CN102836936B - Preparation method of solid titanium microneedle for cutaneous penetration - Google Patents
Preparation method of solid titanium microneedle for cutaneous penetration Download PDFInfo
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- CN102836936B CN102836936B CN201210316602.9A CN201210316602A CN102836936B CN 102836936 B CN102836936 B CN 102836936B CN 201210316602 A CN201210316602 A CN 201210316602A CN 102836936 B CN102836936 B CN 102836936B
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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 for the preparation method of the titanium solid microneedles of cutaneous penetration.
Background technology
Administering mode main is at present oral and injection.Oral drugs, due to the first pass effect of the absorption in stomach and liver, have impact on 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 obvious pain to patient, and also need professional to operate, the local damage that even there will be skin even infects simultaneously, the inadaptable long-term and accurate sustained-release administration controlled of needs.
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 of percutaneous drug absorption.People have employed multiple physicochemical method to promote the percutaneous absorbtion of medicine for this reason.The such as physical method such as electro-ionic osmosis, electroporation, percutaneous absorbtion Be very effective, but most automatically controlled property equipment needing dependence to have energy source, comparatively large to the damage of skin, and medication person cannot independently use voluntarily.Chemical enhancers then to the percutaneous absorbtion DeGrain of macromolecular drug, and generally has comparatively strong and stimulating.
Comparatively speaking, microneedle cutaneous is a kind of administering mode between hypodermic injection and transdermal patch.Micropin also belongs to physical enhancement technology, that the size that is made by distinct methods is in micron-sized acicular texture, by carrying out painless pore process to skin, produce small duct to improve the permeability of medicine at keratoderma, thus greatly improve the especially macromolecular percutaneous absorbtion amount of medicine; Simultaneously because tip dimensions is less, skin is not almost damaged, and easy to usely do not need professional to operate, be applicable to individual independent operation.
Micropin has solid needle and hollow needle two type.In use, following administering mode is adopted usually for solid microneedles: microneedle array is first thrust skin and forms cavity by (1), then pastille is sticked on therapentic part; (2) after the coated medicament of microneedle array surface, continuous skin release is thrust.Empty micropin is normally adopted to the mode delivering medicament of microinjection, be applicable to liquid and that therapeutic dose requirement is larger medicine.In addition, empty micropin can also be used for extraction and the detection of carrying out trace body fluid through skin.
The material manufacturing micropin has polymer, monocrystalline silicon and metal etc.The outstanding problem that existing polymer micro needle exists is that the strength of materials is inadequate, not easily pierces through the cuticula of skin.Monocrystalline silicon material is hard, easy brittle failure, although there is bibliographical information, it has good biocompatibility also not belong to conventional medical material now, whether can be applicable to biological medicine aspect and need further textual criticism.Metal, for the manufacture of acupuncture needle or existing thousand one-hundred-year histories of injection needle, is therefore applicable to manufacturing low cost, micropin in enormous quantities.
Summary of the invention
The object of the invention is to the deficiency overcoming the existence of above-mentioned prior art, provide a kind of preparation method of the pure titanium solid microneedles for cutaneous penetration, the method application plastic forming technology, strengthen the usability of micropin, reduce technology difficulty, be easy to realize batch production.
The object of the invention is to be achieved through the following technical solutions:
The present invention relates to a kind of preparation method of the titanium solid microneedles for cutaneous penetration, comprise the steps:
A, process described titanium solid microneedles preparation required for mould;
B, the pretreatment of titanium plate;
C, be positioned between mould by described pretreated titanium plate, the method adopting pier to squeeze prepares described titanium solid microneedles.
Application scanning electron microscope is observed obtaining micropin, measures micropin size and whether reaches expection requirement.
Preferably, described in steps A, processing is specially: process plane punch and the die with boss feature with wire cutting method, then carry out grinding to described die and punch; The described die with boss feature is provided with the recess measure-alike with described titanium solid microneedles.
Preferably, described in steps A, processing is specially: with Laser Processing out-of-plane punch and the characteristic die of band.
Preferably, the roughness grade of described punch and matrix is 0.2, and upper and lower surface depth of parallelism grade is 0.01mm.
Preferably, pretreatment described in step B is specially: be machined to by titanium plate and be of a size of 2mm × 2mm ~ 3mm × 3mm, roughness grade is 1.6 ~ 6.3, cleaning.
Preferably, described cleaning adopts alcohol to clean.
Preferably, the plate of titanium described in step B is Titanium board.
Preferably, prepared in step C solid microneedles is of a size of diameter 100 μm, length 100 ~ 200 μm.
Preferably, pier described in step C is squeezed and is realized by stretching-machine, and the pressure of described stretching-machine is 2 ~ 10KN.
Compared with prior art, the present invention has following beneficial effect:
1, the present invention prepares the method for micropin is Plastic Forming, is to obtain required micropin shape by the flowing of material, does not have material unaccounted-for (MUF); Meanwhile, this preparation method utilizes die forming to improve production efficiency, reduces technology difficulty, is conducive to batch production.
2, titanium alloy or pure titanium is adopted to improve the biocompatibility of micropin as material; Adopt syringe needle and substrate one, improve the reliability that micropin uses.
Accompanying drawing explanation
Fig. 1 is the present invention's punch-die schematic diagram used;
The structural representation of the titanium solid microneedles of Fig. 2 prepared by the present invention;
In figure, 1 is punch, and 2 is titanium plate, and 3 is die, and 4 is micropin, and 5 is microneedle substrate.
Detailed description of the invention
Below in conjunction with specific embodiments and the drawings, the present invention is described in detail.Following examples will contribute to those skilled in the art and understand the present invention further, but not limit the present invention in any form.It should be pointed out that to those skilled in the art, without departing from the inventive concept of the premise, some distortion and improvement can also be made.These all belong to protection scope of the present invention.
embodiment 1
The preparation method of the titanium solid microneedles for cutaneous penetration of the present embodiment, specifically comprises the steps:
1, Hardmetal materials is adopted, plane punch 1 required for the titanium solid microneedles processing as shown in Figure 1 with wire cutting method and the die 3 with boss feature, then grinding is carried out to described die 3 and punch 1, the roughness grade making described punch and matrix 1,3 is 0.2, and the upper and lower surface depth of parallelism is 0.01mm; Describedly be provided with the recess measure-alike with described titanium solid microneedles with on the die 3 of boss feature; Solid microneedles is of a size of diameter 100 μm, length 150 ~ 200 μm;
2, Titanium board pretreatment: by linear cutter, is machined to Titanium board and is of a size of 2mm × 2mm, roughness grade is 1.6, utilize alcohol to clean to the Titanium board 2 processed;
3, be arranged on cupping machine by convex concave mould, being placed on by pretreated Titanium board 2 between convex concave mould 1,3, is 2 ~ 3KN by the pressure of restrained stretching machine, carries out pier and squeezes, stop after the power set by arrival; Titanium board after being squeezed by pier takes out, and namely obtains the pure titanium solid microneedles of required form, as shown in Figure 2, is included as micropin 4 and microneedle substrate 5.
Observed by 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 for cutaneous penetration of the present embodiment, specifically comprises the steps:
1, Hardmetal materials is adopted, plane punch 1 required for the titanium solid microneedles processing as shown in Figure 1 with wire cutting method and the die 3 with boss feature, then grinding is carried out to described die 3 and punch 1, the roughness grade making described punch and matrix 1,3 is 0.2, and the upper and lower surface depth of parallelism is 0.01mm; Describedly be provided with the recess measure-alike with described titanium solid microneedles with on the die 3 of boss feature; Solid microneedles is of a size of diameter 100 μm, length 100 ~ 150 μm;
2, titanium alloy sheet pretreatment: by linear cutter, is machined to titanium alloy sheet and is of a size of 3mm × 3mm, roughness grade is 6.3, utilize alcohol to clean to the titanium alloy sheet 2 processed;
3, be arranged on cupping machine by convex concave mould, being placed on by pretreated titanium alloy sheet 2 between convex concave mould 1,3, is 10KN by the pressure of restrained stretching machine, carries out pier and squeezes, stop after the power set by arrival; Titanium alloy sheet after being squeezed by pier takes out, and namely obtain the titanium solid microneedles of required form, after thinning plate is substrate, as shown in Figure 2, is included as micropin 4 and microneedle substrate 5.
Observed by SEM, obtain micropin size and surface quality information, whether checking micropin size meets the requirements.
Claims (4)
1., for a preparation method for the titanium solid microneedles of cutaneous penetration, it is characterized in that, comprise the steps:
A, process described titanium solid microneedles preparation required for mould; Described processing is specially: with wire cutting method processing or Laser Processing out-of-plane punch and the die with boss feature, then carry out grinding to described die and punch; The described die with boss feature is provided with the recess measure-alike with described titanium solid microneedles; The roughness grade of described punch and matrix is 0.2, and the upper and lower surface depth of parallelism is 0.01mm;
B, the pretreatment of titanium plate; Described pretreatment is specially: be machined to by titanium plate and be of a size of 2mm × 2mm ~ 3mm × 3mm, roughness grade is 1.6 ~ 6.3, cleaning;
C, be positioned between mould by described pretreated titanium plate, the plastic molding method adopting micro-pier to squeeze prepares described titanium solid microneedles; Described pier is squeezed and is realized by stretching-machine, and the pressure of described stretching-machine is 2 ~ 10KN.
2. the preparation method of the titanium solid microneedles for cutaneous penetration according to claim 1, is characterized in that, described cleaning adopts alcohol to clean.
3. the preparation method of the titanium solid microneedles for cutaneous penetration according to claim 1, is characterized in that, the plate of titanium described in step B is Titanium board.
4. the preparation method of the titanium solid microneedles for cutaneous penetration according to claim 1, is characterized in that, solid microneedles prepared in step C is of a size of diameter 100 μm, length 100 ~ 200 μm.
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| 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 |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210316602.9A CN102836936B (en) | 2012-08-30 | 2012-08-30 | Preparation method of solid titanium microneedle for cutaneous penetration |
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| Publication Number | Publication Date |
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| CN102836936A CN102836936A (en) | 2012-12-26 |
| CN102836936B true CN102836936B (en) | 2014-12-24 |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3188775A4 (en) | 2014-09-03 | 2018-09-05 | 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 |
| 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 |
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 |
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