Manufacturing Device and Method for Microarray Transdermal Drug Delivery Microneedles

Abstract

The present invention provides a manufacturing device and method for microarray transdermal drug delivery microneedles. The device includes: a mold with a preset flexibility, a pressing device, and an input device; the bottom of the mold is placed on a workbench, and a plurality of grooves are formed at the top of the mold, and the shape of each groove matches the shape of the microneedle; the pressing device is detachably arranged on the mold to apply pressure to each groove so that each groove is in a closed state; the input device is detachably arranged on the top of the mold to inject liquid into each groove after each groove is in a closed state, and the liquid in each groove forms a microneedle after solidification. In the present invention, the shape of each groove matches the shape of the microneedle to be manufactured. The input device can inject liquid into each groove to form microneedles with the required shape and size, and can accurately control the morphology of the microneedles. Each groove can be closed under the action of the pressing device, which is convenient for the input device to inject liquid into each groove. The liquid can form microneedles only after solidification, ensuring the effect and quality of the microneedles.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and more particularly, to a device and method for manufacturing microarray transdermal drug delivery microneedles. Background Art

[0002] At present, the use of biodegradable microarrays for drug delivery belongs to painless transdermal drug delivery technology, which can painlessly create micron-sized drug delivery channels on the skin, enabling drugs or active ingredients to penetrate through the natural stratum corneum of the skin into the skin and be absorbed, enhancing the permeability of the skin to active substances or drugs, especially macromolecular drugs. Therefore, soluble microneedles are more widely used.

[0003] The existing manufacturing process of soluble microneedles is mainly the stretching and shaping method. This stretching and shaping method forms a microneedle structure by contacting and stretching a viscous polymer droplet. Since the manufacturing process utilizes the stretching and extension characteristics of the viscous fluid, the morphology of the produced microneedles cannot be freely controlled. Summary of the Invention

[0004] In view of this, the present invention provides a device for manufacturing microarray transdermal drug delivery microneedles, aiming to solve the problem that the morphology of soluble microneedles produced by the stretching and shaping method in the prior art cannot be controlled. The present invention also provides a method for manufacturing microarray transdermal drug delivery microneedles.

[0005] In one aspect, the present invention provides a device for manufacturing microarray transdermal drug delivery microneedles, the device comprising: a mold with a preset flexibility, a pressing device, and an input device; wherein, the bottom of the mold is for placing on a workbench, and a plurality of grooves are formed on the top of the mold, and the shape of each groove matches the shape of the microneedle; the pressing device is detachably arranged on the mold and is used for applying pressure to each groove to make each groove in a closed state; the input device is detachably arranged on the top of the mold and is used for injecting liquid into each groove after each groove is in a closed state, and the liquid in each groove is for forming a microneedle after solidification.

[0006] Further, in the above device for manufacturing microarray transdermal drug delivery microneedles, the input device comprises: a hollow shell, a plurality of input tubes, and a plurality of sealing structures; wherein, the shell is placed on the upper part of the mold, and at least one liquid inlet is formed on the side wall of the shell; each input tube is arranged on the side of the shell facing the mold, and the end of each input tube covers the outside of each groove in a one-to-one correspondence, and each input tube is used for injecting liquid with a preset pressure into the corresponding groove; each sealing structure is arranged at the end of each input tube in a one-to-one correspondence, and each sealing structure is used for sealing the connection between the input tube and the groove.

[0007] Further, in the above-mentioned manufacturing apparatus for microneedles for transdermal drug delivery of the microarray, the pressing device includes: a vacuum pumping device; wherein, the vacuum pumping device is arranged in the input device, and the vacuum pumping device is used to pump vacuum for each groove to close each groove, and stop pumping vacuum when each groove is in a closed state.

[0008] Further, in the above-mentioned manufacturing apparatus for microneedles for transdermal drug delivery of the microarray, the vacuum pumping device includes: a partition plate and a switching valve; wherein, the partition plate is arranged in the shell to divide the shell into a first space and a second space, and the first space is close to the mold; the partition plate is provided with an opening, and the switching valve is arranged at the opening; the shell is provided with an output port corresponding to the second space for connecting with a vacuum pump; the liquid inlet is opened on the side wall of the shell corresponding to the first space.

[0009] Further, in the above-mentioned manufacturing apparatus for microneedles for transdermal drug delivery of the microarray, the pressing device further includes: an auxiliary device; wherein, the auxiliary device is detachably arranged outside the mold, and is used to apply pressure to the outside of the mold when the vacuum pumping device pumps vacuum to assist the closing of each groove; the auxiliary device includes: a housing with a hollow interior; wherein, the top of the housing is provided with a recessed portion for accommodating the mold; the side wall of the housing is provided with a connection port for connecting with a gas delivery device to inflate the housing; the housing has a preset expandability and contractibility, and expands when inflated to squeeze the side and bottom of the mold.

[0010] Further, the above-mentioned manufacturing apparatus for microneedles for transdermal drug delivery of the microarray further includes: a vibration device; the vibration device is detachably arranged on the workbench and is used to vibrate the mold when the input device injects liquid; and / or, further includes: a support frame and a lifting device; the support frame is arranged on the workbench; the lifting device is arranged on the support frame and is placed above the mold; the input device is arranged on the lifting device, and the lifting device is used to drive the input device to lift and lower.

[0011] In the present invention, the shapes of the grooves opened at the top of the mold match the shapes of the microneedles to be manufactured. After the input device injects liquid into each groove, microneedles with the required shapes and sizes can be made, and the morphology of the microneedles can be accurately controlled. Moreover, the mold has a preset flexibility, so that each groove can be in a closed state under the action of the pressing device, which is convenient for the input device to inject liquid into each groove. The liquid only needs to solidify to make microneedles, without high-temperature heating or centrifugation, avoiding the influence of temperature and external force on the physical and chemical properties of the liquid, ensuring the effect and quality of the microneedles, being simple to manufacture and easy to implement, and solving the problem that the morphology of soluble microneedles manufactured by the stretching and shaping method in the prior art cannot be controlled.

[0012] On the other hand, the present invention also provides a method for manufacturing microneedles for microarray transdermal drug delivery, which method comprises the following steps: a pressing step of applying pressure to each groove of a mold to close each groove; an injecting step of injecting a liquid into each groove after each groove is closed; and a solidifying step of allowing the liquid in each groove to solidify into microneedles after standing for a preset time.

[0013] Further, in the method for manufacturing microneedles for microarray transdermal drug delivery, in the pressing step, each groove is evacuated to close each groove.

[0014] Further, in the method for manufacturing microneedles for microarray transdermal drug delivery, in the pressing step, when evacuating, pressure is applied to the bottom and side portions of the mold to assist in discharging the gas from each groove to close it.

[0015] Further, in the method for manufacturing microneedles for microarray transdermal drug delivery, the injecting step further comprises: a first liquid injection sub-step of injecting a preset amount of liquid into each groove after each groove is closed; a liquid extraction sub-step of extracting the liquid in each groove; repeating at least once the liquid injection sub-step and the liquid extraction sub-step; and a second liquid injection sub-step of injecting liquid into each groove until each groove is filled; in the second liquid injection sub-step, when injecting the liquid, the mold is vibrated to avoid generating air bubbles.

[0016] In the present invention, pressure is applied to each groove of the mold. Since the mold has a preset flexibility, each groove can be in a closed state under the action of the pressure, facilitating the injection of liquid into each groove. Each liquid only needs to solidify to form microneedles. The manufacturing method is simple, easy to implement, and can accurately control the shape of the microneedles. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] By reading the detailed description of the preferred embodiments below, various other advantages and benefits will become clear to those of ordinary skill in the art. The drawings are only for the purpose of illustrating the preferred embodiments and are not to be considered as limiting the present invention. Moreover, throughout the drawings, the same reference numerals are used to represent the same components. In the drawings:

[0018] Figure 1 is a schematic structural diagram of a manufacturing apparatus for microneedles for microarray transdermal drug delivery provided by an embodiment of the present invention;

[0019] Figure 2 is a schematic structural diagram of the manufacturing apparatus for microneedles for microarray transdermal drug delivery provided by an embodiment of the present invention when each groove is in a closed state;

[0020] Figure 3 is a schematic structural diagram of the manufacturing apparatus for microneedles for microarray transdermal drug delivery provided by an embodiment of the present invention after injecting the liquid;

[0021] Figure 4Schematic diagram of the structure of the microarray transdermal drug delivery microneedle manufacturing device provided by the embodiment of the present invention after injecting different liquids;

[0022] Figure 5 Schematic diagram of the structure of the groove in the microarray transdermal drug delivery microneedle manufacturing device provided by the embodiment of the present invention;

[0023] Figure 6 Schematic diagram of the side cross-sectional structure of the auxiliary device in the microarray transdermal drug delivery microneedle manufacturing device provided by the embodiment of the present invention;

[0024] Figure 7 Schematic diagram of the top view structure of the auxiliary device in the microarray transdermal drug delivery microneedle manufacturing device provided by the embodiment of the present invention;

[0025] Figure 8 Schematic diagram of the structure at the support frame in the microarray transdermal drug delivery microneedle manufacturing device provided by the embodiment of the present invention;

[0026] Figure 9 Flow chart of the manufacturing method of the microarray transdermal drug delivery microneedle provided by the embodiment of the present invention. Detailed implementation manners

[0027] Hereinafter, the exemplary embodiments of the present disclosure will be described in more detail with reference to the accompanying drawings. Although the exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided so that the present disclosure can be more thoroughly understood and the scope of the present disclosure can be completely conveyed to those skilled in the art. It should be noted that, without conflict, the embodiments in the present invention and the features in the embodiments can be combined with each other. Hereinafter, the present invention will be described in detail with reference to the drawings and in conjunction with the embodiments.

[0028] Device embodiment:

[0029] Refer to Figures 1 to 7 , the figure shows the preferred structure of the microarray transdermal drug delivery microneedle manufacturing device in this embodiment. As shown in the figure, the microarray transdermal drug delivery microneedle manufacturing device includes: a mold 1, a pressing device, and an input device 2. Among them, the bottom of the mold 1 ( Figure 1 the lower part shown) is used to be placed on the workbench 8. Specifically, in implementation, the mold 1 can be only placed on the workbench 8 or detachably connected to the workbench 8.

[0030] A plurality of grooves 11 are formed in the top of the mold 1, and the shape of each groove 11 matches the shape of the microneedle to be made. Specifically, the shape of each groove 11 can be determined according to the shape of the microneedle. Refer to Figure 1 and Figure 5, the shapes of each groove 11 can be the same or different, and the sizes of the grooves 11 can be the same or different. This embodiment does not impose any restrictions on this. In this way, the shapes of different grooves can be set according to actual needs to form various different microneedle shapes. Moreover, it is possible to implement multiple grooves with different shapes, sizes, lengths, and densities on one mold, achieving the coexistence of multiple shapes, sizes, lengths, and densities on the same microneedle.

[0031] During specific implementation, the shape of the groove 11 can be conical, polygonal pyramidal, concave curved surface conical, convex curved surface conical, pointed conical, flat-headed conical, diagonal conical, pointed concave surface conical, flat-headed concave surface conical, pointed convex surface conical, special-shaped conical, etc. This embodiment does not impose any restrictions on this.

[0032] The mold 1 has a preset flexibility, and this preset flexibility can be determined according to actual situations. This embodiment does not impose any restrictions on this. The material of the mold 1 should be a material with a preset flexibility, such as silicon or polydimethylsiloxane PDMS, etc.

[0033] During specific implementation, the diameter range of the groove 11 is 50 - 1500 microns, the length range is 50 - 2000 microns, and the diameter of the tip range is 2 - 200 microns. Of course, the size of the groove 11 can also be determined according to actual situations. This embodiment does not impose any restrictions on this.

[0034] The pressing device is detachably arranged on the mold 1. The pressing device is used to apply pressure to each groove 11 so that each groove 11 is in a closed state. In this way, a pressure difference is generated between each groove 11 and the outside of the mold 1. During specific implementation, the pressing device only needs to be able to close each groove 11. This embodiment does not impose any restrictions on the structure of the pressing device.

[0035] The input device 2 is detachably arranged on the top of the mold 1 ( Figure 1 the upper part shown in the figure). The input device 2 is used to inject liquid into each groove 11 after each groove 11 is in a closed state. The liquid in each groove 11 forms a microneedle after solidification. Specifically, the pressing device applies pressure to each groove 11. Since the mold 1 has a preset flexibility, each groove 11 gradually closes under the action of the pressure. When each groove 11 is in a closed state, a certain pressure difference is generated between the inside of each groove 11 and the outside of the mold 1. Under the action of this pressure difference, the input device 2 injects liquid into each groove 11 until the liquid fills each groove 11. Remove the input device 2 and let it stand for a preset time, and the liquid solidifies into a microneedle. The standing can be carried out at normal temperature or even low temperature without heating. In this way, it is possible to reduce the damage to the liquid components, avoid the inactivation of the liquid, and thus ensure the effect of the microneedle.

[0036] The liquid can be a viscous liquid, which can be a biodegradable polymer material or a non - biodegradable biocompatible polymer material. In specific implementation, the biodegradable polymer material can be one or a mixture of chondroitin sulfate, polylactic acid, polyglycolic acid, poly (lactic - co - glycolic acid), methyl vinyl ether - maleic anhydride copolymer, polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, carboxymethyl cellulose, carbomer, trehalose, maltose, sucrose, raffinose, hyaluronic acid, sodium alginate, amylopectin, dextran, etc. The non - biodegradable biocompatible polymer material can be silicon, polyaryletherketone, etc.

[0037] Preferably, the inner walls of the grooves 11 are subjected to surface activation treatment to make it easy for the liquid to be adsorbed in the grooves.

[0038] See Figure 8 , preferably, the manufacturing device of the microarray transdermal drug - delivery microneedles further includes: a support frame 9 and a lifting device 10. Among them, the support frame 9 is arranged on the workbench 8. Specifically, the bottom ( Figure 8 the lower part shown in the figure) of the support frame 9 is connected to the workbench 8, and the top ( Figure 8 the upper part shown in the figure) of the support frame 9 is placed above the top of the mold 1.

[0039] The lifting device 10 is arranged on the support frame 9, and, the lifting device 10 is placed above the mold 1 (relative to Figure 8 ), specifically, the lifting device 10 is arranged at the top of the support frame 9, and there is a certain distance between the lifting device 10 and the top of the mold 1, and this distance can be determined according to the actual situation, and this embodiment does not make any limitation on this.

[0040] The input device 2 is arranged on the lifting device 10, and the lifting device 10 is used to drive the input device 2 to lift and lower, so that the input device 2 is arranged on the top of the mold 1 or the input device 2 is separated from the mold 1.

[0041] In specific implementation, the lifting device 10 can be a retractable structure or a movable structure, etc., and this embodiment does not make any limitation on this.

[0042] During use, the lifting device 10 controls the input device 2 to descend to the top of the mold 1, and the input device 2 is connected to the top of the mold 1 to facilitate the input device 2 to inject the liquid. After the grooves 11 are filled with the liquid, the lifting device 10 controls the input device 2 to rise above the mold 1, so that the input device 2 is separated from the top of the mold 1, facilitating the liquid in the grooves 11 to stand still to form microneedles.

[0043] It can be seen that in this embodiment, the shapes of the grooves 11 formed at the top of the mold 1 match the shapes of the microneedles to be fabricated. After the input device 2 injects liquid into each groove 11, microneedles with the desired shapes and dimensions can be fabricated, enabling accurate control of the morphology of the microneedles. Moreover, the mold 1 has a preset flexibility, so that each groove 11 can be in a closed state under the action of the pressing device, facilitating the input device 2 to inject liquid into each groove 11. The liquid only needs to solidify to form microneedles, without the need for high-temperature heating or centrifugation, avoiding the influence of temperature and external force on the physical and chemical properties of the liquid, ensuring the effect and quality of the microneedles, with simple fabrication and easy implementation, solving the problem that the morphology of soluble microneedles fabricated by the stretching and shaping method in the prior art cannot be controlled.

[0044] Continuing to refer to Figures 1 to 4 , in the above embodiment, the input device 2 may include: a housing 21, a plurality of input tubes 22, and a plurality of sealing structures. Among them, the interior of the housing 21 is hollow, and both ends of the housing 21 are closed ends. The housing 21 is placed on the upper part of the mold 1. A liquid inlet 211 is formed in the side wall of the housing 21, and the liquid inlet 211 is used to connect with a liquid injection device. The liquid injection device stores liquid, and the liquid injection device injects liquid into the housing 21 through the liquid inlet 211. A valve may be provided at the liquid inlet 211 to facilitate controlling the flow rate of the injected liquid and whether to inject liquid.

[0045] The number of the input tubes 22 is the same as the number of the grooves 11, and the positions of the input tubes 22 correspond to the positions of the grooves 11 one by one. Each input tube 22 is provided on the side of the housing 21 facing the mold 1. Specifically, a plurality of through holes are formed in the side of the housing 21 facing the mold 1. The number of the through holes is the same as the number of the input tubes 22, and the positions of the through holes correspond to the positions of the input tubes 22 one by one. The first end of each input tube 22 is connected to the corresponding through hole, and the second end of each input tube 22 covers the outside of the corresponding groove 11. Each input tube 22 is used to inject liquid with a preset pressure into the corresponding groove 11. Specifically, the second end of each input tube 22 contacts the top of the mold 1, and the end of the second end of each input tube 22 covers the outside of the opening end of the corresponding groove 11.

[0046] The preset pressure of the liquid can be determined according to the actual situation, and this embodiment does not make any restrictions on this. Moreover, the pressure of the liquid can promote the injection of the liquid into each groove 11, ensuring that the groove 11 is filled with liquid and guaranteeing the quality of the microneedles. The liquid with the preset pressure can be injected into the housing 21 through a high-pressure device, and of course, it can also be injected through other devices. This embodiment does not make any restrictions on the structure for applying the liquid pressure.

[0047] The number of the sealing structures is the same as that of the input pipes 22, and each input pipe 22 corresponds to one of the sealing structures. Each sealing structure is arranged at the end of the second end of the corresponding input pipe 22, and each sealing structure is used to seal the connection between the corresponding input pipe 22 and the groove 11.

[0048] Each sealing structure can be a flexible suction cup 23. The suction cup 23 can be adsorbed on the top of the mold 1 and cover the outside of the groove 11. During specific implementation, the contact area between the suction cup 23 and the top of the mold 1 can be polished to improve the tightness between the suction cup 23 and the groove 11. It can also be that the surfaces of the suction cup 23 and the top of the mold 1 are micro heat-treated to soften the suction cup 23 and the mold 1 to improve the adsorption between the suction cup 23 and the mold 1. It can also be that a viscous substance is applied to the surfaces of the suction cup 23 and the top of the mold 1 to promote the adsorption between the suction cup 23 and the mold 1.

[0049] It can be seen that in this embodiment, when each groove 11 is in a closed state, each input pipe 22 injects liquid with a preset pressure into the corresponding groove 11 to ensure that the liquid is stably and smoothly input into the groove 11, and then ensure that the groove 11 is filled with liquid. The setting of the sealing structure can ensure the sealing performance between the input pipe 22 and the groove 11, and then ensure that the liquid is stably injected into each groove 11, avoiding pressure leakage and resulting in the groove 11 not being filled with liquid.

[0050] See Figure 4 In the above embodiment, there are at least two liquid inlets 211, and each liquid inlet 211 is opened on the side wall of the housing 21, and each liquid inlet 211 is opened along the height direction of the housing 21 ( Figure 4 the direction from top to bottom as shown). Specifically, the liquid can be one kind, then a simple microneedle is made; or the liquid is at least two kinds, then a multi-layer stratified capsule-type microneedle is made. When the liquid is at least two kinds, each liquid can be injected into each groove 11 in sequence.

[0051] During specific implementation, a valve is arranged at each liquid inlet 211.

[0052] During specific implementation, when the liquid is at least two kinds, each liquid inlet 211 injects different liquids into the housing 21. First, open the first liquid inlet 211 and control the flow rate of the first liquid. After the first liquid enters each groove 11, it adsorbs on the surface of the groove 11 to form a liquid film. Then, close the first liquid inlet 211, open the second liquid inlet 211, and the second liquid enters each groove 11. Then, close the second liquid inlet 211, open the third liquid inlet 211, and the third liquid enters each groove 11. Repeat the above steps in sequence until each different liquid is injected into each groove 11 in sequence. During specific implementation, different liquid inlets 211 can be selectively opened.

[0053] See Figures 1 to 4 Figures 1 to 4 , in each of the above embodiments, the pressing device may include: a vacuum pumping device. Among them, the vacuum pumping device is disposed on the input device 2, and the vacuum pumping device is detachably connected to the mold 1 through the input device 2. The vacuum pumping device is used to evacuate each groove 11 to close each groove 11, and stop evacuating when each groove 11 is in a closed state. In this way, by evacuating each groove 11, a negative pressure state is presented in each groove 11. Under the action of the internal and external pressure difference, when the valve at the liquid inlet 211 is opened, the liquid will actively flow into each groove 11.

[0054] The vacuum pumping device may include: a partition plate 3 and a switching valve 4. Among them, the partition plate 3 is disposed inside the housing 21. Specifically, the partition plate 3 is horizontally disposed inside the housing 21, and the partition plate 3 is parallel to the side of the housing 21 facing the mold 1. Then, the partition plate 3 divides the housing 21 into a first space 5 and a second space 6. The first space 5 is located at the lower part inside the housing 21 (relative to Figure 1 in terms of) and close to the mold 1, and the second space 6 is located at the upper part inside the housing 21 (relative to Figure 1 in terms of). The partition plate 3 is provided with an opening, and the opening is disposed near the side wall of the housing 21. The switching valve 4 is disposed at the opening to control the closing or opening of the opening.

[0055] The housing 21 is provided with an output port 212 corresponding to the second space 6, and the output port 212 is used to be connected to a vacuum pump to extract the gas in each groove 11 to close each groove 11. The liquid inlet 211 is opened on the side wall of the housing 21 corresponding to the first space 5, and the first space 5 is a space for injecting liquid. When there are at least two liquid inlets 211, each liquid inlet 211 corresponds to the first space 5.

[0056] During specific use, each suction cup 23 adsorbs on the top of the mold 1 and covers the outside of the corresponding groove 11. Close the valve at the liquid inlet 211, open the valve at the switching valve 4 and the output port 212. The vacuum pump evacuates air from the output port 212, so that the first space 5 and the second space 6 reach a vacuum state, and finally each groove 11 is closed due to evacuation. At this time, a pressure difference is generated between the inside of each groove 11 and the outside of the mold 1. At this time, close the switching valve 4 and the valve at the output port 212, and open the valve at the liquid inlet 211. The liquid automatically flows from the liquid inlet 211 into the first space 5 under the action of the pressure difference and flows into each groove 11 through each suction cup 23. The pressure of the liquid is to increase the internal and external pressure difference of each groove 11, so that the liquid is more likely to flow into each groove.

[0057] It can be seen that in this embodiment, before injecting liquid into the input device 2, vacuum is pumped to close each groove 11, so as to discharge the gas in the groove 11 and generate a pressure difference. Under the action of the pressure difference, the liquid can be stably injected into the groove 11. Moreover, the structure of the vacuum pumping device is simple and easy to implement. At the same time, the vacuum pumping device is arranged on the input device 2 to ensure the overall sealing performance of the microarray transdermal drug delivery microneedle manufacturing device, avoid air leakage and pressure leakage, and also ensure the forming quality and effect of the microneedles.

[0058] See Figure 6 and Figure 7 , the pressing device may further include: an auxiliary device 7. The auxiliary device 7 is detachably arranged outside the mold 1. The auxiliary device 7 is used to apply pressure to the outside of the mold 1 when the vacuum pumping device pumps vacuum, so as to assist the closure of each groove 11. In this way, the auxiliary device 7 can accelerate the discharge of air from each groove 11, make each groove 11 close quickly, and ensure the closing effect of each groove 11, avoiding the residue of air.

[0059] The auxiliary device 7 may include: a housing 71. The top of the housing 71 is provided with a recessed part for accommodating the mold 1. The inside of the housing 71 is hollow, and a connection port is provided on the side wall of the housing 71. The connection port is connected to an air delivery device for inflating the inside of the housing 71. The housing 71 has a preset expansion and contraction property, so the housing 71 is in an expanded state when inflated inside, and then squeezes the side and bottom of the mold 1 to promote the discharge of gas in each groove 11, making each groove 11 close.

[0060] Specifically, the preset expansion and contraction can be determined according to the actual situation, and this embodiment does not make any restrictions on this. The material of the housing 71 is a material with a preset expansion and contraction, such as: rubber.

[0061] Specifically, the air delivery device can be a high-pressure pump or other devices, and this embodiment does not make any restrictions on this.

[0062] In the above embodiments, when the input device 2 injects liquid into each groove 11, in order to ensure the forming quality of the microneedles, it is necessary to avoid the generation of bubbles. For this reason, the microarray transdermal drug delivery microneedle manufacturing device may further include: a vibration device. The vibration device is detachably arranged on the workbench 8. The vibration device is used to vibrate the mold 1 when the input device 2 injects liquid, so as to avoid the generation of bubbles, ensure that there are no bubbles in the liquid in each groove 11, and thus improve the forming quality of the microneedles.

[0063] In specific implementation, the vibration device can be a vibrator or an ultrasonic electromagnetic device, as long as it can generate vibration. The structure of the vibration device is not restricted in this embodiment. Preferably, if the vibration device is an ultrasonic electromagnetic device, the template 1 will generate ultrasonic micro-frequency vibration.

[0064] Preferably, the manufacturing device for the microarray transdermal drug delivery microneedles further includes: a vibration device detachably arranged on the workbench and used for vibrating the mold when the input device injects liquid; and / or, the manufacturing device for the microarray transdermal drug delivery microneedles further includes: a support frame 9 and a lifting device 10; the support frame 9 is arranged on the workbench 8; the lifting device 10 is arranged on the support frame 9 and is placed above the mold 1; the input device 2 is arranged on the lifting device 10, and the lifting device 10 is used to drive the input device 2 to move up and down.

[0065] In specific implementation, when each groove 11 is in a closed state, under the action of the pressure difference, the input device 2 injects a certain amount of liquid into each groove 11. Then, the vacuum device sucks away the liquid and discharges the gas, so that each groove 11 is in a closed state. Then, a certain amount of liquid is injected into each groove 11 and then discharged. After at least one cycle is repeated, liquid is injected into each groove 11 and each groove 11 is filled. This is beneficial for the liquid to evenly and fully cover each groove 11 and avoid the appearance of air bubbles.

[0066] In summary, in this embodiment, after the input device 2 injects liquid into each groove 11, microneedles with the required shape and size can be made, and the morphology of the microneedles can be accurately controlled. Moreover, each groove 11 can be in a closed state under the action of the pressing device, which is convenient for the input device 2 to inject liquid into each groove 11. The liquid only needs to solidify to make microneedles, without high-temperature heating or centrifugation, avoiding the influence of temperature and external force on the physical and chemical properties of the liquid, ensuring the effect and quality of the microneedles, and being simple to manufacture and easy to implement.

[0067] Method embodiment:

[0068] This embodiment also proposes a manufacturing method for the microarray transdermal drug delivery microneedles. Refer to Figure 9 , the manufacturing method for the microarray transdermal drug delivery microneedles includes the following steps:

[0069] Pressing step S1: Apply pressure to each groove of the mold to close each groove.

[0070] Specifically, the mold is the mold in the above device embodiment. For the specific implementation process of the mold in this embodiment, refer to the above description, and this embodiment will not be elaborated here.

[0071] Preferably, each groove is evacuated to make each groove in a closed state, so that there is a certain pressure difference between the inside of each groove and the outside of the mold. Specifically, the inside of each groove presents a negative pressure state after evacuation.

[0072] More preferably, when evacuating, pressure is applied to the bottom and side of the mold to assist in discharging the gas in each groove and closing it. Specifically, referring to Figure 6 and Figure 7 , the mold 1 is placed in the recessed part at the top of the accommodating body 71. The inside of the accommodating body 71 is hollow, and a connection port is provided on the side wall of the accommodating body 71. The connection port is connected to an air supply device, and the air supply device is used to inflate the inside of the accommodating body 71. The accommodating body 71 has a preset expansion and contraction property, so the accommodating body 71 expands when inflated inside, and then squeezes the side and bottom of the mold 1 to promote the discharge of gas in each groove 11, so that each groove 11 closes.

[0073] Injection step S2, after each groove is closed, liquid is injected into each groove.

[0074] Specifically, after each groove is closed, the inside of each groove presents a negative pressure state. Under the negative pressure state, the liquid inlet 211 of the housing 21 in the input device 2 is opened, and the liquid can be automatically injected into each groove 11.

[0075] Preferably, the liquid can have a preset pressure, and the preset pressure can be determined according to the actual situation, and this embodiment does not make any restrictions on this. Moreover, the pressure of the liquid can promote the injection of the liquid into each groove, ensure that the liquid fills the groove, and guarantee the quality of the microneedles.

[0076] During the process of injecting the liquid, in order to avoid the appearance of air bubbles, the injection step S2 can further include:

[0077] The first liquid injection sub-step S21, after each groove is closed, inject a preset amount of liquid into each groove.

[0078] Specifically, after each groove is closed, the liquid is injected into each groove by using the pressure difference. The preset amount can be determined according to the actual situation, and this embodiment does not make any restrictions on this.

[0079] The extraction sub-step S22, extract the liquid in each groove.

[0080] Specifically, all the liquid and gas in each groove are extracted through a vacuum device, so that each groove is in a closed state.

[0081] The liquid injection sub-step S21 and the extraction sub-step S22 are repeated at least once. Specifically, the liquid injection sub-step S21 and the extraction sub-step S22 are repeated in sequence. If one liquid injection sub-step S21 and one extraction sub-step S22 are regarded as a cycle, then at least one cycle is repeated.

[0082] Second liquid injection sub-step S23: Inject liquid into each groove until each groove is filled.

[0083] Preferably, when injecting liquid into each groove, vibrate the mold to avoid generating air bubbles. Specifically, a vibration device can be used to vibrate the mold. Preferably, an ultrasonic electromagnetic device is used to generate ultrasonic micro-frequency vibration.

[0084] Solidification step S3: Let it stand for a preset time, and the liquid in each groove solidifies into microneedles.

[0085] Specifically, the liquid in each groove automatically solidifies into microneedles at room temperature. In specific implementation, the preset time can be determined according to actual situations, and this embodiment does not make any restrictions on this.

[0086] Preferably, the injected liquid is at least one kind. When the liquid is one kind, simple microneedles are made; when the liquid is at least two kinds, multi-layer stratified capsule-type microneedles are made.

[0087] When the liquid is at least two kinds, inject different liquids into each groove in sequence.

[0088] In specific implementation, when the liquid is at least two kinds, first inject the first liquid and control the flow rate of the first liquid. After the first liquid enters each groove, it adsorbs on the surface of the groove, thus forming a liquid film. Then, inject the second liquid into each groove and control the flow rate of the second liquid. Then, inject the third liquid into each groove. Repeat the above steps in sequence until all different liquids are injected into each groove.

[0089] For structures such as the mold, vacuum pumping device, input device, and auxiliary device, refer to the specific implementation process of the microneedle manufacturing device for microarray transdermal drug delivery. Refer to the above description for details, and this embodiment will not elaborate here.

[0090] It can be seen that in this embodiment, pressure is applied to each groove of the mold. Since the mold has a preset flexibility, each groove can be in a closed state under the action of the pressure, which is convenient for injecting liquid into each groove. Each liquid only needs to solidify to make microneedles. The manufacturing method is simple, easy to implement, and can accurately control the shape of the microneedles.

[0091] It should be noted that the principles of the microneedle manufacturing device for microarray transdermal drug delivery and the microneedle manufacturing method in the present invention are the same, and the related parts can be referred to each other.

[0092] It should be noted that in the description of the present invention, the terms indicating directions or positional relationships such as "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings. This is only for convenience of description and does not indicate or imply that the device or element must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation to the present invention.

[0093] In addition, it should also be noted that in the description of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "coupled" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be directly connected, or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0094] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these changes and modifications.

Claims

1. A manufacturing device for microarray transdermal drug delivery microneedles, characterized in that, Comprising: A mold (1) with a preset flexibility, a pressing device, and an input device (2); wherein, The bottom of the mold (1) is for placing on a workbench (8), and a plurality of grooves (11) are formed in the top of the mold (1), and the shape of each groove (11) matches the shape of the microneedle; The pressing device is detachably arranged on the mold (1) and is used for applying pressure to each groove (11) so that each groove (11) is in a closed state; The input device (2) is detachably arranged on the top of the mold (1) and is used for generating a pressure difference between the inside and the outside of the mold (1) after each groove (11) is in a closed state. Under the action of the pressure difference, the input device (2) injects liquid into each groove (11), and the liquid in each groove is used to form microneedles after solidification; The input device (2) comprises: a hollow shell (21), a plurality of input pipes (22), and a plurality of sealing structures; wherein, The shell (21) is placed on the upper part of the mold (1), and at least one liquid inlet (211) is formed in the side wall of the shell (21), and each liquid inlet (211) is formed along the height direction of the shell (21); Each input pipe (22) is arranged on the side of the shell (21) facing the mold (1), and the end of each input pipe (22) covers the outside of each groove (11) in a one-to-one correspondence, and each input pipe (22) is used for injecting liquid with a preset pressure into the corresponding groove (11); Each sealing structure is arranged at the end of each input pipe (22) in a one-to-one correspondence, and each sealing structure is used for sealing the connection between the input pipe (22) and the groove (11); The pressing device comprises: a vacuum pumping device; wherein, the vacuum pumping device is arranged on the input device (2), and the vacuum pumping device is used for pumping vacuum for each groove (11) to make each groove (11) closed and stop pumping vacuum when each groove (11) is in a closed state; and, the vacuum pumping device is used for pumping vacuum for each groove (11) to make a negative pressure state present in each groove (11), and under the action of the internal and external pressure difference, the liquid flows into each groove (11) from the liquid inlet (211); The pressing device further comprises: an auxiliary device; wherein, the auxiliary device (7) is detachably arranged outside the mold (1) and is used for applying pressure to the outside of the mold (1) when the vacuum pumping device pumps vacuum to assist each groove (11) to close.

2. The manufacturing apparatus of the microarray transdermal drug delivery microneedles according to claim 1, characterized in that, The vacuum pumping device comprises: a partition plate (3) and a switching valve (4); wherein, The partition plate (3) is arranged in the shell (21) to divide the shell (21) into a first space (5) and a second space (6), and the first space (5) is close to the mold (1); The partition plate (3) is provided with an opening, and the switching valve (4) is arranged at the opening; The housing (21) is provided with an output port (212) corresponding to the second space (6) for connecting to a vacuum pump; The liquid inlet (211) is opened on the side wall of the housing (21) corresponding to the first space (5).

3. The manufacturing device of the microarray transdermal drug delivery microneedle according to claim 1, characterized in that The auxiliary device (7) includes: a hollow accommodating body (71); a concave portion for accommodating the mold (1) is provided at the top of the accommodating body (71), and a connection port is opened on the side wall of the accommodating body (71), and the connection port is used for connecting to a gas transmission device to inflate the accommodating body (71); the accommodating body (71) has a preset expansion and contraction property, and is in an expanded state when inflated to squeeze the side and bottom of the mold (1).

4. The manufacturing device of the microarray transdermal drug delivery microneedle according to claim 1, characterized in that It further includes: a vibration device; the vibration device is detachably arranged on the workbench (8) and is used for vibrating the mold (1) when the input device (2) injects liquid; and / or, It further includes: a support frame (9) and a lifting device (10); the support frame (9) is arranged on the workbench (8); the lifting device (10) is arranged on the support frame (9) and is placed above the mold (1); the input device (2) is arranged on the lifting device (10), and the lifting device (10) is used for driving the input device (2) to lift and lower.

5. A method for fabricating microneedles for transdermal drug delivery using a fabrication device for microneedles for transdermal drug delivery as described in any one of claims 1 to 4, characterized in that, It includes the following steps: A pressing step of applying pressure to each groove of the mold to close each groove; An injection step of injecting liquid into each groove after each groove is closed; wherein, the liquid has a preset pressure; A solidification step of standing for a preset time, and the liquid in each groove solidifies into microneedles; In the pressing step, Vacuum is pumped from each groove to close each groove and make each groove in a negative pressure state; In the injection step, under the action of the pressure difference of the negative pressure, the liquid flows into each groove; In the pressing step, When pumping vacuum, pressure is applied to the bottom and side of the mold to assist each groove in exhausting gas and closing.

6. The manufacturing method of the microarray transdermal drug delivery microneedles according to claim 5, characterized in that, The injection step further includes: A first liquid injection sub-step of injecting a preset amount of liquid into each groove after each groove is closed; An extraction sub-step of extracting the liquid in each groove; Repeating at least once the liquid injection sub-step and the extraction sub-step; A second liquid injection sub-step of injecting liquid into each groove until each groove is filled; In the second liquid injection sub-step, when injecting liquid, the mold is vibrated to avoid generating bubbles.

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