Microneedle assembly and method of manufacturing the same

Abstract

The present application relates to a microneedle assembly and a method for manufacturing the same. The microneedle assembly of the present application includes one or more microneedles, wherein the microneedle has an end located on at least one surface of the microneedle assembly and a tip protruding downward from the one end to extend to the end, and the one end of the microneedle and the tip have openings respectively to form a channel passing through the one end of the microneedle and the tip; and a storage component, at least a portion of which has one or more inner cavities for storing substances, and the inner cavity is located below the end of the tip. The microneedle assembly is configured so that the tip enters the inner cavity. The microneedle assembly can be used to transfer substances, and when a drug is stored in the inner cavity, the microneedle assembly can be used as a drug delivery device, which can be further used for self-disinfection, anti-bacteria, and blocking the spread of bacteria.

Description

Technical Field

[0001] Embodiments of the present application generally relate to microneedle assemblies and methods of making the same. Background Art

[0002] Microneedle assemblies are usually used for painless drug delivery. Microneedles are used to form openings at the drug-receiving site, and then the drug solution flows into the drug-receiving site through the opening. The microneedle structure and material have a great influence on the drug delivery effect. General microneedles have a cavity or microporous structure and can be dissolved in skin tissue fluid, blood, or water. When piercing the skin tissue, the microneedle degrades or dissolves to achieve the purpose of releasing the drug. The sustained release rate can be affected by pH value, temperature, etc. Due to the irreversibility of the microneedle function, the recyclability of the microneedle assembly is affected.

[0003] Therefore, the existing microneedle assembly and its manufacturing method need to be further improved. Summary of the invention

[0004] The present application provides a microneedle assembly and a method for manufacturing the same, in an attempt to solve at least one problem existing in the related art to at least some extent.

[0005] One embodiment of the present application provides a microneedle assembly, which includes one or more microneedles, the microneedle having one end located on at least one surface of the microneedle assembly and a tip protruding downward from the one end to the end, the length of the microneedle can be 1-300 microns, and the one end and the tip of the microneedle respectively have openings to form a channel that passes through the one end and the tip of the microneedle, and the width of the channel is 0.1-20 microns; and a storage component, at least a portion of which has one or more cavities for storing substances, the volume of the cavity is 01.-10000 cubic millimeters, and the cavity is located below the end of the tip, and the closest distance from the end to the cavity is 0.1-20 microns. The microneedle assembly is configured so that the tip enters the cavity.

[0006] Another embodiment of the present application further provides a drug delivery device, which includes the above-mentioned microneedle assembly, and a drug in the form of liquid or gaseous substance can be stored in the inner cavity.

[0007] Another embodiment of the present application also provides a drug administration method, which includes attaching the above-mentioned drug administration device to a site where drug administration is required, including the skin or the surface of a device; and pressing the drug administration device.

[0008] Another embodiment of the present application also provides a method for antibacterial and moisture-proofing, which includes placing the above-mentioned drug delivery device at a location where antibacterial and moisture-proofing is required, such as the inside of a shoe; and pressing the drug delivery device, in which the stored medicine is used for antibacterial and moisture-proofing.

[0009] Another embodiment of the present application further provides a self-disinfecting device, which includes the above-mentioned drug delivery device, wherein the above-mentioned medicine includes a disinfectant, such as alcohol.

[0010] Another embodiment of the present application provides a germ-proof equipment, which includes the self-disinfection device described above, wherein the self-disinfection device is attached to a part of the equipment that is easily pressed. The germ-proof equipment includes protective clothing, protective gloves or a protective box.

[0011] Another embodiment of the present application also provides a method for blocking the spread of germs, which includes: attaching the above-mentioned self-disinfection device to a component that is easy to spread germs, including a door handle, a button or a handrail; and pressing the self-disinfection device.

[0012] Another embodiment of the present application also provides a method for manufacturing the above-mentioned microneedle assembly, which includes separately manufacturing the above-mentioned one or more microneedles and the storage component; and attaching a side of the microneedle with a pointed end to at least one surface of the storage component, wherein manufacturing the microneedle includes manufacturing the microneedle using MEMS technology or LIGA process.

[0013] Another embodiment of the present application also provides a method for manufacturing a drug delivery device, wherein a drug is stored in an inner cavity; and a component defining one or more inner cavities and storing the drug is gelled using a reagent.

[0014] Compared with the prior art, the microneedle assembly provided in the embodiment of the present application has a simple structure, is easy to mass produce, can deliver substances in real time and on demand, and can especially realize multiple and repeated uses of the microneedle assembly for convenient and effective application in a variety of occasions, such as self-disinfection, antibacterial and moisture-proofing, and blocking the spread of pathogens. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The following will briefly describe the drawings necessary for describing the embodiments of the present application or the prior art to facilitate the description of the embodiments of the present application. Obviously, the drawings described below are only some of the embodiments in the present application. For those skilled in the art, without the need for creative work, drawings of other embodiments can still be obtained based on the structures illustrated in these drawings.

[0016] Figure 1 is a cross-sectional view of a microneedle assembly 10 according to some embodiments of the present application;

[0017] Figure 2 (a) to Figure 2 (c) is a schematic diagram of a microneedle 11 according to some embodiments of the present application;

[0018] Figure 3 (a)- Figure 3 (c) is a cross-sectional view of a microneedle assembly 10 for different applications including different storage components 12 according to some embodiments of the present application. DETAILED DESCRIPTION

[0019] The embodiments of the present application will be described in detail below. In the full text of the present application specification, the same or similar components and components with the same or similar functions are represented by similar reference numerals. The embodiments of the accompanying drawings described herein are illustrative, graphical, and are used to provide a basic understanding of the present application. The embodiments of the present application should not be interpreted as limiting the present application.

[0020] As used herein, the terms "substantially", "substantially", "substantially", and "approximately" are used to describe and illustrate small variations. When used in conjunction with an event or situation, the term may refer to an example in which the event or situation occurs precisely and an example in which the event or situation occurs very approximately. For example, when used in conjunction with a numerical value, the term may refer to a range of variation less than or equal to ±10% of the numerical value, such as less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%. For example, if the difference between two numerical values ​​is less than or equal to ±10% of the mean value of the values ​​(e.g., less than or equal to ±5%, less than or equal to ±4%, less than or equal to ±3%, less than or equal to ±2%, less than or equal to ±1%, less than or equal to ±0.5%, less than or equal to ±0.1%, or less than or equal to ±0.05%), then the two numerical values ​​may be considered to be "substantially" the same.

[0021] In this specification, unless otherwise specified or limited, relative terms such as "central", "longitudinal", "lateral", "front", "rear", "right", "left", "inner", "outer", "lower", "higher", "horizontal", "vertical", "above", "below", "above", "below", "top", "bottom" and their derivative terms (such as "horizontally", "downwardly", "upwardly", etc.) should be interpreted as referring to the directions described in the discussion or depicted in the drawings. These relative terms are only used for convenience of description and do not require that the present application be constructed or operated in a specific direction.

[0022] In addition, sometimes amounts, ratios and other numerical values ​​are presented in range format herein. It should be understood that such range format is for convenience and brevity, and should be flexibly understood to include not only the numerical values ​​explicitly specified as range limits, but also all individual numerical values ​​or sub-ranges encompassed within the range, as if each numerical value and sub-range were explicitly specified.

[0023] In the detailed description and claims, a list of items connected by the terms "at least one of," "at least one of," "at least one of," "at least once," or other similar terms may mean any combination of the listed items. For example, if items A and B are listed, the phrase "at least one of A and B" means only A; only B; or A and B. In another example, if items A, B, and C are listed, the phrase "at least one of A, B, and C" means only A; or only B; only C; A and B (excluding C); A and C (excluding B); B and C (excluding A); or all of A, B, and C. Item A may include a single element or multiple elements. Item B may include a single element or multiple elements. Item C may include a single element or multiple elements.

[0024] The embodiment of the present application further improves the microneedle assembly, and the improved microneedle assembly may include one or more microneedles, wherein the microneedle has an end located on at least one surface of the microneedle assembly and a tip extending downward from the one end to the end, and the one end and the tip of the microneedle respectively have openings to form a channel passing through the one end and the tip of the microneedle; and a storage component, at least a portion of which has one or more cavities for storing substances, and the cavities are located below the end of the tip. The microneedle assembly is configured so that the tip enters the cavity.

[0025] The following will be combined Figure 1-Figure 3 (c) To further illustrate the structure of the microneedle assembly in various embodiments of the present application, its material composition, preparation method, and drug delivery device based on the microneedle assembly and its application.

[0026] Figure 1 is a cross-sectional view of a microneedle assembly 10 according to some embodiments of the present application.

[0027] like Figure 1 As shown, the microneedle assembly 10 according to some embodiments of the present application includes one or more microneedles 11 and a storage component 12. The microneedle 11 has an end 11b located on at least one surface of the microneedle assembly 10 and a tip 11a extending downward from the end to a terminal 11c. The tip 11a and the end 11b of the microneedle 11 have openings 18 and 19 respectively to form a channel 20 that passes through the tip 11a and the end 11b of the microneedle 11.

[0028] At least a portion of the storage member 12 has one or more inner cavities 13 for storing substances, and the inner cavities 13 are located below the distal end 11c of the tip 11a.

[0029] The microneedle assembly 10 is configured, such as by pressing or other stimulations, such as heating, cooling, illumination, etc. For example, one end 11b of the microneedle is stimulated as described above, so that the tip 11a moves toward the inner cavity 13, or the storage component is stimulated as described above, so that the inner cavity moves toward the end 11c, which can cause the tip 11a to enter the inner cavity 13, thereby realizing that the channel 20 is connected to the inner cavity 13, so that the microneedle assembly 10 can deliver substances between the inner cavity 13 and the opening 19 through the channel 20, for example, injecting the required substance into the inner cavity 13 through the opening 19 through the channel 20, or storing the required substance, such as medicine, in the inner cavity 13 and delivering it to the part in contact with the opening 19 through the channel 20. The microneedle assembly 10 with medicine stored in the inner cavity can be used as a drug delivery device.

[0030] According to some embodiments of the present application, the entire surface of the storage component (not shown in the figure) may be provided with microneedles 11, so that one or more cavities 13 are surrounded by the microneedles 11. When the microneedle assembly 10 is configured so that the tip 11a enters the cavity 13, the channel 20 is connected with the cavity 13, so that the microneedle assembly 10 can deliver substances between the opening 19 and the cavity 13.

[0031] Figure 2 (a)- Figure 2 (c) is a schematic diagram of a microneedle 11 according to some embodiments of the present application.

[0032] According to some embodiments of the present application, the material of the microneedle 11 can be an organic material such as methyl methacrylate, an inorganic material such as silicon dioxide, or an organic-inorganic composite. Figure 2 As shown in (a), the microneedle 11 can be a single-channel hollow structure with two ends open, cylindrical, square, conical, or a mixed structure thereof; Figure 2 As shown in (b), the microneedle 11 can also be a solid structure in the middle and a hollow structure on the outer edge, or a multi-channel hollow structure such as a multi-channel hollow structure of a lotus root section, but is not limited thereto. The end 11c of the microneedle 11 can be a flat tip structure (capillary tip shape), a single oblique tip structure (syringe needle tip shape), or an oblique tip combination structure; Figure 2 As shown in (c), the microneedle 11 may be a single-channel hollow structure with openings at both ends, and the opening 18 of the tip 11a is located at a certain distance from the end 11c of the tip.

[0033] The microneedle 11 can be prepared by a variety of methods, such as the template method, which usually uses a silicon wafer as a substrate, but is not limited to a silicon wafer. The microneedle structure is etched on the surface of the silicon wafer through micro-electromechanical system (MEMS) processing technology. The process mainly includes: thermal oxidation, photolithography, bulk etching, semiconductor etching process technology (ICP), reactive ion deep etching (RIE), etc.

[0034] According to some embodiments of the present application, a cylindrical groove array is etched on the surface of a silicon wafer by photolithography technology, each groove has a depth of about 1-300 microns, a diameter of 0.1-20 microns, and the grooves are spaced 0.01-1000 mm apart. Another silicon wafer is selected, and a cylindrical protrusion array is etched on the surface, each protrusion has a height of about 1-300 microns and a diameter of 0.1-20 microns. On the silicon template of the cylindrical groove array, an organic material or an inorganic material or an organic-inorganic composite material such as a polymethyl methacrylate (PMMA) melt is evenly laid. Before the solution is completely cooled, the silicon template with a cylindrical protrusion array on the surface is covered on the surface of the PMMA layer with the protrusion array surface to ensure that the protrusion array and the groove array completely overlap. After complete cooling and molding, the template is removed to obtain a PMMA film with an array structure of microneedles 11. The height of the microneedle 11 is about 1-300 microns, for example, about 10-20 microns; the diameter is about 0.1-20 microns, for example, the diameter is about 1-2 microns; the thickness of the other end 11b of the microneedle 11 is about 1-100 microns, for example, about 10-20 microns, and there is an opening 18 with a diameter of about 0.1-20 microns about 0.1-10 microns away from the end 11c.

[0035] According to some embodiments of the present application, another method for preparing the microneedle 11 is through the LIGA process, and the process may include: bonding a 1-400 micron thick PMMA sheet to a titanium and silicon substrate, and etching with X-rays to directly form a microneedle layer having microneedles 11, wherein a plurality of microneedles are spaced 0.01-1000 mm apart from each other, for example, 0.1-1 mm apart from each other. The method is not limited to preparing PMMA microneedle layers, and can be extended to a variety of processing materials, such as metals, ceramics, glass, plastics, and composites of these materials.

[0036] According to some embodiments of the present application, for a specific application, the storage component 12 can be prepared by the following method:

[0037] Preparation of template A: By photolithography, a protrusion array is etched on the surface of a silicon wafer. The size of the array is not specifically limited, and the protrusion structure can be one or more shapes such as round, square, triangle, or a mixture thereof. Each protrusion is about 1-1000 microns in height, about 0.01-1000 square millimeters in cross-sectional area, and about 0-1000 microns apart from each other.

[0038] Preparation of template B: By photolithography, a groove array is etched on the surface of a silicon wafer. The size of the array is not specifically limited, and the groove structure can be one or more shapes such as circular, square, triangular, or a mixture thereof. The groove depth is about 1-300 microns, and the interval between the grooves is about 0-1000 microns, for example, about 10-20 microns, and the interval between the grooves is about 10-50 microns.

[0039] Preparation of the first component 14 whose surface includes a groove array: a uniform mixed solution composed of polydimethylsiloxane (PDMS) and a small amount of curing agent is evenly spread on a template A, the ratio of PDMS to curing agent is about 10:1, the curing temperature is about 45°C ~ 85°C, and the curing time is about 1-24h. The template is removed to obtain a PDMS layer with a groove array structure on one surface. The shape, depth, and cross-sectional area of ​​the grooves can all be determined by the template. For example, the film thickness of the grooves is about 1-1010 microns, the depth of each groove is about 1-1000 microns, the cross-sectional area of ​​each groove is 0.01-1000 square millimeters, and the grooves are spaced about 0-1000 microns apart.

[0040] According to some embodiments of the present application, the material of the first component 14 may also be selected from at least one of glass, silicon, silicon dioxide and a combination thereof.

[0041] Preparation of the second component 15 (which also has grooves between the protrusions) having a surface comprising a protrusion array: a uniform mixed solution such as PDMS and a small amount of curing agent is evenly spread on the template B, the ratio of PDMS to curing agent is about 10:1, the curing temperature is about 45°C to 85°C, and the curing time is about 1-24 hours. The template is removed to obtain a PDMS layer having a protrusion array structure on one surface. The shape, depth, and cross-sectional area of ​​the protrusions are all determined by the template. For example, the protrusion depth is about 1-300 microns, and the spacing between each other is about 0-1000 microns to form grooves for accommodating the microneedles 11.

[0042] Assemble the first component 14 and the second component 15 to prepare the inner cavity 13: Evenly apply a uniform mixed solution composed of PDMS and a curing agent on the groove array surface of the first component 14 and the smooth surface of the second component 15, that is, the reverse surface containing the protrusion array, so that they fit together, thereby forming the inner cavity 13, as shown in FIG. Figure 3 (a) shown.

[0043] It should be understood that the materials of the first component 14 and the second component 15 used in the present application are not particularly limited, and can be prepared using materials, structures and manufacturing methods known in the art, and are not limited to the materials, structures and manufacturing methods in the above-mentioned embodiments. The materials, structures and manufacturing methods of the above-mentioned embodiments are only exemplary embodiments used to illustrate several materials, structures and manufacturing methods used to form the storage component 12 in the present application. According to other embodiments of the present application, the storage component 12 can also be prepared by other materials, structures and manufacturing methods.

[0044] According to another embodiment of the present application, for certain specific applications, a required substance can be stored in the inner cavity 13 to be transferred between the inner cavity 13 and the opening 19 through the channel 20 of the microneedle 11. For example, the microneedle assembly 10 can be used as a drug delivery device for a target site. The corresponding drug delivery method is: Figure 3 As shown in (a), the drug is first stored in the inner cavity 13; the other end 11b of the microneedle 11 is attached to the target site where the drug is to be administered, such as the skin or a device; the component 10 is configured, such as by pressing or other actions that can stimulate the component 10 so that the tip 11a pierces the third component 12a to enter the inner cavity 13; the capillary action is used to transfer the drug in the inner cavity 13 through the channel 20 to the site where the drug is to be administered that contacts the opening 19 on the other end 11b of the microneedle 11, thereby achieving on-demand drug administration at the target site.

[0045] According to some embodiments of the present application, the third component 12a can have a self-recovery force for the deformation caused by the tip 11a penetrating its upper and lower surfaces. When the pressure or other stimulation is removed, the component forming the inner cavity 13 can return to its original state, so that the medicine in the inner cavity 13 will not flow out, thereby allowing the tip 11a to enter and exit the inner cavity 13 multiple times, thereby achieving multiple connections or separations between the channel 20 and the inner cavity 13, and the medicine in the inner cavity 13 can continue to be stored after the tip 11a leaves the inner cavity 13, thereby achieving repeated and effective on-demand drug delivery of the drug delivery device.

[0046] According to some embodiments of the present application, a disinfectant may be stored in the inner cavity 13 to achieve self-disinfection of the microneedle assembly 10 , and the microneedle assembly 10 may also be used to disinfect a target site.

[0047] For example, according to the above-mentioned embodiment of the present application, about 75% alcohol can be injected into the groove of the first component 14, and then the smooth surface of the second component 15 is tightly attached to the groove surface of the first component 14. After thermal curing for about 50-120 minutes, a storage component containing alcohol load is obtained.

[0048] It should be understood that the substance is not limited to 75% alcohol solution. In the above embodiment, alcohol is injected into the groove of the first component 14 so that the alcohol solution is stored in the inner cavity, which is only an exemplary embodiment for illustrating one structure of the storage component of the present application. According to other embodiments of the present application, the storage component 12 can also store other required solutions, such as hydrogen peroxide, 84 disinfection, and aqueous or organic solutions for solid drug preparation.

[0049] According to some embodiments of the present application, the inner cavity 13 may also seal gaseous substances such as ethylene oxide, gaseous hydrogen peroxide, formaldehyde, ozone, etc.

[0050] According to some embodiments of the present application, the method for manufacturing the microneedle assembly 10 includes surface treatment and seamless bonding of the microneedles 11 and the storage component 12 .

[0051] According to some embodiments of the present application, the surface treatment of the microneedle includes using plasma cleaning technology to clean the surface of the PMMA film containing the microneedle structure for 10-50 seconds, and then evenly applying a layer of a uniform mixed solution consisting of PDMS and a curing agent by a casting method under a microscope, taking care to avoid clogging the microneedle holes.

[0052] The surface treatment of the storage component includes using plasma cleaning technology, for example, cleaning the surface of the protrusion array in the above embodiment for 10-50 seconds, and then horizontally contacting the protrusion array surface with the surface of a uniform mixed solution of PDMS and a curing agent under a microscope. This process only treats the protrusion array tip.

[0053] According to some embodiments of the present application, the seamless bonding of the microneedle and the storage component includes a dust-free operating environment and the assistance of a microscope. For example, in the above embodiment, the tip surface of the microneedle is closely bonded to the convex array surface of the second component 15, so that the second component 15 can accommodate the tip of the microneedle, thereby achieving the misaligned engagement of the microneedle array and the convex array to obtain the microneedle assembly 10. The groove of the first component 14 and a portion of the second component 15 together form an inner cavity 13, and a portion of the second component 15 is located between the end 11c and the inner cavity 13.

[0054] Another embodiment of the present application provides another method for preparing the storage component 12 for a specific application, such as a hollow microsphere encapsulation method.

[0055] A gel film is prepared by a photo-initiated free radical polymerization reaction, wherein the monomer material composition includes acrylamide, alginate, N,N'-methylenebisacrylamide, and ammonium persulfate, and their weight ratio is about 1-10:1-10:0.02-0.2:0.02-0.2. The thickness of the composite gel film is about 0.1-5 mm. The prepared gel film is cut into one or more circles, and the diameter is about, for example, 0.1 mm. A solution containing copper sulfate, hydrogen peroxide, and tris(hydroxymethyl)aminomethane / hydrochloric acid buffer with a pH of 7.5 is prepared, and the mass ratio of copper sulfate to hydrogen peroxide is about 4:1-25. The gel circles prepared above are immersed in a solution with a pH of 7.5, and reacted at room temperature for about 50-120 min to prepare one or more hollow gel microspheres with one or more inner cavities, such as Figure 3As shown in (b) (only one microsphere is shown for illustration), one of the microspheres can be formed by enclosing the inner cavity 13 by the fourth component 16. The thickness of each microsphere can be about 1-1000 microns, for example, about 10-100 microns, and a part of the microsphere is located between the end 11c and the inner cavity 13. The microspheres are taken out, treated with calcium chloride aqueous solution, and placed in deionized water for storage.

[0056] It should be understood that the microspheres are not limited to gel materials. The hollow gel microspheres in the above embodiment are only used to illustrate an exemplary embodiment of one of the storage components of the present application. According to other embodiments of the present application, the storage component 12 can also include other materials, structures and shapes that can form an inner cavity, such as materials that are sensitive to light and heat.

[0057] According to some embodiments of the present application, a desired substance can be added to the inner cavity for a specific application. For example, for an application in which the microneedle assembly 10 is used to kill germs, a disinfectant can be added to the inner cavity. For example, 75% medical alcohol can be used for virus inhibition and killing. In the above embodiment, one or more microspheres are dispersed in 10-1000 mL 75% medical alcohol, ultrasonicated for 30-60 minutes, the air in the microspheres is removed, and alcohol is loaded to obtain microspheres containing alcohol.

[0058] It should be understood that the drug loading method is not limited to 75% alcohol solution. Although in the above embodiment, one or more microspheres are dispersed in a certain concentration of alcohol so that the alcohol solution is stored in the inner cavity 13, this is only an exemplary embodiment for illustrating one structure of the drug storage component 12 of the present application. According to other embodiments of the present application, the drug storage component 12 can also store other required solutions, such as hydrogen peroxide, 84 disinfection, and aqueous solutions or organic solutions for solid drug configuration.

[0059] Subsequently, about 0.1-100 g of agarose can be dissolved in about 10-500 mL of deionized water by microwave heating, and when the solution temperature drops to about 30 °C, about 1-100 mL of agarose aqueous solution is mixed evenly with one or more microspheres loaded with alcohol, and the film is quickly spread. When the agarose solution drops to room temperature, it immediately gels and firmly fixes one or more microspheres, thereby preparing a film containing microspheres loaded with alcohol, with a thickness ranging from about 10 to 1000 microns. Figure 3 As shown in (b), the inner cavity 13 formed by the microspheres may be further surrounded by a fifth component 22 to support one or more microspheres.

[0060] According to some embodiments of the present application, the storage component 12 may further include a sixth component for supporting and fixing the microneedles, such as Figure 3The sixth component 17 in (b) has a groove that can accommodate the tip 11a of the microneedle 11. When the tip 11a of the microneedle 11 is configured to enter the inner cavity 13, the sixth component 17 can restore the inner cavity 13 to its original state after the configuration is removed, or restore the tip 11a of the microneedle 11 to its original state. The material composition of the sixth component 17 can be an organic elastomer material such as styrene-butadiene rubber (SBR), an inorganic material such as a nanofiber network structure assembly, an organic-inorganic composite, or an organic-inorganic aerogel material such as graphene aerogel.

[0061] According to some embodiments of the present application, the sixth component 17 and the fourth component 16 enclosing the inner cavity 13 may be made of the same material. The sixth component 17 may have a mesh structure that does not block the tip 11a from entering the inner cavity 13. The mesh structure is limited by the arrangement of the microneedles, and its thickness is equivalent to the height of the microneedles, but not greater than the height of the microneedles. For example, the thickness of the sixth component is equal to the height of the microneedles.

[0062] For example, the sixth component 17 can be prepared by laser cutting, such as PDMS, but not limited thereto. PDMS has a grid structure, each grid size is about 1-100 mm x 1-100 mm, the adjacent spacing between grids is about 0.1-10 mm, and the thickness of the sixth component is about 1-300 microns. The surface of the sixth component of the grid-like PDMS opposite to the side with the groove is attached to the surface of the microsphere film, thereby obtaining the storage component 12.

[0063] It should be understood that the microneedles and storage components used in the present application are not particularly limited, and for specific applications, they can be prepared using materials, structures, and manufacturing methods known in the art, and are not limited to the materials, structures, and manufacturing methods in the above embodiments. The materials, structures, and manufacturing methods in the above embodiments are only exemplary embodiments for illustrating several materials, structures, and manufacturing methods used in the microneedle assembly 10 of the present application, for specific applications.

[0064] According to other embodiments of the present application, the microneedle assembly 10 may also have other structures, for example, one or more inner cavities 13 may be interconnected and connected to a larger storage cavity 21 to provide a continuous supply of substances to one or more inner cavities 13, such as Figure 3 (c) shown.

[0065] Another embodiment of the present application also provides an application method of the microneedle assembly 10. For example, a substance for antibacterial and moisture-proofing can be stored in the inner cavity 13, and the microneedle assembly 10 can be placed in a location that requires antibacterial and moisture-proofing, such as the inside of a shoe. By continuously stepping on the sole, the microneedle assembly 10 continuously releases the antibacterial and moisture-proof substance, thereby keeping the foot clean and sterile.

[0066] Another embodiment of the present application also provides a method for blocking the spread of germs, which includes storing a drug for killing germs in the inner cavity of the microneedle assembly described above to make a drug delivery device, and attaching the drug delivery device to a component that is easy to spread germs, such as various instrument operation buttons, elevator buttons, door handles, handrails and other public facilities that are frequently touched, or shoe soles; when the user touches a component that is easy to spread germs, the drug delivery device will be pressed from time to time. When the drug delivery device is pressed, the drug for killing germs will penetrate the surface of the component from time to time, thereby killing the germs in real time, blocking the spread of germs, and eliminating the risk of infection for the user.

[0067] Another embodiment of the present application further provides an anti-germ equipment, such as protective clothing, protective gloves or protective boxes, in which a microneedle assembly with disinfectant stored in the inner cavity is placed in the part that is easily touched and pressed, so that when the equipment touches and presses parts that are easy to spread germs, such as touching various instrument operation buttons, elevator buttons, door handles, handrails and other public facilities that are frequently touched, the disinfectant will penetrate into the surface of the part from time to time, thereby killing the germs in real time and blocking the spread of germs. At the same time, the equipment can be recycled and the risk of infection is eliminated.

[0068] The microneedle assembly disclosed in the embodiments of the present application is a new type of material delivery structure, which has the characteristics of miniaturization, mass production, and multiple reuse, and can be effectively used in, for example, the field of drug release to achieve real-time and on-demand drug delivery to the target site.

[0069] Another embodiment of the present application provides a test for a drug release application based on a microneedle assembly 10. A microneedle assembly with alcohol stored in the inner cavity is attached to the smooth surface of a component and pressed with a finger. Alcohol exudates from the surface of the component. After the pressure is removed for about 10 minutes, the exudates evaporate completely. The controllability of the microneedle assembly over drug release is tested by repeated pressing, with the removal of pressure and no more alcohol release as the test standard. The results show that the microneedle assembly can effectively release drugs more than 1,000 times under repeated pressing until the alcohol is completely released.

[0070] It should be understood that the drug delivery device described above is not limited to responding to external forces, such as pressing or stepping. Although the drug delivery device in the above embodiment is pressed, so that the tip of the microneedle can enter and exit the inner cavity multiple times to connect the channels at both ends of the microneedle with the inner cavity, thereby achieving substance transfer, this is only an exemplary embodiment for illustrating one structure of the drug delivery device of the present application. According to other embodiments of the present application, the drug delivery device can also respond to other stimuli, such as heating, cooling, light, etc., so that the tip 11a of the microneedle 11 of the microneedle assembly 10 can enter and exit the inner cavity 13 multiple times, so that the channel 20 and the inner cavity 13 can be connected or separated multiple times.

[0071] The technical content and technical features of this application have been disclosed as above, but those skilled in the art may still make various substitutions and modifications based on the teachings and disclosures of this application without departing from the spirit of this application. Therefore, the protection scope of this application should not be limited to the contents disclosed in the embodiments, but should include various substitutions and modifications that do not depart from this application, and are covered by the claims of this patent application.

Claims

1. A microneedle assembly comprising: One or more microneedles, each of which has an end located on at least one surface of the microneedle assembly and a tip protruding downward from the end to extend to a distal end, and each of the end of the microneedle and the tip has an opening to form a channel passing through the end of the microneedle and the tip; as well as The storage component has at least a portion thereof having one or more cavities for storing substances, and the cavities are located below the distal end of the tip. The microneedle assembly is configured to allow the tip to enter the inner cavity, wherein the microneedle assembly is configured to allow the tip to enter the inner cavity in response to at least one of the following stimuli: light, heating, cooling, and external force. 2 . The microneedle assembly according to claim 1 , wherein the reservoir member comprises a first member located between the distal end of the tip and the inner cavity to define at least a portion of the inner cavity. The microneedle assembly according to claim 2 , wherein the thickness of the first component is not greater than the length of the microneedle. 4 . The microneedle assembly according to claim 2 , wherein the first component has a self-restoring force against deformation caused by the tip penetrating through the upper and lower surfaces thereof. The microneedle assembly according to claim 2 , wherein the first component is an elastic material. 6 . The microneedle assembly according to claim 2 , wherein the material of the first component is at least one selected from the group consisting of a polymer of acrylamide and N,N′-vinylbisacrylamide, nanofiber, polydimethylsiloxane (PDMS), and combinations thereof. The microneedle assembly according to claim 1 , wherein the microneedle assembly is configured to allow the channel to be connected to or separated from the inner cavity multiple times. The microneedle assembly according to claim 1 , wherein the microneedle assembly is configured to allow the tip of the microneedle to enter and exit the inner cavity multiple times. 9 . The microneedle assembly according to claim 1 , wherein the storage component further comprises a second component having a groove forming the inner cavity. 10 . The microneedle assembly according to claim 1 , wherein the storage member further comprises a third member having a recess for accommodating the tip of the microneedle. The microneedle assembly according to claim 10 , wherein the third component is an elastic material.

12. The microneedle assembly of claim 2, wherein the first component defines the inner cavity. 13 . The microneedle assembly according to claim 2 , wherein the storage component further comprises a fourth component, and the fourth component is used to support the first component.

14. The microneedle assembly of claim 2, wherein the first component and the one or more cavities constitute one or more microspheres.

15. The microneedle assembly according to claim 1, wherein the storage component further comprises a storage cavity communicating with the one or more inner cavities.

16. A drug delivery device, comprising the microneedle assembly according to any one of claims 1 to 15, wherein the drug is stored in the inner cavity.

17. The drug delivery device of claim 16, wherein the drug comprises a liquid or gaseous substance.

18. An anti-bacteria device, comprising the drug delivery device according to claim 17, wherein the drug is used to kill bacteria, and the drug delivery device is attached to a part of the device that is easily pressed.

19. The germ protection equipment according to claim 18, comprising protective clothing, protective gloves or a protective box.

20. A method for manufacturing a microneedle assembly, comprising: Manufacturing one or more microneedles and a storage component in a microneedle assembly according to any one of claims 1 to 15; as well as The side of the microneedle having a pointed end is attached to at least one surface of the storage component.

21. The method of claim 20, wherein manufacturing the storage component comprises: A first component is fabricated having a tip that houses the one or more microneedles.

22. The method of claim 20, wherein manufacturing the storage component comprises: manufacturing a substrate having a groove; And the two substrates are offset and bonded together.

23. The method of claim 20, wherein manufacturing the storage component comprises preparing one or more microspheres.

24. The method of claim 23, wherein manufacturing the storage component further comprises forming a second component supporting the one or more microspheres to form a microsphere film.

25. The method of claim 24, wherein manufacturing the storage component further comprises: preparing a third component; and The third component is attached to the surface of the microsphere film.

26. A method for manufacturing a drug delivery device, comprising the method for manufacturing a microneedle assembly according to claim 20; storing a drug in the inner cavity; and gelling a component defining the one or more inner cavities in which the drug is stored using a reagent.

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