Apparatus and method for preparing microneedles

Abstract

The present application relates to a kind of equipment and method for preparing microneedle, the equipment includes microneedle negative mould, vacuum chamber, filling mechanism and vacuumizing mechanism, vacuum chamber includes the feeding cavity, filling cavity and discharge cavity independently arranged to each other;Feeding cavity is used to receive microneedle negative mould in non-negative pressure state, vacuumizing mechanism is used to vacuumize the feeding cavity that has received microneedle negative mould, filling cavity is used to receive the microneedle negative mould transferred from the feeding cavity in negative pressure state, discharge cavity is used to receive the microneedle negative mould transferred from the filling cavity in negative pressure state, and is used to break vacuum after receiving microneedle negative mould.The present application can realize the mass production of microneedle, improve the efficiency of microneedle preparation, and can ensure the forming quality of microneedle.

Description

Technical Field

[0001] This invention belongs to the field of microneedle preparation technology, and specifically relates to an apparatus and method for preparing microneedles. Background Technology

[0002] Most therapeutic drugs are administered via subcutaneous injection, a low-cost, rapid, and direct method of drug delivery. However, patients often cannot easily use syringes, and the pain and fear associated with syringes further limit patient compliance. Microneedles (including needles with micrometer-sized tips) loaded with drugs for transdermal delivery offer one solution to these problems. Microneedle transdermal drug delivery enables painless drug transport, improving patient compliance and safety. Simultaneously, microneedles allow for precise and targeted drug delivery, resulting in accurate and effective administration. Furthermore, microneedles can be used for skin pretreatment, enhancing skin permeability. Therefore, microneedles hold promising clinical application potential.

[0003] Polymer microneedle patches utilize polymer microneedles to puncture the stratum corneum, creating channels conducive to drug delivery and promoting transdermal absorption. The current technical route for manufacturing polymer microneedles involves: first, preparing a polymer solution for microneedle preparation; then, filling the polymer solution into a grooved microneedle mold; finally, curing the polymer solution within the mold; and finally, demolding to obtain soluble microneedles. A commonly used method for this approach is the transfer method using a silicone elastic mold. Specifically: first, a grooved silicone elastic mold (the grooves being the microneedle shape) needs to be prepared in advance; then, the prepared polymer solution is coated onto the surface of the grooved silicone elastic mold and placed in a vacuum environment for a certain period; after the polymer solution completely fills the grooves of the silicone elastic mold, it is placed in a natural environment and cured using a method (e.g., drying, cross-linking) to ultimately form soluble microneedles.

[0004] The most critical step in the above preparation method is filling the grooved silicone elastic mold with polymer solution. Because the grooves in the silicone elastic mold are extremely small (some areas are only a few micrometers in size), filling them individually is not only inefficient but also places extremely high demands on the equipment, making it very unfavorable for mass production. Liquid filling can solve the problem of mass production. If these tiny grooves are filled together using a filling method, once the polymer solution covers the surface of the silicone elastic mold, the gas trapped in the grooves below the liquid surface will prevent the polymer solution from seeping into the grooves, thus affecting the molding quality of the soluble microneedles.

[0005] To address the aforementioned technical problems, existing technologies propose pre-treating empty microneedle molds, specifically using plasma gas to improve the hydrophilicity of the mold surface, thereby promoting the filling of polymer solutions into the microneedle grooves. However, the hydrophilicity of the microneedle mold after plasma gas pre-treatment decreases over time. Therefore, due to the residence time of the pre-treated microneedle mold, there are significant differences in hydrophilicity between molds and between different regions within the mold. This affects the filling of grooves in the microneedle mold, consequently impacting the consistency and stability of soluble microneedle molding, making it difficult to guarantee the molding quality of soluble microneedles.

[0006] Existing technologies propose covering the surface of the microneedle mold with a polymer solution under negative pressure, and then using atmospheric pressure to fill the grooves with the polymer solution. This allows for rapid and uniform casting of large-planar microneedle molds, achieving high-precision and rapid replication of micro- and nano-scale structures. However, this approach cannot meet the requirements of mass production, resulting in low production efficiency. Furthermore, it is difficult to ensure the stability of the vacuum filling environment, affecting the molding quality of the microneedles. It also lacks flexibility, being unsuitable for microneedle molds of different sizes, leading to repeated disassembly and assembly, and cumbersome operation. In addition, existing technologies suffer from poor homogenization of the solution on the surface of the microneedle mold, which can contaminate the solution. Additionally, air cannot be fully expelled from the grooves during casting, ultimately failing to effectively guarantee the molding quality of the microneedles. Moreover, the preparation of soluble microneedles also suffers from low automation, low production efficiency, and high labor costs. Summary of the Invention

[0007] The purpose of this invention is to provide an apparatus and method for preparing microneedles, which can realize the mass production of microneedles, increase the production capacity of microneedle preparation, improve production efficiency, and improve the forming quality of microneedles.

[0008] To achieve the above objectives, the present invention provides an apparatus for preparing microneedles, comprising a microneedle negative mold, a vacuum chamber, a filling mechanism, and a vacuuming mechanism; the surface of the microneedle negative mold is formed with grooves matching the microneedle body; the filling mechanism is at least partially disposed within the vacuum chamber and is used to release the solution for preparing the microneedles; the vacuuming mechanism is connected to the vacuum chamber and is used to evacuate the vacuum chamber; the vacuum chamber includes an independently disposed feed chamber, a filling chamber, and a discharge chamber;

[0009] The feeding chamber is used to receive the microneedle female mold under non-negative pressure conditions;

[0010] The vacuuming mechanism is used to evacuate the feed chamber that has received the microneedle negative mold;

[0011] The filling cavity is used to receive the microneedle negative mold transferred from the feeding cavity under negative pressure.

[0012] The discharge chamber is used to receive the microneedle negative mold transferred from the filling chamber under negative pressure, and to break the vacuum after receiving the microneedle negative mold.

[0013] Optionally, the device further includes a controller and a vacuum breaking valve connected by communication, the vacuum breaking valve including a first vacuum breaking valve and a third vacuum breaking valve; the first vacuum breaking valve is disposed on the feed chamber, and the third vacuum breaking valve is disposed on the discharge chamber;

[0014] The controller is used to control the first vacuum breaking valve to open in order to break the vacuum in the feeding chamber, and is also used to control the third vacuum breaking valve to open in order to break the vacuum in the discharging chamber after the microneedle mold in the third state is transferred to the discharging chamber in the negative pressure state.

[0015] Optionally, the controller is also communicatively connected to the vacuuming mechanism; the controller is used to control the vacuuming mechanism to evacuate the discharge chamber, the filling chamber and the feed chamber.

[0016] Optionally, the device further includes a sensor assembly communicatively connected to the controller, the sensor assembly including a first sensor, a second sensor, and a third sensor;

[0017] The feeding chamber is equipped with the first sensor, the filling chamber is equipped with the second sensor, and the discharging chamber is equipped with the third sensor. The controller is used to control the vacuum level of the corresponding chambers based on the pressure information detected by the first, second, and third sensors, respectively.

[0018] Optionally, the equipment further includes a homogenization mechanism, and the filling cavity is provided with a pouring station and a homogenization station;

[0019] When the filling cavity is under negative pressure, the microneedle negative mold inside the filling cavity is used to be placed at the pouring station, and the filling mechanism is used to pour the solution onto the surface of the microneedle negative mold;

[0020] After the solution is poured into the microneedle mold in the filling cavity, it is transferred to the homogenization station, and the homogenization mechanism is used to homogenize the microneedle mold after the solution is poured, so that the solution is uniformly filled on the surface of the microneedle mold.

[0021] Optionally, the homogenization mechanism includes a gripping mechanism and a driving mechanism. The gripping mechanism includes a spindle assembly and a clamping assembly. The driving mechanism includes a servo motor and a transmission assembly. The spindle assembly includes a spindle and a base. The bottom end of the spindle is fixedly connected to the base. The clamping assembly includes at least three jaws. The at least three jaws are evenly distributed on the base around the axis of the spindle and are used to clamp and fix a tray. The tray is loaded with the microneedle mold. The servo motor is used to drive the spindle to rotate through the transmission assembly. The axis of the spindle is parallel to the axis of the groove.

[0022] Optionally, the drive mechanism further includes a cylinder assembly, an elastic component, and a turntable; the turntable is sleeved on the main shaft and is rotatable relative to the main shaft; one end of the elastic component is connected to the main shaft, and the other end is connected to the turntable.

[0023] When the turntable is driven to rotate in the first direction by the cylinder assembly, the elastic component stores elastic potential energy and all the claws move to the released position.

[0024] When the cylinder assembly releases the force on the turntable, the elastic component releases its elastic potential energy and drives the turntable to rotate in the second direction, causing all the claws to move to the locking position.

[0025] Optionally, the homogenizing mechanism further includes pressure blocks, which are fixed to the base and used to press against the turntable in the axial direction; the number of pressure blocks is at least three.

[0026] Optionally, the clamping assembly further includes a guide rail, a slider, a fixed seat, and a limiting pin. The guide rail is arranged radially along the base, the slider is slidably mounted on the guide rail, the fixed seat is fixed on the slider, each of the jaws is fixed on a corresponding fixed seat, the limiting pin is fixed on the fixed seat, the turntable is provided with an arc-shaped limiting groove, the limiting pin is movably mounted in the limiting groove, and the two ends of the arc of the limiting groove are at different distances from the center of the turntable.

[0027] When the turntable rotates in the first direction, the limiting pin moves from the proximal end to the distal end of the arc-shaped limiting groove, and drives the pawl to move outward until the limiting pin engages with the distal end of the limiting groove.

[0028] When the turntable rotates in the second direction, the limiting pin moves from the proximal end to the distal end of the arc-shaped limiting groove, and drives the pawl to move inward until the limiting pin engages with the proximal end of the limiting groove.

[0029] Optionally, the cylinder assembly includes a push rod, and a fixed post is provided on the turntable. The push rod is used to push the fixed post to drive the turntable to rotate in a first direction.

[0030] Optionally, the device further includes a tray and a conveyor line, the tray being used to load the microneedle mold, and the conveyor line being used to transport the tray; the homogenization mechanism is used to drive the tray to move in order to homogenize the microneedle mold, and the movement of the tray includes at least one of horizontal rotation, horizontal movement, shaking, and up-and-down swinging.

[0031] Optionally, the device further includes a tray for loading the microneedle negative mold, and the same tray can load microneedle negative molds of different sizes.

[0032] Optionally, the equipment further includes a feeding conveyor line, a discharging conveyor line, and a transfer conveyor line, wherein the feeding conveyor line is located in the feeding area and the discharging conveyor line is located in the discharging area;

[0033] The loading conveyor line is used to transport the pallet to the feeding chamber, and the unloading conveyor line receives the pallet from the discharging chamber;

[0034] The transfer conveyor line is used to receive the empty pallets from the unloading conveyor line and to transfer the empty pallets to the loading area.

[0035] Optionally, the transfer conveyor line is located below the loading conveyor line and the unloading conveyor line. The equipment also includes an automatic transfer mechanism, which is used to transfer the empty pallet on the unloading conveyor line to the transfer conveyor line and to transfer the empty pallet on the transfer conveyor line to the loading conveyor line.

[0036] Optionally, the device further includes an automatic feeding mechanism and an automatic loading mechanism disposed in the loading area, wherein the automatic feeding mechanism is used to transport the micro needle female mold to a loading station;

[0037] The automatic feeding mechanism is also used to remove the micro-needle negative mold from the feeding station and place it on the tray on the feeding conveyor line.

[0038] Optionally, the device further includes an automatic unloading mechanism and a transfer tray disposed in the unloading area. The automatic unloading mechanism is used to take the micro-needle mold from the tray on the unloading conveyor line and place it on the transfer tray.

[0039] Optionally, the feeding chamber, the filling chamber, and the discharging chamber are arranged adjacent to each other in sequence. A first gate is provided at the inlet of the feeding chamber, a second gate is shared by the outlet of the feeding chamber and the inlet of the filling chamber, a third gate is shared by the outlet of the filling chamber and the inlet of the discharging chamber, and a fourth gate is provided at the outlet of the discharging chamber.

[0040] Optionally, the device further includes a first conveyor line, a second conveyor line, and a third conveyor line, wherein the first conveyor line is disposed in the feeding chamber, the second conveyor line is disposed in the filling chamber, and the third conveyor line is disposed in the discharging chamber.

[0041] Optionally, the filling mechanism is used to pour the solution onto the surface of the microneedle mold within the filling cavity under negative pressure.

[0042] To achieve the above objectives, the present invention also provides a method for preparing microneedles, the method comprising:

[0043] A microneedle negative mold is provided, wherein the surface of the microneedle negative mold is formed with a groove that matches the microneedle body;

[0044] The microneedle mold is placed in the feed chamber under non-negative pressure. Then, the feed chamber is evacuated by the vacuuming mechanism so that the feed chamber and the microneedle mold are under negative pressure.

[0045] The microneedle mold under negative pressure is transferred from the feed chamber under negative pressure to the filling chamber under negative pressure. Under negative pressure, the solution is poured onto the surface of the microneedle mold through the filling mechanism. The solution is then homogenized by the homogenizing mechanism so that the solution is evenly spread on the surface of the microneedle mold.

[0046] The microneedle mold of the casting solution is transferred from the filling cavity under negative pressure to the discharge cavity under negative pressure, and the negative pressure state of the filling cavity is maintained.

[0047] After transferring the microneedle negative mold containing the casting solution to the discharge chamber under negative pressure, the vacuum in the discharge chamber is broken so that the discharge chamber is in a non-negative pressure state, and the microneedle negative mold containing the solution is obtained.

[0048] After the microneedle negative mold containing the solution is solidified and molded, it is demolded to obtain the microneedle.

[0049] Optionally, the method further includes:

[0050] After transferring the microneedle female mold in a negative pressure state from the feed chamber in a negative pressure state to the filling chamber in a negative pressure state, the vacuum in the feed chamber in a negative pressure state is broken so that the feed chamber is in a non-negative pressure state to receive the next microneedle female mold.

[0051] Optionally, the method further includes:

[0052] After breaking the vacuum in the discharge chamber under negative pressure, the microneedle mold containing the solution is transferred from the discharge chamber under non-negative pressure to the outside, so that the discharge chamber under non-negative pressure is in an unloaded state.

[0053] After the discharge chamber is empty in a non-negative pressure state, the discharge chamber is evacuated by the vacuuming mechanism to put the discharge chamber in a negative pressure state so as to receive the next homogenized microneedle mold.

[0054] Optionally, the method further includes:

[0055] At the pouring station within the filling cavity, the solution is poured onto the surface of the microneedle mold under negative pressure via the filling mechanism.

[0056] In the homogenization stage within the filling cavity, the homogenization mechanism homogenizes the microneedle negative mold after the solution has been poured.

[0057] Optionally, in the homogenization station, the microneedle negative mold is loaded onto a tray, and the tray is driven to move by the homogenization mechanism to homogenize the microneedle negative mold. The movement of the tray includes at least one of horizontal rotation, horizontal movement, shaking, and up-and-down swinging.

[0058] Optionally, the method includes: loading the microneedle molds onto a tray and sequentially feeding them into the feed chamber, the filling chamber, and the discharge chamber, with microneedle molds of different sizes being transported through the same tray.

[0059] Optionally, the method further includes:

[0060] The pallet is conveyed to the feeding chamber by a feeding conveyor line in a feeding area, and the pallet from the discharge chamber is received by a discharging conveyor line in a discharging area;

[0061] An empty pallet is received from the unloading conveyor line via a transfer conveyor line, and the empty pallet is then transferred to the loading area by the transfer conveyor line.

[0062] Optionally, the transfer conveyor line is disposed below the loading conveyor line and the unloading conveyor line, and the method further includes:

[0063] An automatic transfer mechanism is used to transfer the empty pallet from the unloading conveyor line to the transfer conveyor line, and the automatic transfer mechanism is used to transfer the empty pallet from the transfer conveyor line to the loading conveyor line.

[0064] Optionally, the method further includes:

[0065] An automatic feeding mechanism in the feeding area transports the micro-needle female mold to a feeding station;

[0066] An automatic feeding mechanism in the feeding area takes the micro-needle negative mold from the feeding station and places it on the tray on the feeding conveyor line.

[0067] Optionally, the method further includes:

[0068] An automatic unloading mechanism in the unloading area takes the micro-needle negative mold from the tray on the unloading conveyor line and places it on the transfer tray in the unloading area.

[0069] Optionally, a controller may control the vacuuming mechanism to evacuate the feed chamber, the filling chamber, and the discharge chamber.

[0070] Optionally, the homogenization mechanism performs accelerated rotation, uniform rotation, and decelerated rotation sequentially when performing homogenization processing on the microneedle negative mold.

[0071] To achieve the above objectives, the present invention also provides a method for preparing microneedles, the method comprising:

[0072] A microneedle negative mold and a vacuum chamber are provided. The surface of the microneedle negative mold is formed with a groove that matches the microneedle body. The vacuum chamber includes an independently set filling chamber and a discharging chamber.

[0073] The microneedle negative mold is placed in a filling cavity under non-negative pressure, and the solution is poured onto the surface of the microneedle negative mold through a filling mechanism;

[0074] The microneedle negative mold is homogenized by a homogenization mechanism so that the solution is evenly spread on the surface of the microneedle negative mold;

[0075] The filling cavity is evacuated by a vacuuming mechanism so that the filling cavity and the microneedle mold are under negative pressure.

[0076] After the homogenized microneedle mold is transferred to the discharge chamber under negative pressure, the vacuum in the discharge chamber is broken so that the discharge chamber is in a non-negative pressure state, and the microneedle mold containing solution is obtained.

[0077] After the microneedle negative mold containing the solution is cured and formed, it is demolded.

[0078] Optionally, the method includes: loading the microneedle negative mold onto a tray and placing it into the filling cavity and the discharge cavity, and at the homogenization station, driving the tray to move via the homogenization mechanism to homogenize the microneedle negative mold, wherein the movement of the tray includes at least one of horizontal rotation, horizontal movement, shaking, and up-and-down swinging.

[0079] The aforementioned equipment and method for preparing microneedles, through independently configured feeding chamber, filling chamber, and discharge chamber, separates the processes of vacuuming, vacuum filling, and vacuum breaking of the microneedle negative mold. This significantly reduces the vacuum filling waiting time and improves the overall vacuum filling efficiency. Moreover, before vacuum filling, the microneedle negative mold has undergone a relatively long vacuuming process, greatly reducing the air in the grooves on the surface of the microneedle negative mold. This allows the solution to completely fill the grooves, resulting in good filling effect and effectively ensuring the molding quality of the microneedles. At the same time, it can also greatly improve the production cycle, increase equipment capacity, and realize the mass production of microneedles.

[0080] The above-mentioned equipment and method for preparing microneedles achieve solution pouring by vacuum filling the microneedle negative mold in the filling chamber of the vacuum chamber. This can fully remove the air in the groove of the microneedle negative mold, ensuring that the groove of the microneedle negative mold is filled with solution after the vacuum is broken, thus ensuring the quality of microneedle forming.

[0081] The aforementioned equipment and method for preparing microneedles uses a homogenization mechanism to homogenize the solution on the surface of the microneedle mold, effectively leveling the viscous solution and ensuring its uniform distribution, thus guaranteeing the quality of microneedle formation. Specifically, the homogenization of the microneedle mold is achieved through the rotation of the homogenization mechanism. The rotation axis of the main shaft is parallel to the depth direction of the groove in the microneedle mold (defined as the axial direction of the groove). The rotation of the main shaft allows the viscous solution on the microneedle mold to be leveled, and then the solution enters the groove of the microneedle mold by gravity. This method effectively levels the viscous solution on the surface of the microneedle mold using centrifugal force, resulting in good homogenization. Furthermore, it avoids direct contact with the solution, preventing contamination and further ensuring the quality of microneedle formation. Attached Figure Description

[0082] Those skilled in the art will understand that the accompanying drawings are provided to better understand the invention and do not constitute any limitation on the scope of the invention. Wherein:

[0083] Figure 1 This is a schematic front view of the device for preparing microneedles provided in a preferred embodiment of the present invention;

[0084] Figure 2 A top view of the external structure of the vacuum chamber provided in a preferred embodiment of the present invention;

[0085] Figure 3 This is a schematic diagram of the internal structure of a vacuum chamber provided in a preferred embodiment of the present invention;

[0086] Figure 4 This is a top view schematic diagram of the device for preparing microneedles provided in a preferred embodiment of the present invention;

[0087] Figure 5 This is a front view of the homogenization mechanism according to a preferred embodiment of the present invention;

[0088] Figure 6 This is a front view of the spindle assembly and clamping assembly according to a preferred embodiment of the present invention;

[0089] Figure 7 This is a perspective view of the spindle assembly and clamping assembly according to a preferred embodiment of the present invention;

[0090] Figure 8 This is a top view of the spindle assembly and clamping assembly according to a preferred embodiment of the present invention;

[0091] Figure 9 This is a schematic diagram illustrating the principle of the cylinder assembly ejecting and the chuck releasing in a preferred embodiment of the present invention.

[0092] Figure 10 This is a schematic diagram illustrating the principle of the cylinder assembly retracting in a preferred embodiment of the present invention, causing the pawl to clamp under the action of a tension spring.

[0093] Figure 11 The rotational speed-time curve is shown in the diagram of the homogenization mechanism in a preferred embodiment of the present invention. Detailed Implementation

[0094] The present invention will now be described in more detail with reference to the accompanying drawings, which illustrate preferred embodiments of the invention. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being of general knowledge to those skilled in the art and is not intended to limit the invention.

[0095] For clarity, not all features of the actual embodiments are described. In the following description, well-known functions and structures are not detailed in detail, as they would obscure the invention with unnecessary detail. It should be understood that in the development of any actual embodiment, numerous implementation details must be made to achieve the developer's specific objectives, such as changes from one embodiment to another according to limitations related to the system or business. Furthermore, it should be understood that such development work may be complex and time-consuming, but is merely routine work for those skilled in the art.

[0096] The invention is described more specifically by way of example in the following paragraphs with reference to the accompanying drawings. The advantages and features of the invention will become clearer from the following description. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the invention.

[0097] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0098] Figure 1 This diagram shows a front view of a preferred embodiment of the apparatus for preparing microneedles according to the present invention. Figure 2 A top view schematic diagram of the external structure of a vacuum chamber according to a preferred embodiment of the present invention is shown. Figure 3 A schematic diagram of the internal structure of a vacuum chamber according to a preferred embodiment of the present invention is shown. Figure 4 A top view schematic diagram of the structure of a device for preparing microneedles provided in a preferred embodiment of the present invention is shown.

[0099] like Figures 1 to 4 As shown, this embodiment provides an apparatus for preparing microneedles. These microneedles can puncture the stratum corneum of the human body, forming channels conducive to drug delivery and thus promoting transdermal drug absorption. This application does not limit the shape of the microneedle body, including but not limited to needle bodies with a convex tip. The tip can be a sharp or non-sharp convex structure; the needle body includes, but is not limited to, conical, pyramidal, or spindle-shaped forms. The solution for preparing the microneedles has a certain viscosity, and the solution includes, but is not limited to, polymer solutions. This application does not particularly limit the type of solution.

[0100] The equipment for preparing microneedles specifically includes a microneedle negative mold 1, a vacuum chamber 2, a filling mechanism 3, and a vacuuming mechanism 4; the surface of the microneedle negative mold 1 has grooves (not shown) that match the microneedle body; the filling mechanism 3 is at least partially disposed in the vacuum chamber and is used to release the solution for preparing microneedles; the vacuum chamber 2 is used to provide a sealed environment to facilitate the preparation of microneedles under vacuum conditions; the vacuuming mechanism 4 is connected to the vacuum chamber 2 and is used to evacuate the vacuum chamber 2.

[0101] like Figure 2As shown, the vacuum chamber 2 includes three independent vacuum chambers: a feeding chamber 21, a filling chamber 22, and a discharging chamber 23, which are arranged sequentially and adjacently. The feeding chamber 21 receives the microneedle mold 1 under non-negative pressure conditions, which is equivalent to atmospheric pressure. It should be understood that atmospheric pressure is not an absolute standard atmospheric pressure; due to differences in geographical location, sea level, temperature, etc., the actual atmospheric pressure may differ from the standard atmospheric pressure. Therefore, this application does not impose any particular limitation on the atmospheric pressure value. The vacuuming mechanism 4 evacuates the feeding chamber 21 after receiving the microneedle mold 1, so that both the microneedle mold 1 and the feeding chamber 21 are under negative pressure. The filling chamber 22 receives the microneedle mold 1 transferred from the negative pressure feeding chamber 21. The filling mechanism 3 fills the microneedle mold 1 into the negative pressure filling chamber 22. A solution for preparing microneedles is poured onto the surface of the needle mold 1, resulting in a microneedle mold 1 with the solution poured in. Further, the microneedle mold 1 with the solution poured in is homogenized to ensure the solution is evenly spread across its surface. The discharge chamber 23 receives the microneedle mold 1 with the casting solution transferred from the filling chamber 22 under negative pressure. After receiving the microneedle mold 1 with the casting solution, the vacuum is broken to bring the discharge chamber 23 to a non-negative pressure state, resulting in a microneedle mold 1 with the solution. At this point, the microneedle mold 1 with the solution is under normal pressure. After the microneedle mold 1 with the solution is further solidified and molded, it is demolded to obtain the microneedles (integrated microneedles).

[0102] This embodiment also provides a method for preparing microneedles, the method comprising:

[0103] Step 11: Place the microneedle female mold 1 in the feed chamber 21 under non-negative pressure. Then, use the vacuum pumping mechanism 4 to evacuate the feed chamber 21 so that the feed chamber 21 and the microneedle female mold 1 are under negative pressure.

[0104] Step 12: Transfer the microneedle mold 1 under negative pressure from the feeding chamber 21 under negative pressure to the filling chamber 22 under negative pressure. Under negative pressure, pour the solution into the surface of the microneedle mold 1 in the filling chamber 22 through the filling mechanism 3. After pouring the solution, preferably use the homogenization mechanism 6 to homogenize the microneedle mold 1 after pouring the solution so that the solution is evenly spread on the surface of the microneedle mold 1.

[0105] Step 13: Transfer the microneedle mold 1 of the casting solution from the filling chamber 22 under negative pressure to the discharge chamber 23 under negative pressure, and maintain the negative pressure state of the filling chamber 22; that is, after the microneedle mold 1 of the casting solution is sent out of the filling chamber 22, the filling chamber 22 is closed, so that the filling chamber 22 can still maintain the negative pressure state, in order to prepare to receive the next microneedle mold 1 to be cast.

[0106] Step 14: After transferring the microneedle mold 1 containing the casting solution to the discharge chamber 23 under negative pressure, the vacuum in the discharge chamber 23 is broken so that the discharge chamber 23 is in a non-negative pressure state, and the microneedle mold 1 containing the solution is obtained; it should be understood that the discharge chamber 23 has been evacuated before receiving the microneedle mold 1 containing the casting solution, and when the vacuum in the discharge chamber 23 is broken, the solution fills the groove of the microneedle mold 1 by its own gravity;

[0107] Step 15: After the microneedle negative mold containing the solution is cured and formed, it is demolded to obtain the microneedles.

[0108] Following step 14, the preferred procedure also includes the following steps:

[0109] After the vacuum in the discharge chamber 23 is broken, the outlet of the discharge chamber 23 is opened, and the microneedle mold 1 loaded with casting solution is transferred to the outside of the discharge chamber 23, so that the discharge chamber 23 is in an empty state after the vacuum is broken. After the discharge chamber 23 is empty, the discharge chamber 23 is closed, and the vacuum in the discharge chamber 23 is evacuated until the vacuum degree in the discharge chamber 23 reaches the set value and then stops, in order to prepare to receive the next microneedle mold 1 for casting solution.

[0110] In addition, in step 12, after the microneedle female mold 1 under negative pressure is sent out of the feeding chamber 21, the feeding chamber 21 is closed, and the vacuum in the feeding chamber 21 is broken until the pressure in the feeding chamber 21 is consistent with the external environment, so as to prepare to receive the next microneedle female mold 1.

[0111] The aforementioned three independent vacuum chambers significantly reduce waiting time during filling operations, effectively improving the vacuum filling efficiency of microneedle preparation. It should be understood that repeatedly vacuuming and breaking the vacuum in a single vacuum chamber not only results in long filling times and low filling efficiency but also high energy consumption and production costs. In contrast, the vacuum chamber of this invention consists of three independent vacuum chambers, where the filling chamber 22 does not require repeated vacuuming and breaking the vacuum, reducing energy consumption and waiting time during filling, thus increasing filling efficiency. Therefore, the three independent vacuum chambers can greatly improve production cycle time and increase equipment capacity, allowing for a single-machine capacity of up to 4 pieces / minute. Especially before filling, the microneedle mold 1 has undergone a relatively long vacuuming process, significantly reducing the air content within the grooves of the microneedle mold 1, ensuring the quality of the final microneedles, and improving the yield rate of microneedle preparation. Furthermore, filling the solution under vacuum conditions can fully expel air from the grooves of the microneedle mold, ensuring that the grooves of the microneedle mold are filled with solution after the vacuum in the discharge chamber 23 is broken, thus ensuring the quality of microneedle molding. Especially under vacuum conditions, combined with the homogenization treatment of the homogenization mechanism 6, the viscous solution on the surface of the microneedle mold can be effectively spread, allowing the solution to be evenly distributed on the surface of the microneedle mold, further ensuring the quality of microneedle molding.

[0112] In other embodiments, the solution can be cast first under non-negative pressure, then homogenized by the homogenization mechanism 6, followed by vacuuming, and then venting the vacuum to achieve solution filling. Specifically, this embodiment also provides another method for preparing microneedles, which includes:

[0113] Step 21: Place the microneedle negative mold 1 in the filling cavity 22 under non-negative pressure, and pour the solution onto the surface of the microneedle negative mold 1 through the filling mechanism 3;

[0114] Step 22: The microneedle mold 1 is homogenized by the homogenization mechanism 6 so that the solution is evenly spread on the surface of the microneedle mold 1;

[0115] Step 23: Vacuum the filling cavity 22 using the vacuuming mechanism 4 to bring the filling cavity 22 and the microneedle mold 1 into a negative pressure state;

[0116] Step 24: After transferring the homogenized microneedle mold 1 to the negative pressure discharge chamber 23, the vacuum of the negative pressure discharge chamber 23 is broken so that the discharge chamber 23 is in a non-negative pressure state, and the microneedle mold 1 containing the solution is obtained.

[0117] Step 25: After the microneedle negative mold 1 containing the solution has been cured and formed, demold it.

[0118] It should be understood that the vacuum pressure of each vacuum chamber is set according to the microneedle product being prepared. The vacuum pressure of each vacuum chamber must meet certain conditions. Insufficient vacuum pressure will affect the microneedle forming quality, while excessive vacuum pressure will increase energy consumption, increase vacuuming and breaking time, and reduce equipment capacity. In this embodiment, the working pressures of the feeding chamber 21, filling chamber 22, and discharging chamber 23 are preferably equal, preferably between -95 kPa and -80 kPa. Under this working pressure, the microneedle forming quality can be guaranteed while reducing vacuuming and breaking time, thus increasing equipment capacity. Furthermore, the control accuracy of the working pressures of the feeding chamber 21, filling chamber 22, and discharging chamber 23 is ±1 kPa. More preferably, the vacuuming time of the feeding chamber 21 and discharging chamber 23 is 10–16 seconds, the vacuum breaking time of the feeding chamber 21 and discharging chamber 23 is 3–5 seconds, while the filling chamber 22, since it is always under negative pressure during production, does not have special requirements for vacuuming and breaking time.

[0119] The device for preparing microneedles preferably also includes a tray 5, which is used to load the microneedle negative mold 1 so that it enters the feeding chamber 21, the filling chamber 22 and the discharging chamber 23 in sequence. More preferably, microneedle negative molds 1 of different sizes can be transported through the same tray 5.

[0120] Furthermore, the preferred steps for using the vacuum chamber 5 include: first, transferring the tray 5 containing the microneedle mold 1 to the infeed chamber 21 under normal pressure; then, closing the infeed chamber 21 to isolate it from the other two vacuum chambers and the external environment; then, evacuating the infeed chamber 21 until the vacuum pressure reaches a set value, stopping the evacuation and maintaining a negative pressure state; next, opening the outlet of the infeed chamber 21 and transferring the evacuated microneedle mold 1 along with the tray 5 to the filling chamber 22, and closing the filling chamber. The filling chamber 22 is isolated from the other two vacuum chambers and the external environment. During this process, the filling chamber 22 has been evacuated before the microneedle mold 1 is inserted. After the microneedle mold 1 is poured, the outlet of the filling chamber 22 is opened, and the microneedle mold 1 filled with solution is transferred to the discharge chamber 23 along with the tray 5. The discharge chamber 23 is then closed to isolate it from the other two vacuum chambers and the external environment. The vacuum in the discharge chamber 23 is then broken until the pressure inside the discharge chamber 23 is consistent with the external environment.

[0121] Furthermore, in step 13, after the solution is poured into the microneedle mold 1, it continues to undergo homogenization treatment within the filling cavity 22. After homogenization treatment, the outlet of the filling cavity 22 is opened. That is, the equipment for preparing microneedles also includes a homogenization mechanism 6, and the filling cavity 22 is preferably provided with a pouring station and a homogenization station. When the filling cavity 22 is under negative pressure, the microneedle mold 1 is transferred from the tray 5 to the pouring station. Then, the filling mechanism 3 is used to pour the solution onto the surface of the microneedle mold 1 under negative pressure. After the solution is poured into the microneedle mold 1, it is transferred to the homogenization station via the tray 5. The homogenization mechanism 6 is then used to homogenize the microneedle mold 1 after the solution has been poured, so that the solution is uniformly filled on the surface of the microneedle mold 1.

[0122] In this embodiment, the homogenization mechanism 6 mainly drives the tray 5 to move in order to achieve homogenization of the microneedle negative mold 1. The movement of the tray 5 can be various movements, such as at least one of horizontal rotation, horizontal movement, shaking, and up-and-down swinging. In this method, the homogenization mechanism 6 does not come into contact with the solution used to prepare the microneedles, reducing the risk of solution contamination. Moreover, the homogenization effect is good, and it can be achieved through a relatively simple structure and operation, thereby ensuring the stability and consistency of the solution content filled in each groove and ensuring the quality of microneedle molding.

[0123] In some embodiments, the homogenization mechanism 6 includes a gripping structure and a driving mechanism. The driving mechanism drives the gripping mechanism to rotate horizontally around its own axis. The gripping mechanism grips the tray 5, and then the driving mechanism drives the tray 5 and the microneedle mold 1 to rotate horizontally together through the gripping mechanism. This causes the solution on the surface of the microneedle mold 1 to be evenly spread and fill each groove through centrifugal force. The homogenization mechanism 6 and the filling mechanism 3 can be arranged in the same filling cavity 22, or a separate vacuum cavity can be arranged between the filling cavity 22 and the discharge cavity 23 to house the homogenization mechanism 6 separately.

[0124] In some embodiments, the homogenization mechanism 6 includes a gripping mechanism and a driving mechanism. The driving mechanism drives the gripping mechanism to swing up and down, gripping the tray 5. The driving mechanism then drives the tray 5 and the microneedle mold 1 to swing up and down together via the gripping mechanism, thereby homogenizing the solution on the surface of the microneedle mold 1 and filling each groove through the up-and-down swinging motion. In other embodiments, the gripping mechanism can be omitted, and the driving mechanism can be configured as a motion platform that carries the tray 5. The motion platform drives the tray 5 to rotate horizontally, swing up and down, shake (including vibrate), or move horizontally.

[0125] Figures 5 to 10A homogenizing mechanism 6 according to a preferred embodiment is shown. The homogenizing mechanism 6 includes a gripping mechanism and a driving mechanism. The gripping mechanism includes a spindle assembly 610 and a clamping assembly 620. The driving mechanism includes a servo motor 630 and a transmission assembly 640. The spindle assembly 610 includes a spindle 611 and a base 612, with the bottom end of the spindle 611 fixedly or detachably connected to the base 612. The clamping assembly 620 includes at least three jaws 621, which are evenly distributed around the axis of the spindle 611 on the base 612. The at least three jaws 621 cooperate to clamp and fix the tray 5. Preferably, there are four jaws 621 for a more stable clamping effect. Each jaw 621 is movable relative to the base 612 to clamp or release the tray 5. The servo motor 630 is connected to the spindle 611 via the transmission assembly 640 to drive the spindle 611 to rotate horizontally around its own axis. The transmission assembly 640 is preferably a pulley assembly. Specifically, the transmission assembly 640 includes a driving pulley 641, a belt 642, and a driven pulley 643. The driving pulley 641 is connected to the motor shaft (not labeled) of the servo motor 630. The belt 642 is sleeved on the driving pulley 641 and the driven pulley 643, and the driven pulley 643 is sleeved on the top of the main shaft 611. Preferably, the servo motor 630 is arranged parallel to the main shaft 611. The servo motor 630 drives the main shaft 611 and the base 612 to rotate through the pulley assembly, thereby driving the tray 5 and the microneedle mold 1 to rotate together, so that the solution is evenly coated on the surface of the microneedle mold 1. The main shaft 611 can be fixed to a bearing seat 615 by a bearing 613 and a nut 614. Both the bearing seat 615 and the servo motor 630 are fixed to the base 650. The base 612 can be of various shapes, preferably circular. It should be understood that the rotation axis of the main shaft 611 is parallel to the depth direction of the groove of the microneedle mold, that is, the rotation axis of the main shaft 611 is parallel to the axial direction of the groove. Thus, the rotation of the main shaft 611 spreads the viscous solution (i.e. the solution for preparing microneedles) on the microneedle mold. Then, the viscous solution enters the groove of the microneedle mold by gravity. This method can effectively spread the viscous solution on the surface of the microneedle mold, with good homogenization effect. Moreover, it does not directly contact the solution, avoiding contamination of the solution and further ensuring the quality of microneedle forming.

[0126] Further preferably, the driving mechanism further includes a cylinder assembly 660, an elastic component 670, and a turntable 680. The turntable 680 is sleeved on the main shaft 611 and can rotate relative to the main shaft 611. One end of the elastic component 670 is connected to the main shaft 611, and the other end is connected to the turntable 680. When the turntable 680 is driven to rotate in the first direction by the cylinder assembly 660, the elastic component 670 stores elastic potential energy and moves the jaws 621 of the clamping assembly 620 to the released position, so as to release the clamp on the tray 5 or to facilitate clamping the tray 5 after release; and when the force of the cylinder assembly 660 is released from the turntable 680, the elastic component 670 releases elastic potential energy and drives the turntable 680 to rotate in the second direction, so that the jaws 621 of the clamping assembly 620 move to the locked position, so as to clamp the tray 5 or to restore the tray 5 to its original position after release. This method of controlling the opening and closing of the gripper 621 using a cylinder and energy storage element eliminates the need for complex auxiliary equipment such as pneumatic and electrical circuits. Therefore, it has a simple structure, high reliability, and the rotation speed of the spindle 611 can be controlled by the servo motor 630 to achieve a good centrifugal effect. The elastic component 670 is generally a tension spring 671, with one end fixed to the spindle 611 and the other end fixed to the turntable 680. In this embodiment, one end of the tension spring 671 is fixed to the first pin 672, which is fixed to the spindle 611, and the other end of the tension spring 671 is fixed to the second pin 673, which is fixed to the turntable 680. The first direction is opposite to the second direction.

[0127] To prevent the turntable 680 from bouncing up and down, the homogenizing mechanism 6 further includes an auxiliary component 690, which can be used to limit the axial position of the turntable 680. Optionally, the auxiliary component 690 includes a pressure block 691, which is fixed to the base 612 and used to press against the turntable 680 in the axial direction. The number of pressure blocks 691 is at least three and they are evenly distributed on the base 612 in a circumferential direction.

[0128] The clamping assembly 620 may include a guide rail 622, a slide rail 623, a fixed base 624, and a limiting pin 625. The guide rail 622 is arranged radially along the base 612, the slide rail 623 is slidably mounted on the guide rail 622, the fixed base 624 is fixed on the slide rail 623, and each claw 621 is fixed on a corresponding fixed base 624. The limiting pin 625 is fixed on the fixed base 624, and the turntable 680 is provided with an arc-shaped limiting groove 681. The limiting pin 625 is movably disposed in the arc-shaped limiting groove 681, and the two ends of the arc of the limiting groove 681 are at different distances from the center of the turntable 680. Before clamping, the clamping assembly 620 is in the initial position, at which time the limiting pin 625 abuts against the proximal end of the arc of the limiting groove 681, and the proximal end of the arc of the limiting groove 681 is closer to the center of the turntable than the distal end of the arc. When the turntable 680 rotates in the first direction, the limiting pin 625 moves from the proximal end to the distal end of the arc-shaped limiting groove 681, and drives the claw 621 to move outward until the limiting pin 625 abuts against the distal end of the limiting groove 681; when the turntable 680 rotates in the second direction, the limiting pin 625 moves from the proximal end to the distal end of the arc-shaped limiting groove 681, and drives the claw 621 to move inward until the limiting pin 625 abuts against the proximal end of the limiting groove 681.

[0129] Combination Figures 7 to 8 The cylinder assembly 660 includes a push rod 661, and a fixing post 682 is provided on the turntable 680. For example... Figure 9 As shown, when it is necessary to release the chuck 621, the cylinder drives the push rod 661 to extend and abut against the fixed post 682, thereby pushing the fixed post 682 to make the turntable 680 rotate in the first direction, and driving the fixed seat 624 to slide radially outward along the guide tube 622 through the limit pin 625, thereby realizing the release of the chuck 621 from the tray 5; Figure 10 As shown, after the push rod 661 is removed, the turntable 680 is pulled to rotate in the second direction under the elastic force of the tension spring 671, and the fixed seat 624 is driven to slide radially inward along the guide tube 622 through the limit pin 625, thereby realizing the clamping of the pallet 5 by the claw 621.

[0130] To further improve the homogenization effect, the homogenization mechanism 6 in this embodiment is configured to have different working stages, namely an acceleration stage, a constant speed stage and a deceleration stage. When performing homogenization treatment on the microneedle mold 1, the homogenization mechanism 6 sequentially performs accelerated rotation, constant speed rotation and deceleration rotation so that the solution is uniformly filled on the surface of the microneedle mold. Figure 11The rotational speed-time curve of the homogenization mechanism 6 is shown, where the horizontal axis represents time (in seconds) and the vertical axis represents rotational speed (in revolutions per minute). In actual use, the main shaft 611 first accelerates its rotation. After the main shaft 611 accelerates to a predetermined rotational speed, it rotates at a constant speed. After rotating at a constant speed for a certain period of time, the main shaft 611 decelerates its rotation until the homogenization operation is completed. Since the rotational speed of the main shaft 611 and the homogenization time will vary depending on the viscosity of the solution during the homogenization of the microneedle product, the speed and time of each stage can be set according to the material and viscosity of the microneedle. This application does not impose any special limitations here. Further optionally, the rotational speed of the constant speed stage is 300-1000 revolutions per minute, the acceleration stage time can be less than 2 seconds, the constant speed stage time can be 2-18 seconds, and the deceleration stage time can be 18-32 seconds.

[0131] Furthermore, the microneedle preparation equipment also includes a conveyor line for automatically transporting the tray 5 and enabling its reuse. The equipment has a loading area and a unloading area; the loading area is located on one side of the infeed chamber 21, and the unloading area is located on one side of the discharge chamber 23. The conveyor line can repeatedly transport the tray 5 from the unloading area to the loading area for reuse.

[0132] like Figure 1 As shown, the conveyor line includes a loading conveyor line 7, a discharging conveyor line 8, and a transfer conveyor line 9. The loading conveyor line 7 is located in the loading area, i.e., at the inlet of the vacuum chamber 5. The discharging conveyor line 8 is located in the discharging area, i.e., at the outlet of the vacuum chamber 5. That is, a vacuum chamber 2 is provided between the loading conveyor line 7 and the discharging conveyor line 8.

[0133] The transfer conveyor line 9 can be directly connected to the loading conveyor line 7 and the unloading conveyor line 8 to form a complete and continuous circulating conveyor line. Alternatively, the transfer conveyor line 9 can be disconnected from the loading and unloading conveyor lines 7 and 8 to form a discontinuous circulating conveyor line. In this case, an automatic transfer mechanism can transfer the tray 5 from the unloading conveyor line 8 to the transfer conveyor line 9, and then the automatic transfer mechanism can transfer the tray 5 from the transfer conveyor line 9 to the loading conveyor line 7. This forms a production cycle. The high degree of automation in microneedle preparation can greatly improve production cycle time and increase equipment capacity.

[0134] Furthermore, the pallet 5 containing the micro-needle female mold 1 under normal pressure is conveyed to the feeding chamber 21 via the feeding conveyor line 7, and the pallet 5 from the discharge chamber 23 is received by the unloading conveyor line 8; the empty pallet 5 from the unloading conveyor line 8 is received by the transfer conveyor line 9, and the empty pallet 5 is transferred to the feeding area by the transfer conveyor line 9. The position of the transfer conveyor line 9 relative to the feeding conveyor line 7 and the unloading conveyor line 8 is not restricted. Figure 1The transfer conveyor line 9 is shown to be positioned below the loading conveyor line 7 and the unloading conveyor line 8, saving space. Correspondingly, the apparatus for preparing microneedles also includes a support 16 for accommodating the vacuum chamber 2 and the conveyor lines.

[0135] The equipment for preparing microneedles preferably further includes an automatic transfer mechanism, which transfers empty trays 5 from the unloading conveyor line 8 to the transfer conveyor line 9, and then transfers empty trays 5 from the transfer conveyor line 9 to the loading conveyor line 7. The automatic transfer mechanism is preferably a lifting device, which includes a loading lift 10 and an unloading lift 11. The loading lift 10 is located in the loading area, and the unloading lift 11 is located in the unloading area. In this case, the transfer conveyor line 9 is positioned at a different horizontal height than the loading conveyor line 7 and the unloading conveyor line 8, for example... Figure 1 The diagram shows a transfer conveyor line 9 positioned below, for example, the loading conveyor line 7 and the unloading conveyor line 8. A loading elevator 10 connects to both the transfer conveyor line 9 and the loading conveyor line 7, and a unloading elevator 11 connects to both the transfer conveyor line 9 and the unloading conveyor line 8. The loading elevator 10 automatically lifts and transfers empty pallets 5 from the transfer conveyor line 9 to the loading conveyor line 7, and the unloading elevator 11 automatically lifts and transfers empty pallets 5 from the unloading conveyor line 8 to the transfer conveyor line 9. Of course, the automatic transfer mechanism is not limited to lifting devices; for example, it could be a robotic arm, an automated transport vehicle, or an automated track, etc.

[0136] Furthermore, one operational step in preparing microneedles using the aforementioned microneedle preparation equipment includes:

[0137] First, in the loading area, the microneedle negative mold 1 is placed on the empty tray 5 of the loading conveyor line 7 by manual or automatic means. After the tray 5 is loaded with the microneedle negative mold 1, it is conveyed by the loading conveyor line 7 into the feeding chamber 21 of the vacuum chamber 2. After the microneedle negative mold 1 has been poured with solution and homogenized, it is conveyed to the discharge chamber 23 through the tray 5 to break the vacuum. After breaking the vacuum, the microneedle negative mold 1 filled with solution is loaded through the tray 5 and enters the unloading conveyor line 8. In the unloading area, the microneedle negative mold 1 filled with solution is taken out from the tray 5 by manual or automatic means. During this process, after the microneedle mold 1 is removed from the tray 5, it is usually placed on the transfer tray 12. The transfer tray 12 then transports the microneedle mold 1 filled with solution to the next process (such as drying or baking process). After the microneedle mold 1 filled with solution is removed from the tray 5, the empty tray 5 is transported to the transfer conveyor line 9 by the unloading elevator 11. The transfer conveyor line 9 transports the empty tray 5 to the loading area. After arriving at the loading area, the loading elevator 10 transports the empty tray 5 to the loading conveyor line 7, so that the empty tray 5 can receive the next mold again.

[0138] Continue reading Figure 2A first vacuum valve 211 is provided on the feeding chamber 21. The first vacuum valve 211 is connected to the feeding chamber 21 and is connected to a vacuuming mechanism 4. The vacuuming mechanism 4 evacuates the feeding chamber 21 through the first vacuum valve 211 to maintain a negative pressure state in the feeding chamber 21. Furthermore, the device for preparing microneedles also includes a sensor assembly, which includes a first sensor 212. The first sensor 212 is provided on the feeding chamber 21 and is used to detect the vacuum level in the feeding chamber 21 in real time. The first sensor 212 is preferably communicatively connected to a controller and preferably feeds back the vacuum level to the controller, which then controls the pressure in the feeding chamber 21 based on the feedback vacuum level. A first vacuum breaking valve 213 is provided on the feeding chamber 21. The first vacuum breaking valve 213 is used to communicate with the external environment to break the vacuum in the feeding chamber 21. Preferably, the first vacuum breaking valve 213 is communicatively connected to the controller, which controls the opening and closing of the first vacuum breaking valve 213. Preferably, the first vacuum valve 211 is communicatively connected to the controller, and the controller controls the opening and closing of the first vacuum valve 211.

[0139] Figure 2 A schematic embodiment of a filling chamber 22 is also shown. A second vacuum valve 221 is provided on the filling chamber 22. The second vacuum valve 221 is connected to the filling chamber 22 and is also connected to a vacuuming mechanism 4. The vacuuming mechanism 4 uses the second vacuum valve 221 to evacuate the filling chamber 22, thereby maintaining a negative pressure state in the filling chamber 22. Preferably, the sensor assembly further includes a second sensor 222, which is provided on the filling chamber 22. The second sensor 222 is used to detect the vacuum level within the filling chamber 22 in real time. Preferably, the second sensor 222 is communicatively connected to a controller, and preferably feeds back the vacuum level to the controller, which then controls the pressure within the filling chamber 22 based on the feedback vacuum level. A second vacuum breaking valve 223 is provided on the filling chamber 22, which is used to communicate with the external environment to break the vacuum in the filling chamber 22. Preferably, the second vacuum breaking valve 223 is communicatively connected to the controller, and the controller controls the opening and closing of the second vacuum breaking valve 223. Preferably, the second vacuum extraction valve 221 is communicatively connected to the controller, and the controller controls the opening and closing of the second vacuum extraction valve 221.

[0140] Figure 2A schematic embodiment of the discharge chamber 23 is also shown. A third vacuum valve 231 is provided on the discharge chamber 23. The third vacuum valve 231 communicates with the discharge chamber 23 and is connected to a vacuuming mechanism 4. The vacuuming mechanism 4 evacuates the discharge chamber 23 through the third vacuum valve 231 to maintain a negative pressure state in the discharge chamber 232. Preferably, the sensor assembly further includes a third sensor 232, which is provided on the discharge chamber 23. The third sensor 232 is used to detect the vacuum level in the discharge chamber 23 in real time. Preferably, the third sensor 232 is communicatively connected to a controller and preferably feeds back the vacuum level to the controller, which then controls the pressure in the discharge chamber 23 based on the feedback vacuum level. A third vacuum breaking valve 233 is provided on the discharge chamber 23 to communicate with the external environment to break the vacuum in the discharge chamber 23. Preferably, the third vacuum breaking valve 233 is communicatively connected to the controller, and the controller controls the opening and closing of the third vacuum breaking valve 233. Preferably, the third vacuum extraction valve 231 is communicatively connected to the controller, and the controller controls the opening and closing of the third vacuum extraction valve 231.

[0141] Figure 3 The internal structure of a vacuum chamber 2 according to an exemplary embodiment is shown. The inlet of the feeding chamber 21 is provided with a first gate 241. Preferably, the outlet of the feeding chamber 21 and the inlet of the filling chamber 22 share a second gate 243. More preferably, the outlet of the filling chamber 22 and the inlet of the discharge chamber 23 share a third gate 247. The outlet of the discharge chamber 23 is provided with a fourth gate 249. The first gate 241 controls the opening and closing of the inlet of the feeding chamber 21, the second gate 243 controls the connection between the feeding chamber 21 and the filling chamber 22, the third gate 247 controls the connection between the filling chamber 22 and the discharge chamber 23, and the fourth gate 249 controls the opening and closing of the outlet of the discharge chamber 23.

[0142] The above-mentioned gate operation steps are as follows: When the feeding chamber 21 is under normal pressure, the first gate 241 is opened, and the tray 5 containing the microneedle mold 1 is conveyed to the first conveyor line 242 of the feeding chamber 21. Then, the first gate 241 is closed, and the feeding chamber 21 is evacuated. After the evacuation is completed, the second gate 243 is opened, and the tray 5 enters the filling chamber 22 via the first conveyor line 242 and the second conveyor line 244, where the second conveyor line 244 is located inside the filling chamber 22. When the tray 5 reaches the station of the filling mechanism 3, the second gate 243 is closed. After the second gate 243 is closed, the vacuum in the feeding chamber 21 can be broken. After the vacuum in the feeding chamber 21 is broken, the first gate 241 is opened, waiting for the next tray 5 to enter. After the tray 5 reaches the station of the filling mechanism 3, the filling mechanism 3 is activated to inject a set amount of solution onto the surface of the microneedle mold 1. After the liquid filling is completed, the second conveyor line 244 sends the tray 5 to the homogenization mechanism 6. After the tray 5 reaches the homogenization position, the homogenization mechanism 6 homogenizes the microneedle mold 1, so that the solution can quickly, evenly and completely cover the surface of the microneedle mold 1. After homogenization is completed, the third gate 247 opens, and the tray 5 is sent to the discharge chamber 23 via the second conveyor line 244 and the third conveyor line 248, where the third conveyor line 248 is set in the discharge chamber 22. After the tray 5 is in place, the third gate 247 closes, and then the discharge chamber 23 begins to break the vacuum until the internal air pressure of the discharge chamber 23 is consistent with the outside air pressure. Then the fourth gate 249 opens, and the tray 5 is sent out of the unloading conveyor line 8 via the third conveyor line 248. Then the fourth gate 249 closes, and then the discharge chamber 23 begins to be evacuated until the vacuum degree inside the discharge chamber 23 reaches the set value and then stops.

[0143] Preferably, the device for preparing microneedles further includes a controller, which is preferably communicatively connected to a vacuum valve, a vacuum breaking valve, a vacuum mechanism 4, and a sensor assembly to control the automated operation of these devices. The vacuum mechanism 4 preferably includes a first vacuum pump, a second vacuum pump, and a third vacuum pump. The first vacuum pump is used to evacuate the feed chamber 21 through a first vacuum valve 211; the second vacuum pump is used to evacuate the filling chamber 22 through a second vacuum valve 221; and the third vacuum pump is used to evacuate the discharge chamber 23 through a third vacuum valve 231. The controller is used to control the opening of the first vacuum breaking valve 213 to break the vacuum in the feed chamber 21, to control the opening of the second vacuum breaking valve 223 to break the vacuum in the filling chamber 22, and to control the opening of the third vacuum breaking valve 233 to break the vacuum in the discharge chamber 23. Preferably, the controller controls the vacuum level of the corresponding cavity based on the information detected by the first sensor 212, the second sensor 222, and the third sensor 232, respectively; that is, it controls the corresponding vacuum pump to evacuate and control the vacuum level within the required range based on the information detected by these sensors. Further, when the microneedle mold 1 in the fourth state is transferred from the vacuum-broken discharge cavity 23 to the outside, the controller controls the third vacuum pump to evacuate the discharge cavity 23. Further, when the microneedle mold 1 in the negative pressure state is transferred to the negative pressure filling cavity 22, the controller controls the first vacuum-breaking valve 213 to open, thereby breaking the vacuum in the feed cavity 21.

[0144] like Figure 4 As shown, to further improve the level of automation, the equipment for preparing microneedles preferably also includes an automatic feeding mechanism 13 and an automatic loading mechanism 14, both of which are located in the loading area. The automatic feeding mechanism 13 and the automatic loading mechanism 14 replace manual operation to automatically load the microneedle negative mold 1.

[0145] The automatic feeding mechanism 13 is used to automatically transport the microneedle mold 1 under atmospheric pressure to a loading station. The automatic loading mechanism 14 is used to automatically remove the microneedle mold 1 under atmospheric pressure from the loading station and place it on the tray 5 of the loading conveyor line 7. This application does not limit the structure of the automatic feeding mechanism 13. For example, it can be an automatic lifting platform, which can be designed to be multi-layered, with each layer capable of holding one or more microneedle molds 1 to be filled. The automatic loading mechanism 14 is preferably a loading robot, which is flexible in movement, easy to operate, and does not occupy space.

[0146] Continue reading Figure 5The equipment for preparing microneedles preferably further includes an automatic feeding mechanism 15 and a transfer tray 12 located in the feeding area. The automatic feeding mechanism 15 is used to take the microneedle negative mold 1 in its fourth state from the tray 5 on the feeding conveyor line 8 and place it on the transfer tray 12. Thus, the automatic feeding mechanism 15 replaces manual labor in completing the feeding operation of the microneedle negative mold 1, further automating the microneedle preparation process. The automatic feeding mechanism 15 automatically removes the filled microneedle negative mold 1 from the tray 5 in the feeding area and places it in the transfer area. If a transfer tray 12 is set in the transfer area, the automatic feeding mechanism 15 places the removed filled microneedle negative mold 1 onto the transfer tray 12, and then the microneedle negative mold 1 is periodically removed from the transfer tray 12 manually. In this way, operators can manage multiple devices simultaneously, greatly reducing manpower input and lowering labor costs. The automatic feeding mechanism 12 is typically a feeding robot.

[0147] This application does not impose any particular limitations on the structure of the infusion mechanism 3. The infusion mechanism 3 may include an outlet head for releasing the solution used to prepare the microneedles. Preferably, there are multiple outlet heads arranged side by side, each outlet head is used to release the solution, and multiple outlet heads release the solution simultaneously, resulting in high solution infusion efficiency and good solution infusion effect.

[0148] This embodiment does not impose any particular limitation on the type of controller. It can be hardware that performs logic operations, such as a microcontroller, microprocessor, programmable logic controller (PLC), or field-programmable gate array (FPGA), or software programs, functional modules, functions, object libraries, or dynamic-link libraries that implement the above functions on a hardware basis. Alternatively, it can be a combination of both. Those skilled in the art should understand how to specifically implement communication between the controller and other devices based on the content disclosed in this application. Furthermore, while using a controller is the preferred method in this embodiment, those skilled in the art can use other technical means, such as manual control or mechanical control, to achieve the same technical effect.

[0149] The above description is merely a description of preferred embodiments of the present invention and is not intended to limit the scope of the present invention in any way. Any changes or modifications made by those skilled in the art based on the above disclosure shall fall within the protection scope of the present invention.

Claims

1. An apparatus for preparing microneedles, characterized by comprising: The device comprises a microneedle negative mold, a vacuum chamber, a filling mechanism, a homogenizing mechanism and a vacuum pumping mechanism; the surface of the microneedle negative mold is formed with grooves matching the microneedle bodies; the filling mechanism is at least partially arranged in the vacuum chamber and is used to release a solution for preparing microneedles; the vacuum pumping mechanism is connected with the vacuum chamber and is used to pump vacuum in the vacuum chamber; the vacuum chamber comprises a feeding cavity, a filling cavity and a discharging cavity arranged independently from each other; The feeding cavity is used to receive the microneedle negative mold in a non-negative pressure state; The vacuum pumping mechanism is used to pump vacuum in the feeding cavity which has received the microneedle negative mold; The filling cavity is provided with a pouring station and a homogenizing station; the filling cavity is used to receive the microneedle negative mold transferred from the feeding cavity in a negative pressure state; The discharging cavity is used to receive the microneedle negative mold transferred from the filling cavity in a negative pressure state and is used to break vacuum after receiving the microneedle negative mold; The filling mechanism is used to pour the solution on the surface of the microneedle negative mold after the microneedle negative mold is transferred to the pouring station; the homogenizing mechanism is used to homogenize the microneedle negative mold with the solution after the microneedle negative mold is poured with the solution and is transferred to the homogenizing station, so that the solution is uniformly filled on the surface of the microneedle negative mold; The homogenizing mechanism comprises a grabbing mechanism and a driving mechanism; the grabbing mechanism is used to grab a tray; the driving mechanism is used to drive the grabbing mechanism to rotate horizontally around its own axis; the rotation axis of the grabbing mechanism is parallel to the depth direction of the grooves; the tray is used to load the microneedle negative mold to enter the feeding cavity, the filling cavity and the discharging cavity in sequence.

2. The apparatus for manufacturing microneedles according to claim 1, wherein Further comprising a controller and a vacuum breaking valve connected in communication; the vacuum breaking valve comprises a first vacuum breaking valve and a third vacuum breaking valve; the first vacuum breaking valve is arranged on the feeding cavity; the third vacuum breaking valve is arranged on the discharging cavity; The controller is used to control the first vacuum breaking valve to open to break vacuum in the feeding cavity and is also used to control the third vacuum breaking valve to open to break vacuum in the discharging cavity.

3. The apparatus for making microneedles of claim 2, wherein, The controller is also connected in communication with the vacuum pumping mechanism; the controller is used to control the vacuum pumping mechanism to pump vacuum in the discharging cavity, the filling cavity and the feeding cavity.

4. The apparatus for making microneedles of claim 3, wherein, The device further comprises a sensor assembly connected in communication with the controller; the sensor assembly comprises a first sensor, a second sensor and a third sensor; The feeding cavity is provided with the first sensor; the filling cavity is provided with the second sensor; the discharging cavity is provided with the third sensor; the controller is used to control the vacuum degree of the corresponding cavity according to the pressure information detected by the first sensor, the second sensor and the third sensor respectively.

5. The apparatus for manufacturing microneedles according to claim 1, wherein The grabbing mechanism comprises a spindle assembly and a clamping assembly, the driving mechanism comprises a servo motor and a transmission assembly, the spindle assembly comprises a spindle and a base, the bottom end of the spindle is fixedly connected with the base, the clamping assembly comprises at least three clamping jaws, the at least three clamping jaws are uniformly distributed around the axis of the spindle on the base and are used for clamping a fixed tray, the tray is loaded with a microneedle negative mold, the servo motor is used for driving the spindle to rotate through the transmission assembly, and the axis of the spindle is parallel to the axis of the groove.

6. The apparatus for making microneedles of claim 5, wherein, The driving mechanism further comprises a cylinder assembly, an elastic component and a rotating disc; the rotating disc is sleeved on the spindle and can rotate relative to the spindle, one end of the elastic component is connected with the spindle, and the other end is connected with the rotating disc; When the rotating disc is driven by the cylinder assembly to rotate in a first direction, the elastic component stores elastic potential energy, and all the clamping jaws are moved to a loosening position; When the rotating disc is released from the action force of the cylinder assembly, the elastic component releases the elastic potential energy and drives the rotating disc to rotate in a second direction, so that all the clamping jaws are moved to a locking position.

7. The apparatus for making microneedles of claim 6, wherein, The homogenizing mechanism further comprises pressing blocks, the pressing blocks are fixed on the base and are used for pressing the rotating disc in the axial direction; the number of the pressing blocks is at least three.

8. The apparatus for making microneedles of claim 6, wherein, The clamping assembly further comprises guide rails, sliding blocks, fixing seats and limit pins, the guide rails are arranged along the radial direction of the base, the sliding blocks are slidably arranged on the guide rails, the fixing seats are fixed on the sliding blocks, each clamping jaw is fixed on a corresponding fixing seat, the limit pins are fixed on the fixing seats, the rotating disc is provided with arc-shaped limit grooves, the limit pins are movably arranged in the limit grooves, and the arc-shaped limit grooves have two ends with different distances from the center of the rotating disc; When the rotating disc rotates in the first direction, the limit pins move from the proximal end to the distal end of the arc-shaped limit grooves and drive the clamping jaws to move outward until the limit pins abut against the distal end of the limit grooves; When the rotating disc rotates in the second direction, the limit pins move from the proximal end to the distal end of the arc-shaped limit grooves and drive the clamping jaws to move inward until the limit pins abut against the proximal end of the limit grooves.

9. The apparatus for making microneedles of claim 8, wherein, The cylinder assembly comprises a push rod, the rotating disc is provided with a fixed column, and the push rod is used for pushing the fixed column to drive the rotating disc to rotate in the first direction.

10. The apparatus for manufacturing microneedles according to claim 1, wherein The device further comprises a tray and a conveying line, the conveying line is used for conveying the tray; the movement of the tray further comprises at least one of horizontal movement, shaking, up-and-down swinging.

11. The apparatus for manufacturing microneedles according to claim 1, wherein The same tray can be loaded with microneedle negative molds of different sizes.

12. The apparatus for making microneedles of claim 11, wherein, The device further comprises an upper feeding conveying line, a lower feeding conveying line and a transfer conveying line, the upper feeding conveying line is arranged in an upper feeding area, and the lower feeding conveying line is arranged in a lower feeding area; The upper feeding conveying line is used for conveying the tray to the feeding cavity and receiving the tray from the discharging cavity by the lower feeding conveying line; The transfer conveying line is used for receiving the empty tray from the lower feeding conveying line and conveying the empty tray to the upper feeding area.

13. The apparatus for making microneedles of claim 12, wherein, The transfer conveying line is arranged below the feeding conveying line and the discharging conveying line, and the device further comprises an automatic transfer mechanism configured to transfer the empty tray on the discharging conveying line to the transfer conveying line and transfer the empty tray on the transfer conveying line to the feeding conveying line.

14. The apparatus for making microneedles of claim 12, wherein, The device further comprises an automatic feeding mechanism and an automatic feeding mechanism arranged in the feeding area, the automatic feeding mechanism is configured to convey the microneedle negative mold to a feeding station; The automatic feeding mechanism is further configured to take away the microneedle negative mold from the feeding station and place it on the tray on the feeding conveying line.

15. The apparatus for making microneedles of claim 12, wherein, The device further comprises an automatic discharging mechanism and a transfer tray arranged in the discharging area, the automatic discharging mechanism is configured to take away the microneedle negative mold from the tray on the discharging conveying line and place it on the transfer tray.

16. The apparatus for manufacturing microneedles of claim 1, wherein, The feeding cavity, the filling cavity and the discharging cavity are arranged in sequence, a first gate is arranged at the inlet of the feeding cavity, the outlet of the feeding cavity and the inlet of the filling cavity share a second gate, the outlet of the filling cavity and the inlet of the discharging cavity share a third gate, and a fourth gate is arranged at the outlet of the discharging cavity.

17. The apparatus for making microneedles of claim 16, wherein, The device further comprises a first conveying line, a second conveying line and a third conveying line, the first conveying line is arranged in the feeding cavity, the second conveying line is arranged in the filling cavity, and the third conveying line is arranged in the discharging cavity.

18. The apparatus for manufacturing microneedles of claim 1, wherein, The filling mechanism is configured to pour the solution into the microneedle negative mold in the filling cavity in a negative pressure state.

19. A method of manufacturing microneedles using the apparatus for manufacturing microneedles according to any one of claims 1 to 18, characterized by, Comprise: A microneedle negative mold is provided, and the surface of the microneedle negative mold is formed with a groove matched with a microneedle body; The microneedle negative mold is loaded by a tray, the microneedle negative mold is conveyed into a feeding cavity in a non-negative pressure state, and then a vacuumizing mechanism is used to vacuumize the feeding cavity, so that the feeding cavity and the microneedle negative mold are in a negative pressure state; The microneedle negative mold in a negative pressure state is transferred from the feeding cavity in a negative pressure state to the filling cavity in a negative pressure state, and in a negative pressure state, the solution is poured onto the surface of the microneedle negative mold at a pouring station in the filling cavity by a pouring mechanism, the tray is gripped by a gripping mechanism of a homogenizing mechanism at a homogenizing station in the filling cavity, and the gripping mechanism is driven by a driving mechanism of the homogenizing mechanism to rotate horizontally around its own axis, so that the microneedle negative mold poured with the solution is homogenized, so that the solution is evenly spread on the surface of the microneedle negative mold; The microneedle negative mold poured with the solution is transferred from the filling cavity in a negative pressure state to the discharging cavity in a negative pressure state, and the negative pressure state of the filling cavity is maintained; After the microneedle negative mold poured with the solution is transferred to the discharging cavity in a negative pressure state, the discharging cavity in a negative pressure state is broken, so that the discharging cavity is in a non-negative pressure state, and the microneedle negative mold with the solution is obtained; After the microneedle negative mold with the solution is solidified and formed, demolding is carried out, and microneedles are obtained.

20. The method of claim 19, wherein the microneedle is prepared by, The method further comprises: After transferring the microneedle negative mold in negative pressure state from the feeding cavity in negative pressure state to the filling cavity in negative pressure state, vacuum breaking is performed on the feeding cavity in negative pressure state, so that the feeding cavity is in non-negative pressure state, and the next microneedle negative mold is received.

21. The method of claim 19, wherein the microneedle is prepared by, The method further comprises: After vacuum breaking is performed on the discharging cavity in negative pressure state, the microneedle negative mold with solution is transferred from the discharging cavity in non-negative pressure state to the outside, so that the discharging cavity in non-negative pressure state is in empty state; After the discharging cavity in non-negative pressure state is empty, vacuum suction is performed on the discharging cavity by the vacuum suction mechanism, so that the discharging cavity is in negative pressure state, and the next homogenized microneedle negative mold is received.

22. The method of claim 19, wherein the microneedle is prepared by a method comprising: In the homogenization station, the movement of the tray further comprises at least one of horizontal movement, shaking, and up-and-down swinging.

23. The method of claim 19, wherein the microneedle is prepared by a method comprising: The method comprises: microneedle negative molds of different sizes are transported by the same tray.

24. The method of claim 23, wherein the microneedle is prepared by, The method further comprises: The tray is conveyed to the feeding cavity by a feeding conveying line of an upper loading area, and the tray is received from the discharging cavity by a discharging conveying line of a lower loading area; The empty tray on the discharging conveying line is received by a transfer conveying line, and the empty tray on the transfer conveying line is conveyed to the upper loading area by the transfer conveying line.

25. The method of claim 24, wherein the microneedles are prepared by, The transfer conveying line is arranged below the feeding conveying line and the discharging conveying line, and the method further comprises: The empty tray on the discharging conveying line is transferred to the transfer conveying line by an automatic transfer mechanism, and the empty tray on the transfer conveying line is transferred to the feeding conveying line by the automatic transfer mechanism.

26. The method of claim 24, wherein the microneedles are prepared by, The method further comprises: The microneedle negative mold is transported to an upper loading station by an automatic feeding mechanism of the upper loading area; The microneedle negative mold is taken away from the tray on the discharging conveying line by an automatic discharging mechanism of the lower loading area and placed on a transfer tray of the lower loading area.

27. The method of claim 24, wherein the microneedles are prepared by, The vacuum suction mechanism is controlled by a controller to perform vacuum suction on the feeding cavity, the filling cavity, and the discharging cavity. The homogenization mechanism sequentially performs accelerated rotation, constant-speed rotation, and decelerated rotation when performing homogenization treatment on the microneedle negative mold.

28. The method of claim 19, wherein the microneedles are prepared by a method comprising: It comprises:

29. The method of claim 19, wherein the microneedles are prepared by, A microneedle negative mold and a vacuum chamber are provided, a surface of the microneedle negative mold is formed with a groove matched with a microneedle body, and the vacuum chamber comprises a filling cavity and a discharging cavity arranged independently; 30. A method of making microneedles, the method comprising: The microneedle negative mold is conveyed into the filling cavity in non-negative pressure state by a tray, and solution is poured onto the surface of the microneedle negative mold by a pouring mechanism at a pouring station in the filling cavity; ​ ​ Further, in the homogenizing station in the filling cavity, the tray is grabbed by a grabbing mechanism of a homogenizing mechanism, and the grabbing mechanism is driven by a driving mechanism of the homogenizing mechanism to rotate horizontally around its own axis, so that the micro-needle negative mold filled with the solution is subjected to homogenization treatment, so that the solution is evenly spread on the surface of the micro-needle negative mold, and the rotation axis of the grabbing mechanism is parallel to the depth direction of the groove; The filling cavity is vacuumized by a vacuumizing mechanism, so that the filling cavity and the micro-needle negative mold after homogenization treatment are in a negative pressure state; The micro-needle negative mold after homogenization treatment is transferred to the discharging cavity in a negative pressure state by the tray, the discharging cavity in a negative pressure state is broken, so that the discharging cavity is in a non-negative pressure state, and the micro-needle negative mold with solution is obtained; After the micro-needle negative mold with solution is solidified and formed, demolding is performed.

31. The method of claim 30, wherein the microneedle is prepared by, In the homogenizing station, the movement of the tray further includes at least one of horizontal movement, shaking, and up-and-down swinging.

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