CN104096311A - High voltage electric field-based manufacturing method for microneedle array - Google Patents
High voltage electric field-based manufacturing method for microneedle array Download PDFInfo
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Abstract
The invention relates to the technical field of biomedical engineering, in particular to a high voltage electric field-based manufacturing method for a microneedle array. The speed, flowing into a substrate die, of a substrate mixture solution is controlled by arranging a push injection device, and the substrate mixture solution is uniformly distributed on the substrate die, and is prevented from being accumulated; the substrate mixture solution is enabled to form a taylor cone, namely a microneedle array structure, on a hole die by using the mutual action between the electric field generated by an electric field generation device and the substrate mixture solution through controlling the voltage size, the manufacturing cost of the micronedle array structure is reduced, and the manufacturing method of the micronedle technology is simple and easy to operate.
Description
Technical field
The present invention relates to a kind of technical field of biomedical engineering method, more specifically, relate to a kind of manufacture method of the microneedle array based on high voltage electric field.
Background technology
in therapeutic treatment field, although present biotechnology many very ripe and effective medicines of production department, the transmission of many medicines is subject to some and limits, and is exactly the most significantly the injection of the oral and medicine of medicine.
The main problem of oral administration medicine supplying is just in the Degradation of gastrointestinal tract Chinese medicine with by the discharge of liver drug.The another kind of approach of the dispensing of use is conventionally through intravenous injection, and this method is difficult in non-medical space using, the also bad release that maintains and control medicine, and for patient inconvenience, have pain.By skin, transmitting medicine is very attractive novel method, and still this method is because the permeability of skin extreme difference is restricted.Microneedle array provides a kind of method of novel transmission medicine, can strengthen the transmission to drug molecule through skin, realizes efficient, painless dispensing.Microneedle array thrusts skin, has created the conduit that transmits medicine by horny layer, once medicine through horny layer, it just can be by deep tissues diffusion absorbed formation administration system by blood capillary below rapidly.
Micropin is widely used at biomedical sector, for example, for biomedical measurement system, and drug delivery system and microsampling analytical system etc.Micropin not only volume is small, and in performance, also has accurately, and painless, efficient, feature, more strengthens the advantage of its application easily, and the scope of corresponding application is more widened.
The method of making at present micropin is not too many, and the processing that the LIGA technology based on MEMS (MEMS technology) is microneedle array is a kind of effective way wherein.LIGA technology is a kind of advanced manufacturing technology of utilizing synchrotron radiation X ray to manufacture three-dimension device.It is comprised of the preparation of X radiation masks plate, synchronous X X-ray lithography X, microstructural mold, micro-electroforming and micro-duplication process, by LIGA technology, can carry out the production in enormous quantities of micro element, and cost is reduced greatly.But due to synchronous X ray comparatively costliness and fabrication cycle long, the cost of LIGA fabrication techniques micropin is very high, and process complexity is wayward.
Early stage micropin is mainly usingd silicon as material, and not high owing to having mechanical strength, fragility is large, easily ruptures, and the biocompatibility of human body is still not clear, processing charges more high defect still, and present stage is not had condition and the potentiality of popularization.Metal micro-needle is except having significant advantage in physical and mechanical properties, mechanical property, aspect biocompatibility, still there is certain shortcoming, and course of processing more complicated, the metal micro-needle obtaining is acquiring a certain degree of difficulty aspect medicine carrying and drug release, and effect is not necessarily desirable.And curable degradable high polymer material feature low with its processing cost and that be suitable for producing in enormous quantities demonstrates outstanding advantage, and this high molecular polymer micropin has good biocompatibility.In addition, this degradable polymer material micropin can be realized direct medicine carrying, can be directly medicine be joined in the middle of the biomaterial that can be degraded by human body, directly pin is inserted to human body and discharges medicine, avoided that metal micro-needle medicine carrying extracts after loading time break and fall to causing micropin to stay human body.Especially, this curable degradable macromolecule polymer material cost is low, there is the directly advantage of medicine carrying, can realize by changing polymeric material the mechanical strength of micropin, and treatment technology is ripe, its formability and the compatibility, than more excellent, are suitable for the batch production of micropin in addition.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, a kind of manufacture method of the microneedle array based on high voltage electric field is provided, setting by infusing device makes the speed of inflow substrate mould of substrate mixture solution controlled, and it is uniformly distributed on substrate mould, avoids occurring piling up; The electric field and the mutual effect of substrate mixture solution phase that utilize electric field generation device to produce, by controlling the size of voltage, make the ionization of substrate mixture solution on casement, form taylor cone, form microneedle array structure, reduce the cost of manufacture of microneedle array structure, make the manufacture method of micropin technology simple and easy to operate, can avoid the technical process of MEMS technical sophistication, be convenient to realize batch production.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
A kind of manufacture method of the microneedle array based on high voltage electric field is provided, making apparatus based on microneedle array comprises substrate mould, has the casement of some apertures, for generating the electric field generation device of high voltage electric field, for substrate mixture solution being injected to the infusing device of substrate mould, described infusing device is connected with substrate mould, and the manufacture method of microneedle array comprises the following steps:
A. make substrate mixture solution, described substrate mixture solution is by epoxy resin, epoxy curing agent, needs the medicament mixed of injection to form, and the substrate mixture solution of mix homogeneously is loaded in infusing device;
B. casement is positioned over to the upper surface of substrate mould, opens in the basad mould of infusing device and inject substrate mixture solution, the some apertures on casement are placed in the top of substrate mixture solution;
C. the substrate mould of step b is positioned in electric field generation device, by controlling the size of voltage, makes the ionization of substrate mixture solution on casement, form the microneedle array structure of stable curing.
The present invention is based on the manufacture method of the microneedle array of high voltage electric field, by the substrate mould of having built substrate mixture solution and upper surface and be placed with casement is positioned in electric field generation device, can make the ionization of substrate mixture solution on casement, form taylor cone, form the microneedle array structure of stable curing.And the medicine that comprises needs injections due to substrate mixture solution and other materials be degradable in vivo, has avoided patient in medication process, to need to extract the misery of micropin.Making apparatus is simple in structure, can reduce the cost of manufacture of micropin.
For substrate mould is stable, place substrate mixture solution, the surface of described substrate mould is provided with for placing the groove of substrate mixture solution, and described casement is positioned in groove, and the size of described casement and the size of groove match.The size of casement and the size of groove match and are positioned in groove and slide for fear of casement, and it is placed steadily, are convenient to producing of microneedle array structure.
In order to simplify the generating mode of electric field, simultaneously can be by the ionization of substrate mixture solution, described electric field generation device comprises high-voltage DC power supply, plate electrode and electrode slice, and described plate electrode is located at the top of groove, and described electrode slice is located in groove; The earth terminal of described high-voltage DC power supply is connected with plate electrode, voltage output end is connected with electrode slice.High voltage direct current source generator adopts HVDC constant current source, and the voltage of high-voltage DC power supply output can carry out coarse adjustment and fine setting.
In order to impel the microneedle array structure in step c to solidify, described making apparatus also comprises the solidification equipment being cured for the micropin on substrate mould.Micropin need to select to be used to form micropin and curable degradable substrate mixture solution.In order to accelerate solidifying of micropin, can select curable condition according to the condition of cure of selected curable materials, select corresponding solidification equipment to be cured the micropin forming.Curing is mainly heating and curing, radiation curing, microwave curing etc., and concrete curing mode is made material according to selected micropin and specifically determined.
In order to make mixture solution be more prone to form micropin, described infusing device comprises for providing the syringe pump of propulsive force to syringe and for installing the syringe of substrate mixture solution, described substrate mold bottom is provided with the intercommunicating pore being communicated with infusing device; Described syringe is connected with connecting hole by rubber hose.Described infusing device needs strict control when injecting, and it injects speed and flow, and substrate mixture solution is injected in the aperture on casement, and the mixture solution of take reaches the top of aperture and do not overflow casement surface as excellent.
For fear of substrate mould, be subject to the impact of uniform magnetic field, described substrate mould is non-conducting material structure, and described casement is dull and stereotyped dielectric materials structure.Preferably, substrate mould is glass material structure, and casement is silicane rubber plate.Substrate mould is that the setting of glass material structure is because glass material can not be subject to electric field influence, and the dielectric constant of the glass material of substrate mould is larger than the dielectric constant of the silicane rubber plate material of casement, the electric field influence that makes glass material as substrate mould not affect the electric field of formation and casement is formed is not remarkable, and transparent being easy to observed.Casement is silicane rubber plate, and advantage is to have good heat-resistant air aging property, ozone resistance, insulating properties, and fuel oil resistance and lubricating oil, can be placed in the air or oils medium under the condition of temperature-60 ~+250 ℃.Silicane rubber plate has been inherited the good characteristic of silica gel, has the feature of dielectricity, corrosion-resistant, high temperature high voltage resistant, colorless and odorless.In addition, silicane rubber plate has low-k, is placed under high voltage electric field, and the formed internal field of aperture above it is equivalent to the internal field that sharp-pointed metal needle produces.
Preferably, the aperture of the some apertures on described casement is 0.3 ~ 0.5mm, and the spacing between described some apertures is 15 ~ 30mm.The aperture of some apertures is that 0.3 ~ 0.5mm is the preferably aperture of measuring according to experiment, and the size in aperture can affect the diameter of micropin, and can affect the distribution number of aperture on casement.Spacing between some apertures is to interfere with each other for fear of the electric field producing between adjacent holes for 15 ~ 30mm.
Substrate mixture solution is by curable degradable macromolecular material, needs the medicament mixed of injection to form, can take solidification equipment according to the condition of cure of base mixture, and the substrate mixture solution of mix homogeneously is loaded on to infusing device, just can open solidification equipment form pin under high voltage electric field after micropin is cured.
In order to simplify the generating mode of electric field, simultaneously can be by the ionization of substrate mixture solution, the output end voltage of described high-voltage DC power supply is 1KV ~ 50KV.High voltage power supply output voltage is 1KV-50KV, and 0 is adjustable continuously to ceiling voltage, can realize the control to different experimental conditions, improves the success rate that micropin forms.High-voltage DC power supply is mainly for generation of high voltage electric field, and by the ionization of substrate mixture solution, so power do not need too greatly, and security performance is high.
Compared with prior art, the invention has the beneficial effects as follows:
The present invention is based on the manufacture method of the microneedle array of high voltage electric field, the setting by infusing device makes the speed of inflow substrate mould of substrate mixture solution controlled, and it is uniformly distributed on substrate mould, avoids occurring piling up; The electric field and the mutual effect of substrate mixture solution phase that utilize electric field generation device to produce, by controlling the size of voltage, make the ionization of substrate mixture solution on casement, form taylor cone, form microneedle array structure, the cost of manufacture that reduces microneedle array structure, makes the manufacture method of micropin technology simple and easy to operate.The polymer solution that substrate mixture solution of the present invention was comprised of curable macromolecular material and mixing of medicine, the micropin of its formation can directly act on after human body without extracting, medicine can be directly released into human body lentamente, realize the direct transmission of medicine, and its one-tenth needle material can be in people's vivo degradation.The present invention can be by regulating the pore size of some apertures and the group grading mode of mixture solution on high-voltage DC power supply voltage, pore membrane to change microneedle array length and micropin thickness, make the shape of micropin there is controllability, and making apparatus is simple in structure, with low cost, easy to use.
Accompanying drawing explanation
Fig. 1 is the structural representation of embodiment 1 substrate mould.
Fig. 2 is the structural representation of embodiment 1 casement.
Fig. 3 is the making apparatus structural representation that embodiment 1 adds the front microneedle array of casement.
Fig. 4 is that embodiment 1 microneedle array is made the structural representation after molding.
Fig. 5 is the structural representation of the making apparatus of embodiment 2 microneedle arrays.
The specific embodiment
Below in conjunction with the specific embodiment, the present invention is further illustrated.Wherein, accompanying drawing is only for exemplary illustration, expression be only schematic diagram, but not pictorial diagram can not be interpreted as the restriction to this patent; For embodiments of the invention are described better, some parts of accompanying drawing have omission, zoom in or out, and do not represent the size of actual product; For a person skilled in the art, in accompanying drawing some known configurations and explanation thereof may to omit be understandable.
The corresponding same or analogous parts of same or analogous label in the accompanying drawing of the embodiment of the present invention, in description of the invention, it will be appreciated that, if have term " on ", D score, " left side ", orientation or the position relationship of indications such as " right sides " are based on orientation shown in the drawings or position relationship, only the present invention for convenience of description and simplified characterization, rather than device or the element of indication or hint indication must have specific orientation, with specific orientation structure and operation, therefore the term of describing position relationship in accompanying drawing is only for exemplary illustration, can not be interpreted as the restriction to this patent, for the ordinary skill in the art, can understand as the case may be the concrete meaning of above-mentioned term.
Embodiment 1
As shown in Figures 1 to 4 for the present invention is based on first embodiment of manufacture method of the microneedle array of high voltage electric field, as shown in Figure 4, making apparatus based on microneedle array comprises substrate mould 1, has the casement 2 of some apertures, for generating the electric field generation device 3 of high voltage electric field, for substrate mixture solution being injected to the infusing device 4 of substrate mould 1, infusing device 4 is connected with substrate mould 1, and the manufacture method of microneedle array comprises the following steps:
A. make substrate mixture solution, described substrate mixture solution is by epoxy resin, epoxy curing agent, needs the medicament mixed of injection to form, and the substrate mixture solution of mix homogeneously is loaded in infusing device 4;
B. casement 2 is positioned over to the upper surface of substrate mould 1, opens the interior injection substrate mixture of the basad mould 1 of infusing device 4 solution, the some apertures on casement 2 are placed in the top of substrate mixture solution;
C. the substrate mould 1 of step b is positioned in electric field generation device 3, by controlling the size of voltage, makes the ionization of substrate mixture solution on casement 2, form the microneedle array structure of stable curing.
Particularly, as shown in Figure 1, the surface of substrate mould 1 is provided with for placing the groove 11 of substrate mixture solution, and casement 2 is positioned in groove 11, and the size of the size of casement 2 and groove 11 matches.The size of the size of casement 2 and groove 11 matches and is positioned in groove 11 and slides for fear of casement 2, and it is placed steadily, is convenient to producing of microneedle array structure.The substrate mould 1 of selecting in the present embodiment is square structure; Groove 11 is square groove, and long is 150mm, and wide is 100mm, and the degree of depth is 2mm.
Wherein, as shown in Figure 3 to Figure 4, electric field generation device 3 comprises high-voltage DC power supply 31, plate electrode 32 and electrode slice 33, and plate electrode 32 is located at the top of groove 11, and electrode slice 33 is located in groove 11; The earth terminal of high-voltage DC power supply 31 is connected with plate electrode 32, voltage output end is connected with electrode slice 33.High voltage direct current source generator adopts HVDC constant current source, and the voltage of high-voltage DC power supply 31 outputs can carry out coarse adjustment and fine setting.The output end voltage of high-voltage DC power supply 31 is 1KV ~ 50KV.High compacting stream power supply 31 output voltages are 1KV-50KV, and 0 is adjustable continuously to ceiling voltage, can realize the control to different experimental conditions, improve the success rate that micropin forms.High-voltage DC power supply 31 is mainly for generation of high voltage electric field, and by the ionization of substrate mixture solution, so power do not need too greatly, and security performance is high.
In addition, as shown in Figs. 3-4, making apparatus also comprises for giving the curing curing source of the formed micropin of casement 2 on substrate mould 1.The application's curing source adopts heating source.Heating source comprises heating film 5 and the extraneous DC source 6 for power supply being provided to heating film 5 that is positioned over substrate mould 1 bottom, and heating film 5 is carbon fibre material formation.Heating film 5 for the setting that carbon fibre material forms be because carbon fiber electrically thermal conversion efficiency is high, long service life, fatigue durability is high, and can not be subject to externally-applied magnetic field impact.By 5 pairs of substrate mixture solution of heating film are heated, accelerate epoxy resin cure, accelerate solidifying of microneedle array structure.
Wherein, infusing device 4 comprises for providing the syringe pump of propulsive force to syringe and for installing the syringe of substrate mixture solution, substrate mould 1 bottom is provided with the intercommunicating pore 12 being communicated with infusing device 4; Syringe is connected with connecting hole 12 by rubber hose 7.Infusing device 4 needs strict control when injecting, and it injects speed and flow, and substrate mixture solution is injected in the aperture on casement 2, and the mixture solution of take reaches the top of aperture and do not overflow casement 2 surfaces as excellent.Groove 11 bottoms have aperture to draw rubber hose 7 connection infusing devices 4, and are fixed with electrode slice 33 in groove 11 bottoms, to fully contact and ionize with the substrate mixture solution of injecting groove 11.
In addition, substrate mould 1 is non-conducting material structure, and casement 2 is dull and stereotyped dielectric materials structure.In the present embodiment, substrate mould 1 is glass material structure, and casement 2 is silicane rubber plate.Substrate mould 1 for the setting of glass material structure be because glass material can not be subject to electric field influence, and transparent being easy to observed.As shown in Figure 2, the aperture of the some apertures on casement 2 is 0.3 ~ 0.5mm, and the spacing between some apertures is 15 ~ 30mm.The aperture of some apertures is that 0.3 ~ 0.5mm is the preferably aperture of measuring according to experiment, and the size in aperture can affect the diameter of micropin, and can affect the distribution number of aperture on casement.Spacing between some apertures is to interfere with each other for fear of the electric field producing between adjacent holes for 15 ~ 30mm.The number of its aperture can design according to practical situation, and in the present embodiment, selecting aperture is the aperture of 0.4mm, and pitch-row is 20mm, is uniformly distributed 35 apertures on casement 2,7, long limit, 5 of minor faces.
In addition, the weight ratio of the part composition of substrate mixture solution is, epoxy resin: epoxy curing agent=3:1.The setting of the weight ratio of the composition of substrate mixture solution is in order not cause the waste of material and the deficiency of mixed proportion to affect the generation quality of micropin.
Operating procedure concrete in the present embodiment is as follows:
Step 1: make the groove structure substrate mould 1 of glass material, it is long is 150mm, and wide is 100mm, is 2mm deeply, is connected substrate mould 1 is communicated with infusing device 4 with connecting hole 12 by rubber hose 7.
Step 2: form casement 2 by laser etching on silicane rubber plate.Aperture pitch-row on casement 2 is 0.4mm, is uniformly distributed 35 apertures on casement 2,7, long limit, 5 of minor faces.
Step 3: make substrate mixture solution.Wherein the weight ratio of epoxy resin and epoxy curing agent is 3:1.
Step 4: utilize infusing device 4 to draw substrate mixture solution, and infusing device 4 is connected to groove 11 bottoms by rubber hose 7 by aperture 12 and connects, and high-voltage DC power supply 31 voltage output ends are connected with the electrode slice 33 that is fixed on groove 11 bottoms.
Step 5: casement 2 is positioned in groove 11, the plate electrode 3 that is connecting high-voltage DC power supply 4 earth terminals is placed in apart from groove 11 opening 4mm places.
Step 6: start infusing device 4, substrate mixture solution is injected in groove 11, until substrate mixture solution stops injecting when arriving casement 2 tops and not overflowing aperture.
Step 7: open high-voltage DC power supply 31 switches, start boosted voltage gradually from 0kV, finely tune when being elevated to 3kV, utilize magnifier to observe, until there is micropin, keep this voltage.
Step 8: place the heating film 5 that a slice is electrically connected to extraneous DC source 6 below substrate mould 1, open extraneous DC source 6, regulating its output dc voltage is 5.0V, under this voltage, the temperature of heating film 8 is 90 to 130 ℃, the heating of substrate mould 1, until microneedle array structure is completely curing, is formed to microneedle array.
Embodiment bis-
Be illustrated in figure 5 the second embodiment of the manufacture method of the microneedle array that the present invention is based on high voltage electric field, the present embodiment and embodiment mono-are similar, institute's difference is, in the present embodiment, selecting aperture is the aperture of 0.5mm, pitch-row is 30mm, on casement 2, be uniformly distributed 35 apertures, 7, long limit, 5 of minor faces.In the present embodiment, substrate mould 1 does not add heating source, and microneedle array structure is air-dry solidifying directly, escapable cost.
Obviously, the above embodiment of the present invention is only for example of the present invention is clearly described, and is not the restriction to embodiments of the present invention.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here exhaustive without also giving all embodiments.All any modifications of doing within the spirit and principles in the present invention, be equal to and replace and improvement etc., within all should being included in the protection domain of the claims in the present invention.
Claims (9)
1. the manufacture method of the microneedle array based on high voltage electric field, it is characterized in that, making apparatus based on microneedle array comprises substrate mould (1), has the casement (2) of some apertures, for generating the electric field generation device (3) of high voltage electric field, for substrate mixture solution being injected to the infusing device (4) of substrate mould (1), described infusing device (4) is connected with substrate mould (1), and the manufacture method of microneedle array comprises the following steps:
A. make substrate mixture solution, described substrate mixture solution is by curable degradable macromolecular material, needs the medicament mixed of injection to form, and the substrate mixture solution of mix homogeneously is loaded in infusing device (4);
B. casement (2) is positioned over to the upper surface of substrate mould (1), opens in the basad mould of infusing device (4) (1) and inject substrate mixture solution, the some apertures on casement (2) are placed in the top of substrate mixture solution;
C. the substrate mould (1) of step b is positioned in electric field generation device (3), by controlling the size of voltage, makes the ionization of substrate mixture solution upper at casement (2), form the microneedle array structure of stable curing.
2. the manufacture method of the microneedle array based on high voltage electric field according to claim 1, it is characterized in that, the surface of described substrate mould (1) is provided with the groove (11) for placing substrate mixture solution, described casement (2) is positioned in groove (11), and the size of the size of described casement (2) and groove (11) matches.
3. the manufacture method of the microneedle array based on high voltage electric field according to claim 2, it is characterized in that, described electric field generation device (3) comprises high-voltage DC power supply (31), plate electrode (32) and electrode slice (33), described plate electrode (32) is located at the top of groove (11), and described electrode slice (33) is located in groove (11); The earth terminal of described high-voltage DC power supply (31) is connected with plate electrode (32), voltage output end is connected with electrode slice (33).
4. according to the manufacture method of the microneedle array based on high voltage electric field described in claims 1 to 3 any one, it is characterized in that, described making apparatus also comprises for going up the curing curing source of the formed micropin of casement (2) to substrate mould (1).
5. according to the manufacture method of the microneedle array based on high voltage electric field described in claims 1 to 3 any one, it is characterized in that, described infusing device (4) comprises for providing the syringe pump of propulsive force to syringe and for installing the syringe of substrate mixture solution, and described substrate mould (1) bottom is provided with the intercommunicating pore (12) being communicated with infusing device (4); Described syringe is connected with connecting hole (12) by rubber hose.
6. the manufacture method of the microneedle array based on high voltage electric field according to claim 1, is characterized in that, described substrate mould (1) is non-conducting material structure, and described casement (2) is dull and stereotyped dielectric materials structure.
7. the manufacture method of the microneedle array based on high voltage electric field according to claim 1, is characterized in that, the aperture of the some apertures on described casement (2) can be according to specific requirement adjustment, and the spacing between described some apertures is 15 ~ 30mm.
8. the manufacture method of the microneedle array based on high voltage electric field according to claim 1, is characterized in that, the part composition of described substrate mixture solution comprises curable degradable high molecular polymer.
9. the manufacture method of the microneedle array based on high voltage electric field according to claim 3, is characterized in that, the output end voltage of described high-voltage DC power supply can be adjusted according to concrete curable materials, and scope is 1KV ~ 50KV.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104307097A (en) * | 2014-10-28 | 2015-01-28 | 中山大学 | Method for manufacturing flexible-substrate metal microneedle array |
| KR20160053114A (en) * | 2014-10-30 | 2016-05-13 | 서울대학교산학협력단 | Method for manufacturing electro induced microstructure and manufacturing apparatus for the same |
| CN106727273A (en) * | 2017-03-02 | 2017-05-31 | 李成国 | The manufacture method of soluble micropin |
| WO2017140239A1 (en) * | 2016-02-15 | 2017-08-24 | Shanghai Jiao Tong University | Method to print microneedle patches rapidly |
| CN108714273A (en) * | 2018-06-08 | 2018-10-30 | 广州蔻原生物科技有限责任公司 | A kind of macromolecule micropin preparation system and macromolecule microneedle preparation method |
| CN110087723A (en) * | 2016-12-23 | 2019-08-02 | 赛诺菲 | Medicament delivery device |
| CN110860033A (en) * | 2019-12-19 | 2020-03-06 | 陈强 | Device capable of continuously covering and injecting liquid medicine |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040126707A1 (en) * | 2002-12-27 | 2004-07-01 | Industrial Technology Research Institute | Method for manufacturing 3-D high aspect-ratio microneedle array device |
| CN101441962A (en) * | 2007-11-21 | 2009-05-27 | 中国科学院微电子研究所 | Micro-tip array device based on field electron emission principle and manufacturing method thereof |
| CN102657914A (en) * | 2012-05-17 | 2012-09-12 | 吉林大学 | Micro-needle transdermal delivery patch with high penetration efficiency |
| JP2013094662A (en) * | 2012-05-02 | 2013-05-20 | Kosumedei Seiyaku Kk | Microneedle welding method |
| CN103260693A (en) * | 2010-10-19 | 2013-08-21 | 塔夫茨大学信托人 | Silk fibroin-based microneedles and methods of making the same |
| US20140142492A1 (en) * | 2011-07-26 | 2014-05-22 | Industry-Acadmic Cooperation Foundation, Yonsei Univ. | Electro-microneedle integrated body for in-situ cutaneous gene transfer and method of manufacturing same |
-
2014
- 2014-07-01 CN CN201410308295.9A patent/CN104096311B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040126707A1 (en) * | 2002-12-27 | 2004-07-01 | Industrial Technology Research Institute | Method for manufacturing 3-D high aspect-ratio microneedle array device |
| CN101441962A (en) * | 2007-11-21 | 2009-05-27 | 中国科学院微电子研究所 | Micro-tip array device based on field electron emission principle and manufacturing method thereof |
| CN103260693A (en) * | 2010-10-19 | 2013-08-21 | 塔夫茨大学信托人 | Silk fibroin-based microneedles and methods of making the same |
| US20140142492A1 (en) * | 2011-07-26 | 2014-05-22 | Industry-Acadmic Cooperation Foundation, Yonsei Univ. | Electro-microneedle integrated body for in-situ cutaneous gene transfer and method of manufacturing same |
| EP2737923A2 (en) * | 2011-07-26 | 2014-06-04 | Raphas Co., Ltd. | Electro-microneedle integrated body for in-situ cutaneous gene transfer and method of manufacturing same |
| JP2013094662A (en) * | 2012-05-02 | 2013-05-20 | Kosumedei Seiyaku Kk | Microneedle welding method |
| CN102657914A (en) * | 2012-05-17 | 2012-09-12 | 吉林大学 | Micro-needle transdermal delivery patch with high penetration efficiency |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104307097B (en) * | 2014-10-28 | 2017-04-05 | 中山大学 | A kind of manufacture method of flexible substrates metal micro-needle array |
| CN104307097A (en) * | 2014-10-28 | 2015-01-28 | 中山大学 | Method for manufacturing flexible-substrate metal microneedle array |
| KR20160053114A (en) * | 2014-10-30 | 2016-05-13 | 서울대학교산학협력단 | Method for manufacturing electro induced microstructure and manufacturing apparatus for the same |
| KR101691403B1 (en) * | 2014-10-30 | 2017-01-03 | 서울대학교산학협력단 | Method for manufacturing electro induced microstructure and manufacturing apparatus for the same |
| WO2017140239A1 (en) * | 2016-02-15 | 2017-08-24 | Shanghai Jiao Tong University | Method to print microneedle patches rapidly |
| US11116954B2 (en) | 2016-02-15 | 2021-09-14 | Shanghai Jiao Tong University | Method to print microneedle patches rapidly |
| CN110087723A (en) * | 2016-12-23 | 2019-08-02 | 赛诺菲 | Medicament delivery device |
| US11666739B2 (en) | 2016-12-23 | 2023-06-06 | Sanofi | Medicament delivery device |
| WO2018157783A1 (en) * | 2017-03-02 | 2018-09-07 | 优微（珠海）生物科技有限公司 | Method and device for manufacturing soluble micro-needles |
| CN106727273A (en) * | 2017-03-02 | 2017-05-31 | 李成国 | The manufacture method of soluble micropin |
| CN108714273B (en) * | 2018-06-08 | 2021-02-05 | 广州蔻原生物科技有限责任公司 | Polymer microneedle preparation system and polymer microneedle preparation method |
| CN108714273A (en) * | 2018-06-08 | 2018-10-30 | 广州蔻原生物科技有限责任公司 | A kind of macromolecule micropin preparation system and macromolecule microneedle preparation method |
| CN110860033A (en) * | 2019-12-19 | 2020-03-06 | 陈强 | Device capable of continuously covering and injecting liquid medicine |
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