CN112720967A

CN112720967A - Device and method for manufacturing micro-array transdermal drug delivery micro-needle

Info

Publication number: CN112720967A
Application number: CN202110061908.3A
Authority: CN
Inventors: 不公告发明人
Original assignee: Youwei Zhidian Beijing Biotechnology Co ltd
Current assignee: Youwei Zhidian Beijing Biotechnology Co ltd
Priority date: 2021-01-18
Filing date: 2021-01-18
Publication date: 2021-04-30
Anticipated expiration: 2041-01-18
Also published as: CN112720967B

Abstract

The invention provides a manufacturing device and method of micro-array transdermal drug delivery micro-needles. The device includes: a mold with preset flexibility, a pressing device and an input device; the bottom of the mold is placed on the worktable, and the top of the mold is provided with a plurality of grooves, and the shape of each groove matches the shape of the microneedles ; The pressing device is detachably arranged on the mold, and applies pressure to each groove to make each groove in a closed state; Liquid is injected, and the liquid in each groove solidifies to form microneedles. In the present invention, the shape of each groove matches the shape of the microneedle to be made, and the input device injects liquid into each groove to form a microneedle of the required shape and size, and the shape of the microneedle can be accurately controlled. It can be closed under the action of the pressing device, which is convenient for the input device to inject liquid into each groove, and the liquid only needs to be solidified to make the microneedle, which ensures the effect and quality of the microneedle.

Description

Device and method for manufacturing micro-array transdermal drug delivery micro-needle

Technical Field

The invention relates to the technical field of medical equipment, in particular to a device and a method for manufacturing a micro-array transdermal drug delivery microneedle.

Background

At present, the biodegradable microarray drug delivery belongs to painless transdermal drug delivery technology, and micron-sized drug delivery channels can be painlessly created on the skin, so that drugs or effective components can be introduced into the skin through the natural skin horny layer of the skin and then absorbed, and the permeability of the skin to active substances or drugs, especially macromolecular drugs, is enhanced. Therefore, soluble microneedles are more widely used.

The existing manufacturing process of the soluble microneedle mainly comprises a stretching and shaping method, wherein a microneedle structure is formed by contacting and stretching viscous macromolecule liquid drops, and the shape of the manufactured microneedle cannot be freely controlled because the manufacturing process utilizes the stretching and extending characteristics of viscous fluid.

Disclosure of Invention

In view of this, the invention provides a device for manufacturing a micro-array transdermal drug delivery microneedle, which aims to solve the problem that the shape of a soluble microneedle manufactured by a stretch-molding method in the prior art cannot be controlled. The invention also provides a manufacturing method of the micro-array transdermal drug delivery micro-needle.

In one aspect, the present invention provides an apparatus for fabricating micro-array transdermal drug delivery microneedles, the apparatus comprising: the device comprises a mould with preset flexibility, a pressure applying device and an input device; the bottom of the mold is used for being placed on the workbench, the top of the mold is provided with a plurality of grooves, and the shape of each groove is matched with that of the microneedle; the pressing device is detachably arranged on the die and used for applying pressure to the grooves so as to enable the grooves to be in a closed state; the input device is detachably arranged at the top of the mold and used for injecting liquid into the grooves after the grooves are in a closed state, and the liquid in each groove is used for forming the micro-needle after solidification.

Further, in the apparatus for manufacturing the micro-array transdermal delivery microneedle, the input device includes: the device comprises a shell with a hollow interior, a plurality of input pipes and a plurality of sealing structures; wherein, the shell is arranged at the upper part of the mould, and the side wall of the shell is provided with at least one liquid inlet; each input pipe is arranged on one surface of the shell facing the mold, the end parts of the input pipes are correspondingly covered outside the grooves one by one, and each input pipe is used for injecting liquid with preset pressure into the corresponding groove; each seal structure sets up in the tip of each input tube one-to-one, and each seal structure all is used for sealing the junction of input tube and recess.

Further, in the apparatus for manufacturing the micro-array transdermal delivery microneedle, the pressure applying device includes: a vacuum pumping device; the vacuumizing device is arranged on the input device and used for vacuumizing each groove to close the grooves and stopping vacuumizing when each groove is in a closed state.

Further, in the apparatus for manufacturing the micro-array transdermal delivery microneedle, the vacuum pumping apparatus includes: a partition plate and a switching valve; the partition plate is arranged in the shell to divide the shell into a first space and a second space, and the first space is close to the mold; the partition board is provided with an opening, and the switch valve is arranged at the opening; an output port used for being connected with a vacuum pump is formed in the position, corresponding to the second space, of the shell; the liquid inlet is arranged on the side wall of the shell corresponding to the first space.

Further, in the apparatus for manufacturing a micro-array transdermal delivery microneedle, the pressure applying device further includes: an auxiliary device; the auxiliary device is detachably arranged outside the mold and is used for applying pressure to the outside of the mold when the vacuumizing device vacuumizes to assist the closing of the grooves; the assist device includes: a hollow accommodating body; wherein, the top of the containing body is provided with a concave part for containing the mould; a connecting port is formed in the side wall of the accommodating body and is used for being connected with the gas transmission device so as to charge gas into the accommodating body; the accommodating body has preset expansion and contraction properties so as to be in an expansion state when inflated, and further extrude the side part and the bottom part of the die.

Further, the apparatus for manufacturing the micro-array transdermal delivery microneedle further comprises: a vibrating device; the vibration device is detachably arranged on the workbench and is used for vibrating the mould when the input device injects liquid; and/or, further comprising: a support frame and a lifting device; the support frame is arranged on the workbench; the lifting device is arranged on the support frame and is arranged at the upper part of the mould; the input device is arranged on the lifting device, and the lifting device is used for driving the input device to lift.

In the invention, the shape of each groove formed in the top of the mold is matched with the shape of a microneedle to be manufactured, the microneedle with the required shape and size can be manufactured after the input device injects liquid into each groove, the shape of the microneedle can be accurately controlled, and the mold has preset flexibility, so that each groove can be in a closed state under the action of the pressure device, the input device can conveniently inject the liquid into each groove, the microneedle can be manufactured only by solidifying the liquid, high-temperature heating and centrifugation are not needed, the influence of temperature and external force on the physicochemical property of the liquid is avoided, the effect and the quality of the microneedle are ensured, the manufacture is simple, the implementation is convenient, and the problem that the shape of the soluble microneedle manufactured by a stretching and shaping method in the prior art can not be controlled is solved.

On the other hand, the invention also provides a manufacturing method of the micro-array transdermal drug delivery micro-needle, which comprises the following steps: a pressure applying step of applying pressure to each groove of the mold to close each groove; injecting liquid into each groove after each groove is closed; and a solidification step, standing for a preset time, and solidifying the liquid in each groove into the microneedle.

Further, in the manufacturing method of the micro-array transdermal drug delivery microneedle, in the pressure applying step, each groove is vacuumized to close the groove.

Furthermore, in the manufacturing method of the micro-array transdermal drug delivery micro-needle, in the pressure applying step, when the vacuum is pumped, the pressure is applied to the bottom and the side of the mould so as to assist the grooves to exhaust gas and close.

Further, in the method for manufacturing the micro-array transdermal delivery microneedle, the injecting step further comprises: a first liquid injection sub-step, after each groove is closed, injecting a preset amount of liquid into each groove; a drawing-out substep of drawing out the liquid in each groove; repeating the sub-steps of injecting liquid and extracting at least once; a second liquid injection sub-step, wherein liquid is injected into each groove until each groove is filled with the liquid; in the second liquid injection sub-step, when liquid is injected, the mold is vibrated, and bubbles are prevented from being generated.

In the invention, pressure is applied to each groove of the mold, and the mold has preset flexibility, so each groove can be in a closed state under the action of the pressure, liquid is conveniently injected into each groove, and each liquid can be prepared into the microneedle only by solidification.

Drawings

Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention. Also, like reference numerals are used to refer to like parts throughout the drawings. In the drawings:

fig. 1 is a schematic structural diagram of a device for fabricating a micro-array transdermal drug delivery microneedle according to an embodiment of the present invention;

fig. 2 is a schematic structural diagram of a micro-array transdermal drug delivery microneedle manufacturing apparatus provided in an embodiment of the present invention, in which each groove is in a closed state;

fig. 3 is a schematic structural diagram of a microarray transdermal microneedle manufacturing apparatus according to an embodiment of the present invention after injecting a liquid;

fig. 4 is a schematic structural diagram of a microarray transdermal microneedle manufacturing apparatus according to an embodiment of the present invention after injecting different liquids;

fig. 5 is a schematic structural diagram of a groove in a device for manufacturing a micro-array transdermal drug delivery microneedle according to an embodiment of the present invention;

fig. 6 is a schematic side sectional view of an auxiliary device in a device for manufacturing a micro-array transdermal drug delivery microneedle according to an embodiment of the present invention;

fig. 7 is a schematic top view of an auxiliary device in a device for manufacturing a micro-array transdermal delivery microneedle according to an embodiment of the present invention;

fig. 8 is a schematic structural diagram of a support frame in a device for manufacturing a micro-array transdermal drug delivery microneedle according to an embodiment of the present invention;

fig. 9 is a flowchart of a method for fabricating a micro-array transdermal delivery microneedle according to an embodiment of the present invention.

Detailed Description

Exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it should be understood that the present disclosure may be embodied in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the disclosure to those skilled in the art. It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict. The present invention will be described in detail below with reference to the embodiments with reference to the attached drawings.

The embodiment of the device is as follows:

referring to fig. 1 to 7, a preferred structure of the device for fabricating the micro-array transdermal delivery microneedle of the present embodiment is shown. As shown in the figure, the device for fabricating the micro-array transdermal drug delivery microneedle comprises: a mould 1, a pressing device and an input device 2. The bottom (the lower part shown in fig. 1) of the mold 1 is used for being placed on the workbench 8, and in specific implementation, the mold 1 may be placed only on the workbench 8, or may be detachably connected to the workbench 8.

The top of the mold 1 is provided with a plurality of grooves 11, the shape of each groove 11 is matched with the shape of a microneedle to be manufactured, and the shape of each groove 11 can be determined according to the shape of the microneedle. Referring to fig. 1 and 5, the shape of each groove 11 may be the same or different, and the size of each groove 11 may be the same or different, which is not limited in this embodiment. Thus, different groove shapes can be arranged according to actual requirements to form various microneedle shapes. In addition, a plurality of grooves with different shapes, sizes, lengths and densities on one mold can be realized, and the condition that the same microneedle has the coexistence of various shapes, sizes, lengths and densities is realized.

In specific implementation, the shape of the groove 11 may be a cone, a polygonal cone, a concave-curved cone, a convex-curved cone, a pointed cone, a truncated cone, a diagonal cone, a pointed concave cone, a truncated concave cone, a pointed convex cone, a special-shaped cone, and the like, which is not limited in this embodiment.

The mold 1 has a predetermined flexibility, which can be determined according to actual conditions, and this embodiment does not limit this. The material of the mold 1 should be a material with a predetermined flexibility, such as silicon or polydimethylsiloxane PDMS.

In specific implementation, the diameter of the groove 11 ranges from 50 to 1500 micrometers, the length ranges from 50 to 2000 micrometers, and the diameter of the tip ranges from 2 to 200 micrometers. Of course, the size of the groove 11 can be determined according to practical situations, and the embodiment does not limit this.

A pressing device is detachably provided to the mold 1, and the pressing device is configured to apply pressure to each groove 11 to make each groove 11 in a closed state, so that a pressure difference is generated between each groove 11 and the outside of the mold 1. In specific implementation, the pressing device only needs to be capable of closing each groove 11, and the structure of the pressing device is not limited in this embodiment.

The input device 2 is detachably disposed on the top (upper portion shown in fig. 1) of the mold 1, the input device 2 is used for injecting liquid into each groove 11 after each groove 11 is in a closed state, and the liquid in each groove 11 is solidified to form microneedles. In particular, the pressing means exert a pressure on each groove 11, each groove 11 being progressively closed under the effect of the pressure, due to the preset flexibility of the mould 1. When the grooves 11 are closed, a certain pressure difference is generated between the inside of each groove 11 and the outside of the mold 1, and the input device 2 injects liquid into each groove 11 under the action of the pressure difference until the grooves 11 are filled with the liquid. The input device 2 is disassembled, and the liquid is solidified into the micro-needle after standing for a preset time. The process of standing can be carried out at normal temperature or even low temperature without heating, thus reducing the damage to liquid components, avoiding liquid inactivation and further ensuring the effect of the microneedle.

The liquid can be viscous liquid, and the liquid can be biodegradable high molecular material or non-degradable biocompatible high molecular material. In specific implementation, the biodegradable polymer material may be one or more of chondroitin sulfate, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, methyl vinyl ether-maleic anhydride copolymer, polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, carboxymethyl cellulose, carbomer, trehalose, maltose, sucrose, raffinose, hyaluronic acid, sodium alginate, pullulan, dextran, and the like. The non-degradable biocompatible polymer material may be silicon, polyaryl ether ketone, etc.

Preferably, the inner wall of each groove 11 is surface-activated to facilitate the adsorption of liquid into the groove.

Referring to fig. 8, preferably, the apparatus for fabricating the micro-array transdermal delivery microneedle further includes: a support frame 9 and a lifting device 10. Wherein, the supporting frame 9 is arranged on the working platform 8, specifically, the bottom (the lower part shown in fig. 8) of the supporting frame 9 is connected with the working platform 8, and the top (the upper part shown in fig. 8) of the supporting frame 9 is arranged on the upper part of the top of the mould 1.

The lifting device 10 is disposed on the supporting frame 9, and the lifting device 10 is disposed on the upper portion (with respect to fig. 8) of the mold 1, specifically, the lifting device 10 is disposed at the top of the supporting frame 9, and the lifting device 10 and the top of the mold 1 have a certain distance therebetween, which may be determined according to practical situations, and the embodiment does not limit this.

The input device 2 is disposed on the lifting device 10, and the lifting device 10 is configured to drive the input device 2 to lift, so that the input device 2 is disposed on the top of the mold 1, or the input device 2 is separated from the mold 1.

In a specific implementation, the lifting device 10 may be a retractable structure or a movable structure, and the present embodiment does not limit this.

In use, the lifting device 10 controls the input device 2 to fall to the top of the mould 1, and the input device 2 is connected with the top of the mould 1, so that the input device 2 can inject liquid conveniently. After the grooves 11 are filled with liquid, the lifting device 10 controls the input device 2 to lift to the upper part of the mold 1, so that the input device 2 is separated from the top of the mold 1, and the liquid in each groove 11 is convenient to stand into a microneedle.

It can be seen that, in this embodiment, the shape of each recess 11 that the top of mould 1 was seted up matches with the shape of the micropin that will make, then input device 2 can make the micropin of required shape and size after pouring into liquid into each recess 11, can the form of accurate control micropin, and mould 1 has predetermined flexibility, like this each recess 11 can be the closed condition under pressure device's effect, be convenient for input device 2 pours into liquid into each recess 11 into, the micropin can be made only to liquid need solidify, need not high temperature heating, centrifugation, avoid the influence of temperature and external force to liquid physicochemical property, guarantee the effect and the quality of micropin, simple manufacture, convenient to implement, the problem of the form uncontrollable of the soluble micropin of stretching moulding method preparation among the prior art has been solved.

With continued reference to fig. 1-4, in the above-described embodiment, the input device 2 may include: a housing 21, a plurality of inlet pipes 22 and a plurality of sealing structures. The interior of the housing 21 is hollow, and both ends of the housing 21 are closed ends. The shell 21 is arranged on the upper part of the mold 1, the side wall of the shell 21 is provided with a liquid inlet 211, the liquid inlet 211 is used for being connected with a liquid injection device, liquid is stored in the liquid injection device, and then the liquid injection device injects liquid into the shell 21 through the liquid inlet 211. The inlet 211 may be provided with a valve to control the flow rate of the injected liquid and whether the liquid is injected.

The number of the input pipes 22 is the same as that of the grooves 11, and the positions of the input pipes 22 correspond to those of the grooves 11 one by one, and each input pipe 22 is arranged on one surface of the shell 21 facing the mold 1. Specifically, a plurality of through holes are formed in one surface of the housing 21 facing the mold 1, the number of the through holes is the same as that of the input pipes 22, and the positions of the through holes correspond to those of the input pipes 22 one by one. The first end of each input pipe 22 is connected with the corresponding through hole, the second end of each input pipe 22 covers the outside of the corresponding groove 11, and each input pipe 22 is used for injecting liquid with preset pressure into the corresponding groove 11. Specifically, the second end of each input pipe 22 is in contact with the top of the mold 1, and the end of the second end of each input pipe 22 is covered outside the open end of the corresponding groove 11.

The preset pressure of the liquid can be determined according to actual conditions, and the embodiment does not limit the preset pressure. In addition, the pressure of the liquid can promote the liquid to be injected into each groove 11, so that the grooves 11 are filled with the liquid, and the quality of the micro-needles is ensured. The liquid with the preset pressure can be injected into the housing 21 through a high-pressure device, and of course, the liquid can be injected through other devices, and the structure for applying the liquid pressure is not limited in this embodiment.

The number of seal structures is the same as the number of inlet pipes 22, and each inlet pipe 22 corresponds to each seal structure one-to-one. Each sealing structure is provided at the end of the second end of the corresponding inlet pipe 22, and each sealing structure is used for sealing the joint of the corresponding inlet pipe 22 and the groove 11.

Each sealing structure may be a flexible suction cup 23, and the suction cup 23 may be attached to the top of the mold 1 and cover the outside of the groove 11. In specific implementation, the contact position between the suction cup 23 and the top of the mold 1 may be polished to improve the sealing between the suction cup 23 and the groove 11. The surface of the suction pad 23 and the top of the mold 1 may be subjected to a micro-heat treatment to soften the suction pad 23 and the mold 1 and to improve the adsorption between the suction pad 23 and the mold 1. It is also possible to apply an adhesive substance to the surface of the suction cup 23 and the top of the mold 1 to promote the adsorption between the suction cup 23 and the mold 1.

It can be seen that, in this embodiment, when each recess 11 is the closure state, every input tube 22 all injects the liquid that has preset pressure into corresponding recess 11, guarantees that liquid is stable, input smoothly to the recess 11 in, and then ensures that liquid is full of recess 11, and the sealing performance between input tube 22 and the recess 11 can be guaranteed in the setting of seal structure, and then ensures that liquid is stable to be injected into each recess 11 in, avoid pressure to reveal and lead to liquid can't be full of recess 11.

Referring to fig. 4, in the above embodiment, there are at least two liquid inlets 211, each liquid inlet 211 is disposed on a side wall of the housing 21, and each liquid inlet 211 is disposed along a height direction of the housing 21 (a direction from top to bottom shown in fig. 4). Specifically, the liquid can be one, and then the pure microneedle is prepared; or, the liquid is at least two, so that the multilayer layered capsule type microneedle is prepared. When the liquid is at least two kinds, the respective liquids may be injected into the respective grooves 11 in sequence.

In specific implementation, each liquid inlet 211 is provided with a valve.

In specific implementation, when the number of the liquids is at least two, each liquid inlet 211 injects a different liquid into the housing 21. First, the first liquid inlet 211 is opened, the flow rate of the first liquid is controlled, and the first liquid enters each groove 11 and then is adsorbed on the surface of the groove 11, so that a liquid film is formed. Then, the first liquid inlet 211 is closed, the second liquid inlet 211 is opened, and the second liquid enters each groove 11. Then, the second liquid inlet 211 is closed, the third liquid inlet 211 is opened, the third liquid enters each groove 11, and the steps are repeated in sequence until different liquids are injected into each groove 11 in sequence. In particular embodiments, different loading ports 211 may be selectively opened.

Referring to fig. 1 to 4, in each of the above embodiments, the pressing device may include: and (4) a vacuumizing device. Wherein, the vacuumizing device is arranged on the input device 2, and the vacuumizing device is detachably connected with the mould 1 through the input device 2. The vacuum-pumping device is used for vacuumizing each groove 11 to close each groove 11, and stops vacuumizing when each groove 11 is in a closed state. Therefore, the grooves 11 are vacuumized, so that the grooves 11 are in a negative pressure state, and the liquid can actively flow into the grooves 11 by opening the valve at the liquid inlet 211 under the action of the difference between the internal pressure and the external pressure.

The vacuum-pumping means may include: a partition 3 and an on-off valve 4. The partition plate 3 is disposed inside the housing 21, specifically, the partition plate 3 is disposed transversely inside the housing 21, the partition plate 3 is parallel to a surface of the housing 21 facing the mold 1, the partition plate 3 divides the housing 21 into a first space 5 and a second space 6, the first space 5 is disposed at a lower portion (with respect to fig. 1) inside the housing 21 and is close to the mold 1, and the second space 6 is disposed at an upper portion (with respect to fig. 1) inside the housing 21. The partition 3 is opened with an opening provided near a side wall of the case 21, and the on-off valve 4 is provided at the opening to control the opening to be closed or opened.

An output port 212 is opened in the housing 21 corresponding to the second space 6, and the output port 212 is used for connecting with a vacuum pump, and the vacuum pump is used for pumping the gas in each groove 11 so as to close each groove 11. The liquid inlet 211 is opened on a side wall of the housing 21 corresponding to the first space 5, and the first space 5 is a space for injecting liquid. When the number of the liquid inlet ports 211 is at least two, each liquid inlet port 211 corresponds to the first space 5.

During the specific use, each sucking disc 23 adsorbs in the top of mould 1 and covers the outside of establishing in corresponding recess 11, close the valve of inlet 211 department, open the valve of ooff valve 4 and delivery outlet 212 department, the vacuum pump is bled from delivery outlet 212 department, make first space 5 and second space 6 reach vacuum state, finally make each recess 11 closed because of the evacuation, at this moment, the inside of each recess 11 produces the pressure differential with the outside of mould 1, close the valve of ooff valve 4 and delivery outlet 212 department this moment, open the valve of inlet 211 department, liquid flows into first space 5 from inlet 211 automatically under the effect of pressure differential, flow into in each recess 11 through each sucking disc 23. The pressure of the liquid is to increase the difference between the internal and external pressure of each recess 11 so that the liquid can flow more easily into each recess.

It can be seen that in the present embodiment, before the liquid is injected into the input device 2, vacuum is pumped to close each groove 11, so that the gas in the groove 11 can be exhausted, and a pressure difference is generated, and the liquid is stably injected into the groove 11 under the action of the pressure difference. And the vacuum pumping device has simple structure and is convenient to implement. Meanwhile, the vacuumizing device is arranged on the input device 2, the integral sealing performance of the manufacturing device of the micro-needle for transdermal administration of the micro-array is guaranteed, air leakage and pressure leakage are avoided, and the forming quality and effect of the micro-needle can be guaranteed.

Referring to fig. 6 and 7, the pressing device may further include: an auxiliary device 7. Wherein, auxiliary device 7 is detachably arranged outside the mould 1, and the auxiliary device 7 is used for applying pressure to the outside of the mould 1 when the vacuum-pumping device pumps vacuum so as to assist the closing of each groove 11. In this way, the auxiliary device 7 can accelerate the air discharge of the grooves 11, and can rapidly close the grooves 11, and can ensure the closing effect of the grooves 11 and avoid the air residue.

The auxiliary device 7 may comprise: the housing 71. The top of the accommodating body 71 is provided with a concave portion for accommodating the mold 1. The accommodating body 71 is hollow, and a connecting port is formed in the side wall of the accommodating body 71 and connected with a gas transmission device, and the gas transmission device is used for inflating the inside of the accommodating body 71. The accommodating body 71 has a predetermined expansion and contraction property, so that the accommodating body 71 is in an expanded state when the inside is inflated, and further, the side portion and the bottom portion of the mold 1 are pressed, thereby promoting the discharge of the gas in each groove 11, and closing each groove 11.

In specific implementation, the preset expansion and contraction may be determined according to actual conditions, and this embodiment does not limit this. The material of the container 71 is a material with preset expansion and contraction, for example: rubber.

In specific implementation, the gas transmission device may be a high-pressure pump, or may be another device, and this embodiment does not limit this.

In the above embodiments, when the input device 2 injects liquid into each groove 11, in order to ensure the quality of microneedle formation, it is necessary to avoid air bubbles, and for this reason, the apparatus for manufacturing a micro-array transdermal delivery microneedle may further include: a vibrating device. Wherein, vibrating device detachably sets up in workstation 8, and vibrating device is used for making mould 1 vibration when input device 2 pours into liquid into to avoid producing the bubble, guarantee that the liquid in each recess 11 does not have the bubble, and then improve the shaping quality of micropin.

In specific implementation, the vibration device may be a vibrator, and may also be an ultrasonic electromagnetic device, as long as the vibration device can generate vibration, and the structure of the vibration device is not limited in this embodiment. Preferably, the vibration device is an ultrasonic electromagnetic device, so that the template 1 generates ultrasonic micro-frequency vibration.

Preferably, the apparatus for fabricating the micro-array transdermal delivery microneedle further comprises: the vibration device is detachably arranged on the workbench and is used for vibrating the mould when the liquid is injected by the input device; and/or, the manufacturing device of the micro-array transdermal drug delivery micro-needle further comprises: a support frame 9 and a lifting device 10; the support frame 9 is arranged on the workbench 8; the lifting device 10 is arranged on the support frame 9 and is arranged at the upper part of the mould 1; the input device 2 is disposed on the lifting device 10, and the lifting device 10 is used for driving the input device 2 to lift.

In specific implementation, when each groove 11 is in a closed state, the input device 2 injects a certain amount of liquid into each groove 11 under the action of pressure difference, and then the vacuumizing device pumps away the liquid and exhausts gas, so that each groove 11 is in a closed state. Then, a certain amount of liquid is injected into each groove 11, the liquid is discharged, and after at least one cycle is repeated, the liquid is injected into each groove 11 and fills each groove 11, so that the liquid can be uniformly and fully covered in each groove 11, and bubbles are avoided.

In conclusion, in this embodiment, the microneedle with the required shape and size can be manufactured by injecting the liquid into each groove 11 through the input device 2, the shape of the microneedle can be accurately controlled, each groove 11 can be in a closed state under the action of the pressing device, so that the input device 2 can inject the liquid into each groove 11 conveniently, the microneedle can be manufactured by solidifying the liquid, high-temperature heating and centrifugation are not needed, the influence of temperature and external force on the physicochemical property of the liquid is avoided, the effect and the quality of the microneedle are ensured, the manufacture is simple, and the implementation is convenient.

The method comprises the following steps:

this embodiment also provides a method for manufacturing a micro-array transdermal drug delivery microneedle, and referring to fig. 9, the method for manufacturing a micro-array transdermal drug delivery microneedle includes the following steps:

a pressing step S1 of applying pressure to the respective grooves of the mold to close the respective grooves.

Specifically, the mold is a mold in the above device embodiment, and for the specific implementation process of the mold, reference may be made to the above description in this embodiment, and details of this embodiment are not repeated herein.

Preferably, the grooves are evacuated to close the grooves, so that a pressure difference is maintained between the inside of the grooves and the outside of the mold. Specifically, the interior of each groove exhibits a negative pressure state after evacuation.

More preferably, the vacuum is applied by applying pressure to the bottom and sides of the mold to assist in the venting of the gas from the grooves to close. Specifically, referring to fig. 6 and 7, the mold 1 is placed in a recessed portion at the top of the accommodating body 71, the accommodating body 71 is hollow, and a connecting port is formed on a side wall of the accommodating body 71 and connected to an air conveying device for inflating the inside of the accommodating body 71. The accommodating body 71 has a predetermined expansion and contraction property, so that the accommodating body 71 is in an expanded state when the inside is inflated, and further, the side portion and the bottom portion of the mold 1 are pressed, thereby promoting the discharge of the gas in each groove 11, and closing each groove 11.

In the injecting step S2, after the grooves are closed, a liquid is injected into each groove.

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

Preferably, the liquid may have a preset pressure, and the preset pressure may be determined according to actual conditions, and the embodiment does not limit this. And the pressure of the liquid can promote the liquid to be injected into each groove, so that the grooves are filled with the liquid, and the quality of the micro-needle is ensured.

In the process of injecting the liquid, in order to avoid the occurrence of bubbles, the injecting step S2 may further include:

in the first liquid injection substep S21, after each groove is closed, a predetermined amount of liquid is injected into each groove.

Specifically, after each groove is closed, the liquid is injected into each groove by using the pressure difference, and the preset amount can be determined according to actual conditions, which is not limited in this embodiment.

And a drawing-out substep S22 of drawing out the liquid in each groove.

Specifically, the liquid and the gas in each groove are completely pumped out through a vacuum pumping device, so that each groove is in a closed state.

The primary filling substep S21 and the extraction substep S22 are repeated at least once, specifically, the filling substep S21 and the extraction substep S22 are repeated in this order, and if the primary filling substep S21 and the primary extraction substep S22 are described as one cycle, at least one cycle is repeated.

In the second liquid injection substep S23, a liquid is injected into each groove until each groove is filled.

Preferably, the mold is vibrated while injecting the liquid into each groove to prevent the generation of bubbles. Specifically, the mold may be vibrated using a vibration device. Preferably, ultrasonic micro-frequency vibration is generated by using an ultrasonic electromagnetic device.

And a solidification step S3, standing for a preset time, and solidifying the liquid in each groove into the microneedle.

Specifically, the liquid in each groove is automatically solidified into the microneedle at normal temperature. In specific implementation, the preset time may be determined according to actual conditions, and this embodiment does not limit this.

Preferably, the injected liquid is at least one. When the liquid is one, simple micro-needles are made; when the liquid is at least two, the multilayer layered capsule type microneedle is prepared.

When the number of the liquid is at least two, different liquids are injected into the grooves in sequence.

When the liquid is at least two types, the first liquid is injected firstly, the flow rate of the first liquid is controlled, and the first liquid enters each groove and then is adsorbed on the surface of the groove, so that a liquid film is formed. Then, a second liquid is injected into each groove, and the flow rate of the second liquid is controlled. Then, a third liquid is injected into each groove. And repeating the steps in sequence until different liquids are injected into the grooves.

The specific implementation process of the mold, the vacuum pumping device, the input device, the auxiliary device, and the like, referring to the device for manufacturing the micro-array transdermal drug delivery microneedle, may be as described above, and this embodiment is not described herein again.

It can be seen that, in this embodiment, pressure is applied to each groove of the mold, and since the mold has a preset flexibility, each groove can be in a closed state under the action of the pressure, so that liquid can be conveniently injected into each groove, and each liquid can be prepared into the microneedle only by solidification.

The principles of the apparatus for fabricating a micro-array transdermal delivery microneedle and the method for fabricating a micro-array transdermal delivery microneedle according to the present invention are the same, and the related points can be referred to each other.

It should be noted that in the description of the present invention, the terms of direction or positional relationship indicated by the terms "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, which are only for convenience of description, and do not indicate or imply that the device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present invention.

Furthermore, it should be noted that, in the description of the present invention, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.

It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims

1. A device for making microarray transdermal drug delivery microneedles, characterized in that, comprising: a mold (1) with a preset flexibility, a pressure applying device and an input device (2); wherein,

The bottom of the mold (1) is used to be placed on the workbench (8), and the top of the mold (1) is provided with a plurality of grooves (11), each of the grooves (11) having the same shape as the microscopic grooves (11). Match the shape of the needle;

The pressing device is detachably arranged on the mold (1), and is used for applying pressure to each of the grooves (11), so that each of the grooves (11) is in a closed state;

The input device (2) is detachably arranged on the top of the mold (1), and is used for injecting liquid into each of the grooves (11) after each of the grooves (11) is in a closed state. The liquid in each of the grooves is used to form the microneedles after solidification.

2 . The device for making microarray transdermal drug delivery microneedles according to claim 1 , wherein the input device ( 2 ) comprises: a shell ( 21 ) with a hollow interior, a plurality of input tubes ( 22 ) and multiple sealing structures; of which,

The casing (21) is placed on the upper part of the mold (1), and at least one liquid inlet (211) is opened on the side wall of the casing (21);

Each of the input pipes (22) is arranged on the side of the casing (21) facing the mold (1), and the ends of each of the input pipes (22) are covered in each of the recesses in a one-to-one correspondence. Outside the groove (11), each of the input pipes (22) is used to inject liquid with a preset pressure into the corresponding groove (11);

Each of the sealing structures is provided at the end of each of the input pipes (22) in a one-to-one correspondence, and each of the sealing structures is used for connecting the input pipe (22) and the groove (11) sealed at the place.

3 . The device for making microarray transdermal drug delivery microneedles according to claim 2 , wherein the pressure applying device comprises: a vacuuming device; wherein,

The vacuuming device is arranged on the input device (2), and the vacuuming device is used for vacuuming each of the grooves (11) so as to close each of the grooves (11), and in each of the grooves (11) When the groove (11) is in a closed state, the vacuuming is stopped.

4. The device for making microarray transdermal drug delivery microneedles according to claim 3, wherein the vacuuming device comprises: a partition plate (3) and an on-off valve (4); wherein,

The partition plate (3) is arranged in the casing (21) to divide the casing (21) into a first space (5) and a second space (6), the first space (5) ) close to the mould (1);

The partition plate (3) is provided with an opening, and the on-off valve (4) is arranged at the opening;

The casing (21) is provided with an output port (212) corresponding to the second space (6) for connecting with the vacuum pump;

The liquid inlet (211) is opened on the side wall of the casing (21) corresponding to the first space (5).

5 . The device for making microarray transdermal drug delivery microneedles according to claim 3 , wherein the pressure applying device further comprises: an auxiliary device; wherein,

The auxiliary device (7) is detachably arranged on the outside of the mold (1), and is used for applying pressure to the outside of the mold (1) when the vacuuming device is evacuated, so as to assist each of the The groove (11) is closed;

The auxiliary device (7) comprises: an inner hollow accommodating body (71); the top of the accommodating body (71) is provided with a concave portion for accommodating the mold (1), The side wall of (71) is provided with a connection port, and the connection port is used for connecting with an air delivery device to inflate the accommodating body (71); the accommodating body (71) has a preset expansion and contraction properties, so as to be in an expanded state when inflated to squeeze the sides and bottom of the die (1).

6. The device for making microarray transdermal drug delivery microneedles according to claim 1, wherein,

It also includes: a vibration device; the vibration device is detachably arranged on the workbench (8), and is used to make the mold (1) vibrate when the input device (2) is injected with liquid; and/or,

It also includes: a support frame (9) and a lifting device (10); the support frame (9) is arranged on the workbench (8); the lifting device (10) is arranged on the support frame (9) and placed on the upper part of the mold (1); the input device (2) is arranged on the lifting device (10), and the lifting device (10) is used to drive the input device (2) to rise and fall.

7. a preparation method of microarray transdermal administration microneedle, is characterized in that, comprises the steps:

Step of applying pressure, applying pressure to each groove of the mold to close each of the grooves;

In the injection step, after each of the grooves is closed, inject liquid into each of the grooves;

In the solidification step, the liquid in each of the grooves is solidified into microneedles after standing for a preset time.

8. The method for making microarray transdermal administration microneedles according to claim 7, wherein in the pressing step,

Each of the grooves is evacuated to close each of the grooves.

9. The method for making microarray transdermal administration microneedles according to claim 8, wherein in the pressing step,

During evacuation, pressure is applied to the bottom and sides of the mold to assist in closing each of the grooves by outgassing.

10. The method for making microarray transdermal administration microneedles according to any one of claims 7 to 9, wherein the injecting step further comprises:

In the first liquid injection sub-step, after each of the grooves is closed, inject a preset amount of liquid into each of the grooves;

The extraction sub-step is to extract the liquid in each of the grooves;

repeating the liquid injection sub-step and the extraction sub-step at least once;

In the second liquid injection sub-step, inject liquid into each of the grooves until each of the grooves is filled;

In the second liquid injection sub-step, when the liquid is injected, the mold is vibrated to avoid the generation of air bubbles.