CN102836936A - Preparation method of solid titanium microneedle for cutaneous penetration - Google Patents
Preparation method of solid titanium microneedle for cutaneous penetration Download PDFInfo
- Publication number
- CN102836936A CN102836936A CN2012103166029A CN201210316602A CN102836936A CN 102836936 A CN102836936 A CN 102836936A CN 2012103166029 A CN2012103166029 A CN 2012103166029A CN 201210316602 A CN201210316602 A CN 201210316602A CN 102836936 A CN102836936 A CN 102836936A
- Authority
- CN
- China
- Prior art keywords
- titanium
- preparation
- solid microneedles
- die
- cutaneous penetration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Abstract
The invention discloses a preparation method of a solid titanium microneedle for cutaneous penetration, comprising the following steps of: processing dies for preparing the solid titanium microneedle; and putting a pre-treated titanium plate among the dies and preparing the solid titanium microneedle through a micro-pier extruding method. The dies are processed through the following concrete steps of: processing a planar male die and a female die with a boss through a line-cutting method and then grinding the female die and the male die, wherein a recess with the size as same as the size of the solid titanium microneedle is arranged on the female die with the boss. Compared with the prior art, the preparation method disclosed by the invention has the advantages that the biocompatibility of the microneedle is improved due to the adoption of pure titanium or titanium alloy, the use reliability of the microneedle is improved through the integration of a needle head and a base, the production efficiency is increased and batch production is favorably realized through die formation.
Description
Technical field
The present invention relates to plastic forming technology, particularly be used for the preparation method of the titanium solid microneedles of cutaneous penetration.
Background technology
Main administering mode is oral and injection at present.Oral drugs are because the absorption in stomach and the first pass effect of liver have influenced the practical effect of medicine to site of action greatly, and some medicine also can bring injury to stomach simultaneously.Injection not only can bring tangible pain to the patient, also needs the professional to operate simultaneously, even the local damage even the infection of skin can occur, and incompatible long-term reaching needs the accurately sustained-release administration of control.
Percutaneous dosing is a reasonable solution.Skin is divided into three layers from outside to inside: epidermis, corium and hypodermis.Cuticula in its mesocuticle is the maximum barrier that medicine absorbs through skin.People have adopted multiple physicochemical method to promote absorbing through skin of medicine for this reason.Such as physical methods such as ion importing, electroporations, remarkable through the skin assimilation effect, but majority need rely on the automatically controlled property equipment that energy source is arranged, and bigger to the damage of skin, and medication person can't independently voluntarily use.Chemical penetrating agent is not obvious through the skin assimilation effect to macromolecular drug then, and generally have than strong and stimulating.
Comparatively speaking, microneedle cutaneous is a kind of administering mode between hypodermic injection and transdermal patch.Micropin also belongs to the short technology of oozing of physics; Be that the size that is made by distinct methods is in micron-sized acicular texture; Handle through skin being carried out painless pore; Produce the permeability that medicine is improved in small duct at keratoderma, thereby it is especially macromolecular through the skin uptake to improve medicine greatly; Simultaneously because the needle point size is less, to almost not infringement of skin, and easy to usely do not need the professional to operate, be fit to individual independent operation.
Micropin has two types of solid needle and hollow needles.In use, adopt following administering mode usually for solid microneedles: (1) is thrust skin with microneedle array earlier and is formed the cavity, again pastille is sticked on therapentic part; (2) behind microneedle array surface-coated medicine, thrust skin and continue release.Normally adopt the mode of microinjection to carry medicine for empty micropin, be applicable to liquid and the bigger medicine of therapeutic dose requirement.In addition, empty micropin can also be used for carrying out through skin the extraction and the detection of trace body fluid.
The material of making micropin has polymer, monocrystalline silicon and metal etc.The outstanding problem that existing polymer micro needle exists is that the strength of materials is not enough, is difficult for the cuticula of pierce.The monocrystalline silicon material is hard, is prone to brittle failure, and it has better biocompatibility also not belong to conventional medical material now though bibliographical information is arranged, and whether can be applicable to that the biological medicine aspect is still waiting further textual criticism.Metal is used for manufacturing needles acupuncture needle or existing thousand one-hundred-year histories of injection needle, therefore is fit to make low cost, micropin in enormous quantities.
Summary of the invention
The objective of the invention is to overcome the deficiency that above-mentioned prior art exists, a kind of preparation method who is used for the pure titanium solid microneedles of cutaneous penetration is provided, this method is used plastic forming technology, strengthens the usability of micropin, reduces technology difficulty, is easy to realize producing in batches.
The objective of the invention is to realize through following technical scheme:
The present invention relates to a kind of preparation method who is used for the titanium solid microneedles of cutaneous penetration, comprise the steps:
A, the said titanium solid microneedles of processing prepare needed mould;
B, the preliminary treatment of titanium plate;
C, said pretreated titanium plate is positioned between mould, the method that adopts pier to squeeze prepares described titanium solid microneedles.
The application scanning electron microscope is observed obtaining micropin, measures the micropin size and whether reaches the expection requirement.
Preferably, processing described in the steps A is specially: process plane punch and the die that has the boss characteristic with wire cutting method, then said die and punch are carried out grinding; Be provided with and the measure-alike recess of said titanium solid microneedles on the said die that has a boss characteristic.
Preferably, processing is specially described in the steps A: with Laser Processing out-of-plane punch and the die that has characteristic.
Preferably, said roughness grade protruding, die is 0.2, and upper and lower surfaces depth of parallelism grade is 0.01mm.
Preferably, preliminary treatment described in the step B is specially: the titanium plate is machined to is of a size of 2mm * 2mm～3mm * 3mm, roughness grade is 1.6～6.3, clean.
Preferably, said cleaning adopts alcohol to clean.
Preferably, titanium plate described in the step B is pure titanium plate.
Preferably, prepared solid microneedles is of a size of diameter 100 μ m among the step C, length 100～200 μ m.
Preferably, pier described in the step C squeezes and realizes that through stretching-machine the pressure of said stretching-machine is 2～10KN.
Compared with prior art, the present invention has following beneficial effect:
1, to prepare the method for micropin be Plastic Forming in the present invention, is to obtain needed micropin shape through material mobile, do not have material unaccounted-for (MUF); Simultaneously, this preparation method utilizes die forming to improve production efficiency, has reduced technology difficulty, helps producing in batches.
2, adopt titanium alloy or pure titanium to improve the biocompatibility of micropin as material; Adopt syringe needle and substrate one, improved the reliability that micropin uses.
Description of drawings
Fig. 1 is the used punch-die sketch map of the present invention;
Fig. 2 is the structural representation of the prepared titanium solid microneedles of the present invention;
Among the figure, 1 is punch, and 2 is the titanium plate, and 3 is die, and 4 is micropin, and 5 is the micropin substrate.
The specific embodiment
Below in conjunction with specific embodiment and accompanying drawing the present invention is elaborated.Following examples will help those skilled in the art further to understand the present invention, but not limit the present invention in any form.Should be pointed out that to those skilled in the art, under the prerequisite that does not break away from the present invention's design, can also make some distortion and improvement.These all belong to protection scope of the present invention.
The preparation method of the titanium solid microneedles that is used for cutaneous penetration of present embodiment specifically comprises the steps:
1, adopts Hardmetal materials; Process the needed plane of titanium solid microneedles punch as shown in Figure 11 and the die 3 that has the boss characteristic with wire cutting method; Then said die 3 is carried out grinding with punch 1; Make that said roughness grade protruding, die 1,3 is 0.2, the upper and lower surfaces depth of parallelism is 0.01mm; Be provided with and the measure-alike recess of said titanium solid microneedles on the said die 3 that has a boss characteristic; Solid microneedles is of a size of diameter 100 μ m, length 150～200 μ m;
2, pure titanium plate preliminary treatment: through the line cutting processing, pure titanium plate is machined to is of a size of 2mm * 2mm, roughness grade is 1.6, utilizes alcohol to clean to the pure titanium plate 2 that processes;
3, convex concave mould is installed on the cupping machine, pretreated pure titanium plate 2 is placed on convex concave mould 1, between 3, is 2～3KN through the pressure of controlling stretching-machine, carry out pier and squeeze, stop after the power that arrival sets; Pure titanium plate after pier squeezed takes out, and promptly obtains the pure titanium solid microneedles of required form, and is as shown in Figure 2, is included as micropin 4 and micropin substrate 5.
Observe through SEM, obtain micropin size and surface quality information, whether checking micropin size meets the requirements.
Embodiment 2
The preparation method of the titanium solid microneedles that is used for cutaneous penetration of present embodiment specifically comprises the steps:
1, adopts Hardmetal materials; Process the needed plane of titanium solid microneedles punch as shown in Figure 11 and the die 3 that has the boss characteristic with wire cutting method; Then said die 3 is carried out grinding with punch 1; Make that said roughness grade protruding, die 1,3 is 0.2, the upper and lower surfaces depth of parallelism is 0.01mm; Be provided with and the measure-alike recess of said titanium solid microneedles on the said die 3 that has a boss characteristic; Solid microneedles is of a size of diameter 100 μ m, length 100～150 μ m;
2, titanium alloy sheet preliminary treatment: through the line cutting processing, titanium alloy sheet is machined to is of a size of 3mm * 3mm, roughness grade is 6.3, utilizes alcohol to clean to the titanium alloy sheet 2 that processes;
3, convex concave mould is installed on the cupping machine, pretreated titanium alloy sheet 2 is placed on convex concave mould 1, between 3, is 10KN through the pressure of controlling stretching-machine, carry out pier and squeeze, stop after the power that arrival sets; Titanium alloy sheet after pier squeezed takes out, and promptly obtains the titanium solid microneedles of required form, and behind the attenuation plate is substrate, as shown in Figure 2, is included as micropin 4 and micropin substrate 5.
Observe through SEM, obtain micropin size and surface quality information, whether checking micropin size meets the requirements.
Claims (9)
1. a preparation method who is used for the titanium solid microneedles of cutaneous penetration is characterized in that, comprises the steps:
A, the said titanium solid microneedles of processing prepare needed mould;
B, the preliminary treatment of titanium plate;
C, said pretreated titanium plate is positioned between mould, the plastic molding method that adopts little pier to squeeze prepares described titanium solid microneedles.
2. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 1; It is characterized in that; Processing described in the steps A is specially: process plane punch and the die that has the boss characteristic with wire cutting method, then said die and punch are carried out grinding; Be provided with and the measure-alike recess of said titanium solid microneedles on the said die that has a boss characteristic.
3. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 1 is characterized in that, processing described in the steps A is specially: with Laser Processing out-of-plane punch and the die that has characteristic.
4. according to claim 2 or the 3 described preparation methods that are used for the titanium solid microneedles of cutaneous penetration, it is characterized in that said roughness grade protruding, die is 0.2, the upper and lower surfaces depth of parallelism is 0.01mm.
5. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 1; It is characterized in that; Preliminary treatment described in the step B is specially: the titanium plate is machined to is of a size of 2mm * 2mm～3mm * 3mm, roughness grade is 1.6～6.3, clean.
6. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 5 is characterized in that, said cleaning adopts alcohol to clean.
7. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 1 is characterized in that, the plate of titanium described in the step B is pure titanium plate.
8. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 1 is characterized in that, prepared solid microneedles is of a size of diameter 100 μ m among the step C, length 100～200 μ m.
9. the preparation method who is used for the titanium solid microneedles of cutaneous penetration according to claim 1 is characterized in that, pier described in the step C squeezes and realizes that through stretching-machine the pressure of said stretching-machine is 2～10KN.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210316602.9A CN102836936B (en) | 2012-08-30 | 2012-08-30 | Preparation method of solid titanium microneedle for cutaneous penetration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210316602.9A CN102836936B (en) | 2012-08-30 | 2012-08-30 | Preparation method of solid titanium microneedle for cutaneous penetration |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102836936A true CN102836936A (en) | 2012-12-26 |
| CN102836936B CN102836936B (en) | 2014-12-24 |
Family
ID=47364812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210316602.9A Expired - Fee Related CN102836936B (en) | 2012-08-30 | 2012-08-30 | Preparation method of solid titanium microneedle for cutaneous penetration |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102836936B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104959502A (en) * | 2015-05-21 | 2015-10-07 | 上海交通大学 | Ultrasonic vibration-assisted forming process of pure-titanium solid microneedles |
| CN105665713A (en) * | 2016-01-28 | 2016-06-15 | 中山大学 | Porous microneedle array based on metal sintering and manufacturing method thereof |
| CN107073210A (en) * | 2014-09-03 | 2017-08-18 | 新南创新私人有限公司 | Microfluidic device and manufacture |
| CN108836354A (en) * | 2018-04-24 | 2018-11-20 | 中山大学 | A kind of preparation method of microneedle array biosensor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU979009A1 (en) * | 1981-02-18 | 1982-12-07 | Московский Ордена Октябрьской Революции И Ордена Трудового Красного Знамени Институт Стали И Сплавов | Die for forming articles such as panels |
| CN1426332A (en) * | 2000-04-28 | 2003-06-25 | 莫菲克科技股份公司 | Method for manufacturing of plate involving intermediate proforming and final shaping |
| CN101297989A (en) * | 2008-06-19 | 2008-11-05 | 上海交通大学 | Batch preparation of hollow micro-needle based on molding |
| CN201564970U (en) * | 2009-07-31 | 2010-09-01 | 清华大学 | Transdermal medicine supply patch based on micro needle array flexible chip |
-
2012
- 2012-08-30 CN CN201210316602.9A patent/CN102836936B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU979009A1 (en) * | 1981-02-18 | 1982-12-07 | Московский Ордена Октябрьской Революции И Ордена Трудового Красного Знамени Институт Стали И Сплавов | Die for forming articles such as panels |
| CN1426332A (en) * | 2000-04-28 | 2003-06-25 | 莫菲克科技股份公司 | Method for manufacturing of plate involving intermediate proforming and final shaping |
| CN101297989A (en) * | 2008-06-19 | 2008-11-05 | 上海交通大学 | Batch preparation of hollow micro-needle based on molding |
| CN201564970U (en) * | 2009-07-31 | 2010-09-01 | 清华大学 | Transdermal medicine supply patch based on micro needle array flexible chip |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107073210A (en) * | 2014-09-03 | 2017-08-18 | 新南创新私人有限公司 | Microfluidic device and manufacture |
| US10850082B2 (en) | 2014-09-03 | 2020-12-01 | Newsouth Innovations Pty Limited | Microfluidic devices and fabrication |
| CN104959502A (en) * | 2015-05-21 | 2015-10-07 | 上海交通大学 | Ultrasonic vibration-assisted forming process of pure-titanium solid microneedles |
| CN105665713A (en) * | 2016-01-28 | 2016-06-15 | 中山大学 | Porous microneedle array based on metal sintering and manufacturing method thereof |
| CN105665713B (en) * | 2016-01-28 | 2017-11-17 | 中山大学 | One kind is based on porous microneedle array of metal sintering and preparation method thereof |
| CN108836354A (en) * | 2018-04-24 | 2018-11-20 | 中山大学 | A kind of preparation method of microneedle array biosensor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102836936B (en) | 2014-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6928735B2 (en) | Hollow microneedle with beveled opening | |
| AU2012328037B2 (en) | Transdermal delivery of high viscosity bioactive agents | |
| JP5486211B2 (en) | Transdermal administration device and needle forming body used in the device | |
| CN104321105B (en) | Micropin and microneedle array | |
| CN101618250B (en) | Percutaneous dosing paster based on microneedle array flexible chip and preparation method thereof | |
| CN104117137A (en) | Capsule type hollow medicine loading micro-needle array and producing method thereof | |
| CN109045460B (en) | Microneedle patch and preparation method thereof | |
| CN101553275A (en) | High-aspect-ratio microdevices and methods for transdermal delivery and sampling of active substances | |
| JP2007190112A (en) | Microneedle | |
| CN102836936B (en) | Preparation method of solid titanium microneedle for cutaneous penetration | |
| CN201564970U (en) | Transdermal medicine supply patch based on micro needle array flexible chip | |
| CN104888343A (en) | Macromolecule solid micro needle and batched preparing method thereof | |
| JP2015192872A (en) | Microneedle which stays at stratum corneum | |
| JPWO2012057345A1 (en) | Micro needle | |
| CN107913459A (en) | A kind of liquid quantitative conveying device | |
| CN113926072A (en) | Multi-channel microneedle electroporation composite transdermal drug delivery device | |
| CN100579599C (en) | Preparation of micro-needle array injection syringe | |
| CN206660295U (en) | A kind of liquid quantitative conveying device | |
| CN107913460B (en) | Liquid quantitative conveying system | |
| CN111298280A (en) | Soft back microneedle and manufacturing method thereof | |
| CN109689149A (en) | Micropin | |
| JP2015016160A (en) | Microneedle | |
| CN113082500A (en) | Transdermal delivery device and method of manufacture | |
| CN209302014U (en) | A kind of high-intensitive soluble micropin | |
| JP2015231476A (en) | Needle-like body pad |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141224 Termination date: 20190830 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |