阅读说明：本技术 微针制备装置及微针制备方法 (Microneedle preparation device and microneedle preparation method ) 是由 颜平 曲秋羽 于 2019-10-24 设计创作，主要内容包括：本发明涉及一种微针制备装置及微针制备方法,旨在降低微针制备的生产成本,提高微针制备的效率和质量。所述微针制备装置包括基板、弹性阴模、水平运动机构、竖直运动机构、填充器和辊轴机构；弹性阴模设置在基板上,弹性阴模的表面形成有与针体相匹配的凹坑；填充器包括存储腔体,用于存储制备微针的溶液；辊轴机构设置在填充器上并包括辊轴。实际应用时,所述辊轴在竖直运动机构的驱动下向弹性阴模施加压力至压力预设值,然后在水平运动机构驱动下在弹性阴模上沿水平方向运动,排除凹坑中的空气,将从存储腔体中释放的溶液涂覆于弹性阴模上；这样做,填充效率高,填充效果好。(The invention relates to a microneedle preparation device and a microneedle preparation method, and aims to reduce the production cost of microneedle preparation and improve the efficiency and quality of microneedle preparation. The microneedle preparation device comprises a substrate, an elastic female die, a horizontal movement mechanism, a vertical movement mechanism, a filler and a roll shaft mechanism; the elastic female die is arranged on the base plate, and a concave pit matched with the needle body is formed on the surface of the elastic female die; the filler comprises a storage cavity for storing the solution for preparing the micro-needle; the roller mechanism is disposed on the filler and includes a roller. In practical application, the roller shaft applies pressure to the elastic female die to a preset pressure value under the driving of the vertical movement mechanism, then moves on the elastic female die in the horizontal direction under the driving of the horizontal movement mechanism, removes air in the pits, and coats the solution released from the storage cavity on the elastic female die; by doing so, fill efficiently, it is effectual to fill.)

1. A microneedle preparation apparatus for preparing microneedles, the microneedles comprising a substrate and a plurality of needle bodies formed on the substrate, the microneedle preparation apparatus comprising:

a substrate;

the elastic female die is arranged on the base plate, and a concave pit matched with the needle body is formed on the surface of the elastic female die;

a filler comprising a storage cavity for containing a solution for preparing microneedles;

a roller mechanism disposed on the stuffer, the roller mechanism including a roller rotating about a rotational axis;

the horizontal movement mechanism is used for driving the filler to do horizontal movement; and

the vertical movement mechanism is used for driving the filler to do vertical movement;

wherein: the storage cavity comprises a closed state and an open state; when the storage cavity is in a closed state, the storage cavity is a closed space so as to prevent the solution for preparing the microneedles from being released; when the storage cavity is in an open state, the storage cavity is an open space so as to release the microneedle preparation solution;

the roller is configured to apply pressure to the elastic female mold to a preset pressure value under the driving of the vertical movement mechanism and then move on the elastic female mold in a horizontal direction under the driving of the horizontal movement mechanism when the storage cavity is in an open state, and to remove air in the pits and apply the solution flowing out of the open space on the elastic female mold.

2. The microneedle preparation apparatus according to claim 1, wherein the roller mechanism further comprises a roller driving assembly connected to the roller, the roller driving assembly being configured to drive the roller to rotate around the rotation axis, so as to form rolling friction between the roller and the female elastic mold.

3. The microneedle preparation apparatus according to claim 2, further comprising a controller in communication connection with the vertical motion mechanism, the horizontal motion mechanism, the roller mechanism, and the filler, respectively; the controller is respectively used for controlling the motion states of the vertical motion mechanism, the horizontal motion mechanism, the roll shaft mechanism and the filler.

4. A microneedle preparation device according to claim 1, wherein the filler is mounted on the vertical motion mechanism, which is mounted on the horizontal motion mechanism;

the horizontal movement mechanism is configured to drive the vertical movement mechanism and the filler to move in a first direction of a horizontal direction, the first direction being a direction perpendicular to both a rotation axis of the roller shaft and a vertical direction.

5. The microneedle preparation device according to claim 4, wherein the horizontal motion mechanism is further configured to urge the vertical motion mechanism and the filler to move in a second direction of the horizontal direction, the second direction being a direction parallel to the rotational axis of the roller shaft.

6. The microneedle preparation device according to claim 1 or 4, wherein the horizontal movement mechanism comprises a horizontal movement assembly, a support structure and a first driver, the support structure is disposed on the horizontal movement assembly, the horizontal movement assembly is used for driving the support structure to move along a horizontal direction under the driving of the first driver, and the support structure is used for driving the filler to move horizontally.

7. The microneedle preparation device according to claim 6, further comprising a controller communicatively connected to the first driver, the controller being configured to control a motion state of the first driver.

8. The microneedle preparation device according to claim 1 or 4, wherein the vertical motion mechanism comprises a vertical motion assembly, a second driver and a support, the support is disposed on the vertical motion assembly, the vertical motion assembly is configured to drive the support to move in a vertical direction under the driving of the second driver, and the support is configured to drive the filler to move vertically.

9. The microneedle preparation device according to claim 8, further comprising a controller communicatively connected to the second driver, the controller being configured to control a motion state of the second driver.

10. A microneedle preparation device as claimed in claim 1 or 4, wherein the filler is rotatably connected to the vertical motion mechanism.

11. The microneedle preparation device of claim 1, wherein the horizontal motion mechanism and the vertical motion mechanism are part of an XZ axis gantry slide module or a three axis gantry slide module.

12. The microneedle preparation device according to claim 1, wherein the filler further comprises an upper housing, a fixed flap and a movable flap, the fixed flap and the movable flap being disposed adjacently, the fixed flap being fixed to the upper housing, at least one of the movable flaps being movably provided to the upper housing; the roll shaft is rotatably arranged on the fixed baffle and is opposite to the upper shell; the upper shell, the fixed baffle, the roll shaft and the movable baffle jointly form the storage cavity;

when the storage cavity is in a closed state, the movable baffle is in sealing contact with the roller shaft;

when the storage cavity is in an open state, at least one movable baffle is separated from the roller shaft.

13. The microneedle preparation device of claim 12, wherein the movable baffles are two and disposed on opposite sides of the rotational axis of the roller shaft.

14. The microneedle preparation device according to claim 13, wherein the filler further comprises a horizontal adjustment assembly connected to at least one of the movable flaps, the horizontal adjustment assembly being adapted to adjust a horizontal distance between two of the movable flaps, thereby effecting a change in the state of the storage chamber.

15. A microneedle preparation device as claimed in claim 14, wherein the level adjustment assembly comprises an elastic member and a level driver;

the horizontal driver is configured to drive the two movable baffles to move relatively against the action force of the elastic piece; the elastic piece is configured to store elastic potential energy in the process that the horizontal driver drives the two movable baffles to move relatively; the elastic piece is also configured to release elastic potential energy when the acting force of the horizontal driver is released by the two movable baffles so as to drive the two movable baffles to move oppositely in opposite directions.

16. A microneedle preparation device as claimed in claim 15, further comprising a controller in communication with the horizontal drive, the controller being configured to control the state of motion of the horizontal drive.

17. The microneedle preparation device according to claim 15, wherein the elastic member is a compression spring, and the horizontal driver includes a direct-acting electromagnet; the output end of the direct-acting electromagnet is connected with the movable baffle; the compression spring is sleeved on the output end of the direct-acting electromagnet, one end of the compression spring is abutted against the direct-acting electromagnet, the other end of the compression spring is connected with the movable baffle plate, or,

the filler also comprises a side shell positioned on the outer side of the movable baffle, the elastic piece is a pressure spring, and the horizontal driver comprises a direct-acting electromagnet; the output end of the direct-acting electromagnet is connected with one side of the movable baffle; the other side of the movable baffle is connected with one end of the pressure spring, and the other end of the pressure spring is connected with the side shell.

18. The microneedle preparation device according to claim 14, wherein the horizontal adjustment assembly comprises a link mechanism and a link driving device for driving the link mechanism to move, the link mechanism being used for effecting horizontal movement of at least one of the movable baffles away from or close to the roller shaft.

19. A microneedle preparation device as claimed in claim 12, wherein the filler further comprises a height adjustment assembly connected to the movable flap for adjusting a vertical gap between at least one of the movable flap and the female elastic block, the vertical gap defining a base thickness of the microneedles.

20. A microneedle preparation device as claimed in claim 19, wherein the movable barrier comprises a first barrier and a second barrier, the second barrier being adjacent to the elastic negative mold and telescopically disposed on the first barrier; the height adjusting assembly is mounted on the first baffle plate to drive the second baffle plate to do telescopic motion, so that a vertical gap between the at least one movable baffle plate and the elastic female die is adjusted.

21. The microneedle preparation device of claim 20, wherein the height adjustment assembly comprises a rack and pinion motion mechanism for driving the second baffle plate to move telescopically relative to the first baffle plate.

22. The microneedle preparation device according to claim 21, wherein a cavity is provided inside the first baffle plate, the rack and pinion movement mechanism is installed inside the cavity of the first baffle plate, and an upper end of the second baffle plate is provided inside the cavity of the first baffle plate and connected to a rack of the rack and pinion movement mechanism, or,

the inside of first baffle is provided with the cavity, rack and pinion motion sets up in first baffle keeps away from on the lateral wall of storage cavity, the upper portion of second baffle movably stretches into in the cavity of first baffle or with first baffle is close to movably the adjacency of the inside wall of storage cavity.

23. The microneedle preparation device of claim 21, wherein the height adjustment assembly further comprises a height driver for electrically driving the rack and pinion motion mechanism in motion, or,

the height adjusting assembly further comprises an adjusting knob, and the adjusting knob is installed outside the first baffle and connected with a gear in the gear rack movement mechanism so as to manually drive the gear rack movement mechanism to move.

24. A microneedle preparation device as claimed in claim 23, further comprising a controller in communicative connection with the elevation drive, the controller for controlling the state of motion of the elevation drive.

25. The microneedle preparation device of claim 12, wherein the filler further comprises a height adjustment assembly connected to the movable flap, the height adjustment assembly comprising a height driver, a slide rail, a spreader carriage assembly;

the movable baffle is formed by hinging a plurality of strip baffles; the upper end of the movable baffle plate is wound on the travelling wheel component of the lifting appliance, and the lower end of the movable baffle plate is movably arranged on the slide rail; the lifting appliance travelling wheel component is in transmission connection with the height driver so as to drive the movable baffle to move along the direction constrained by the sliding rail under the driving of the height driver.

26. The microneedle preparation apparatus according to claim 1, further comprising a pressure sensor for sensing a pressure applied to the elastic female mold and generating pressure information, wherein the pressure information is used for determining whether a current pressure applied to the elastic female mold reaches a preset pressure value.

27. A microneedle preparation device as claimed in claim 26, further comprising a controller in communicative connection with the pressure sensor;

the controller is configured to judge whether the current pressure applied to the elastic female die reaches a preset pressure value according to the pressure information; if so, the controller controls the vertical movement mechanism to stop moving downwards continuously so as to maintain the current pressure of the elastic female die.

28. The utility model provides a microneedle preparation method, is based on a microneedle preparation device, microneedle preparation device includes base plate, elasticity bed die, tucker, roller mechanism, horizontal motion and vertical motion, the elasticity bed die sets up on the base plate, just the surface of elasticity bed die forms the pit with needle body assorted, the tucker is including the storage cavity that is used for holding the solution of preparing the microneedle, storage cavity includes airtight state and open state, roller mechanism sets up on the tucker and including the roller around rotation axis pivoted, its characterized in that, microneedle preparation method includes:

the storage cavity is in an open state, and the solution for preparing the microneedle is released;

driving the roll shaft to move downwards along the vertical direction by using the vertical movement mechanism, and applying pressure to the elastic female die to a preset pressure value;

and driving the roller shaft to move on the elastic female die along the square direction by using the horizontal movement mechanism, discharging air in a pit of the elastic female die, and coating the released solution on the elastic female die.

29. A method of microneedle preparation according to claim 28, further comprising:

monitoring the pressure applied to the elastic female die by using a pressure sensor and generating pressure information in the process of applying pressure to the elastic female die by the roller;

and controlling the pressure applied to the elastic female die according to the pressure information.

30. A method of preparing microneedles in claim 28, wherein the step of leaving the storage cavities open and releasing the solution for preparing microneedles comprises:

two movable baffle plates are arranged on two sides of the roller shaft, at least one movable baffle plate is driven to be far away from the roller shaft, so that the storage cavity is in an open state, and solution in the storage cavity flows out of a gap between the movable baffle plates and the roller shaft to the surface of the elastic female die.

31. A method of preparing microneedles in claim 30, wherein the step of leaving the storage cavities open further comprises:

the movable baffle is of a telescopic structure, and the thickness of the solution coated on the surface of the elastic female die is limited by the telescopic movable baffle, so that the thickness of the substrate of the microneedle is limited.

32. A method of preparing microneedles in claim 31, wherein the step of limiting the thickness of the solution coated on the surface of the female elastic mold with a retractable movable baffle comprises:

the number of the movable baffle plates is two, the vertical gap between the two telescopic movable baffle plates and the elastic female die is adjusted, and the thickness of the solution positioned on two sides of the roll shaft is limited through the vertical gap.

33. A method of preparing microneedles in claim 28, wherein the step of leaving the storage cavities open and releasing the solution for preparing microneedles is preceded by the step of:

and driving the filler to move by utilizing the horizontal movement mechanism and/or the vertical movement mechanism until the roller shaft is contacted with the surface of the elastic female die.

Technical Field

The invention belongs to the technical field of medical instruments, and particularly relates to a microneedle preparation device and a microneedle preparation method.

Background

Most therapeutic agents are delivered to the body by subcutaneous injection, which is a low cost, rapid and straightforward way of administering the drug. Patients themselves, however, do not have the ability to use syringes with greater ease, and the pain and fear associated with syringes further limit patient compliance. Microneedles (including needles with micron-sized dimensions) are loaded with drugs and administered transdermally, which is one of the solutions to the above-mentioned problems. The microneedle transdermal drug delivery mode can realize drug delivery without pain, and improves the compliance and safety of patients. Meanwhile, the micro-needle can realize quantitative and positioning delivery of medicaments and the like, can realize accurate administration and has good administration effect. In addition to this, microneedles can also be used as a skin pretreatment, with the ability to enhance skin permeability. Therefore, the microneedle has better clinical application prospect.

Microneedles may be classified into solid microneedles and hollow microneedles according to needle structures. In general, solid microneedles can increase the permeability of the skin, pierce cell membranes, deliver drugs, etc. into the blood or cells in a released or permeated manner. For the solid microneedles, the material of the microneedles may be selected from one or more of silicon, photo-lithography epoxy, copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA), polylactic-co-glycolic acid (PLGA), maltose, etc., according to different preparation methods. The current technical route for manufacturing solid microneedles is as follows: the preparation method comprises the steps of preparing a polymer, a prepolymer, a monomer or a mixture thereof for preparing the solid microneedles, forming a solution with certain viscosity from the polymer, the prepolymer, the monomer or the mixture, and forming the microneedles by drying or crosslinking (such as photo-crosslinking, thermal crosslinking, radiation crosslinking or chemical crosslinking). The method which is commonly adopted in the technical route at present is a method of silicone elastic female die transfer. The method specifically comprises the following steps: firstly, preparing a silica gel elastic female die with a pit in advance (the pit is in the shape of a microneedle body); then coating the prepared polymer, prepolymer, polymer monomer or mixture solution on the surface of a silica gel elastic female die with a pit, and placing the silica gel elastic female die in a vacuum environment for a certain time; after the solution completely fills the pits of the silicone elastic female mold, the silicone elastic female mold is placed in the natural environment and is cured by some method (such as drying and crosslinking), and finally the microneedle is formed.

The preparation method needs to discharge the air in the concave pit of the silica gel elastic female die in a vacuum environment, so that the concave pit is fully filled with the polymer, the prepolymer, the polymer monomer or the mixture solution. Moreover, for a high-viscosity solution, air in the concave pits of the silica gel elastic female die cannot be completely removed in a vacuum environment, and the solution cannot be filled, so that a microneedle body cannot be formed. In addition, in order to provide a vacuum environment, the whole device is complex, continuous operation cannot be realized, and the production efficiency is low.

Disclosure of Invention

The invention aims to provide a microneedle preparation device and a microneedle preparation method, which are used for simplifying the structure of equipment for preparing microneedles, reducing the production cost, simultaneously reducing the defects of the microneedles in the preparation process and improving the microneedle preparation efficiency and preparation quality.

In order to achieve the above objects, the present invention provides a microneedle preparation apparatus for preparing microneedles, the microneedles including a substrate and a plurality of needle bodies formed on the substrate, the microneedle preparation apparatus including:

a substrate;

the elastic female die is arranged on the base plate, and a concave pit matched with the needle body is formed on the surface of the elastic female die;

a filler comprising a storage cavity for containing a solution for preparing microneedles;

a roller mechanism disposed on the stuffer, the roller mechanism including a roller rotating about a rotational axis;

the horizontal movement mechanism is used for driving the filler to do horizontal movement; and

the vertical movement mechanism is used for driving the filler to do vertical movement;

wherein: the storage cavity comprises a closed state and an open state; when the storage cavity is in a closed state, the storage cavity is a closed space so as to prevent the solution for preparing the microneedles from being released; when the storage cavity is in an open state, the storage cavity is an open space so as to release the microneedle preparation solution;

the roller is configured to apply pressure to the elastic female mold to a preset pressure value under the driving of the vertical movement mechanism and then move on the elastic female mold in a horizontal direction under the driving of the horizontal movement mechanism when the storage cavity is in an open state, and to remove air in the pits and apply the solution flowing out of the open space on the elastic female mold.

Optionally, the roller mechanism further comprises a roller driving assembly connected with the roller, and the roller driving assembly is used for driving the roller to rotate around a rotation axis so as to form rolling friction between the roller and the elastic female die.

Optionally, the filling machine further comprises a controller which is respectively connected with the vertical motion mechanism, the horizontal motion mechanism, the roller mechanism and the filling machine in a communication way; the controller is respectively used for controlling the motion states of the vertical motion mechanism, the horizontal motion mechanism, the roll shaft mechanism and the filler.

Optionally, the filler is mounted on the vertical motion mechanism, which is mounted on the horizontal motion mechanism;

the horizontal movement mechanism is configured to drive the vertical movement mechanism and the filler to move in a first direction of a horizontal direction, the first direction being a direction perpendicular to both a rotation axis of the roller shaft and a vertical direction.

Optionally, the horizontal movement mechanism is further configured to drive the vertical movement mechanism and the filler to move in a second direction of the horizontal direction, the second direction being a direction parallel to the rotation axis of the roller shaft.

Optionally, the horizontal movement mechanism includes a horizontal movement assembly, a support structure and a first driver, the support structure is disposed on the horizontal movement assembly, the horizontal movement assembly is configured to drive the support structure to move along the horizontal direction under the driving of the first driver, and the support structure is configured to drive the filler to move horizontally.

Optionally, the microneedle preparation device further comprises a controller in communication with the first driver, the controller being configured to control a motion state of the first driver.

Optionally, the vertical movement mechanism includes a vertical movement assembly, a second driver, and a support member, the support member is disposed on the vertical movement assembly, the vertical movement assembly is configured to drive the support member to move in a vertical direction under the driving of the second driver, and the support member is configured to drive the filler to move vertically.

Optionally, the microneedle preparation device further comprises a controller in communication with the second driver, the controller being configured to control a motion state of the second driver.

Optionally, the filler is rotatably connected to the vertical movement mechanism.

Optionally, the horizontal movement mechanism and the vertical movement mechanism are part of an XZ-axis gantry sliding table module or a three-axis gantry sliding table module.

Optionally, the filler further comprises an upper shell, a fixed baffle and a movable baffle, the fixed baffle and the movable baffle are arranged adjacently, the fixed baffle is fixed to the upper shell, and at least one movable baffle is movably arranged on the upper shell; the roll shaft is rotatably arranged on the fixed baffle and is opposite to the upper shell; the upper shell, the fixed baffle, the roll shaft and the movable baffle jointly form the storage cavity;

when the storage cavity is in a closed state, the movable baffle is in sealing contact with the roller shaft;

when the storage cavity is in an open state, at least one movable baffle is separated from the roller shaft.

Optionally, the movable baffles are two and are arranged on opposite sides of the rotation axis of the roll shaft.

Optionally, the filler further comprises a horizontal adjustment assembly connected to at least one of the movable baffles, the horizontal adjustment assembly being configured to adjust a horizontal distance between two of the movable baffles to effect a change in the state of the storage chamber.

Optionally, the horizontal adjustment assembly comprises an elastic member and a horizontal driver;

the horizontal driver is configured to drive the two movable baffles to move relatively against the action force of the elastic piece; the elastic piece is configured to store elastic potential energy in the process that the horizontal driver drives the two movable baffles to move relatively; the elastic piece is also configured to release elastic potential energy when the acting force of the horizontal driver is released, and the two movable baffles are driven to move oppositely in opposite directions.

Optionally, the microneedle preparation apparatus further comprises a controller in communication with the horizontal drive, the controller being configured to control a motion state of the horizontal drive.

Optionally, the elastic member is a compression spring, and the horizontal driver includes a direct-acting electromagnet; the output end of the direct-acting electromagnet is connected with the movable baffle; the pressure spring is sleeved on the output end of the direct-acting electromagnet, one end of the pressure spring is abutted against the direct-acting electromagnet, and the other end of the pressure spring is connected with the movable baffle plate, or the filler further comprises a side shell positioned on the outer side of the movable baffle plate, the elastic part is a pressure spring, and the horizontal driver comprises the direct-acting electromagnet; the output end of the direct-acting electromagnet is connected with one side of the movable baffle; the other side of the movable baffle is connected with one end of the pressure spring, and the other end of the pressure spring is connected with the side shell.

Optionally, the horizontal adjustment assembly comprises a link mechanism and a link driving device, the link driving device is used for driving the link mechanism to move, and the link mechanism is used for realizing the horizontal movement of at least one movable baffle plate so as to be far away from or close to the roller shaft.

Optionally, the filler further comprises a height adjustment assembly connected to the movable baffle for adjusting a vertical gap between at least one of the movable baffles and the female elastic block, the vertical gap defining a base thickness of the microneedles.

Optionally, the movable baffle comprises a first baffle and a second baffle, and the second baffle is close to the elastic female die and is telescopically arranged on the first baffle; the height adjusting assembly is mounted on the first baffle plate to drive the second baffle plate to do telescopic motion, so that a vertical gap between the at least one movable baffle plate and the elastic female die is adjusted.

Optionally, the height adjustment assembly includes a rack and pinion movement mechanism, and the rack and pinion movement mechanism is configured to drive the second baffle to perform telescopic movement relative to the first baffle.

Optionally, a cavity is arranged inside the first baffle, the rack and pinion movement mechanism is installed inside the cavity of the first baffle, the upper end of the second baffle is arranged inside the cavity of the first baffle and connected with a rack of the rack and pinion movement mechanism, or the cavity is arranged inside the first baffle, the rack and pinion movement mechanism is arranged on the outer side wall of the storage cavity far away from the first baffle, and the upper portion of the second baffle movably extends into the cavity of the first baffle or is close to the inner side wall of the storage cavity and movably abuts against the inner side wall of the storage cavity.

Optionally, the height adjusting assembly further comprises a height driver, the height driver is used for electrically driving the rack and pinion movement mechanism to move, or the height adjusting assembly further comprises an adjusting knob, the adjusting knob is installed outside the first baffle and connected with a gear in the rack and pinion movement mechanism, so as to manually drive the rack and pinion movement mechanism to move.

Optionally, the microneedle preparation device further comprises a controller in communication with the height actuator, the controller being configured to control a motion state of the height actuator.

Optionally, the filler further comprises a height adjustment assembly connected to the movable baffle, the height adjustment assembly comprising a height driver, a slide rail, a spreader travelling wheel assembly;

the movable baffle is formed by hinging a plurality of strip baffles; the upper end of the movable baffle plate is wound on the travelling wheel component of the lifting appliance, and the lower end of the movable baffle plate is movably arranged on the slide rail; the lifting appliance travelling wheel component is in transmission connection with the height driver so as to drive the movable baffle to move along the direction constrained by the sliding rail under the driving of the height driver.

Optionally, the microneedle preparation apparatus further includes a pressure sensor, configured to sense a pressure applied to the elastic female mold and generate pressure information, where the pressure information is used to determine whether a current pressure applied to the elastic female mold reaches a preset pressure value.

Optionally, the microneedle preparation device further comprises a controller in communication with the pressure sensor;

the controller is configured to judge whether the current pressure applied to the elastic female die reaches a preset pressure value according to the pressure information; if so, the controller controls the vertical movement mechanism to stop moving downwards continuously so as to maintain the current pressure of the elastic female die.

In order to achieve the above object, the present invention also provides a microneedle preparation method, which is based on a microneedle preparation apparatus, including:

the storage cavity is in an open state, and the solution for preparing the microneedle is released;

driving the roll shaft to move downwards along the vertical direction by using the vertical movement mechanism, and applying pressure to the elastic female die to a preset pressure value;

and driving the roller shaft to move on the elastic female die along the horizontal direction by using the horizontal movement mechanism, discharging air in a pit of the elastic female die, and coating the released solution on the elastic female die.

Optionally, the microneedle preparation method further comprises:

monitoring the pressure applied to the elastic female die by using a pressure sensor and generating pressure information in the process of applying pressure to the elastic female die by the roller;

and controlling the pressure applied to the elastic female die according to the pressure information.

Optionally, the storage cavity is in an open state, and the step of releasing the solution for preparing the microneedle comprises:

two movable baffle plates are arranged on two sides of the roller shaft, at least one movable baffle plate is driven to be far away from the roller shaft, so that the storage cavity is in an open state, and solution in the storage cavity flows out of a gap between the movable baffle plates and the roller shaft to the surface of the elastic female die.

Optionally, the step of releasing the solution for preparing the microneedle further comprises:

the movable baffle is of a telescopic structure, and the thickness of the solution coated on the surface of the elastic female die is limited by the telescopic movable baffle, so that the thickness of the substrate of the microneedle is limited.

Optionally, the step of defining the thickness of the solution applied on the surface of the female elastic mold with a retractable movable baffle comprises:

the number of the movable baffle plates is two, the vertical gap between the two telescopic movable baffle plates and the elastic female die is adjusted, and the thickness of the solution positioned on two sides of the roll shaft is limited through the vertical gap.

Optionally, the step of opening the storage cavity and releasing the solution for preparing the microneedle further comprises:

and driving the filler to move by utilizing the horizontal movement mechanism and/or the vertical movement mechanism until the roller shaft is contacted with the surface of the elastic female die.

The microneedle preparation device and the microneedle preparation method have at least one of the following advantages:

firstly, in the microneedle preparation process, the roller is used for applying pressure to the elastic female die to enable the elastic female die to generate elastic deformation, so that air in a concave pit on the elastic female die can be fully exhausted, particularly, the roller is used for extruding the elastic female die and coating the solution flowing out from an open space on the elastic female die, the filling efficiency is high, and the filling effect is good. But also can save a vacuum extractor, greatly simplify the equipment structure and reduce the production cost. Meanwhile, continuous production can be realized, and the production efficiency is improved.

Secondly, the storage cavity of the filler can be opened and closed, and the solution for preparing the microneedles is contained by the storage cavity, so that the use is convenient, and the filling efficiency of the solution is further improved.

Thirdly, in the microneedle preparation process, the vertical gap between the movable baffle and the elastic female die is adjusted by the height adjusting assembly, so that the thickness of the solution coated on the surface of the female die is accurately controlled through the vertical gap, the thickness of the substrate on the microneedle is accurately controlled, and the microneedle preparation processing precision is improved.

Fourthly, in the microneedle preparation process, utilize the roller to install between two adjustable fender, realized the reposition of redundant personnel of solution for solution flows into along the place ahead of roller direction of roll all the way, and another way solution flows into along the rear of roller direction of roll, makes the solution in place ahead can be rolled the pit by the roller, and the solution at rear can be backfilled in the pit again, does so, and solution filling efficiency is higher, and the filling effect is better.

Drawings

It will be appreciated by those skilled in the art that the drawings are provided for a better understanding of the invention and do not constitute any limitation to the scope of the invention. Wherein:

fig. 1 is a schematic structural view of a microneedle preparation apparatus according to a preferred embodiment of the present invention;

fig. 2 is a schematic diagram of an implementation of microneedle fabrication according to a preferred embodiment of the present invention;

fig. 3 is a schematic structural view of a filler in the microneedle preparation apparatus according to the preferred embodiment of the present invention;

fig. 4 is a partial sectional view of the microneedle preparation apparatus according to the preferred embodiment of the present invention, in which a filler is open;

fig. 5 is a partial sectional view of a closed state of a filler in the microneedle preparation apparatus according to the preferred embodiment of the present invention.

In the figure:

10-microneedle preparation device;

11-a vertical movement mechanism; 111-a support;

12-a horizontal movement mechanism; 121-a scaffold structure; 122-a base;

13-a roller mechanism; 131-a roller shaft; 132-a roller drive assembly; 14-an elastic female die;

141-pits; 15-a substrate;

16-a filler; 161-storage cavity; 162-a fixed baffle; 163-flapper; 1631-a first baffle; 1632-a second baffle; 164-a rack and pinion motion; 165-adjusting knob; 166-a return spring; 167-direct acting electromagnet; 168-a liquid supply line; 169-a liquid level sensor;

17-a controller; 18-solution; 19-pressure sensor.

Detailed Description

The present invention will now be described in more detail with reference to the accompanying schematic drawings, in which preferred embodiments of the invention are shown, it being understood that one skilled in the art may modify the invention herein described while still achieving the advantageous effects of the invention. Accordingly, the following description should be construed as broadly as possible to those skilled in the art and not as limiting the invention.

In the interest of clarity, not all features of an actual implementation are described. In the following description, well-known functions or constructions are not described in detail since they would obscure the invention in unnecessary detail. It will of course be appreciated that in the development of any such actual embodiment, numerous implementation-specific details must be set forth in order to achieve the developer's specific goals, such as compliance with system-related and business-related constraints, which will vary from one implementation to another. Moreover, it will be appreciated that such a development effort might be complex and time-consuming, but would nevertheless be a routine undertaking for those of ordinary skill in the art.

The invention is described in more detail in the following paragraphs by way of example with reference to the accompanying drawings. The advantages and features of the present invention will become more apparent from the following description. It is to be noted that the drawings are in a very simplified form and are not to precise scale, which is merely for the purpose of facilitating and distinctly claiming the embodiments of the present invention.

The embodiment provides a microneedle preparation method for preparing microneedles, in particular solid microneedles, more particularly integrally molded solid microneedles, the microneedles comprise a substrate and a plurality of needle bodies formed on the substrate, and the specific preparation idea is as follows: provides a microneedle preparation device, and the microneedle preparation device is utilized to realize the preparation of microneedles. Specifically, the microneedle preparation device comprises a substrate, an elastic female die, a filler, a roller mechanism, a horizontal movement mechanism and a vertical movement mechanism; wherein: the elastic female die is arranged on the substrate, and a concave pit matched with the needle body is formed on the surface of the elastic female die; the filler comprises a storage cavity, the storage cavity is used for containing a solution for preparing the microneedles and comprises a closed state and an open state; the roller shaft mechanism is arranged on the filler and comprises a roller shaft rotating around a rotating axis; the horizontal movement mechanism is used for driving the filler to do horizontal movement; the vertical movement mechanism is used for driving the filler to vertically move.

And the microneedle preparation method implemented based on the microneedle preparation apparatus includes:

the storage cavity is in an open state, and the solution for preparing the microneedle is released;

driving the roll shaft to move downwards along the vertical direction by using a vertical movement mechanism, and applying pressure to the elastic female die to a preset pressure value;

and driving the roller shaft to move on the elastic female die along the square direction by using a horizontal movement mechanism, discharging air in a pit of the elastic female die, and coating the released solution on the elastic female die.

Specifically, in actual preparation, the roller shaft is driven to move downwards by the vertical movement mechanism, pressure is applied to the elastic female die to a preset pressure value, the elastic female die is elastically deformed, air in a pit on the elastic female die can be sufficiently exhausted, then, the roller shaft is driven to move horizontally on the elastic female die by the horizontal movement mechanism, and at the moment, the roller shaft preferably rolls relative to the elastic female die (namely rolling friction is formed between the elastic female die and the roller shaft), so that the released solution is rolled into the pit in time while the air in the pit is exhausted. The method for pressing the elastic female die by the roller shaft while horizontally moving the roller shaft on the elastic female die to roll the solution into the concave pit in time has the advantages of high solution filling efficiency and good filling effect, can save a vacuumizing device, greatly simplifies the structure of equipment for preparing the microneedles, reduces the cost for preparing the microneedles, and can realize continuous production and high production efficiency.

The following detailed description is made with reference to the accompanying drawings.

Fig. 1 is a schematic structural view of a microneedle preparation apparatus according to a preferred embodiment of the present invention. Fig. 2 is a schematic diagram of microneedle fabrication according to a preferred embodiment of the present invention. Fig. 3 is a schematic structural diagram of the filler provided by the preferred embodiment of the present invention. Figure 4 is a partial cross-sectional view of the preferred embodiment of the present invention providing the filler in an open state. Fig. 5 is a partial sectional view of a closed state of a filler in the microneedle preparation apparatus according to the preferred embodiment of the present invention. As shown in fig. 1 to 5, the present embodiment provides a microneedle preparation apparatus 10 for preparing microneedles, particularly solid microneedles, which includes a substrate and a plurality of needles formed on the substrate. Specifically, the microneedle preparation apparatus 10 includes a vertical movement mechanism 11, a horizontal movement mechanism 12, a roller mechanism 13, an elastic female mold 14, a base plate 15, and a filler 16.

Preferably, the microneedle preparation apparatus 10 further includes a controller 17 for controlling the motion state of other devices. Specifically, the controller 17 is in communication connection with the vertical movement mechanism 11, the horizontal movement mechanism 12, the roller mechanism 13 and the filler 16, and is mainly in communication connection with electrical components in the devices, so that the automatic operation of action components in the devices is controlled, the automatic production of microneedles is realized, and the production efficiency is improved. The type of the Controller 17 is not particularly limited in this embodiment, and may be hardware for executing Logic operations, such as a single chip, a microprocessor, a Programmable Logic Controller (PLC) or a Field Programmable Gate Array (FPGA), or a software program, a function module, a function, an Object library (Object Libraries) or a Dynamic Link library (Dynamic-Link Libraries) for implementing the above functions on a hardware basis. Alternatively, a combination of the above two. Those skilled in the art will know how to implement communication between the controller 17 and other devices based on the disclosure herein. In addition, the controller 17 is a preferred mode of the present embodiment, and those skilled in the art can adopt other technical means, such as manual control and mechanical control, to achieve the same technical effect.

The material of the female elastic die 14 is an elastic material to impart good deformation restorability (i.e., good elasticity) to the female elastic die 14. Preferably, the material of the female elastic die 14 is silicone. As shown in fig. 2, a plurality of concave pits 141 are formed on the surface of the female elastic mold 14, and the shape, size, number, and arrangement of the concave pits 141 are all matched with the shape, size, number, and arrangement of the needles of the solid microneedles to be prepared. For example, the shape of the pit 141 is a regular rectangular pyramid, but is not limited thereto.

The female elastic mold 14 is provided on a base plate 15, and the female elastic mold 14 is rigidly supported by the base plate 15. Further, the substrate 15 is preferably made of a rigid material, but the present invention is not particularly limited to a specific kind of the rigid material as long as the substrate 15 is not deformed or deformed enough to be ignored by the roller mechanism 13. In other embodiments, the base plate 15 may also be made of a flexible material with a certain hardness, such as a silicone plate with a sufficient hardness, so as to support the female elastic mold 14 to a certain extent without affecting the rolling deformation of the female elastic mold 14. Further, the base plate 15 is fixedly connected with the female elastic die 14 in a detachable manner, for example, by clamping two ends of the female elastic die 14 by a clamp, and a certain safety distance is ensured between the clamp and the concave pit 141 of the female elastic die 14 so as to prevent the clamp from interfering with the filler 16 in operation.

As shown in fig. 3, 4, and 5, the roller mechanism 13 includes a roller 131 that rotates about a rotation axis. The roller 131 is used as a key component for preparing the microneedles, and is used for pressing the elastic female die 14 to elastically deform the elastic female die 14, thereby exhausting air in the concave pit 141, and is also used for rolling the released solution 18 into the concave pit 141 in time, thereby sufficiently filling the released solution 18 into the concave pit 141. Preferably, the roller mechanism 13 further includes a roller driving assembly 132 connected to the roller 131 for driving the roller 131 to rotate around the rotation axis to prevent dry friction between the roller 131 and the elastic female mold 14. Preferably, the roller drive assembly 132 is communicatively coupled to the controller 17.

As shown in fig. 1, the roller mechanism 13 is mounted on a filler 16, the filler 16 is mounted on a vertical movement mechanism 11, and the vertical movement mechanism 11 is mounted on a horizontal movement mechanism 12. In other embodiments, the vertical movement mechanism 11 may not be mounted on the horizontal movement mechanism 12. Preferably, the controller 17 controls the horizontal movement mechanism 12 to drive the vertical movement mechanism 11 and the filler 16 to move along a first direction of the horizontal direction. The first direction is defined as a direction perpendicular to both the rotation axis and the vertical direction of the roller shaft 131, and is also denoted as "X direction" in this embodiment. The controller 17 also controls the vertical motion mechanism 11 to move the filler 16 in the vertical direction. In the present embodiment, the vertical direction is again denoted by "Z direction". More preferably, the controller 17 further controls the horizontal moving mechanism 12 to move the vertical moving mechanism 11 and the filler 16 in a second direction of the horizontal direction. The second direction is a direction parallel to the rotational axis of the roller shaft 131. In this embodiment, the second direction is again denoted by "Y direction".

The material of the roller shaft 131 is not particularly limited in the present invention. Preferably, the roller shaft 131 is made of stainless steel to provide the roller shaft 131 with good corrosion resistance and polishing performance. More preferably, the surface of the stainless steel roller 131 is electropolished, so that the surface smoothness of the roller 131 is improved, and the damage to the elastic female die is reduced.

The present invention is also not limited to the roller drive assembly 132 and can be selected by one skilled in the art based on installation requirements. For example, the roller shaft driving assembly 132 includes a stepping motor and a decelerator, and the stepping motor is connected to the roller shaft 131 through the decelerator. And the roller shaft driving assembly 132 is in communication connection with the controller 17, and the controller 17 controls the stopping and running of the roller shaft driving assembly 132, thereby controlling the motion state of the roller shaft 131.

Referring to fig. 4 and 5 in conjunction with fig. 2, the filler 16 includes a storage chamber 161 for storing the microneedle preparation solution 18. The solution 18 is a solution with a certain dynamic viscosity, preferably, the dynamic viscosity of the solution is 5000-20000 cps. The present invention is not particularly limited with respect to the type of the solution 18. Preferably, the solution 18 is an aqueous polymer solution, a prepolymer solution, a monomer solution or a monomer mixture solution. The storage chamber 161 has a closed state and an open state. For example, when the storage chamber 161 is in a sealed state, the storage chamber 161 is a sealed space to facilitate storing the solution 18; when the storage chamber 161 is in an open state, the storage chamber 161 is changed from a closed space to an open space to release the solution 18. Preferably, the storage chamber 161 can be switched between a closed state and an open state under the control of the controller 17, so that the use is more convenient and the solution filling efficiency is high. Preferably, the roller 131 of the roller mechanism 13 is disposed in the storage cavity 161, so that on one hand, the storage cavity 161 is conveniently sealed by the roller 131, and on the other hand, the solution is conveniently distributed by the roller.

With continued reference to fig. 3-5, the filler 16 further includes an upper housing (not labeled), a fixed stop 162, and a movable stop 163. The fixed barrier 162 and the movable barrier 163 are disposed adjacent to each other, the fixed barrier 162 is fixed to the upper case, and at least one movable barrier 163 is movably disposed in the upper case. Further, the roller shaft 131 is rotatably disposed at the fixed barrier 162 and is disposed opposite to the upper case. Further, the upper case, the fixed barrier 162, the roller shaft 131, and the movable barrier 163 collectively define the storage chamber 161. When the storage cavity 161 is in a sealed state, the movable baffle 163 is in contact with the roller 131, and the storage cavity 161 is a sealed space; when the storage chamber 161 is in an open state, at least one of the movable shutters 163 is separated from the roller shaft 131, and at this time, the storage chamber 161 is an open space. In this embodiment, the roller shaft 131 forms the bottom of the storage chamber 161, and the two movable shutters 163 are disposed on opposite sides of the rotational axis of the roller shaft 131.

Further, the filler 16 further comprises a horizontal adjustment assembly connected to at least one movable baffle 163, the horizontal adjustment assembly being used for adjusting a horizontal distance between two movable baffles 163, thereby enabling a change in the state of the storage chamber. In some embodiments, one flapper 163 can be movable while the other flapper 163 is stationary, with the level adjustment assembly coupled to one flapper. In some embodiments, both of the movable barriers 163 can be movable, and the horizontal adjustment assembly is coupled to both of the movable barriers 163. In this embodiment, both of the movable baffles 163 can be movable, and when the horizontal adjustment assembly drives the two movable baffles 163 to move away from each other, the storage cavity 161 can be opened; the storage chamber 161 may be enclosed when the horizontal adjustment assembly drives the two flapper 163 toward each other. In a closed state, the two movable baffles 163 are in sealing contact with the roller shaft 131; when the two movable baffles 163 are separated from each other, the two movable baffles 163 form gaps with the roller 131, and the solution 18 flows out from the gaps on both sides of the roller, wherein the gap on one side is formed in front of the roller in the rolling direction, and the gap on the other side is formed behind the roller in the rolling direction. In this embodiment, the roller shaft 131 is at least partially disposed in the storage cavity 161, and both ends of the roller shaft 131 are rotatably mounted on the fixed barrier 162.

Further, the horizontal adjustment assembly may include an elastic member and a horizontal driver. The horizontal driver is used to drive the two movable baffles 163 away from each other against the force of the elastic member, so that the storage cavity 161 is in an open state. The elastic member is used for storing elastic potential energy in the process that the horizontal driver drives the two movable baffles 163 to move away, and releasing the elastic potential energy when the horizontal driver releases the acting force of the horizontal driver, so that the two movable baffles 163 are driven to approach each other until the two movable baffles 163 are in sealing contact with the roller shaft 131, and the storage cavity 161 is closed. Alternatively, the horizontal driver is used for driving the two movable baffles 163 to approach each other against the action force of the elastic member until the two movable baffles are in sealing contact with the roller shaft 131, so that the storage cavity 161 is in a sealed state; the elastic member is used for storing elastic potential energy when the horizontal driver drives the two movable baffles 163 to approach each other, and releasing the elastic potential energy when the horizontal driver removes the acting force of the horizontal driver, so as to drive the two movable baffles 163 to move away from each other, thereby opening the storage cavity 161. Preferably, the horizontal drive is communicatively connected to the controller 17 and changes the motion state, such as turning on, turning off, adjusting the rotational speed or changing the rotational direction, under the control of the controller 17.

Optionally, the elastic member is a compression spring 166, and the horizontal driver includes a direct acting electromagnet 167. In an embodiment, the output end of the direct-acting electromagnet 167 is connected to the movable baffle 163, and the pressure spring 166 is sleeved on the output end of the direct-acting electromagnet 167, and one end of the pressure spring abuts against the direct-acting electromagnet 167, and the other end of the pressure spring is connected to the movable baffle 163. Taking two movable baffles 163 as an example, the two movable baffles 163 are respectively connected with a pressure spring 166, each pressure spring 166 is sleeved on the direct-acting electromagnet 167 (for example, the output end of the direct-acting electromagnet 167), and one end of each pressure spring is abutted against the direct-acting electromagnet 167, and the other end of each pressure spring is connected with the movable baffle 163. Further, the direct acting electromagnet 167 is fixed to the upper case. When the electromagnet 167 of the direct acting type is energized under the control of the controller 17, the output end of the electromagnet 167 of the direct acting type gives a force to the movable baffle 163 away from the roller shaft 131, and separation of the two movable baffles 163 is achieved. The present embodiment is not particularly limited in terms of the specific structure and type of the linear electromagnet 167. In an alternative embodiment, the filler 16 further comprises a side housing (not labeled) located outside the flapper 163. The output end of the direct-acting electromagnet 167 is connected to one side of the movable baffle 163, the other side of the movable baffle 163 is connected to one end of the compression spring 166, and the other end of the compression spring 166 is connected to the side housing.

More specifically, as shown in fig. 2, 4 and 5, when the acting force generated by the electromagnet 167 acts on the movable baffle 163, the movable baffle 163 is horizontally separated from the roller shaft 131, so that a lower portion (hereinafter, the second baffle 1632) of the movable baffle 163 forms a certain horizontal distance with the roller shaft 131, thereby allowing the solution 18 to flow out of the storage cavity 161, and during this process, the compressed spring 166 stores elastic potential energy. Furthermore, when the direct-acting electromagnet 167 is controlled to be powered off and no longer acts on the movable baffle 163, the pressure spring 166 releases elastic potential energy to drive the two movable baffles 163 to move close to each other until the second baffle 1632 contacts the roller shaft 131, and forms a closed space together with the fixed baffle 162 and the second baffle 1632, so that the solution 18 is sealed in the storage cavity 161, and the solution 18 is prevented from leaking when the filler 16 does not work.

In an alternative embodiment, the electromagnetic spring mode formed by the compression spring 166 and the direct-acting electromagnet 167 can be replaced by a link mechanism and a link driving device. The link driving means is used to drive the link mechanism for achieving the horizontal movement of the movable baffle 163 away from or close to the roller shaft 131, such as a crank-slider mechanism. Further, the connecting rod driving device may be a power source such as a motor or an air cylinder. This is also within the scope of the invention. The invention is not limited to the implementation of the level adjustment assembly.

The filler 16 further includes a height adjustment assembly connected to the movable baffles 163 for adjusting a vertical gap (i.e., vertical spacing) between at least one movable baffle 163 and the female elastomeric mold 14, the vertical gap for defining the base thickness of the solid microneedles. That is, the vertical gap between the movable baffle 163 and the female elastic mold 14 is adjusted by the height adjusting assembly, so as to adjust the thickness of the solution 18 coated on the female elastic mold 14 during the rolling process, and the thickness of the finally formed solid microneedle substrate is determined in combination with the properties of the solution (e.g., whether the solution contains moisture, the difference in polymerization shrinkage caused by different types of monomers, etc.). Preferably, the height adjustment assembly is communicatively coupled to the controller 17.

In this embodiment, the height adjustment assembly is used to drive the movable baffle 163 to perform a telescopic motion along the vertical direction, so as to change the length of the movable baffle 163. As shown in fig. 4 and 5, for the retractable movable baffle 163, the movable baffle 163 may include a first baffle 1631 and a second baffle 1632, the second baffle 1632 is telescopically disposed on the first baffle 1631, and the second baffle 1632 is disposed below the first baffle 1631 and close to the elastic female mold 14. The height adjustment assembly is mounted on the first blocking plate 1631 and is used for driving the second blocking plate 1632 to perform telescopic movement, so as to adjust the vertical gap between the at least one movable blocking plate 163 and the elastic female die 14.

In one embodiment, only one flapper 163 can make a telescopic motion, that is, the thickness of the solution on one side of the roller 131 can be defined, but at this time, the microneedle preparation device 10 can work only in one direction, that is, after each coating, the filler 16 needs to return to the original starting position to start coating again. In an alternative embodiment, both of the movable baffles 163 can perform a telescopic motion, and in particular, the height adjusting assembly is connected with the two movable baffles 163 and respectively used for adjusting a vertical gap between each movable baffle and the elastic female mold. By this arrangement, the thickness of the solution on both sides of the roller 131 can be limited, and at this time, the microneedle preparation apparatus 10 can operate in both directions without returning to the origin again after each coating, and the operation efficiency is higher compared to one-way coating. Also, the vertical clearance between the two shutters 163 and the female elastic die 14 should be the same, so as to obtain a base of uniform thickness. Preferably, the second baffle 1632 is an arc-shaped baffle for reducing the resistance of the solution flow and guiding the solution flow better, and the use effect is better.

Optionally, the height adjustment assembly includes a rack and pinion movement mechanism 164 (see fig. 4 and 5) for driving the second barrier 1632 to move telescopically relative to the first barrier 1631. Preferably, a cavity is disposed inside the first blocking plate 1631, the rack and pinion movement mechanism 164 is preferably installed inside the cavity of the first blocking plate 1631, and at least a portion (e.g., the upper end) of the second blocking plate 1632 extends into the cavity of the first blocking plate 1631 and is connected to the rack in the rack and pinion movement mechanism 64. Further, a sealing process is performed between the upper end of the second baffle 1632 and the lower end of the first baffle 1631, for example, a sealing strip is used for static sealing, so as to avoid the leakage of the solution. Optionally, the height adjustment assembly further includes an adjustment knob 165, and the adjustment knob 165 is disposed outside the first blocking plate 1631 and connected to a gear in the rack-and-pinion movement mechanism 14, so that the adjustment knob 165 can be manually operated to drive the gear in the rack-and-pinion movement mechanism 164 to rotate, and further drive the rack to move telescopically. In other embodiments, the adjustment knob 165 may be replaced by a height driver (e.g., a motor) such that the rack and pinion motion mechanism 1644 is electrically driven by the height driver, and the controller 17 is communicatively coupled to the height driver such that the controller 17 controls the motion state of the rack and pinion motion mechanism 16 via the height driver. In an alternative embodiment, the rack and pinion movement mechanism 164 is disposed on the outer sidewall of the first blocking plate 1631 away from the storage cavity 161 to simplify the manufacturing process, in which case, the upper portion of the second blocking plate 1632 may be movably disposed to extend into the cavity of the first blocking plate 1631, or the second blocking plate 1632 may be movably abutted to the inner sidewall of the first blocking plate 1631 close to the storage cavity 161.

As previously described, when one of the movable shutters 163 cannot be retracted, the microneedle preparation apparatus 10 can only operate unidirectionally, i.e., the filler 16 can only coat unidirectionally. Specifically, after each coating, the controller 17 controls the horizontal adjustment assembly to close the storage cavity 161, controls the vertical movement mechanism 11 to drive the filler 16 to move upward, controls the horizontal adjustment assembly to open the storage cavity 161, further controls the horizontal movement mechanism 12 to drive the filler 16 to move horizontally to the initial position at the time of coating operation, finally controls the vertical movement mechanism 11 to drive the filler 16 to move downward until contacting the roller 131 and pressing the elastic female die 14, and then controls the horizontal movement mechanism 12 to drive the filler 16 to coat from the initial position again.

In an alternative embodiment, the height adjustment assembly is of a roller door-like construction, i.e. comprising height drive, slide and spreader carriage components. Correspondingly, the movable baffle 163 is formed by hinging a plurality of strip-shaped baffles, the upper end of the movable baffle 163 is wound on the travelling wheel component of the lifting appliance, and the lower end is movably arranged on the sliding rail. The spreader travelling wheel component is in transmission connection with the height driver so as to drive the movable baffle 163 to move along the direction constrained by the slide rail under the driving of the height driver.

Preferably, the filler 16 is also capable of spinning to promote flexibility and adaptability of microneedle preparation and to facilitate positioning of the female elastomeric mold 14. For example, the filler 16 is rotatably connected to the vertical moving mechanism 11. Further, a rotation driver (e.g., a motor) is installed on the vertical movement mechanism 11 to drive the filler 16 to perform rotation movement. For a microneedle preparation device 10 in which the flapper 163 is not retractable, bidirectional coating can be achieved by the rotatable filler 16.

Referring back to fig. 1, the horizontal movement mechanism 12 includes a support structure 121, a horizontal movement assembly, and a first driver (not shown). The mounting structure 121 is disposed on the horizontal motion assembly. The horizontal moving assembly drives the supporting structure 121 to move in the horizontal direction under the driving of the first driver, and the supporting structure 121 drives the filler 16 to move in the horizontal direction through the vertical moving mechanism 11. The horizontal movement assembly is not particularly limited in this embodiment, and may be, for example, a slider-rail assembly, a rack-and-pinion assembly, or a ball screw assembly. The first drive may be, for example, an electric motor, hydraulic or pneumatic device. Preferably, the horizontal movement mechanism 12 further includes a base 122, the horizontal movement component is disposed on the base 122, and in addition, the substrate 14 is also disposed on the base 122. The susceptor 122 may be used as it is as the substrate 15.

The vertical movement mechanism 11 includes a vertical movement assembly, a support 111, and a second driver (not shown). The support 111 is provided on the vertical motion assembly. The vertical movement assembly drives the support 111 to move in the vertical direction under the driving of the second driver, the support 111 is used for connecting the filler 16, and the filler 16 is driven by the support 111 to move in the vertical direction. Further, the vertical movement assembly is disposed on the horizontal movement mechanism 12, for example, on the support structure 121 of the horizontal movement mechanism 12. The vertical motion assembly is not particularly limited by the present embodiment, and may be, for example, a slide rail assembly, a rack and pinion assembly, or a ball screw assembly. The second drive may be, for example, an electric motor, hydraulic or pneumatic device. Preferably, the first driver and the second driver are both connected to the controller 17 in communication, so as to control the motion state (such as turning on, turning off, changing the rotation speed or changing the rotation direction, etc.) of the first driver and the second driver respectively through the controller 17, and more specifically, by receiving the instruction of the controller 17, the first driver or the second driver turns on, turns off, changes the rotation speed or changes the rotation direction, etc.

In an alternative embodiment, the functions of the horizontal movement mechanism 12 and the vertical movement mechanism 11 can be realized by one mechanism, which is also within the protection scope of the present invention. For example, the horizontal movement mechanism 12 and the vertical movement mechanism 11 may be replaced by an XZ-axis gantry slide module. Or, the horizontal movement mechanism 12 and the vertical movement mechanism 11 can be replaced by a three-axis gantry sliding table module, so that the degree of freedom of movement in the horizontal direction is increased, and the application range of the microneedle preparation device can be widened.

Further, the microneedle preparation apparatus 10 further includes a pressure sensor 19 for sensing the pressure applied to the female elastic mold 14 and generating pressure information. Preferably, the controller 17 is communicatively connected to a pressure sensor 19. In practice, the vertical movement mechanism 11 drives the filler 16 to move downwards until the roller 131 contacts the elastic female die 14 and applies a certain pressure. The pressure sensor 19 acquires a pressure value and feeds back pressure information to the controller 17. The controller 17 judges whether the current pressure applied to the elastic female die 14 reaches a preset pressure value or not according to the pressure information, if so, the controller 17 controls the vertical movement mechanism 11 to stop moving downwards continuously to keep the current pressure, and if not, the controller 17 controls the vertical movement mechanism 11 to continue moving downwards until the pressure reaches the preset pressure value. By controlling the pressing force to which the female elastic element 14 is subjected, it is ensured that the female elastic element is deformed sufficiently to ensure the filling effect. The pressure sensor 19 may be installed at a lower end of the support 111 and connected to the filler 16 and the support 111, respectively. However, the actual mounting position of the pressure sensor 19 is not particularly limited in the present invention. In addition, the pressure preset value of the pressure can be determined by those skilled in the art according to the viscosity of the solution, the material of the elastic female die, the shape and the size of the concave pit, and the like, and is set to be, for example, 20 to 40N, preferably, for example, 20 to 30N, and further preferably, for example, 30N. Further, the filler 16 and the pressure sensor 19 may be screwed, and the pressure sensor 19 and the support 111 may be screwed. It will be understood by those skilled in the art that the present invention is not limited to the manner of connection of the filler 16 to the pressure sensor 19, and is selected based on the configuration of the pressure sensor. Preferably, the microneedle preparation apparatus 10 further includes a display device for displaying the pressure information.

The filler 16 further includes a liquid supply line 168 in communication with the storage chamber 161 for supplying an external solution to the storage chamber 161. Preferably, the filler 16 further comprises a level sensor 169 (see fig. 4 and 5) disposed in the storage chamber 161 for sensing the level of the solution in the storage chamber 161 and generating level information. Preferably, the liquid level sensor 169 is in communication connection with a controller 17, and the controller 17 is configured to receive the liquid level height information, and determine whether the current liquid level in the storage cavity 161 is lower than a preset value according to the liquid level height information: if yes, the controller 17 sends early warning information to the outside and/or controls the solution 18 to be pumped into the storage cavity. More preferably, the height information may be displayed by the display device.

Further, the embodiment described above provides an exemplary microneedle making process of the microneedle preparation apparatus 10 with the controller 17, which more specifically includes:

first, the controller 17 controls the filler 16 to be reset to the closed state. In use, the elastic female die 14 is placed on the base plate 15, and the elastic female die 14 is fixed by a jig. The solution 18 is a low molecular sodium hyaluronate aqueous solution (for example, the low molecular sodium hyaluronate aqueous solution has a molecular weight range of 300000-1000000 and a dynamic viscosity of 10000cps) as an example. Thereafter, a low molecular sodium hyaluronate solution is pumped into the storage chamber 161 through the fluid supply line 168. Then, the horizontal movement mechanism 12 and the vertical movement mechanism 11 are controlled by the controller 17 to move the filler 16 to a proper position so that the roller 131 comes into surface contact with the elastic female mold 14. Then, the controller 17 is used to control the direct-acting electromagnet 167 to be energized, so that a horizontal gap with a certain distance is formed between the two movable baffles 163 and the roller shaft 131, and the height adjusting assembly is adjusted at the same time, so that a set distance is formed between the surface of the elastic female die 14 and the second baffle 1632, wherein the set distance is the thickness of the low-molecular sodium hyaluronate solution coated on the surface of the elastic female die 14. After the adjustment is finished, the controller 17 controls the vertical movement mechanism 11 to continue moving downwards until the pressure sensed by the pressure sensor 19 reaches a preset pressure value, and after the pressure reaches the preset pressure value, the vertical movement mechanism 11 is stationary. Then, the controller 17 controls the horizontal movement mechanism 12 to make a linear reciprocating movement several times within a certain distance, and the movement times and speed are determined according to the characteristics of the solution and the size of the die pit. And finally, resetting all parts of the device to finish filling the low-molecular sodium hyaluronate aqueous solution on the elastic female die. And after the low-molecular sodium hyaluronate aqueous solution is dried, taking down the low-molecular sodium hyaluronate aqueous solution from the elastic female die to finish the preparation of the microneedle. In the preparation method, the formed microneedle is a solid microneedle with a substrate and a needle body which are integrally formed. It is apparent that the microneedle preparation apparatus 10 without the controller 17 can also implement the above-described preparation of microneedles (particularly, solid microneedles), but need only be manually substituted for the controller 17 to implement the functions of the controller 17.

In other exemplary methods of manufacture, the height adjustment assembly is adjusted to set the surface of the female elastic mold 14 to a set distance from the second baffle 1632, which is small relative to the distance in the above-described methods of manufacture. After the parts of the resetting device are filled with the low-molecular sodium hyaluronate aqueous solution on the elastic female die, the low-molecular sodium hyaluronate aqueous solution except the needle body part can be removed, and before or after drying, a substrate formed by other materials is jointed with the needle body to finally form the microneedle. In the preparation method, the formed micro-needle is a micro-needle formed by separately molding the substrate and the needle body.

The above description is only for the purpose of describing the preferred embodiments of the present invention, and is not intended to limit the scope of the present invention, and any variations and modifications made by those skilled in the art based on the above disclosure are within the scope of the present invention.