CN101670611A - Preparation method for preparing plaster mold of transdermal micro needle array - Google Patents
Preparation method for preparing plaster mold of transdermal micro needle array Download PDFInfo
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- CN101670611A CN101670611A CN200910308299A CN200910308299A CN101670611A CN 101670611 A CN101670611 A CN 101670611A CN 200910308299 A CN200910308299 A CN 200910308299A CN 200910308299 A CN200910308299 A CN 200910308299A CN 101670611 A CN101670611 A CN 101670611A
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Abstract
A preparation method for preparing a plaster mold of a transdermal micro needle array belongs to the technical field of medical apparatus and comprises the following steps: blending plaster powder andwater, well stirring, and then spreading out mixture on a platform, and finally rolling out the mixture until flake-like plaster microchip is obtained; adopting a hole pricking tool for pricking holes after hardening plaster microchip in the room temperature for 5-20 minutes, and obtaining the micro needle mould with a plurality single holes after plaster is completely hardened. Preparation materials used in the preparation method are convenient to buy and have low cost. The tool used in the preparation method belong to daily necessaries and can be easily found in a laboratory or a workshop;the technique in the preparation method is simple and easy to operate; the prepared mould can be used for preparing the micro needles by a centrifuge method and a suction method.
Description
Technical field
That the present invention relates to is a kind of preparation method of technical field of medical instruments, specifically is a kind of preparation method who is used to prepare the gypsum mold of transdermal micro needle array.
Background technology
The advantage of micropin transdermal technology maximum is that it can sting saturating biggest obstacle Zhao epidermis and the cuticula thereof that hinders drug absorption under the prerequisite that does not injure corium and nerve.Owing to do not contact nerve, micropin does not create a painful feeling to piercing through of epidermis, even also be that the reversible deformation of skin is greater than wound for the Wicresoft of epidermis, but micropin is removed back reinstatement in a few hours, and water soluble drug, comprise polypeptide, then the pin hole that can sting out by micropin and entering in the body effectively.The cutaneous penetration that the micropin dot matrix is used for medicine is Prausnitz and team thereof the at first proposition before the more than ten years of U.S. Georgia Institute of Technology.No matter be metal micro-needle originally or the polymer micro needle that grew up in recent years, a key player has been taken in the preparation of mould therein.
The most frequently used mold materials is a silicon chip, and silicon chip is a kind of hard material, and processing microwell array in the above has certain degree of difficulty.Can handle with microelectromechanical systems (MEMS), but this operating process more complicated, parameter is loaded down with trivial details, and angle is not easy control; Also can utilize laser boring, but the laser ratio is easier to beat columniform micropore, for the tapered micro holes that the preparation micropin needs, laser is difficult to accomplish simply; For chemical etching method, chemical reagent can etching portal, but the tip angle in hole is very big, can not prepare the hole shape of demand.
Find through retrieval prior art, people such as Jung-Hwan Park have delivered one piece and have been entitled as " the Tapered Conical Polymer MicroneedlesFabricated Using an Integrated Lens Technique for Transdermal Drug Delivery " article of (the synthetic lens technologies making of employing is used for the taper polymer micro needle that transdermal drug discharges) on " IEEE TRANSACTIONS ONBIOMEDICAL ENGINEERING ", used ultraviolet photolithographic to add chemical method in this article, used this micropin mould to prepare dimethyl silicone polymer (PDMS) micropore mold then at the microneedle array that processed on glass.PDMS is a kind of fine moulding material, can be used to prepare micropore mold, but to there be the needle mould tool to cooperate with it just earlier and can prepares microwell array, and its hardness is softer, easy deformation, from the physical chemistry aspect, its hydrophily and gas permeability are bad, are not easy to utilize the method that filters for polymer solution.
Summary of the invention
The present invention is directed to the prior art above shortcomings, a kind of preparation method who is used to prepare the gypsum mold of transdermal micro needle array is provided, what combine gypsum is convenient to moulding, hydrophilic, ventilative characteristics, and designing and prepared can be by suction filtration or the centrifugal micropin forming mould that makes.Preparation method of the present invention is simple and easy to do, and the microneedle array that produces meets the transdermal requirement.
The present invention is achieved by the following technical solutions, the present invention includes following steps:
Method one: adopt and prick hole tool manufacture transdermal micro needle array gypsum mold
The first step, stir after gypsum powder and water mixed, then mixture is spread on the platform, the gypsum microplate of mixture flattening-out to sheet;
Described gypsum powder is a powder any in plaster of Paris, model plaster, high strength gypsum, anhydrite cement or the floor gypsum.
The thickness of described gypsum microplate is 1-10cm, and surface area is 0.25cm
2-400cm
2
Sclerosis adopts bundle hole instrument to prick the hole under second step, the gypsum microplate room temperature after 5-20 minute, treats promptly to get the micropin mould that has some single holes after gypsum hardens fully.
Described bundle hole instrument is taper shape or n pyramid (n 〉=3) structure; This tip of rolling the sky instrument is sphere passivation or plane passivating structure, and rolling the height of sky instrument and the length ratio of base diameter is 3: 1-10: 1.
The aperture of the single hole of described micropin mould is 1 μ m-1000 μ m, and hole depth is 100-1000 μ m.
Method two: adopt the hole graticule mesh to prepare the transdermal micro needle array gypsum mold
The first step, stir after gypsum powder and water mixed, then mixture is spread on the platform, the gypsum microplate of mixture flattening-out to sheet;
Described gypsum powder is a powder any in plaster of Paris, model plaster, high strength gypsum, anhydrite cement or the floor gypsum.
The thickness of described gypsum microplate is 1-10cm.
Second goes on foot, after the coverage hole graticule mesh it is rolled in the embedding gypsum microplate on the gypsum microplate, makes the upper surface of gypsum microplate and the upper surface of hole graticule mesh maintain an equal level;
Described hole graticule mesh is that thickness is that metal, metal oxide, plastics or the silicate of 1-1000 μ m is made, and the mesh of this hole graticule mesh is shaped as circle or polygon, and the mesh radius is 0.5-5000 μ m.
After the 3rd gypsum microplate room temperature environment that goes on foot, will be embedded with the hole graticule mesh hardened 5-20 minute down, adopt the pore instrument in the mesh of hole graticule mesh, to prick the hole;
Described pore instrument is taper shape or n pyramid (n 〉=3) structure; The tip of this pore instrument is sphere passivation or plane passivating structure, and the height of pore instrument and the length ratio of base diameter are 3: 1-10: 1.
The 4th step, will prick gypsum thin slice behind the hole and place and carry out cure process under the room temperature environment, promptly get the micropin mould that has some single holes after hardening fully.
The aperture of the single hole of described micropin mould is 1 μ m-1000 μ m, and hole depth is 100-1000 μ m.
The preparation material that uses among the present invention is bought convenient, low price; The instrument that uses in the invention is articles for daily use, and common laboratory or workshop are easy to realize; Technology is simple in the invention, easy operating; The mould of preparation can be used for centrifugal process and suction method prepares micropin.
Description of drawings
Fig. 1: gypsum mold and micropin preparation flow figure.
Fig. 2: pore instrument schematic diagram.
Fig. 3: hole graticule mesh pictorial diagram.
Fig. 4: gypsum micropore mold pictorial diagram.
Fig. 5: the micropore pictorial diagram that has been coated with polymer.
Fig. 6: the method that the filters polymer micro needle pictorial diagram of gypsum mold preparation.
Fig. 7: the centrifugal process polymer micro needle pictorial diagram of gypsum mold preparation.
The specific embodiment
Below embodiments of the invention are elaborated, present embodiment is being to implement under the prerequisite with the technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
First group of embodiment: the preparation of gypsum mold and filter legal system and be equipped with polylactic acid-glycolic guanidine-acetic acid (PLGA) micropin
The preparation of gypsum mold: as shown in Figure 1, gypsum or gypsum and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, spread over glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) on, use another piece glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) it gently is pressed into level and smooth gypsum plate, the steel wire gauze is layered on the gypsum plate, with glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) the light pressure make steel wire gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use pin to prick the hole before the sclerosis fully across the steel wire gauze, just prick at every turn when gauze blocks pin and don't distortion and transfer to, prick another hole again, until pricked till the array of expection.After treating that gypsum hardens fully, take the steel wire gauze gently off, gypsum plate is processed into the shape that conveniently filters with scissors, fully can use after the drying.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list one.
Perhaps gypsum or the gypsum and the additive agent mixture of mould size as required and thickness selection certain mass, adding water mixes, spread over glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) on, use another piece glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) it gently is pressed into level and smooth gypsum plate, with glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) the light pressure make gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use major part pinprick hole before the sclerosis fully, prick another hole again, pricked the array of expection always.After treating that gypsum hardens fully, gypsum plate is processed into the shape that conveniently filters with scissors, fully can uses after the drying.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list one.
As shown in Figure 2, rolled hole instrument schematic diagram for what this group embodiment adopted.
As shown in Figure 3, the gauze schematic diagram that is adopted for this group embodiment.
As described in Figure 4, prepare gained mould schematic diagram for this group embodiment.
The preparation of micropin: as Fig. 5, Fig. 6 and shown in Figure 7, gypsum mold is positioned in Bush's funnel, uses the wax sealing the margin, with the PLGA solution coat on the microwell array surface, use vavuum pump to be evacuated to the polymer drying, polymer sheet is peeled off then promptly got PLGA micropin sheet.
Optimum condition is for using the floating gypsum of sheet glass, and gypsum and alundum (Al mix at 50: 1, and gypsum and water ratio are 1: 3, and needle tip is conical 3: 1, and the degree of depth is 800 μ m, and drying mode is drying at room temperature 480min.
Subordinate list one:
Second group of embodiment: the preparation of plaster of Paris mould and filter legal system and be equipped with polylactic acid-glycolic guanidine-acetic acid (PLGA) micropin
The preparation of gypsum mold: plaster of Paris or plaster of Paris and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, spread over glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) on, use another piece glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) it gently is pressed into level and smooth gypsum plate, the steel wire gauze is layered on the gypsum plate, with glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) the light pressure make steel wire gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use pin to prick the hole before the sclerosis fully across the steel wire gauze, just prick at every turn when gauze blocks pin and don't distortion and transfer to, prick another hole again, until pricked till the array of expection.After treating that gypsum hardens fully, take the steel wire gauze gently off, gypsum plate is processed into the shape that conveniently filters with scissors, fully can use after the drying.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list one.
Perhaps plaster of Paris or the plaster of Paris and the additive agent mixture of mould size as required and thickness selection certain mass, adding water mixes, spread over glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) on, use another piece glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) it gently is pressed into level and smooth gypsum plate, with glass plate (plank, iron plate, zine plate, steel plate, slabstone, copper coin or other flat board) the light pressure make gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use major part pinprick hole before the sclerosis fully, prick another hole again, pricked the array of expection always.After treating that gypsum hardens fully, gypsum plate is processed into the shape that conveniently filters with scissors, fully can uses after the drying.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list two.
The preparation of micropin: gypsum mold is positioned in Bush's funnel, uses the wax sealing the margin, on the microwell array surface, use vavuum pump to be evacuated to the polymer drying PLGA solution coat, polymer sheet is peeled off then promptly got PLGA micropin sheet.
Optimum condition is for using the floating gypsum of sheet glass, and gypsum and alundum (Al mix at 50: 1, and gypsum and water ratio are 1: 3, and needle tip is conical 3: 1, and the degree of depth is 800 μ m, and drying mode is drying at room temperature 480min.
Subordinate list two:
The 3rd group of embodiment: preparation of plaster of Paris mould and centrifugal process prepare the glucan micropin
The preparation of gypsum mold: become the pin array of 10*10 with 100 pins (sharp shaped materials of embroidery needle, draw point, lithostyle, metal oxide needle, duroplasts pin, silicon pin or silica pin or above-mentioned these materials) stationary arrangement, plaster of Paris or plaster of Paris and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, be poured into afterwards on the pin array, treat that gypsum solidifies and take off the pin array, fully drying has just become a gypsum micropore mold.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list three.
The preparation of micropin: use scissors that gypsum plate is processed into suitable size and shape, be placed in then in the centrifuge tube, it is centrifugal to the polymer drying to use centrifuge 4000r/min to carry out behind the surface coating glucan, and the polymer-stripping sheet then gets glucan micropin sheet.
Optimum condition forms the pin array for using pin, and plaster of Paris and alundum (Al mix at 50: 1, and plaster of Paris and water ratio are 1: 3, and the degree of depth is 800 μ m, and drying mode is 80 ℃ of 120min.
Subordinate list three:
The 4th group of embodiment: floor gypsum mould preparation and filter legal system and be equipped with the PLGA micropin
The preparation of gypsum mold: floor gypsum or floor gypsum and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, spread on the glass plate, use another piece glass plate that it gently is pressed into level and smooth gypsum plate, the steel wire gauze is layered on the gypsum plate, the light pressure of sheet glass makes gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use pin to prick the hole before the sclerosis fully across gauze, just prick at every turn when steel wire blocks pin and don't distortion and transfer to, prick another hole again, pricked the array of expection always.After treating that gypsum hardens fully, take the steel wire gauze gently off, gypsum plate is processed into the shape that conveniently filters with scissors, fully can use after the drying.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list four.
The preparation of micropin: gypsum mold is positioned in Bush's funnel, uses the wax sealing the margin, on the microwell array surface, use vavuum pump to be evacuated to the polymer drying PLGA solution coat, polymer sheet is peeled off then promptly got PLGA micropin sheet.
Optimum condition is that gypsum and alundum (Al mix at 50: 1, and gypsum and water ratio are 1: 3, and needle tip is conical 3: 1, and the degree of depth is 800 μ m, and drying mode is drying at room temperature 480min.
Subordinate list four:
The 5th group of embodiment: preparation of floor gypsum mould and centrifugal process prepare the PLGA micropin
The preparation of gypsum mold: the pin array that becomes 10*10 with 100 pin stationary arrangement, floor gypsum or floor gypsum and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, spread on the glass plate, use another piece glass plate that it gently is pressed into level and smooth gypsum plate, when treating that gypsum is in shaping period, with the pore on gypsum of pin array, gypsum takes off the pin array after solidifying, and fully drying has just become a gypsum micropore mold.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list five.
The preparation of micropin: use scissors that gypsum plate is processed into suitable size and shape, be placed in then in the centrifuge tube, it is centrifugal to the polymer drying to use centrifuge 4000r/min to carry out behind the surface coating PLGA, and the polymer-stripping sheet then gets PLGA micropin sheet.
Optimum condition is that gypsum and alundum (Al mix at 50: 1, with the water ratio be 1: 3, the degree of depth is 800 μ m, drying mode is 80 ℃ of 120min.
Subordinate list five:
The 6th group of embodiment: model plaster mould preparation and filter legal system and be equipped with the PLA micropin
The preparation of gypsum mold: model plaster or model plaster and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, spread on the glass plate, use another piece glass plate that it gently is pressed into level and smooth gypsum plate, the steel wire gauze is layered on the gypsum plate, the light pressure of sheet glass makes gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use pin to prick the hole before the sclerosis fully across gauze, just prick at every turn when steel wire blocks pin and don't distortion and transfer to, prick another hole again, pricked the array of expection always.After treating that gypsum hardens fully, take the steel wire gauze gently off, gypsum plate is processed into the shape that conveniently filters with scissors, fully can use after the drying.Gypsum takes off the pin array after solidifying, and fully drying has just become a gypsum micropore mold.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list six.
The preparation of micropin: gypsum mold is positioned in Bush's funnel, uses the wax sealing the margin, on the microwell array surface, use vavuum pump to be evacuated to the polymer drying PLGA solution coat, polymer sheet is peeled off then promptly got PLGA micropin sheet.
Optimum condition is that gypsum and alundum (Al mix at 50: 1, and gypsum and water ratio are 1: 3, and needle tip is conical 3: 1, and the degree of depth is 800um, and drying mode is drying at room temperature 480min.
Subordinate list six:
The 7th group of embodiment: preparation of model plaster mould and centrifugal process prepare the PLA micropin
The preparation of gypsum mold: the pin array that becomes 10*10 with 100 pin stationary arrangement, model plaster or model plaster and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, be poured into afterwards on the pin array, treat that gypsum solidifies and take off the pin array, fully drying has just become a gypsum micropore mold.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list seven.
The preparation of micropin: use scissors that gypsum plate is processed into suitable size and shape, be placed in then in the centrifuge tube, it is centrifugal to the polymer drying to use centrifuge 4000r/min to carry out behind the surface coating PLGA, and the polymer-stripping sheet then gets PLGA micropin sheet.
Optimum condition is that gypsum and alundum (Al mix at 50: 1, with the water ratio be 1: 3, the degree of depth is 800 μ m, drying mode is 80 ℃ of 120min.
Subordinate list seven:
The 8th group of embodiment: high strength gypsum mould preparation and filter legal system and be equipped with the glucose micropin
The preparation of gypsum mold: high strength gypsum or high strength gypsum and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, spread on the metallic plate, use another piece glass plate that it gently is pressed into level and smooth gypsum plate, the steel wire gauze is layered on the gypsum plate, the light pressure of sheet glass makes gauze and gypsum plate surface agree with fully, treat that gypsum solidifies but bring into use pin to prick the hole before the sclerosis fully across gauze, just prick at every turn when steel wire blocks pin and don't distortion and transfer to, prick another hole again, pricked the array of expection always.After treating that gypsum hardens fully, take the steel wire gauze gently off, gypsum plate is processed into the shape that conveniently filters with scissors, fully can use after the drying.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list eight.
The preparation of micropin: gypsum mold is positioned in Bush's funnel, uses the wax sealing the margin, on the microwell array surface, use vavuum pump to be evacuated to the polymer drying PLGA solution coat, polymer sheet is peeled off then promptly got PLGA micropin sheet.
Optimum condition is that gypsum and alundum (Al mix at 50: 1, and gypsum and water ratio are 1: 3, and needle tip is conical 3: 1, and the degree of depth is 800 μ m, and drying mode is drying at room temperature 480min.
Subordinate list eight:
The 9th group of embodiment: preparation of high strength gypsum mould and centrifugal process prepare the glucan micropin
The preparation of gypsum mold: the pin array that becomes 10*10 with 100 pin stationary arrangement, high strength gypsum or high strength gypsum and additive agent mixture that mould size as required and thickness are selected certain mass, adding water mixes, be poured into afterwards on the pin array, treat that gypsum solidifies and take off the pin array, fully drying has just become a gypsum micropore mold.The mass ratio of gypsum and water, additive types and with the mass ratio of gypsum, the degree of depth in hole, the shape of pin and length-width ratio, drying mode and time see attached list nine.
The preparation of micropin: use scissors that gypsum plate is processed into suitable size and shape, be placed in then in the centrifuge tube, it is centrifugal to the polymer drying to use centrifuge 4000r/min to carry out behind the surface coating PLGA, and the polymer-stripping sheet then gets PLGA micropin sheet.
Optimum condition is that gypsum and alundum (Al mix at 50: 1, with the water ratio be 1: 3, the degree of depth is 800 μ m, drying mode is 80 ℃ of 120min.
Subordinate list nine:
Claims (9)
1. a preparation method who is used to prepare the gypsum mold of transdermal micro needle array is characterized in that, may further comprise the steps:
The first step, stir after gypsum powder and water mixed, then mixture is spread on the platform, the gypsum microplate of mixture flattening-out to sheet;
The sclerosis back adopts bundle hole instrument to prick the hole under second step, the gypsum microplate room temperature, treats promptly to get the micropin mould that has some single holes after gypsum hardens fully.
2. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 1 is characterized in that described gypsum powder is a powder any in plaster of Paris, model plaster, high strength gypsum, anhydrite cement or the floor gypsum.
3. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 1 is characterized in that the thickness of described gypsum microplate is 1-10cm, and surface area is 0.25cm2-400cm2.
4. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 1 is characterized in that described bundle hole instrument is taper shape or n pyramid, the wherein structure of n 〉=3; This tip of rolling the sky instrument is sphere passivation or plane passivating structure, and rolling the height of sky instrument and the length ratio of base diameter is 3: 1-10: 1.
5. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 1 is characterized in that the aperture of the single hole of described micropin mould is 1 μ m-1000 μ m, and hole depth is 100-1000 μ m.
6. one kind according to arbitrary described preparation method who is used to prepare the gypsum mold of transdermal micro needle array in the claim 1 to 5, it is characterized in that,
After finishing the first step, carry out following operation:
Second goes on foot, after the coverage hole graticule mesh it is rolled in the embedding gypsum microplate on the gypsum microplate, makes the upper surface of gypsum microplate and the upper surface of hole graticule mesh maintain an equal level;
After the 3rd gypsum microplate room temperature environment that goes on foot, will be embedded with the hole graticule mesh hardens down, adopt the pore instrument in the mesh of hole graticule mesh, to prick the hole;
The 4th step, will prick gypsum thin slice behind the hole and place and carry out cure process under the room temperature environment, promptly get the micropin mould that has some single holes after hardening fully.
7. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 6, it is characterized in that, described hole graticule mesh is that thickness is that metal, metal oxide, plastics or the silicate of 1-1000 μ m is made, the mesh of this hole graticule mesh is shaped as circle or polygon, and the mesh radius is 0.5-5000 μ m.
8. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 6 is characterized in that described pore instrument is taper shape or n pyramid, the wherein structure of n 〉=3; The tip of this pore instrument is sphere passivation or plane passivating structure, and the height of pore instrument and the length ratio of base diameter are 3: 1-10: 1.
9. the preparation method who is used to prepare the gypsum mold of transdermal micro needle array according to claim 6 is characterized in that the aperture of the single hole of described micropin mould is 1 μ m-1000 μ m, and hole depth is 100-1000 μ m.
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| CN103691878A (en) * | 2013-12-30 | 2014-04-02 | 机械科学研究总院先进制造技术研究中心 | Mould |
| CN109020280A (en) * | 2018-07-18 | 2018-12-18 | 贵州紫云月华新材料有限公司 | A kind of production method and technique of microcellular structure gypsum material |
| CN109278219A (en) * | 2018-11-14 | 2019-01-29 | 大连理工大学 | A kind of microneedles template and the preparation method and application thereof |
| US20210085944A1 (en) * | 2015-12-30 | 2021-03-25 | Quadmedicine | Microneedle for inhibiting deformation and degeneration in moisture environment and manufacturing method thereof |
| CN112904666A (en) * | 2021-01-22 | 2021-06-04 | 佛山科学技术学院 | High aspect ratio microstructure array mold core, processing device and manufacturing method |
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| DE10065168A1 (en) * | 2000-12-23 | 2002-07-11 | Lohmann Therapie Syst Lts | Device for transdermal administration of active substances, with a plurality of micro needles or blades on a plaster for penetration of the outer skin layer, is provided with a biocidal agent |
| US6875613B2 (en) * | 2001-06-12 | 2005-04-05 | Lifescan, Inc. | Biological fluid constituent sampling and measurement devices and methods |
| AU2003251831B2 (en) * | 2002-07-19 | 2009-06-11 | 3M Innovative Properties Company | Microneedle devices and microneedle delivery apparatus |
| CN101347652B (en) * | 2008-09-09 | 2011-01-12 | 南京大学 | Method for preparing hollow micro-needle array injection syringe |
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| CN103691878B (en) * | 2013-12-30 | 2015-11-11 | 机械科学研究总院先进制造技术研究中心 | Mould |
| US20210085944A1 (en) * | 2015-12-30 | 2021-03-25 | Quadmedicine | Microneedle for inhibiting deformation and degeneration in moisture environment and manufacturing method thereof |
| CN109020280A (en) * | 2018-07-18 | 2018-12-18 | 贵州紫云月华新材料有限公司 | A kind of production method and technique of microcellular structure gypsum material |
| CN109278219A (en) * | 2018-11-14 | 2019-01-29 | 大连理工大学 | A kind of microneedles template and the preparation method and application thereof |
| CN112904666A (en) * | 2021-01-22 | 2021-06-04 | 佛山科学技术学院 | High aspect ratio microstructure array mold core, processing device and manufacturing method |
| CN112904666B (en) * | 2021-01-22 | 2024-06-11 | 佛山科学技术学院 | High aspect ratio microstructure array mold core, processing device and manufacturing method |
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