CN111388861A

CN111388861A - Microneedle assembly and method for manufacturing same

Info

Publication number: CN111388861A
Application number: CN202010304589.XA
Authority: CN
Inventors: 张利东
Original assignee: East China Normal University
Current assignee: East China Normal University
Priority date: 2020-04-17
Filing date: 2020-04-17
Publication date: 2020-07-10

Abstract

The present application relates to microneedle assemblies and methods of making the same. A microneedle assembly of the present application comprises one or more microneedles having an end on at least one surface of the microneedle assembly and a tip protruding downward from the end to an end, and having openings on the end and the tip, respectively, to form a channel through the end and the tip of the microneedle; and a storage component having at least a portion with one or more lumens for storing a substance, the lumens being located below the tip end. Wherein the microneedle assembly is configured to enter the tip into the lumen. The microneedle assembly can be used to deliver a substance and, when a drug is stored in the interior chamber, can be used as a drug delivery device for further self-disinfection, pathogen protection, and blocking of pathogen transmission.

Description

Microneedle assembly and method for manufacturing same

Technical Field

Embodiments of the present application relate generally to microneedle assemblies and methods of making the same.

Background

The micro-needle assembly is generally applied to painless drug delivery, an opening is formed at a drug receiving part by utilizing a micro-needle, then a liquid medicine flows into the drug receiving part through the opening, wherein the structure and the material of the micro-needle have great influence on the drug delivery effect, the general micro-needle has a cavity or a micropore structure, can be dissolved in skin tissue liquid, blood or water, and can be degraded or dissolved when penetrating into the skin tissue to achieve the purpose of releasing the drug, the slow release speed can be influenced by pH value, temperature and the like, and the recycling performance of the micro-needle assembly is influenced due to the irreversibility of the function of the micro-needle.

Accordingly, further improvements are needed in the art of microneedle assemblies and methods of making the same.

Disclosure of Invention

The present application provides a microneedle assembly and a method of manufacturing the same in an attempt to solve at least one of the problems existing in the related art to at least some extent.

An embodiment of the present application provides a microneedle assembly, which includes one or more microneedles 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, wherein the length of the microneedles may be 1-300 micrometers, and the one end and the tip of the microneedles respectively have openings to form a channel penetrating through the one end and the tip of the microneedles, and the width of the channel is 0.1-20 micrometers; and a storage component, at least a portion of which has one or more cavities for storing a substance, the cavities having a volume of 01 DEG-10000 cubic millimeters and being located below the tip of the tip, the tip being located at a closest distance of 0.1-20 micrometers from the cavity. Wherein the microneedle assembly is configured to have a tip enter the lumen.

Another embodiment of the present application also provides a drug delivery device comprising the microneedle assembly described above, wherein a drug of a liquid or gaseous substance can be stored in the lumen.

Another embodiment of the present application further provides a drug delivery method, which comprises attaching the drug delivery device to a site to be administered, including skin or equipment surface; and pressing the drug delivery device.

Another embodiment of the present application further provides a method for inhibiting bacteria and preventing moisture, which comprises placing the drug delivery device in a position requiring bacteria and preventing moisture, such as the inside of a shoe; and a pressing administration device, wherein the stored medicine is used for bacteriostasis and moisture protection.

Another embodiment of the present application also provides a self-disinfecting device comprising an administration device as described above, wherein said device comprises a disinfecting liquid, such as alcohol.

Another embodiment of the present application further provides an anti-microbial device, which includes the self-disinfecting device, wherein the self-disinfecting device is attached to a portion of the device, which is easily pressed. The anti-bacteria equipment comprises protective clothing, protective gloves or protective boxes.

Another embodiment of the present application also provides a method for blocking transmission of pathogens, comprising: the self-disinfection device is attached to a part which is easy to transmit pathogenic bacteria, and comprises a door handle, a button or a support rod; and a press self-disinfecting device.

Another embodiment of the present application also provides a method of manufacturing the microneedle assembly, which includes manufacturing the one or more microneedles and the storage member, respectively, and attaching one surface of the microneedles having the sharp ends to at least one surface of the storage member, wherein manufacturing the microneedles includes manufacturing the microneedles using a MEMS technology or an L IGA process.

Another embodiment of the present application also provides a method of manufacturing a drug delivery device, storing a drug in a lumen; and gelling the member defining the one or more lumens in which the drug is stored using the agent.

Compared with the prior art, the micro-needle assembly provided by the embodiment of the application has the advantages of simple structure, easiness in batch production, capability of conveying substances in real time as required, and especially capability of realizing multiple times and repeated use of the micro-needle assembly so as to be conveniently and effectively applied to various occasions, such as self-disinfection, bacteriostasis, moisture prevention, germ transmission blocking and the like.

Drawings

Drawings necessary for describing embodiments of the present application or the prior art will be briefly described below in order to describe the embodiments of the present application. It is to be understood that the drawings in the following description are only some of the embodiments of the present application. It will be apparent to those skilled in the art that other embodiments of the drawings can be obtained from the structures illustrated in these drawings without the need for inventive work.

Fig. 1 is a cross-sectional view of a microneedle assembly 10 according to some embodiments of the present application;

fig. 2 (a) to 2 (c) are schematic views of microneedles 11 according to some embodiments of the present application;

fig. 3 (a) -3 (c) are cross-sectional views of microneedle assemblies 10 for different applications including different reservoir components 12 according to some embodiments of the present application.

Detailed Description

Embodiments of the present application will be described in detail below. Throughout the specification, the same or similar components and components having the same or similar functions are denoted by like reference numerals. The embodiments described herein with respect to the figures are illustrative in nature, are diagrammatic in nature, and are used to provide a basic understanding of the present application. The embodiments of the present application should not be construed as limiting the present application.

As used herein, the terms "substantially", "substantially" and "about" are used to describe and illustrate minor variations. When used in conjunction with an event or circumstance, the terms can refer to instances where the event or circumstance occurs precisely as well as instances where the event or circumstance occurs in close proximity. For example, when used in conjunction with numerical values, the term can refer to a range of variation that is less than or equal to ± 10% of the stated 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, two numerical values are considered to be "substantially" identical if the difference between the two numerical values is less than or equal to ± 10% (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%) of the mean of the values.

In this specification, unless specified or limited otherwise, relative terms such as: terms of "central," "longitudinal," "lateral," "front," "rear," "right," "left," "inner," "outer," "lower," "upper," "horizontal," "vertical," "above," "below," "top," "bottom," and derivatives thereof (e.g., "horizontally," "downwardly," "upwardly," etc.) should be construed to refer to the orientation as then described in the discussion or as shown in the drawing figures. These relative terms are for convenience of description only and do not require that the present application be constructed or operated in a particular orientation.

Additionally, amounts, ratios, and other numerical values are sometimes presented herein in a range format. It is to be understood that such range format is used for convenience and brevity, and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited.

In the detailed description and claims, a list of items connected by the terms "at least one of," "at least one time," 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 a only; 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 a only; or only B; only C; a and B (excluding C); a and C (excluding B); b and C (excluding A); or A, B and C. Item a may comprise a single element or multiple elements. Item B may comprise a single element or multiple elements. Item C may comprise a single element or multiple elements.

In a further improvement of the microneedle assembly according to the embodiments of the present application, the modified microneedle assembly may include one or more microneedles having one end located on at least one surface of the microneedle assembly and a tip protruding downward from the one end to an end, and the one end and the tip of the microneedles are respectively provided with openings to form a channel penetrating through the one end and the tip of the microneedles; and a storage component having at least a portion with one or more lumens for storing a substance, the lumens being located below the tip end. Wherein the microneedle assembly is configured to enter the tip into the lumen.

The structure of the microneedle assembly and its material composition, preparation method, and drug delivery device based on the microneedle assembly and its application in various embodiments of the present application will be further described with reference to fig. 1-3 (c).

Fig. 1 is a cross-sectional view of a microneedle assembly 10 according to some embodiments of the present application.

As shown in fig. 1, a microneedle assembly 10 according to some embodiments of the present application includes one or more microneedles 11 and a reservoir 12. The microneedle 11 has an end 11b located on at least one surface of the microneedle assembly 10 and a tip 11a protruding downward from the end to a distal end 11c, and the tip 11a and the end 11b of the microneedle 11 have

openings

18 and 19, respectively, to form a channel 20 extending through the tip 11a and the end 11b of the microneedle 11.

At least a portion of the storage component 12 has one or more cavities 13 for storing a substance, the cavities 13 being located below the end 11c of the tip 11 a.

The microneedle assembly 10 is configured, such as pressed or otherwise energized, such as heated, cooled, illuminated, etc., such that one end 11b of the microneedle is energized as described above, such that the tip 11a moves toward the lumen 13, or the reservoir component is energized as described above, such that the lumen moves toward the end 11c, which may cause the tip 11a to enter the lumen 13, thereby placing the passageway 20 in communication with the lumen 13, such that the microneedle assembly 10 may deliver a substance between the lumen 13 and the opening 19 through the passageway 20, e.g., by injecting a desired substance through the opening 19 into the lumen 13 via the passageway 20, or by storing a desired substance, such as a drug, in the lumen 13 via the passageway 20 to a location in contact with the opening 19. The microneedle assembly 10 having a drug stored in its interior cavity may be used as a drug delivery device.

According to some embodiments of the present application, all surfaces (not shown) of the reservoir component may be provided with microneedles 11 such that one or more lumens 13 are surrounded by microneedles 11. When the microneedle assembly 10 is configured such that the tip 11a enters the lumen 13, the channel 20 is in communication with the lumen 13 such that the microneedle assembly 10 can deliver a substance between the opening 19 and the lumen 13.

Fig. 2 (a) -2 (c) are schematic views of microneedles 11 according to some embodiments of the present application.

According to some embodiments of the present application, the material of the microneedles 11 may be an organic material such as methyl methacrylate, an inorganic material such as silica, or an organic-inorganic composite. As shown in fig. 2 (a), the microneedles 11 may be single-channel hollow structures with both ends open, cylindrical, square, conical, or a mixture thereof; as shown in fig. 2 (b), the microneedle 11 may be a solid central hollow structure or a multi-channel hollow structure such as a lotus root section multi-channel hollow structure, but is not limited thereto. The distal end 11c of the microneedle 11 may have a flat-tip structure (capillary tip shape), a single oblique-tip structure (syringe tip shape), or an oblique-tip combined structure; as shown in fig. 2 (c), the microneedle 11 may be a single channel hollow structure with both ends open, and the opening 18 of the tip 11a is located at a distance from the tip end 11c of the tip.

The Micro-needle 11 can be prepared by various methods, such as a template method, which generally uses a silicon wafer as a substrate, but is not limited to a silicon wafer, and etches a Micro-needle structure on the surface of the silicon wafer by a Micro-Electro-Mechanical System (MEMS) processing technology, and the process mainly includes: thermal oxidation, photolithography, bulk resist etching, semiconductor etching process technology (ICP), reactive ion etch back (RIE), and the like.

According to some embodiments of the present application, an array of, for example, cylindrical grooves, each having a depth of about 1-300 microns and a diameter of 0.1-20 microns, are etched into a silicon wafer surface by photolithography techniques, the grooves being spaced apart from one another by 0.01-1000 mm. Selecting another silicon wafer, and etching a cylindrical bump array on the surface, wherein the height of each bump is about 1-300 microns, and the diameter of each bump is 0.1-20 microns. Organic materials or inorganic materials or organic-inorganic composite materials such as polymethyl methacrylate (PMMA) molten liquid are uniformly paved on the silicon template of the cylindrical groove array. And covering the silicon template with the cylindrical protrusion array on the surface of the PMMA layer by the protrusion array surface before the solution is completely cooled, so as to ensure that the protrusion array and the groove array are completely overlapped. After completely cooling and forming, removing the template to obtain the PMMA film with the array structure of the micro-needles 11. The microneedles 11 may have a height of about 1-300 microns, for example, about 10-20 microns; about 0.1 to about 20 microns in diameter, for example, about 1 to about 2 microns in diameter; the microneedle 11 has a thickness at the opposite end 11b of about 1 to about 100 micrometers, for example about 10 to about 20 micrometers, and an opening 18 having a diameter of about 0.1 to about 20 micrometers at about 0.1 to about 10 micrometers from the distal end 11 c.

According to some embodiments of the present application, another method of fabricating the microneedles 11 is via the L IGA process, which may include bonding a thin PMMA sheet 1-400 microns thick to a substrate of titanium and silicon, and etching with X-ray to directly form a microneedle layer having the microneedles 11, wherein a plurality of the microneedles are spaced 0.01-1000 mm apart from each other, for example, 0.1-1 mm apart from each other.

According to some embodiments of the present application, the storage component 12 may be prepared for a particular application by:

preparing a template A: the projection array is etched on the surface of the silicon wafer by the photolithography technique, the size of the array is not particularly limited, and the projection structure may be one or more shapes such as a circle, a square, a triangle, or a mixture thereof. Each protrusion has a height of about 1 to 1000 microns, a cross-sectional area of about 0.01 to 1000 square millimeters, and a spacing of about 0 to 1000 microns.

Preparing a template B: by the photolithography technique, a groove array is etched on the surface of the silicon wafer, the size of the array is not particularly limited, and the groove structure may be one or more shapes such as a circle, a square, a triangle, or a mixture thereof. The grooves may have a depth of about 1 to about 300 microns, may be spaced about 0 to about 1000 microns, such as about 10 to about 20 microns apart, and may be spaced about 10 to about 50 microns apart.

Preparation of a first part 14 comprising an array of grooves on its surface: uniformly spreading a uniformly mixed solution of Polydimethylsiloxane (PDMS) and a small amount of curing agent on the template A, wherein the ratio of PDMS to curing agent is about 10:1, the curing temperature is about 45-85 ℃, the curing time is about 1-24h, removing the template to obtain a PDMS layer with a groove array structure on one surface, and the shape, depth and cross-sectional area of the grooves can be determined by the template, for example, the film thickness of the grooves is about 1-1010 micrometers, the depth of each groove is about 1-1000 micrometers, the cross-sectional area of each groove is 0.01-1000 square millimeters, and the grooves are spaced about 0-1000 micrometers.

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 dioxide, and combinations thereof.

Preparation of a second part 15 whose surface comprises an array of projections (also with grooves between the projections, respectively): uniformly paving a uniformly mixed solution consisting of PDMS and a small amount of curing agent on the template B, wherein the ratio of PDMS to curing agent is about 10:1, the curing temperature is about 45-85 ℃, the curing time is about 1-24h, removing the template to obtain a PDMS layer with one surface comprising a protrusion array structure, and the shape, depth and cross-sectional area of the protrusions are determined by the template, for example, the protrusion depth is about 1-300 microns, and the protrusions are spaced from each other by about 0-1000 microns to form grooves for accommodating the microneedles 11.

The first member 14 and the second member 15 are assembled to prepare the cavity 13 by uniformly applying a uniformly mixed solution of PDMS and a curing agent on the groove array surface of the first member 14 and the smooth surface of the second member 15, i.e., the reverse surface containing the protrusion array, and bonding them, thereby forming the cavity 13, as shown in fig. 3 (a).

It is to be understood that the materials of the first member 14 and the second member 15 used in the present application are not particularly limited, and may be prepared using materials, configurations, and manufacturing methods known in the art, and are not limited to the materials, configurations, and manufacturing methods in the above-described embodiments. The materials, configurations, and methods of manufacture of the above-described embodiments are merely exemplary embodiments for illustrating several of the materials, configurations, and methods of manufacture used to form the storage component 12 in the present application. According to other embodiments of the present application, the storage component 12 can be prepared from other materials, configurations, and manufacturing methods.

According to another embodiment of the present application, a desired substance may be stored in the lumen 13 for transfer between the lumen 13 and the opening 19 through the channel 20 of the microneedle 11 for certain specific applications. For example, the microneedle assembly 10 may be used as a drug delivery device for a target site. The corresponding administration method comprises the following steps: as shown in fig. 3 (a), the drug is stored in the inner cavity 13; attaching the other end 11b of the microneedle 11 to a target site to be administered, such as skin or equipment; configuring the assembly 10, such as by depressing or otherwise actuating the assembly 10 such that the tip 11a pierces the third member 12a to access the lumen 13; the drug in the lumen 13 is transferred to the site to be administered through the channel 20 in contact with the opening 19 on the other end 11b of the microneedle 11 by capillary action, thereby achieving the administration on demand of the target site.

According to some embodiments of the present application, the third member 12a may have a self-restoring force to the deformation caused by the penetration of the tip 11a through the upper and lower surfaces thereof, and when the pressing or other stimulus is removed, the members forming the lumen 13 may return to their original shape so that the drug in the lumen 13 does not flow out, so that the tip 11a may enter and exit the lumen 13 multiple times, so that the passageway 20 and the lumen 13 may communicate or separate multiple times, and the drug in the lumen 13 may continue to be preserved after the tip 11a leaves the lumen 13, thereby achieving repeated, effective on-demand administration of the drug delivery device.

According to some embodiments of the present disclosure, a disinfecting solution 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.

For example, according to the above embodiment of the present application, about 75% alcohol may be injected into the groove of the first member 14, and then the smooth surface of the second member 15 is closely adhered to the groove surface of the first member 14, and heat cured for about 50-120 min, to obtain the storage member containing alcohol load.

It should be understood that the substance is not limited to 75% alcohol solutions. The above embodiment in which alcohol is injected into the groove of the first member 14 so that the alcohol solution is stored in the cavity is merely an exemplary embodiment for explaining one of the structures of the storage member of the present application. According to other embodiments of the present application, the storage component 12 can also store other desired solutions, such as aqueous or organic solutions of hydrogen peroxide, 84 sterilization, and solid drug formulations, among others.

According to some embodiments of the present application, the lumen 13 may also enclose gaseous substances such as ethylene oxide, gaseous hydrogen peroxide, formaldehyde, ozone, and the like.

According to some embodiments of the present application, the method of manufacturing the microneedle assembly 10 includes surface treatment and seamless fitting of the microneedles 11 and the reservoir part 12.

According to some embodiments of the present application, the surface treatment of the microneedle comprises cleaning the surface of the PMMA thin film containing the microneedle structure for 10-50 seconds by using a plasma cleaning technique, and then coating a layer of a uniformly mixed solution of PDMS and a curing agent under a microscope by a casting method, taking care to avoid blocking the pinhole.

The surface treatment of the reservoir part comprises surface-cleaning the protrusion array in the above-described embodiment for, for example, 10 to 50 seconds using a plasma cleaning technique, and then, under a microscope, horizontally contacting the protrusion array surface with the surface of a uniformly mixed solution composed of PDMS and a curing agent, which process treats only the protrusion array tips.

According to some embodiments of the present application, the seamless fitting of the microneedles to the reservoir component includes a close fitting of the tip faces of the microneedles to the surface of the raised array of the second component 15 in a dust-free operating environment and microscope assistance, for example, in the above embodiments, such that the second component 15 can accommodate the tips of the microneedles, thereby achieving a malocclusion of the microneedle array to the raised array to obtain the microneedle assembly 10. Wherein the recess of the first part 14 forms the cavity 13 together with a portion of the second part 15, and a portion of the second part 15 is located between the end 11c and the cavity 13.

In another embodiment of the present application, another method of making the storage component 12 is provided for a particular application, such as hollow microsphere encapsulation.

The gel film is prepared by photo-initiation free radical polymerization, and the monomer material comprises acrylamide, alginic acid, N '-methylene bisacrylamide and ammonium persulfate, and the weight ratio of the acrylamide to the alginic acid to the N, N' -methylene bisacrylamide is 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 having a diameter of about, for example, 0.1 mm. Preparing a buffer solution containing copper sulfate, hydrogen peroxide and trihydroxymethyl aminomethane/hydrochloric acid with the pH value of 7.5, wherein the mass ratio of the copper sulfate to the hydrogen peroxide is about 4: 1-25. The gel pellet prepared above is immersed in a solution with pH 7.5 and reacted at room temperature for about 50-120 min to prepare one or more hollow gel microspheres having one or more inner cavities, as shown in fig. 3 (b) (only one microsphere is shown as an illustration), wherein one microsphere may be formed by a fourth member 16 enclosing the inner cavity 13. Each microsphere may have a thickness of about 1 to about 1000 microns, for example about 10 to about 100 microns, with a portion of the microsphere located between end 11c and lumen 13. Taking out the microspheres, treating the microspheres with calcium chloride aqueous solution, and placing the microspheres in deionized water for storage for later use.

It should be understood that the microspheres are not limited to gel materials. The hollow gel microspheres in the above embodiments are merely exemplary embodiments for illustrating 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 interior cavity, such as materials that are sensitive to light or heat.

For example, for applications where the microneedle assembly 10 is used to kill germs, a disinfecting solution may be added to the lumen, for example, medical alcohol at a concentration of 75% may be used for viral suppression and killing, in the above-described embodiments, one or more microspheres are dispersed in 10-1000 m L75% medical alcohol, sonicated for 30-60 minutes, and the air within the microspheres is removed and loaded with alcohol, thereby producing alcohol-containing microspheres.

It should be understood that the drug loading method is not limited to 75% alcohol solutions. Although the above embodiments have been described with one or more microspheres dispersed in a concentration of alcohol such that an alcohol solution is stored in the interior chamber 13, this is merely illustrative of one of the configurations 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 desired solutions, such as aqueous or organic solutions of hydrogen peroxide, 84 sterilization, and solid drug formulations, among others.

Subsequently, about 0.1-100 grams of agarose may be dissolved in about 10-500 m L g of deionized water by microwave heating, and when the temperature of the solution is reduced to about 30 ℃, about 1-100 m L g of the agarose solution is uniformly mixed with the alcohol-loaded microsphere or microspheres and rapidly filmed, the agarose solution is cooled to room temperature, immediately gelled, and the microsphere or microspheres are firmly immobilized, thereby producing a membrane comprising alcohol-loaded microspheres having a thickness in the range of about 10 to 1000 microns, as shown in fig. 3 (b), the interior cavity 13 formed by the microspheres may be further surrounded by a fifth member 22 to support the microsphere or microspheres.

According to some embodiments of the present application, the reservoir part 12 may further include a sixth part for supporting and fixing the microneedles, such as the sixth part 17 in fig. 3 (b), which has a recess for receiving the tip 11a of the microneedle 11. When the tip 11a of the microneedle 11 is disposed into the lumen 13, the sixth member 17 may restore the lumen 13 or the tip 11a of the microneedle 11 after the disposition is removed. The material composition of the sixth member 17 may be an organic elastomer material such as Styrene Butadiene Rubber (SBR), an inorganic material such as a nanofiber network assembly, an organic-inorganic composite, or an organic-inorganic aerogel material such as graphene aerogel.

According to some embodiments of the present application, the sixth member 17 and the fourth member 16 enclosing the inner cavity 13 may be composed of the same material. The sixth member 17 may have a net structure, which does not block the tip 11a from entering the inner cavity 13, and the net structure is limited by the arrangement of the microneedles, and has a thickness corresponding to the height of the microneedles but not larger than the height of the microneedles, for example, the thickness of the sixth member is equal to the height of the microneedles.

For example, the sixth member 17 may be prepared by a laser cutting method, such as PDMS, but is not limited thereto. The PDMS has a grid structure, each grid 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 feature is about 1-300 microns. The surface of the sixth member of the mesh-like PDMS opposite to the surface having the groove was attached to the surface of the microsphere film, thereby obtaining the storage member 12.

It is to be understood that the microneedles and reservoir components used herein are not particularly limited and may be prepared using materials, configurations and manufacturing methods known in the art for a particular application and are not limited to the materials, configurations and manufacturing methods described in the above examples. The materials, configurations, and fabrication methods of the above-described embodiments are merely illustrative of exemplary embodiments of several of the materials, configurations, and fabrication methods that may be used with microneedle assemblies 10 of the present application to address particular applications.

According to other embodiments of the present application, the microneedle assembly 10 may have other structures, such as a structure in which one or more inner cavities 13 are in communication with each other and connected to a larger reservoir 21 to provide a continuous supply of a substance to one or more inner cavities 13, as shown in fig. 3 (c).

Another embodiment of the present application also provides an application method of the microneedle assembly 10, for example, substances for bacteriostasis and moisture protection can be stored in the inner cavity 13, and the microneedle assembly 10 is placed at a part needing bacteriostasis and moisture protection, such as the inside of a shoe, so that the microneedle assembly 10 continuously releases the substances for bacteriostasis and moisture protection by continuously stepping on the sole, thereby keeping the foot in a clean and sterile state.

Another embodiment of the present application also provides a method for blocking the transmission of germs, which comprises storing the above-mentioned medicine for killing germs in the inner cavity of the microneedle assembly to make a drug delivery device, attaching the drug delivery device to a component which is easy to transmit germs, such as all public facilities which are frequently contacted, such as various instrument operation buttons, elevator buttons, door handles, handrails, and the like, or a sole; the medication delivery device is pressed from time to time when the user is in contact with a component that is susceptible to the transmission of pathogens. When the administration device is pressed, the medicine for exterminating germs may permeate the surface of the component from time to time, thereby exterminating germs in real time, blocking the spread of germs, and eliminating the risk of infection of the user.

Another embodiment of the present application further provides an anti-bacteria device, such as a protective suit, a protective glove or a protective box, in which a microneedle assembly with a disinfecting liquid stored in an inner cavity is disposed at a position where the microneedle assembly is easily touched and pressed, so that when the device touches and presses a component which is easily spread germs, for example, a public facility which is frequently touched such as various instrument operation buttons, elevator buttons, door handles, and handrails is touched, the disinfecting liquid can permeate the surface of the component from time to time, thereby killing germs in real time, blocking the spread of germs, realizing the recyclable use of the device, and eliminating the risk of infection.

The microneedle assembly disclosed in the embodiments of the present application is a novel substance delivery structure, has the characteristics of miniaturization, mass production, and repeated use, and can be effectively used in, for example, the field of drug release to realize the real-time and on-demand administration of a target site.

In another embodiment of the present application, testing for microneedle assembly 10-based drug release applications is provided. And (3) adhering the microneedle assembly with the alcohol stored in the inner cavity to the smooth surface of the component, pressing with fingers, and completely evaporating the exudate after the pressure is removed for about 10 minutes. The controllability of the microneedle assembly on the drug release is tested by repeatedly pressing, so that the pressure is removed and the release of alcohol is avoided as a test standard. The results show that the micro-needle assembly can effectively release the drug for more than 1000 times under repeated pressing until the alcohol is completely released.

It will be appreciated that the drug delivery device described above is not limited to responding to an external force, such as a press or a trample. Although the drug delivery device of the above embodiments is pressed so that the tips of the microneedles can enter and exit the lumen multiple times to communicate the channels at both ends of the microneedles with the lumen, thereby achieving substance transfer, this is merely an exemplary embodiment for illustrating one of the structures 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 heat, cold, light, etc., so that the tips 11a of the microneedles 11 of the microneedle assembly 10 can enter and exit the lumen 13 multiple times, enabling the channel 20 and the lumen 13 to communicate or separate multiple times.

The technical content and technical features of the present application have been disclosed as above, however, those skilled in the art may still make various substitutions and modifications based on the teaching and disclosure of the present application without departing from the spirit of the present application. Therefore, the protection scope of the present application should not be limited to the disclosure of the embodiments, but should include various alternatives and modifications without departing from the scope of the present application, which is covered by the claims of the present patent application.

Claims

1. A microneedle assembly, comprising:

one or more microneedles having one end on at least one surface of the microneedle assembly and a tip protruding downward from the one end to an end, and having openings on the one end and the tip, respectively, to form a channel through the one end and the tip of the microneedle; and a storage component having at least a portion with one or more lumens for storing a substance, the lumens being located below the tip end; wherein the microneedle assembly is configured to enter the tip into the lumen.

2. The microneedle assembly of claim 1, wherein the microneedle assembly is configured to enter the tip into the lumen in response to at least one of the following stimuli: light, heat, refrigeration, and external forces.

3. The microneedle assembly of claim 1, wherein the reservoir component comprises a first component located between the end of the tip and the lumen to define at least a portion of the lumen.

4. The microneedle assembly of claim 3, wherein the first component has a thickness no greater than the length of the microneedles.

5. The microneedle assembly of claim 3, wherein the first component has a self-restoring force to deformation caused by the piercing of the tip through its upper and lower surfaces.

6. The microneedle assembly of claim 3, wherein the first component is an elastomeric material.

7. The microneedle assembly of claim 3, wherein the material of the first component is selected from at least one of a polymer of acrylamide and N, N' -vinyl bisacrylamide, a nanofiber, Polydimethylsiloxane (PDMS), and a combination thereof.

8. The microneedle assembly of claim 1, wherein the microneedle assembly is configured to place the channel in communication with or separate from the lumen a plurality of times.

9. The microneedle assembly of claim 1, wherein the microneedle assembly is configured to pass the tip of the microneedle into and out of the lumen a plurality of times.

10. The microneedle assembly of claim 1, wherein the reservoir component further comprises a second component having a recess forming the lumen.

11. The microneedle assembly of claim 1, wherein the reservoir component further comprises a third component having a recess that receives the tip of the microneedle.

12. The microneedle assembly of claim 11, wherein the third component is an elastomeric material.

13. The microneedle assembly of claim 3, wherein the first component defines the lumen.

14. The microneedle assembly of claim 13, wherein the reservoir component further comprises a fourth component for supporting the first component.

15. The microneedle assembly of claim 13, wherein the first member and the one or more lumens constitute one or more microspheres.

16. The microneedle assembly of claim 1, wherein reservoir component further comprises a reservoir cavity in communication with the one or more inner cavities.

17. A drug delivery device comprising the microneedle assembly of any one of claims 1-16, and the drug is stored in the lumen.

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

19. A method of administering a drug comprising attaching a drug delivery device according to claim 17 to a site at which administration is desired; and pressing the drug delivery device.

20. A bacteria prevention kit comprising the drug delivery device of claim 17, wherein the drug is for killing bacteria and the drug delivery device is attached to a readily depressible portion of the kit.

21. The anti-microbial kit of claim 20, comprising a protective garment, protective gloves or protective boxes.

22. A method for blocking the spread of a pathogen, comprising:

attaching the drug delivery device of claim 17 to a component susceptible to transmission of pathogens; and pressing the drug delivery device, wherein the drug is used to destroy pathogens.

23. The method of claim 22, wherein the pathogen-transmissible component comprises a door handle, a button, a handrail, or a shoe sole.

24. A method of manufacturing a microneedle assembly, comprising:

manufacturing one or more microneedles and a reservoir component in a microneedle assembly according to any one of claims 1-16; and fitting one surface of the microneedle with the tip end to at least one surface of the storage part.

25. The method of claim 24, wherein fabricating the storage component comprises: a first component having a tip that receives the one or more microneedles is fabricated.

26. The method of claim 24, wherein fabricating the storage component comprises: manufacturing a substrate having a groove; and attaching the two substrates in a staggered manner.

27. The method of claim 24, wherein fabricating the storage component comprises preparing one or more microspheres.

28. The method of claim 27, wherein fabricating the reservoir component further comprises forming a second component supporting the one or more microspheres to form a microsphere film.

29. The method of claim 28, wherein fabricating the storage component further comprises:

preparing a third component; and attaching the third component to the surface of the microsphere film.

30. A method of manufacturing a drug delivery device comprising the method of manufacturing a microneedle assembly according to claim 24; storing a drug in the lumen; and gelling the member defining the one or more lumens in which the drug is stored using the agent.