattoo pigments are contained in addition to the thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof. The method of forming the microneedle layer 400b with biocompatible materials and tattoo pigments, thermochromic material, photochromic material, thermochromic substance, photochromic substance or a combination thereof may be as described above; and the microneedle layer 400b may also be manufactured as described above. It is known that the tattoo pigments may be distributed in the microneedles 410b and the base layer 420b of the microneedle layer 400b, or only in the microneedles 410b.

[0074] The tattoo pigment may be distributed indiscriminately in all microneedles 410b, or may be further distributed in the microneedles 410b in the first area A2. Fig.12 As shown, the microneedle patch 40b may further be formed with a pre-cut (as shown by the dotted line in the figure) along the contour of the first area A2, for example, for the user to tear off the first area A2 of the microneedle patch 40b for use.

[0075] In some embodiments of the present invention, microneedle patches such as 40, 40a, 40b may further contain bioactive substances, such as pharmacologically active molecules that can be delivered transdermally. The microneedle patches 40, 40a, 40b, for example, can not only remind the user that the medication is being taken, but also other people such as family members and medical staff can know the medication situation. The color development, color loss or color conversion is not limited to what is visible to the naked eye. For example, it can be presented by light of a specific wavelength. Furthermore, through time-sensitive thermochromic substances, photochromic substances, tattoo pigments or combinations thereof, the metabolism and / or absorption of certain drugs can be tracked from their color change states. For example, when the color development weakens, it can reflect the decrease in the effective amount of the drug, which can be used to remind the user to replenish the medication, for example.

[0076] In summary, the microneedle patch manufacturing method of the present invention uses a thermochromic material, a photochromic material or a combination thereof, with a mask and a heat source, a cold source or a light source, and the mask can be easily made with conventional technology. Therefore, compared with the current method for manufacturing a microneedle tattoo patch, the preparation process of the present invention is relatively simple, the cost is low, and the process is more simplified. And because the process is simplified, it is conducive to reducing the occurrence of errors, and thus the microneedle yield can be improved; because the preparation process is simple, the cost is low, and the process is simplified, it is conducive to the mass production of microneedle patches. On the other hand, because the material of the microneedle patch of the present invention includes a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof, it can be used for tattoos and can achieve the effect of decoration or marking.

[0077] Of course, the present invention may have many other embodiments. Without departing from the spirit and essence of the present invention, those skilled in the art may make various corresponding changes and modifications based on the present invention, but these corresponding changes and modifications should all fall within the scope of protection of the claims attached to the present invention.

Claims

1. A microneedle patch, characterized in that: Comprising a microneedle layer, wherein: The microneedle layer has a total area, and includes a first region on the microneedle layer; wherein the first region has a first area that is less than or equal to the total area; and The material of the microneedle layer includes a biocompatible material and a thermochromic material, a photochromic material, a thermochromic substance, a photochromic substance or a combination thereof.

2. The microneedle patch according to claim 1, characterized in that The microneedle layer further comprises a base layer and a plurality of microneedles, and the base layer has a first surface and a second surface opposite to each other; the first region is located on the first surface, and the microneedles are spaced from each other and arranged on the first surface.

3. The microneedle patch according to claim 2, characterized in that: The invention further comprises a carrier layer, and the microneedle layer is arranged on the carrier layer with the second surface of the base layer.

4. The microneedle patch according to claim 1, characterized in that The thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance or a combination thereof is further distributed on a plurality of microneedles located in the first area.

5. The microneedle patch according to claim 1, characterized in that The thermochromic material includes thermochromic liquid crystal, spirolactone, fluoroline, spiropyran, fulgide, triarylmethane, bis(methyldimethylamino)tetrachloronickelate (II), bis(ethyldiethylamino)tetrachlorocuprate (II), tetraorganoarsenic, tetraorganotin, tetraorganobismuth, ammonium metavanadate, manganese violet, metal oxide, metal sulfide, iodide or a combination thereof.

6. The microneedle patch according to claim 1, characterized in that The photochromic material includes triarylmethane, spiropyran, spiropyran, diarylethene, azobenzene, nitrone, fulgide, naphthopyran, quinone, chloride, halide, hydroxide, metal complex, coordination compound, dark color-changing mineral or a combination thereof.

7. The microneedle patch according to claim 1, characterized in that The biocompatible material includes hyaluronic acid, polyvinyl pyrrolidone, polyvinyl alcohol, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, pullulan, collagen, xanthan gum, pectin, polyglutamic acid, short-chain polypeptide, sodium alginate, maltodextrin, cyclodextrin, propylene glycol alginate, gelatin, gum arabic, methyl cellulose, polysaccharides, disaccharides, monosaccharides, polyols or a combination thereof.

8. The microneedle patch according to claim 1, characterized in that The amount of the thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance or the combination thereof accounts for 0.1-40 wt % of the microneedle layer material.

9. The microneedle patch according to claim 8, characterized in that The amount of the thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance or the combination thereof accounts for 2-35 wt % of the microneedle layer material.

10. The microneedle patch according to claim 9, characterized in that: The amount of the thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance or the combination thereof accounts for 10-25 wt % of the microneedle layer material.

11. The microneedle patch according to claim 1, characterized in that: The material of the microneedle layer further comprises a tattoo pigment, and the amount of the thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance, the tattoo pigment or a combination thereof accounts for 0.1-40wt% of the material of the microneedle layer.

12. The microneedle patch according to claim 11, characterized in that The tattoo pigment is further distributed on a plurality of microneedles located in the first area.

13. The microneedle patch according to claim 1, characterized in that: The thermochromic material, the photochromic material, the thermochromic substance, the photochromic substance or a combination thereof is further a component having a tattoo effect.

14. The microneedle patch according to claim 1, characterized in that: The first region has a pattern, and the first area of ​​the first region is smaller than the total area.

15. A method for manufacturing a microneedle patch, characterized in that: include: A mold is provided; the internal space of the mold includes a bottom surface, and a plurality of tapered holes are formed on the bottom surface, the tapered holes are spaced apart from each other and extend in a direction away from the bottom surface; Providing a biocompatible material; mixing a thermochromic material, a photochromic material or a combination thereof into the biocompatible material to form a first mixture; Distributing the first mixture to the mold to form a microneedle layer; the microneedle layer comprises a plurality of microneedles spaced apart from each other; Disposing a mask above the microneedle layer; the mask has a pattern area, and the pattern area is projected onto the microneedle layer; and A heat source, a cold source, a light source or a combination thereof is provided, and temperature change, light or a combination thereof is applied to the microneedle layer through the mask so that the microneedle layer displays a pattern; wherein the pattern corresponds to the pattern area of ​​the mask.

16. The method for manufacturing a microneedle patch according to claim 15, characterized in that: The amount of the thermochromic material, the photochromic material or the combination thereof accounts for 0.1-40 wt % of the first mixture.

17. The method for manufacturing a microneedle patch according to claim 15, wherein: The step of providing the biocompatible material further includes mixing a tattoo pigment into the first mixture to form a second mixture, and the amount of the thermochromic material, the photochromic material, the tattoo pigment or a combination thereof accounts for 0.1-40wt% of the second mixture.

18. The method for manufacturing a microneedle patch according to claim 15, characterized in that: The pattern area is further a hollow area on the mask.

19. The method for manufacturing a microneedle patch according to claim 15, wherein: The step of applying the temperature change to the microneedle layer through the mask further includes causing the thermochromic material to produce a thermochromic substance by temperature change; the step of applying the light to the microneedle layer through the mask further includes causing the photochromic material to produce a photochromic substance by light.

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