CN115137964B - Microneedle preparation mold, microneedle preparation method and microneedle preparation production line - Google Patents
Microneedle preparation mold, microneedle preparation method and microneedle preparation production line Download PDFInfo
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- CN115137964B CN115137964B CN202210618585.8A CN202210618585A CN115137964B CN 115137964 B CN115137964 B CN 115137964B CN 202210618585 A CN202210618585 A CN 202210618585A CN 115137964 B CN115137964 B CN 115137964B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2207/00—Methods of manufacture, assembly or production
- A61M2207/10—Device therefor
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Abstract
The invention provides a microneedle preparation mould, a microneedle preparation method and a microneedle preparation production line, wherein the microneedle preparation mould is provided with at least two air outlets penetrating through the inner peripheral wall surface of a cavity, the air outlets are communicated with a capillary, the air outlets of the capillary penetrate through the outer surface of the microneedle preparation mould, at least one air outlet is close to the needle base end of the cavity, at least one air outlet is close to the needle tail end of the cavity, the maximum width of each air outlet is between 0.1 and 50 micrometers, the contact angle of a solution filled into the cavity on the inner peripheral wall surface of the cavity is greater than or equal to 90 degrees, and the viscosity of the solution is greater than or equal to 10 centipoise. The microneedle preparation mould provided by the invention can be used for preparing integrated microneedles and multistage microneedles, is high in universality and yield, can be used for automatically preparing microneedles in batches, and is high in preparation efficiency and low in preparation cost.
Description
Technical Field
The invention relates to the technical field of production and manufacturing equipment of medical and cosmetic microneedle patches, in particular to a microneedle preparation mould, a microneedle preparation method of the microneedle preparation mould and a microneedle preparation production line with the microneedle preparation mould.
Background
The microneedle product is provided with a microneedle array, active ingredients such as medicines are arranged on the needle tip body of the microneedle array, the needle tip body of the microneedle array can be penetrated into the skin to act on the skin, a micron-sized medicine transmission channel is formed in the skin safely and painlessly, and the permeability of the skin to macromolecular active ingredients and medicines is enhanced, so that the active ingredients such as medicines of the needle tip body are effectively conveyed into the skin, the transdermal administration is safe and painless, and the transdermal administration is realized.
Because the volume of the needle tip body of the microneedle array is tiny, the preparation process of the needle tip body is generally a mould preparation mode or a stretching preparation mode, the stretching preparation mode can only prepare the needle tip body with a volcanic structure, and can not prepare the needle tip bodies with other different shapes, however, the needle tip body with a fire mountain structure can cause lower content of effective components such as carried medicines due to the limitation of the structure of the needle tip body, so that the transdermal drug delivery quantity requirement of most medicines can not be met. In addition, the mould preparation mode forms the needlepoint body of the microneedle array by pouring the needlepoint body solution into the micropores of the mould, and the micropores of the mould can be set into different shape structures, so that the needlepoint body of the microneedle array is prepared by the mould preparation mode more widely in the industry.
Referring to fig. 1 to 4, a conventional mold for manufacturing a microneedle array is provided with a plurality of cavities 12 on a female mold 11, the shape of which is adapted to the shape of the tip body of the microneedle array, each cavity 12 having a filling inlet and an exhaust outlet 13, the filling inlet being located on one side surface of the female mold 11 and located at the needle base end of the cavity 12, the exhaust outlet 13 being located on the other side surface of the female mold 11 and located at the needle end of the cavity 12, the surface of the female mold 11 having a plurality of exhaust outlets 13 forming an exhaust surface, a breathable film being covered on the exhaust surface for preventing liquid permeation and gas permeation, the breathable film being in a positive pressure range of 0.001Mpa to 0.5Mpa or in a negative pressure range of-0.5 Mpa to-0.001 Mpa, and having a certain air permeation amount. Therefore, in order to prevent the liquid from permeating and discharging the gas from the gas outlet 13, the existing mold for preparing the microneedle array needs to be additionally provided with a ventilated membrane and a pressurizing system for giving positive pressure to the ventilated membrane or a vacuum system for giving negative pressure, so that the number of preparation devices is large, the cost for preparing the microneedles is greatly increased, meanwhile, the existing mold is unfavorable for the production line of the flow line type, the universality is limited, and complicated ventilation membrane and pressurizing system or vacuum system debugging procedures are needed before the preparation, thereby influencing the preparation efficiency.
The multi-stage microneedle tip body at least comprises a needle end made of the first solution 14 and a needle base end made of the second solution 15, and has the advantage that the multi-stage microneedle tip body can intensively carry active ingredients such as various different medicines on one microneedle tip body. However, when the air vent 13 of the existing mold for preparing the microneedle array is located on the other side surface of the female mold 11 and located at the needle end of the cavity 12, the first solution 14 can smoothly enter the needle end of the filling cavity 12 to be solidified and formed under the action of the air vent 13 and the air-permeable membrane when the air vent 13 is covered by the first solution 14 (as shown in fig. 2), when the second solution 15 enters the needle base end of the cavity 12, the air between the second solution 15 and the first solution 14 cannot be discharged, the second solution 15 cannot completely fill the needle base end of the cavity 12 and a crack 16 exists between the second solution 15 and the first solution 14 (as shown in fig. 4), the multi-stage microneedle needle end is easy to break during demolding, the yield is low, and the preparation efficiency is further affected.
Disclosure of Invention
The first object of the invention is to provide a microneedle preparation mold with high yield, strong universality, high preparation efficiency and low preparation cost.
A second object of the present invention is to provide a microneedle preparation line having the above microneedle preparation mold.
A third object of the present invention is to provide a method for preparing a microneedle of the above microneedle preparation mold.
In order to achieve the first object of the present invention, there is provided a microneedle preparation mold provided with a plurality of cavities adapted to the shape of needle tip bodies of a microneedle array, each cavity having an injection port, the injection port being located on a first side surface of the microneedle preparation mold and located at a needle base end of the cavity, a needle end of the cavity being located near a second side surface of the microneedle preparation mold, and the second side surface of the microneedle preparation mold being disposed opposite to the first side surface of the microneedle preparation mold in a normal direction of the microneedle preparation mold, the microneedle preparation mold further being provided with at least two air outlets penetrating through an inner peripheral wall surface of the cavity, one air outlet being in communication with at least one capillary, or a plurality of air outlets being in communication with one capillary, an air outlet of the capillary being disposed through an outer surface of the microneedle preparation mold, at least one air outlet being located near a needle base end of the cavity, and at least one air outlet being located near a needle end of the cavity, each air outlet having a maximum width in a direction of the microneedle preparation mold of 0.1 to 50 micrometers, and/or a contact angle of each air outlet being in a tangential direction of the microneedle preparation mold of 0.1 to 50 micrometers, and/or a solution viscosity being filled in the cavity having a contact angle of 10 ° or more than or equal to or more than 10 centipoise.
When a solution is filled from an injection port of a cavity into the cavity of the microneedle preparation mold for preparing the integrated microneedle, as the air outlet penetrating through the inner peripheral wall surface of the cavity is 0.1-50 microns in the normal direction of the microneedle preparation mold and/or in the tangential direction of the microneedle preparation mold, the contact angle of the solution on the inner peripheral wall surface of the cavity is greater than or equal to 90 degrees, the viscosity of the solution is greater than or equal to 10 centipoise, the solution can be effectively prevented from entering the capillary through the air outlet, and meanwhile, the gas in the cavity can smoothly pass through the air outlet and enter the capillary and be discharged out of the microneedle preparation mold through the air outlet of the capillary, so that defective products are prevented from being caused when the solution is filled into the cavity of the microneedle preparation mold for preparing the integrated microneedle tip body, the integrated microneedle preparation mold has good preparation effect, the preparation yield is improved, the contact angle of the solution on the inner peripheral wall surface of the cavity is greater than or equal to 90 degrees, the upper liquid surface of the needle proximal to the cavity can be forced to the tip of the needle to enter the capillary, the liquid at the end of the needle proximal end of the cavity can be pressurized, and the gas can be rapidly forced to be discharged out of the cavity, and the microneedle can be prepared.
When at least two solutions are respectively filled into the cavity of the microneedle preparation mould from the injection port of the cavity to prepare the multi-section microneedle, as at least one air outlet is arranged close to the needle base end of the cavity and at least one air outlet is arranged close to the needle tail end of the cavity, the air outlet arranged close to the needle tail end of the cavity when the needle tail end of the cavity is filled with the first solution can smoothly discharge air in the needle tail end of the cavity, and then the air outlet arranged close to the needle base end of the cavity when the needle base end of the cavity is filled with the second solution can smoothly discharge air in the needle base end of the cavity, so that defective products caused by air lock phenomenon of a certain section of microneedle needle point body when the at least two solutions are filled into the cavity of the microneedle preparation mould are avoided, the defective products caused by cracks between different solutions can be effectively avoided, the preparation effect of the multi-section microneedle needle point body is improved, and the preparation efficiency of the microneedle can be improved.
Therefore, the microneedle preparation mould can prepare integrated microneedles and multistage microneedles, has wide application range and strong universality, has a good microneedle tip preparation effect and high yield, can be placed on a production line of the microneedle preparation, can automatically control a conveying line of the microneedle preparation production line to move for preparing large quantities of microneedles, greatly improves the microneedle preparation efficiency, and compared with the traditional microneedle array mould, the microneedle preparation mould needs to be additionally provided with a breathable film and a pressurizing system or a negative pressure vacuum system for giving positive pressure to the breathable film, has ingenious design and simple structure, greatly reduces the microneedle preparation cost, simplifies the microneedle preparation process, and further improves the microneedle preparation efficiency.
In a further scheme, the maximum width of the air outlet in the tangential direction of the microneedle preparation mould is between 0.1 and 50 microns, the capillary is arranged on the inner peripheral wall surface of the cavity, the capillary extends from the needle base end of the cavity to the needle tail end of the cavity along the inner peripheral wall surface of the cavity, a plurality of communicated air outlets are formed by the openings of the capillary on the inner peripheral wall surface of the cavity, and the ports of the capillary on the surface of the first side of the microneedle preparation mould are air outlets.
In a further embodiment, the number of capillaries is at least two, and the plurality of capillaries are arranged in the circumferential direction of the cavity.
Further, a plurality of capillaries are disposed in communication with each other at the needle ends of the cavity.
Still further, at least one vent is located on a first side surface of the microneedle preparation mold and/or at least one vent is located on a second side surface of the microneedle preparation mold.
In a further scheme, a plurality of air outlets which are arranged near the needle base end of the cavity are distributed in the circumferential direction of the cavity; and/or a plurality of air outlets arranged near the tail end of the needle of the cavity are distributed in the circumferential direction of the cavity.
In a further scheme, the maximum width of the air outlet in the normal direction of the microneedle preparation mould is between 0.1 micrometers and 50 micrometers, the air outlet arranged close to the needle base end of the cavity extends annularly in the circumferential direction of the cavity, and/or the air outlet arranged close to the needle tail end of the cavity extends annularly in the circumferential direction of the cavity.
In a further aspect, the plurality of air outlets are arranged along the inner peripheral wall surface of the cavity from the needle base end of the cavity toward the needle tip end of the cavity.
In order to achieve the second object of the present invention, the present invention provides a microneedle preparation production line, which comprises a conveying line and a microneedle preparation mould, wherein the conveying line can control the movement of the microneedle preparation mould, and the microneedle preparation mould is the microneedle preparation mould.
In order to achieve the third object of the present invention, the present invention provides a method for preparing a microneedle preparation mold, the microneedle preparation mold being the above-mentioned microneedle preparation mold, the method for preparing a microneedle comprising: filling a solution into a cavity of a microneedle preparation mold from an injection port of the cavity, wherein the viscosity of the solution is greater than or equal to 10 centipoise; alternatively, the method of preparing the microneedle comprises: and filling at least two solutions into the cavity of the microneedle preparation mold from the injection port of the cavity respectively, wherein the solutions are distributed in the normal direction of the microneedle preparation mold, and the viscosity of the solutions is more than or equal to 10 centipoise.
Still further, the viscosity of the solution is greater than or equal to 100 centipoise.
In a further scheme, one solution or at least two solutions are controlled to be filled into the cavity in the normal direction of the microneedle preparation mould at an acceleration of between 1 and 50 m/s.
Still further, after one solution or at least two solutions are filled into the cavity, the microneedle preparation mold is controlled to rotate about a normal direction of the microneedle preparation mold, and the rotating speed of the microneedle preparation mold is between 100RPM and 3000 RPM.
In a further aspect, one solution or at least two solutions are controlled to be injected into the cavity under pressure.
Still further, the microneedle preparation mold is made of elastic silica gel, and the microneedle preparation mold is compressed to close the air outlet of the microneedle preparation mold before one solution or at least two solutions are filled into the cavity, and is elastically reset to open the air outlet of the microneedle preparation mold after one solution or at least two solutions are filled into the cavity.
Drawings
Fig. 1 to 4 are schematic views of a process of preparing a multi-stage microneedle array mold in the prior art.
Fig. 5 is a schematic structural view of a first embodiment of a microneedle preparation mold of the present invention.
Fig. 6 is a schematic structural view of a first embodiment of a cavity of a first example of a microneedle preparation mold of the present invention.
Fig. 7 is a cross-sectional view of a first embodiment of a cavity of a first example of a microneedle preparation mold of the invention.
Fig. 8 is a schematic structural view of a second embodiment of a cavity of a first example of a microneedle preparation mold of the present invention.
Fig. 9 is a cross-sectional view of a second embodiment of a cavity of a first example of a microneedle preparation mold of the invention.
Fig. 10 is a schematic structural view of a third embodiment of a cavity of a first example of a microneedle preparation mold of the present invention.
Fig. 11 is a cross-sectional view of a third embodiment of a cavity of a first example of a microneedle preparation mold of the invention.
Fig. 12 is a top view of a third embodiment of a cavity of a first example of a microneedle preparation mold of the invention.
Fig. 13 is an effect diagram of preparing a multi-stage microneedle tip body according to a first embodiment of the microneedle preparation mold of the present invention.
Fig. 14 is an effect diagram of the first embodiment of the microneedle preparation mold of the present invention for preparing a multi-stage microneedle tip body under comparative experimental conditions.
Fig. 15 is a schematic view of a cavity structure of a second embodiment of the microneedle preparation mold of the present invention.
Fig. 16 is a schematic view of a cavity structure of a third embodiment of a microneedle preparation mold of the present invention.
Fig. 17 is a schematic view of a cavity structure of a fourth embodiment of a microneedle preparation mold of the present invention.
Fig. 18 is a schematic view of a first embodiment of a method for preparing a microneedle of the present invention for filling with vertical acceleration.
Fig. 19 is a schematic view of filling with a horizontal acceleration in a first embodiment of a method for preparing a microneedle according to the present invention.
The invention is further described below with reference to the drawings and examples.
Detailed Description
Microneedle preparation die first example:
referring to fig. 5 to 12, the present embodiment discloses a microneedle preparation mold 2 provided with a plurality of cavities 21 adapted to the shape of the tip bodies of the microneedle array, each cavity 21 having an injection port 211, the injection port 211 being located on a first side surface of the microneedle preparation mold 2 and at a needle base end of the cavity 21, a needle tip of the cavity 21 being disposed near a second side surface of the microneedle preparation mold 2, and the second side surface of the microneedle preparation mold 2 being disposed opposite to the first side surface of the microneedle preparation mold 2 in a normal direction of the microneedle preparation mold 2. Meanwhile, the microneedle preparation mold 2 of the present embodiment is further provided with at least two air outlets 221 penetrating through the inner peripheral wall surface of the cavity 21, one air outlet 221 being communicated with at least one capillary 22, or a plurality of air outlets 221 being communicated with one capillary 22. The air outlet 222 of the capillary 22 of this embodiment is disposed through the outer surface of the microneedle preparation mold 2, at least one air outlet 221 is disposed near the needle base end of the cavity 21, and at least one air outlet 221 is disposed near the needle tip end of the cavity 21. The maximum width of each air outlet 221 in the direction of the microneedle preparation mould 2 in this embodiment is between 0.1 micrometers and 50 micrometers, and/or the maximum width w of each air outlet 221 in the direction of the tangent of the microneedle preparation mould 2 is between 0.1 micrometers and 50 micrometers. Further, the contact angle of the solution filled into the cavity 21 of the microneedle preparation mold 2 of the present embodiment on the inner peripheral wall surface of the cavity 21 is 90 ° or more, and the viscosity of the solution is 10 centipoise or more. The normal direction of the microneedle preparation mold 2 in this embodiment is the injection direction of the solution filled into the cavity 21, the normal direction of the microneedle preparation mold 2 is also the height direction of the needle tip body of the microneedle array, and the tangential direction of the microneedle preparation mold 2 and the normal direction of the microneedle preparation mold 2 are perpendicular to each other. Preferably, the viscosity of the solution of this embodiment is greater than or equal to 100 centipoise. Optionally, the at least one vent 222 of the present embodiment is located on a first side surface of the microneedle preparation mould 2 and/or the at least one vent 222 is located on a second side surface of the microneedle preparation mould 2.
When a solution is filled from the filling port 211 of the cavity 21 into the cavity 21 of the microneedle preparation mold 2 of the present embodiment to prepare the integrated microneedle tip body, since the air outlet 221 penetrating through the inner peripheral wall surface of the cavity 21 is between 0.1 micrometer and 50 micrometers in the normal direction of the microneedle preparation mold 2 and/or in the tangential direction of the microneedle preparation mold 2, and at the same time, the contact angle of the solution on the inner peripheral wall surface of the cavity 21 is greater than or equal to 90 degrees, and the viscosity of the solution is greater than or equal to 10 centipoise, the solution is kept in a state of converging into liquid drops after entering the cavity 21, and when the microneedles are prepared, the solution can be effectively prevented from entering into the capillary 22 through the air outlet 221 when the liquid completely fills the cavity 21, so that the air in the cavity 21 can smoothly pass through the air outlet 221 to enter into the capillary 22 and exit the microneedle preparation mold 2 through the air outlet 222 of the capillary 22, thereby avoiding occurrence of a phenomenon of a latch when the solution is filled into the cavity 21 of the microneedle preparation mold 2 of the present embodiment to prepare the integrated microneedle tip body, and thus good product yield is improved.
When at least two solutions are respectively filled into the cavity 21 of the microneedle preparation mold 2 of the embodiment from the filling opening 211 of the cavity 21 to prepare the multi-stage microneedle, as the at least one air outlet 221 is arranged close to the needle base end of the cavity 21 and the at least one air outlet 221 is arranged close to the needle end of the cavity 21, the air outlet 221 arranged close to the needle end of the cavity 21 when the needle end of the cavity 21 is filled with the first solution can smoothly discharge the air in the needle end of the cavity 21, and then the air outlet 221 arranged close to the needle base end of the cavity 21 when the needle base end of the cavity 21 is filled with the second solution can smoothly discharge the air in the needle base end of the cavity 21, thereby avoiding the occurrence of defective products caused by the air lock phenomenon of a certain stage microneedle tip body when the at least two solutions are filled into the cavity 21 of the microneedle preparation mold 2 of the embodiment, effectively avoiding the occurrence of defective products caused by the occurrence of cracks between different solutions due to incomplete filling, having better multi-stage microneedle preparation effects (see effect figure 13), improving the preparation effect of the air in the cavity 21, and further improving the preparation efficiency of the microneedle.
Therefore, the microneedle preparation mould 2 of this embodiment can prepare integrative microneedle and multistage microneedle, application scope is extensive, the commonality is strong, and have better microneedle preparation effect, the yields is high, simultaneously this embodiment microneedle preparation mould 2 can be placed on the microneedle preparation production line of pipelined, the transfer chain of microneedle preparation production line can automated control microneedle preparation mould 2 remove and carry out a large batch of microneedle preparation, improve microneedle preparation efficiency greatly, and need add ventilated membrane and give ventilated membrane positive pressure's pressurized system or negative pressure's vacuum system than current preparation microneedle array mould, the design benefit and the simple structure of this embodiment microneedle preparation mould 2 have significantly reduced microneedle preparation cost, and the microneedle preparation process has been simplified, and then microneedle preparation efficiency is improved.
Specifically, referring to fig. 6 and 7, which are a first embodiment of the cavity 21 of the microneedle preparation mold 2 of the present embodiment, the maximum width w of the air outlet 221 of the first embodiment of the cavity 21 in the tangential direction of the microneedle preparation mold 2 is between 0.1 micrometers and 50 micrometers, the inner circumferential wall surface of the cavity 21 is provided with a capillary tube 22, the capillary tube 22 extends from the needle base end of the cavity 21 to the needle end of the cavity 21 along the inner circumferential wall surface of the cavity 21, the openings of the capillary tube 22 on the inner circumferential wall surface of the cavity 21 form a plurality of air outlets 221 which are communicated with each other, and the ports of the capillary tube 22 on the first side surface of the microneedle preparation mold 2 are air outlets 222. Therefore, the air outlet 221 penetrating through the inner peripheral wall surface of the cavity 21 extends from the needle base end of the cavity 21 to the needle end of the cavity 21 along the inner peripheral wall surface of the cavity 21, so that the air at any position in the cavity 21 in the normal direction of the microneedle preparation mold 2 can be effectively, smoothly and rapidly discharged through the air outlet 221, and the preparation effect and the preparation efficiency of the microneedle tip body are improved.
Specifically, referring to fig. 8 and 9, in the second embodiment of the cavity 21 of the microneedle preparation mold 2 of the present embodiment, based on the first embodiment of the cavity 21 of the microneedle preparation mold 2 of the present embodiment, the number of capillaries 22 extending from the needle base end of the cavity 21 to the needle end of the cavity 21 along the inner peripheral wall surface of the cavity 21 in the second embodiment of the cavity 21 is two, the two capillaries 22 are uniformly arranged in the circumferential direction of the cavity 21, and the two capillaries 22 are disposed in the needle end of the cavity 21 in a mutually communicating manner, so that the number of air outlets 221 extending from the needle base end of the cavity 21 to the needle end of the cavity 21 along the inner peripheral wall surface of the cavity 21 is two, thereby further improving the preparation effect and the preparation efficiency of the microneedle tip body.
Specifically, referring to fig. 10 to 12, in the third embodiment of the cavity 21 of the microneedle preparation mold 2 according to the present embodiment, based on the second embodiment of the cavity 21 of the microneedle preparation mold 2 according to the present embodiment, the number of capillaries 22 extending from the needle base end of the cavity 21 to the needle end of the cavity 21 along the inner peripheral wall surface of the cavity 21 in the third embodiment of the cavity 21 is plural, the capillaries 22 are uniformly arranged in the circumferential direction of the cavity 21, and the capillaries 22 are disposed in the needle end of the cavity 21 in a mutually communicating manner, so that the number of air outlets 221 extending from the needle base end of the cavity 21 to the needle end of the cavity 21 along the inner peripheral wall surface of the cavity 21 is plural, thereby further improving the preparation effect and the preparation efficiency of the microneedles.
The microneedle preparation mold 2 of the present embodiment was subjected to an experiment in which the air outlet 221 of the microneedle preparation mold 2 was provided along the inner peripheral wall surface of the cavity 21 from the needle base end of the cavity 21 to the needle tip end of the cavity 21 and penetrating the inner peripheral wall surface of the cavity 21.
List one
As can be seen from the first table, the microneedles can be prepared under the conditions from the experiment 1 to the experiment 5 of the invention, the effect diagram of the prepared microneedles is shown in fig. 13, and as can be seen from fig. 13, the prepared multistage microneedle tip body is complete and free, the peripheral surface is flat and smooth, and the preparation effect of the multistage microneedle tip body is good. In contrast, in the conditions of comparative experiment 1 and comparative experiment 2 in table one, good-quality microneedles could not be prepared, the effect diagram of the prepared microneedles is shown in fig. 14, and as can be seen from fig. 14, the prepared multistage microneedle tip body has a breakage and missing phenomenon, and is a defective product.
Watch II
As can be seen from the second table, the microneedles can be prepared under the conditions from the experiment 6 to the experiment 10 of the invention, the prepared multistage microneedles are complete and have smooth outer peripheral surfaces, and the preparation effect of the multistage microneedles is good. And under the conditions of the comparative experiment 3 and the comparative experiment 4 in the second table, good-quality microneedles cannot be prepared, and the prepared multistage microneedles have fracture defect phenomena and are defective products.
Watch III
From Table III, the microneedles can be prepared under the conditions from experiment 11 to experiment 14 of the invention, the prepared multistage microneedles are complete and have smooth outer peripheral surfaces, and the preparation effect of the multistage microneedles is good. In contrast experiments 5 to 7 of table three, good microneedles cannot be prepared, the contact angle is too small, the solution is easy to adhere to the surface of the mold, when the solution is filled into the cavity 21, part of the solution is easy to enter the capillary tube 22 through the air outlet 221 to cause blockage, the gas in the cavity 21 cannot be discharged to cause the solution to be completely filled so as to cause cracks, and the tips of the multistage microneedles prepared after demolding of the microneedles have fracture and missing phenomena, so that the microneedles are defective products.
The microneedle preparation mold 2 of this embodiment is made of one material selected from metal, plastic and elastic silica gel, and the preparation process of the microneedle preparation mold 2 may be directly prepared by a laser cutting method, or by a 3D printing method, or may be prepared by preparing a female mold first and then preparing a female mold by using the female mold.
Microneedle preparation mould second example:
as a description of the second embodiment of the microneedle preparation mold of the present invention, only the differences from the first embodiment of the microneedle preparation mold will be described below.
Referring to fig. 15, a plurality of air outlets 32 provided near the needle base end of the cavity 31 of the microneedle preparation mold 3 of the present embodiment are arranged in the circumferential direction of the cavity 31, and a plurality of air outlets 32 provided near the needle tip end of the cavity 31 are arranged in the circumferential direction of the cavity 31, so that the air in the cavity 31 is accelerated to be effectively and smoothly discharged through the air outlets.
Microneedle preparation mould third example:
as a description of the third embodiment of the microneedle preparation mold of the present invention, only the differences from the first embodiment of the microneedle preparation mold will be described below.
Referring to fig. 16, the air outlet 42 of the microneedle preparation mold 4 of the present embodiment has a maximum width of 0.1 to 50 μm in the normal direction of the microneedle preparation mold 4, and the air outlet 42 provided near the needle base end of the cavity 41 extends annularly in the circumferential direction of the cavity 41, and the air outlet 42 provided near the needle tip end of the cavity 41 extends annularly in the circumferential direction of the cavity 41, thereby accelerating the effective and smooth discharge of the air in the cavity 41 through the air outlet 42.
Fourth example of microneedle preparation mold:
as a description of the fourth embodiment of the microneedle preparation mold of the present invention, only the differences from the first embodiment of the microneedle preparation mold will be described below.
Referring to fig. 17, the plurality of air outlets 52 of the microneedle preparation mold 5 of the present embodiment are arranged along the inner peripheral wall surface of the cavity 51 from the needle base end of the cavity 51 toward the needle tip end of the cavity 51, so that the air in the cavity 51 at any position in the normal direction of the microneedle preparation mold 5 can be effectively and smoothly discharged through the air outlets 52.
Microneedle preparation method of microneedle preparation mold first example:
as the method for preparing the microneedles of the above four microneedle preparation molds 2, 3, 4, 5 examples, the method for preparing the microneedles of this example includes: filling a solution into the cavities 21, 31, 41, 51 of the microneedle preparation mould 2, 3, 4, 5 from the injection port of the cavities 21, 31, 41, 51 to prepare the integrated microneedle, wherein the viscosity of the solution is more than or equal to 10 centipoise; alternatively, the method of preparing the microneedle comprises: at least two solutions are respectively filled into the cavities 21, 31, 41 and 51 of the microneedle preparation molds 2, 3, 4 and 5 from the injection openings of the cavities 21, 31, 41 and 51 to prepare multi-section microneedles, the solutions are distributed in the normal direction of the microneedle preparation molds 2, 3, 4 and 5, and the viscosity of the solutions is more than or equal to 10 centipoise. The method for preparing the microneedle of the microneedle preparation mould can be used for controlling one solution or at least two solutions to be sprayed into the cavities 21, 31, 41 and 51 of the microneedle preparation mould 2, 3, 4 and 5 under pressure. Preferably, the viscosity of the solution is greater than or equal to 100 centipoise.
The method for preparing the microneedle of the microneedle preparation mold of the embodiment is an acceleration filling mode, namely, one solution or at least two solutions are controlled to be filled into a cavity in the normal direction of the microneedle preparation mold at an acceleration of between 1 and 50 m/s.
Referring to fig. 18, the normal direction of the microneedle preparation mold 6 extends in the vertical direction, and thus one solution or at least two solutions are controlled to be filled into the cavity 61 with a vertical acceleration of between 1m/s and 50 m/s.
Referring to fig. 19, the normal direction of the microneedle preparation mold 6 extends in the horizontal direction, and thus one solution or at least two solutions are controlled to be filled into the cavity 61 with a horizontal acceleration of between 1m/s and 50 m/s.
The microneedle manufacturing method of the microneedle manufacturing mold of the present embodiment was subjected to an experiment in which the air outlet 62 of the microneedle manufacturing mold 6 was provided along the inner peripheral wall surface of the cavity 61 from the needle base end of the cavity 61 to the needle tip end of the cavity 61 and through the inner peripheral wall surface of the cavity 61, and the microneedle manufacturing method of the microneedle manufacturing mold was an acceleration filling method.
Table four
As can be seen from Table IV, the microneedles can be prepared under the conditions from experiment 15 to experiment 20 of the present invention, the prepared multistage microneedles are intact, the outer peripheral surfaces are flat and smooth, and the preparation effect of the multistage microneedles is good. Meanwhile, as can be seen from table four, the method for preparing the microneedle of the microneedle preparation mold of the embodiment is that the total acceleration continuous filling time of the solution 1 and the solution 2 in an acceleration filling mode is within 5min, and compared with the traditional method for preparing the microneedle of the microneedle array mold, the method for preparing the microneedle of the embodiment needs more than 15min for preparation, and the preparation time of the microneedle is greatly shortened, so that the preparation efficiency is greatly improved.
Preparation of microneedle preparation mold microneedle method second example:
as a description of the second embodiment of the method for producing a microneedle of the microneedle production mold of the present invention, only the differences from the first embodiment of the method for producing a microneedle of the microneedle production mold will be described below.
In the method for preparing the microneedle of the microneedle preparation mold of the embodiment, after one solution or at least two solutions are filled into the cavity, the microneedle preparation mold is controlled to rotate around the normal direction of the microneedle preparation mold, and the rotating speed of the microneedle preparation mold is between 100RPM and 3000 RPM.
The microneedle preparation method of the microneedle preparation mold of the embodiment is subjected to an experiment that an air outlet of the microneedle preparation mold extends from a needle base end of a cavity to a needle tail end of the cavity along an inner peripheral wall surface of the cavity and penetrates through the inner peripheral wall surface of the cavity, and the microneedle preparation method of the microneedle preparation mold is a centrifugal rotary filling mode.
TABLE five
As can be seen from Table five, the microneedles can be prepared under the conditions from experiment 21 to experiment 23 of the present invention, the prepared multistage microneedles are complete and have smooth outer peripheral surfaces, and the preparation effect of the multistage microneedles is good. Meanwhile, as can be seen from table five, the microneedle preparation method of the microneedle preparation mold of the embodiment adopts a centrifugal rotation filling mode, the total continuous filling time of the solution 1 and the solution 2 is within 5min, and compared with the existing microneedle preparation method of the microneedle array mold, the microneedle preparation method of the microneedle preparation mold of the embodiment needs more than 15min for preparation, and the microneedle preparation time is greatly shortened, so that the preparation efficiency is greatly improved.
Preparation of microneedle preparation mold microneedle method third example:
as a description of the third embodiment of the method for producing a microneedle of the present invention, only the differences from the first embodiment of the method for producing a microneedle of the present invention will be described below.
The microneedle preparation mold of the embodiment is made of elastic silica gel, and the method for preparing the microneedle of the elastic silica gel microneedle preparation mold compresses the elastic silica gel microneedle preparation mold before one solution or at least two solutions are filled into the cavity so that the air outlet of the elastic silica gel microneedle preparation mold is closed or basically closed; after one solution or at least two solutions are filled into the cavity, the elastic silica gel microneedle preparation mould is elastically reset so that the air outlet of the elastic silica gel microneedle preparation mould is opened, and air in the cavity of the elastic silica gel microneedle preparation mould can be effectively, smoothly and rapidly discharged through the opened air outlet, and finally, the effective filling of the solution is realized.
The above embodiments are only preferred examples of the present invention and are not intended to limit the scope of the present invention, so that all equivalent changes or modifications made according to the construction, characteristics and principles of the present invention shall be included in the scope of the present invention.
Claims (10)
1. The microneedle preparation mould is provided with a plurality of die cavities which are matched with the shape of the needle tip body of the microneedle array, each die cavity is provided with an injection opening, the injection opening is positioned on the first side surface of the microneedle preparation mould and positioned at the needle base end of the die cavity, the needle tail end of the die cavity is close to the second side surface of the microneedle preparation mould, and the second side surface of the microneedle preparation mould and the first side surface of the microneedle preparation mould are oppositely arranged in the normal direction of the microneedle preparation mould, and the microneedle preparation mould is characterized in that:
the microneedle preparation mould is also provided with at least two air outlets penetrating through the inner peripheral wall surface of the cavity, one air outlet is communicated with at least one capillary tube, or a plurality of air outlets are communicated with one capillary tube;
the exhaust port of the capillary tube penetrates through the outer surface of the microneedle preparation mould, at least one air outlet is arranged close to the needle base end of the cavity, and at least one air outlet is arranged close to the needle tail end of the cavity;
the contact angle of the solution filled in the cavity on the inner peripheral wall surface of the cavity is more than or equal to 90 degrees, and the viscosity of the solution is more than or equal to 10 centipoise;
the maximum width of the air outlet in the tangential direction of the microneedle preparation mould is between 0.1 and 50 microns, the capillary is arranged on the inner peripheral wall surface of the cavity, and the capillary extends from the needle base end of the cavity to the needle tail end of the cavity along the inner peripheral wall surface of the cavity;
the openings of the capillary tube positioned on the inner peripheral wall surface of the cavity form a plurality of communicated air outlets, and the ports of the capillary tube positioned on the first side surface of the microneedle preparation mould are the air outlets.
2. The microneedle preparation mold of claim 1, wherein:
the number of the capillaries is at least two, and a plurality of the capillaries are arranged in the circumferential direction of the cavity.
3. The microneedle preparation mold of claim 2, wherein:
the capillaries are mutually communicated at the needle tail ends of the die cavities.
4. The utility model provides a microneedle preparation production line, includes transfer chain and microneedle preparation mould, the transfer chain is steerable microneedle preparation mould removes its characterized in that:
the microneedle preparation mold is the microneedle preparation mold of any one of the above claims 1 to 3.
5. A method of preparing a microneedle, characterized in that the microneedle preparation mold is the microneedle preparation mold according to any one of the above claims 1 to 3;
the method for preparing the microneedle comprises the following steps: filling a solution into a cavity of the microneedle preparation mold from an injection port of the cavity, wherein the viscosity of the solution is greater than or equal to 10 centipoise;
alternatively, the method of preparing the microneedle comprises: and filling at least two solutions into the cavity of the microneedle preparation mould from the injection opening of the cavity respectively, wherein a plurality of solutions are distributed in the normal direction of the microneedle preparation mould, and the viscosity of the solutions is more than or equal to 10 centipoise.
6. The method for preparing a microneedle according to claim 5, wherein:
the viscosity of the solution is greater than or equal to 100 centipoise.
7. The method for preparing a microneedle according to claim 6, wherein:
controlling one solution or at least two solutions to be filled into the cavity at an acceleration in the normal direction of the microneedle preparation mould, wherein the acceleration is between 1m/s and 50 m/s.
8. The method for preparing a microneedle according to claim 6, wherein:
after one solution or at least two solutions are filled into the cavity, controlling the microneedle preparation mold to rotate around the normal direction of the microneedle preparation mold, wherein the rotating speed of the microneedle preparation mold is between 100RPM and 3000 RPM.
9. The method for preparing a microneedle according to claim 6, wherein:
controlling one solution or at least two solutions to be injected into the cavity under pressure.
10. The method for preparing a microneedle according to claim 6, wherein:
the microneedle preparation mould is made of elastic silica gel;
compressing the microneedle preparation mold such that an air outlet of the microneedle preparation mold is closed before one solution or at least two solutions are filled into the cavity;
after one solution or at least two solutions are filled into the cavity, the microneedle preparation mold is elastically reset so that the air outlet of the microneedle preparation mold is opened.
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| WO2015016235A1 (en) * | 2013-07-30 | 2015-02-05 | Ａｓｔｉ株式会社 | Microneedle array and microneedle array manufacturing method |
| JP5931130B2 (en) * | 2014-06-20 | 2016-06-08 | 三島光産株式会社 | Microneedle array manufacturing method and injection mold used therefor |
| WO2017007156A1 (en) * | 2015-06-24 | 2017-01-12 | 부산대학교 산학협력단 | Continuous production process of needle patch using centrifugal force |
| CN105498082B (en) * | 2015-12-24 | 2017-10-27 | 广州新济药业科技有限公司 | Micropin chip and preparation method thereof |
| US20200230846A1 (en) * | 2016-04-12 | 2020-07-23 | Juvic Inc. | Rotating assembly and apparatus for manufacturing microstructure comprising same |
| CN109693323A (en) * | 2019-01-11 | 2019-04-30 | 江苏熙美生物科技有限公司 | The forming method of micropin mold, mold and micropin mold |
| JP6730720B1 (en) * | 2019-02-12 | 2020-07-29 | 近畿精工株式会社 | Microneedle molding method and molding die |
| CN211334342U (en) * | 2019-11-01 | 2020-08-25 | 重庆福特尔科技有限公司 | Mold for manufacturing soluble microneedle patch |
| CN111688127A (en) * | 2020-07-08 | 2020-09-22 | 成都工业学院 | Injection molding mold of microneedle chip and manufacturing method thereof |
| KR102363524B1 (en) * | 2020-10-21 | 2022-02-16 | 인제대학교 산학협력단 | Mold for microneedle manufacturing and manufacturing method thereof |
| CN112720967A (en) * | 2021-01-18 | 2021-04-30 | 优微智点(北京)生物科技有限公司 | Device and method for manufacturing micro-array transdermal drug delivery micro-needle |
| CN113580491B (en) * | 2021-07-21 | 2022-05-17 | 优微（珠海）生物科技有限公司 | Spraying manufacturing equipment and method for soluble micro-needle |
| CN114211699A (en) * | 2021-11-10 | 2022-03-22 | 武汉南望环保技术研究有限责任公司 | Preparation mold and preparation method of high-molecular microneedle |
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