CN104706626B - A kind of microneedle patch for being easy to animal vaccine to be administered and preparation method thereof - Google Patents
A kind of microneedle patch for being easy to animal vaccine to be administered and preparation method thereof Download PDFInfo
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- CN104706626B CN104706626B CN201510131662.7A CN201510131662A CN104706626B CN 104706626 B CN104706626 B CN 104706626B CN 201510131662 A CN201510131662 A CN 201510131662A CN 104706626 B CN104706626 B CN 104706626B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0046—Solid microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
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- Engineering & Computer Science (AREA)
- Dermatology (AREA)
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- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to which equipment technical field is administered, it particularly relates to a kind of microneedle patch for being easy to animal vaccine to be administered and preparation method thereof.The microneedle patch includes the soluble micropin needle body of soluble paster substrate and array distribution in paster substrate；The micropin needle body is loaded with drug target on its top, and the material for preparing of the micropin needle body is included by water miscible biodegradable high polymer material.Compared with prior art, what the microneedle patch of the present invention for being easy to animal vaccine to be administered will not cause animal in vaccine inoculation fears reaction, is easy to be administered, easy to operate, it is not necessary to inoculation staff training；One can complete vaccine inoculation work, efficiency high；Complete during vaccine inoculation to be not required to that additionally animal is marked；It is disposable, avoid the possibility of cross-infection；Material therefor is biodegradable, and no medical waste produces；Preparation method simple economy；Product is without stored refrigerated or vacuum preservation etc.；Convenient transportation.
Description
Technical field
The invention belongs to which equipment technical field is administered, it particularly relates to a kind of microneedle patch for being easy to animal vaccine to be administered
Piece and preparation method thereof.
Background technology
Vaccine is the important weapon for controlling a certain communicable disease.Animal vaccine belongs to the model of veterinary biologicses
Farmland, veterinary biologicses are according to immunology principle, utilize microorganism, parasite and its metabolite or immune response product system
Standby a kind of material.This kind of material specializes in the diagnosis of the corresponding disease of animal, treatment or prevention are used.The invention of animal vaccine is with pushing away
Wide prevention well, the generation of control zoonosis make a great contribution with popular for the sound development of China's animal husbandry.
The traditional methods of administration of animal vaccine is parental injection.Intramuscular injection using syringe is that medicine is passed through into thorn
Enter the injection needle of skin drug delivery to musculature, absorbed after diffusion by human body, cause immune response.Conventional injection mode
When vaccinating, there can be many problems：What the pain caused by injection caused animal fears reaction, causes injection inconvenience；
The injury of skin and muscle is caused during injection or causes skin infection；There is the danger of broken needle during injection；There is the possibility of cross-infection
Property；To avoid cross-infection syringe needle from needing to change, the biologic garbage that disposable syringe is brought causes environmental pollution and resource wave
Take；The operation of specification needs to give operating personnel training；Generally require more people during injection to coordinate, efficiency is low；Injection is completed
Be marked afterwards for the animal to be completed to injection of avoiding confusion etc..
Alternative method of vaccination mainly has cutaneous penetration technology at present.Cutaneous penetration is administered in skin surface,
Make medicine to approach constant speed by skin layers, enter body circulation through capillary absorbance and produce whole body or local treatment work
With.Transdermal vaccine administration belongs to non-invasive vaccine administration, dependent on the percutaneous diffusion of medicine.Due to skin surface cutin
The protection and barrier action of layer, the efficiency of drug percutaneous diffusion is very low, has the efficacy data of administration not abundant enough for vaccine.
The content of the invention
In order to solve the above technical problems, the invention provides a kind of microneedle patch for being easy to animal vaccine to be administered and its preparation
Method.
A kind of microneedle patch for being easy to animal vaccine to be administered of the present invention, the microneedle patch include soluble patch
The soluble micropin needle body of piece substrate and array distribution in paster substrate；The micropin needle body is loaded with target on its top
Medicine, the material for preparing of the micropin needle body are included by water miscible biodegradable high polymer material.
It is of the present invention it is a kind of be easy to animal vaccine be administered microneedle patch, the high polymer material be polyvinyl alcohol,
In poly- carboxymethyl cellulose, chondroitin sulfate, PLGA, fibroin, dextrin, hyaluronic acid, gelatin
It is one or more of.
A kind of microneedle patch for being easy to animal vaccine to be administered of the present invention, the animal vaccine are blue ear vaccine, pig
Pestilence seedling, aftosa vaccine, dog cough vaccine, dog hexavaccine, rabies vaccine, Bovine Ephemeral Fever vaccine, Anthrax vaccine, Niu Bulushi
Coli vaccine, sheep pox seedling, pseudorabies vaccines, hog cholera lapinised virus vaccine, swine plague attenuated vaccine, brickpox aluminium hydroxide bacterium
One or more in seedling, piglet red dysentery vaccine, Streptococcus suis aluminium hydroxide vaccine, mycoplasma pneumonia of swine vaccine.
A kind of microneedle patch for being easy to animal vaccine to be administered of the present invention, the material for preparing also include stabilizer,
The stabilizer is one or more of in sucrose, glucose, russule ketone terpene, trehalose, chitosan.
A kind of microneedle patch for being easy to animal vaccine to be administered of the present invention, the load prescription formula of the drug target is will
Medicine is applied to the appearance on micropin needle body top, mixes on micropin needle body top or concentrate on micropin needle body top.
A kind of microneedle patch for being easy to animal vaccine to be administered of the present invention, the microneedle patch is that the length of side is 2-50mm
It is square, share 1-10000 micropin, the spacing between adjacent micropin is 0.2-5mm.
A kind of microneedle patch for being easy to animal vaccine to be administered of the present invention, the micropin needle body are shaped as cone
Or class cone, the micropin needle body length are 200-3000 μm, bottom footpath is 100-1500 μm.
A kind of preparation method of microneedle patch for being easy to animal vaccine to be administered of the present invention, the preparation method include
Following steps：5%-50% high polymer material, 0%-50% stabilizer are mixed with the water of surplus by mass percentage,
Stirring and dissolving at 40 DEG C -100 DEG C；Bubble removing is vacuumized after dissolving completely, obtains the highly concentrated solution of high polymer material/sugar,
Sealing；By measuring requirement, compound concentration scope 0.1-1000mg/ml vaccine solution；Vaccine solution 0.01-5ml is taken to be coated in micro-
On needle mould plate, after vacuumizing 0.5-60min, unnecessary vaccine solution is reclaimed, continues to dry 0.5-60min in vacuum environment, treats
Vaccine solution deposits to micropin top；Take highly concentrated solution 0.01-5ml be coated onto it is above-mentioned be loaded with the microneedles template of vaccine solution,
1-300min is vacuumized again；5-600min is freeze-dried, is stripped after drying, is 15-25 DEG C in temperature, humidity 10%-30%
It is packaged in confined space under RH, obtains microneedle patch.
Compared with prior art, it is of the present invention be easy to animal vaccine be administered microneedle patch in vaccine inoculation not
Animal can be caused fears reaction, is easy to be administered, easy to operate, it is not necessary to being inoculated with staff training；One can complete to be inoculated with
Vaccine works, efficiency high；Complete during vaccine inoculation to be not required to that additionally animal is marked；It is disposable, avoid intersection sense
The possibility of dye；Material therefor is biodegradable, and no medical waste produces；Preparation method simple economy；Product is protected without refrigerating
Deposit or vacuum preserve etc.；Convenient transportation.
Brief description of the drawings
Fig. 1：Microneedles template schematic diagram；Fig. 2：Microneedle patch preparation flow figure；Fig. 3：Microneedle patch schematic diagram；Fig. 4：Micropin
Paster side schematic view；Fig. 5：Microneedle patch micrograph；Fig. 6：Microneedle patch pricks pigskin experiment micrograph.
Embodiment
The microneedle patch of the present invention for being easy to animal vaccine to be administered is done further with reference to specific embodiment
Illustrate, but protection scope of the present invention is not limited to this.
Embodiment 1
A kind of microneedle patch for being easy to animal vaccine to be administered, the microneedle patch include soluble microneedle substrate and solubility
Micropin needle body；The soluble micropin needle body is loaded with drug target, and it, which prepares material, is included by the degradable height of water-soluble biological
Molecular material；The high polymer material is the polyvinyl alcohol that weight average molecular weight is 2000-300000；The material for preparing also includes
Stabilizer, the stabilizer are sucrose；The load prescription formula of the drug target carries medicine for tip；The microneedle patch is that the length of side is
10mm's is square, shares 100 micropins, and the spacing between adjacent micropin is 0.5mm；The micropin needle body is shaped as cone
Or class cone, the micropin needle body length are 700 μm, bottom footpath is 500 μm.
A kind of preparation method of microneedle patch for being easy to animal vaccine to be administered of the present invention, the preparation method include
Following steps：50mg Sulforhodamines are taken (aubergine, to show shiny red under fluorescence irradiation, in this, as the mould of soluble micropin
Type medicine) prepare 1mg/ml Sulforhodamine solution；18g polyvinyl alcohol, 12g sucrose, the mixing of 30g water are taken, is added at 90 DEG C
Thermal agitation, bubble removing is vacuumized after being completely dissolved, it is 30% that polyvinyl alcohol mass fraction, which is made, sucrose quality fraction 20%
Highly concentrated solution；Sulforhodamine solution is coated on microneedles template, after vacuumizing 15min, reclaims unnecessary sulphonyl Luo Dan
Bright solution, continue to dry 20min in vacuum environment, treat Sulforhodamine liquid deposition to micropin top；Highly concentrated solution is covered
Above-mentioned be loaded with the microneedles template of Sulforhodamine solution is covered (to note：Paster substrate can with one piece of the hypomere of micropin needle body into
Shape), unnecessary highly concentrated solution is reclaimed, after vacuumizing 1h again, 20 DEG C of fume hoods is positioned over and dries, by it after curing molding
It is transferred on thickness 1mm paster, is freeze-dried 5h dehydrations again, is 20 DEG C in temperature, the confined space under humidity 20%RH
In be packaged, obtain microneedle patch.
The microneedle patch obtained in the present embodiment can be clearly observed 100 needle bodies under an optical microscope, single
Each micropin in paster has sharp keen tip, size uniformity coniform in class；There is aubergine each micropin needle body front end
Medicine is accumulated, and top color is most deep, and the following part in micropin tip and base part do not have aubergine medicine.In fluorescence microscopy
Micropin tip portion can be clearly observed under mirror shiny red fluorescence, and needle body other parts and micropin base part redfree are glimmering
Light.Above light microscope and fluorescence microscope to phenomenon show that model Sulforhodamine solution is loaded with well
Micropin needle body tip portion, needle body other parts and micropin base part have no medicine.
Embodiment 2
A kind of microneedle patch for being easy to animal vaccine to be administered, the microneedle patch include soluble microneedle substrate and solubility
Micropin needle body；The soluble micropin needle body is loaded with drug target, and it, which prepares material, is included by the degradable height of water-soluble biological
Molecular material；The high polymer material is the polyvinyl alcohol that weight average molecular weight is 2000-300000；The material for preparing also includes
Stabilizer, the stabilizer are russule ketone terpene；The load prescription formula of the drug target carries medicine for tip；The microneedle patch is the length of side
For the square of 10mm, 100 micropins are shared, the spacing between adjacent micropin is 0.7mm；The micropin needle body is shaped as circular cone
Shape or class cone, the micropin needle body length are 700 μm, and bottom footpath is 500 μm.
A kind of preparation method of microneedle patch for being easy to animal vaccine to be administered of the present invention, the preparation method include
Following steps：Pig blue-ear disease vaccine is taken to prepare the vaccine solution that vaccine quality percentage is 0.5% with vaccine adjuvant；18g is taken to gather
Vinyl alcohol, 12g russule ketone terpene, the mixing of 30g water, the heating stirring at 90 DEG C, bubble removing are vacuumized after being completely dissolved, and are made poly-
Vinyl alcohol mass fraction is 30%, and russule ketone terpene mass fraction is 20% highly concentrated solution；Vaccine solution is coated in micropin mould
On plate, after vacuumizing 60min, unnecessary vaccine solution is reclaimed, continues to dry 60min in vacuum environment, treats that vaccine solution deposits
To micropin top；Highly concentrated solution is covered into above-mentioned be loaded with the microneedles template of vaccine solution (to note：The meeting of paster substrate and micropin
One piece of shaping of hypomere of needle body), unnecessary highly concentrated solution is reclaimed, after vacuumizing 5h again, 20 DEG C of fume hoods is positioned over and dries
On, it is transferred into after curing molding on thickness 1mm paster, is freeze-dried 5h dehydrations again, is 25 DEG C in temperature, humidity
It is packaged in confined space under 30%RH, obtains microneedle patch.By comparing, relative to sucrose, glucose, trehalose and shell
Glycan, the russule ketone terpene isolated from smelly russule is used as stabilizer, its vaccine activity of obtained microneedle patch at least will
12.4% is higher by, but its cost is at least higher by 4 times, should not also routinize at present.
Using 10 body weight about 20kg age in the female pigs of 7 weeks or so as experimental subjects, wherein 5 are only used as experiment pair
As vaccine inoculation, 5 are not inoculated with as a control group in addition.The blue-ear disease vaccine microneedle patch obtained in the present embodiment is pressed against
The left buttocks of pig, micropin is vertically pierced into porcine skin as far as possible during pressing, compressing time 2 minutes, make soluble vaccine micropin top
Vaccine be completely discharged in porcine skin, complete percutaneous dosing.Above-mentioned administration is repeated once after two weeks.And before second is administered
From pigtail vein haemospasia and obtain serum within one day, pass through ELISA method and determine the specificity that blue-ear disease vaccine is directed in serum
The titre of IgG1 antibody.Experimental result is the experiment pig that control group is inoculated with by the blue-ear disease vaccine microneedle patch of above-mentioned preparation
The average titer titre of the antibody of specific IgG 1 in serum is 6log2, and the average titer of the antibody of control group specific IgG 1 drips
Spend for 0log2.Illustrate the administration success for being used for pig blue-ear disease vaccine by soluble high-molecular microneedle patch of the present invention,
Significant effect.
Embodiment 3
A kind of microneedle patch for being easy to animal vaccine to be administered, the microneedle patch include soluble microneedle substrate and solubility
Micropin needle body；The soluble micropin needle body is loaded with drug target, and it, which prepares material, is included by the degradable height of water-soluble biological
Molecular material；The high polymer material is the polyvinyl alcohol that weight average molecular weight is 2000-300000；The material for preparing also includes
Stabilizer, the stabilizer are trehalose；The load prescription formula of the drug target carries medicine for tip；The microneedle patch is that the length of side is
10mm's is square, shares 100 micropins, and the spacing between adjacent micropin is 0.6mm；The micropin needle body is shaped as cone
Or class cone, the micropin needle body length are 600 μm, bottom footpath is 500 μm.
A kind of preparation method of microneedle patch for being easy to animal vaccine to be administered of the present invention, the preparation method include
Following steps：Rabies vaccine is taken to prepare the vaccine solution that vaccine quality percentage is 0.5% with vaccine adjuvant；Take 18g polyethylene
Alcohol, 12g trehaloses, the mixing of 30g water, the heating stirring at 90 DEG C, bubble removing are vacuumized after being completely dissolved, polyvinyl alcohol are made
Mass fraction is 30%, and trehalose mass fraction is 20% highly concentrated solution；Vaccine solution is coated on microneedles template, taken out true
After empty 15min, unnecessary vaccine solution is reclaimed, continues to dry 20min in vacuum environment, treats that vaccine solution deposits to micropin top
End；Highly concentrated solution is covered into above-mentioned be loaded with the microneedles template of vaccine solution (to note：Paster substrate can with micropin needle body
One piece of shaping of section), unnecessary highly concentrated solution is reclaimed, after vacuumizing 1h again, 20 DEG C of fume hoods is positioned over and dries, be solidified into
It is transferred into after type on thickness 1mm paster, is freeze-dried 0.5h dehydrations again, is 15 DEG C in temperature, under humidity 10%RH
Confined space in be packaged, obtain microneedle patch.
Using 5 body weight about 10kg age in the female dog of 7 weeks or so as experimental subjects.It is mad by what is obtained in the present embodiment
Canine vaccines microneedle patch is pressed against the left lower abdomen of dog, micropin is vertically pierced into skin as far as possible, compressing time 2 minutes,
The vaccine on soluble vaccine micropin top is completely discharged in dog skin, complete percutaneous dosing.It is repeated once after two weeks above-mentioned
Administration.And from vein haemospasia and serum is obtained second of administration the previous day, determine in serum and be directed to streptococcic specificity
IgG1 antibody average titers.Experimental result is the experimental dog that control group is inoculated with by the rabies vaccine microneedle patch of above-mentioned preparation
The average titer titre of the antibody of specific IgG 1 in serum is 4log2, and the average titer of the antibody of control group specific IgG 1 drips
Spend for 0log2.Illustrate to be administered successfully for rabies vaccine by soluble high-molecular microneedle patch of the present invention, effect shows
Write.
Compliance test result
1st, micropin Skin-test
Prepare the smooth fresh porcine skin not lost hair or feathers in advance, take and obtained above load with fluorescent sample medicine Sulforhodamine
The polyvinyl alcohol micropin paster of solution, micropin tip alignment pigskin top layer is vertically pierced into, the back side of microneedle patch is pressed with hand,
The time of pressing is 2min, the microneedle patch after the effect of then removing, and can be made in light microscope and fluorescence microscopy Microscopic observation
Pigskin after.Can be observed under an optical microscope, the pig skin surfaces after effect have 100 clearly red pin holes, its
His partial skin surface is intact, the aubergine model drug that red pin hole is loaded with for the soluble micropin needle body top of microneedle patch
Sulforhodamine solution is stayed, and is shown the soluble micropin needle body of microneedle patch and can effectively be pierced through pigskin top layer, subcutaneous molten
Solve and the model drug Sulforhodamine solution that soluble micropin top is loaded with is discharged among pigskin.Likewise, glimmering
It can be observed under light microscope, the pig skin surfaces after effect have 100 pin holes for clearly sending red fluorescence, and other parts show
Show black, illustrate the aubergine model drug sulphur that the pin hole of red fluorescence is loaded with for the soluble micropin needle body top of microneedle patch
Acyl rhodamine liquor is stayed, and is shown the soluble micropin needle body of microneedle patch and can effectively be pierced through pigskin top layer, is subcutaneously dissolving
And the model drug Sulforhodamine solution that soluble micropin top is loaded with is discharged among pigskin.
2nd, the subcutaneous dissolution kinetics of micropin
200 microneedle patch, each microneedle patch area 1cm are prepared according to the step in embodiment 12Have 10 × 10 it is micro-
Pin, 700 μm of needle body length, spacing 0.5mm；The quality that each microneedle patch loads with model drug Sulforhodamine solution is
0.2mg.Every ten one group of microneedle patch, 20 groups altogether.According to the Skin-test step in embodiment 2, by above-mentioned microneedle patch
The pigskin of same experimental conditions is inserted, every group of micropin compressing time is different, is removed after 1 group of compressing time 10s, 2 groups of compressing times
It is 20s, 3 groups of compressing times are 30s, the like, the 20th group of compressing time is 200s.After skin experiment, detection is each
Effective administration rate on porcine skin after piece administration, i.e., the medicine deposited on skin account for the percentage of the total drugloading rate of microneedle patch
Than as a result as shown in table 1.
Table 1：Effective administration rate of different compressing times
| Administration time/s | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
| Effective administration rate/% | 30.5 | 42.1 | 48.3 | 59.3 | 65.7 | 68.9 | 72.7 | 74 | 77.3 | 79.6 |
| Administration time/s | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 |
| Effective administration rate/% | 83.6 | 86.8 | 90.2 | 92.9 | 94.2 | 95.9 | 97.6 | 98.2 | 99 | 99.6 |
Compared with prior art, the microneedle patch of the present invention for being easy to animal vaccine to be administered will not in vaccine inoculation
Cause animal fears reaction, is easy to be administered, easy to operate, it is not necessary to being inoculated with staff training；One can complete to be inoculated with epidemic disease
Seedling works, efficiency high；Complete during vaccine inoculation to be not required to that additionally animal is marked；It is disposable, avoid cross-infection
Possibility；Material therefor is biodegradable, and no medical waste produces；Preparation method simple economy；Product is without stored refrigerated
Or vacuum preservation etc.；Convenient transportation.
Claims (3)
1. it is a kind of be easy to animal vaccine be administered microneedle patch preparation method, it is characterised in that the preparation method include with
Lower step：5%-50% high polymer material, 0%-50% stabilizer are mixed with the water of surplus by mass percentage, 40 DEG C-
Stirring and dissolving at 100 DEG C；Bubble removing is vacuumized after dissolving completely, obtains highly concentrated solution, is sealed；By measuring requirement, prepare
Concentration range 0.1-1000mg/ml vaccine solution；Take vaccine solution 0.01-5ml to be coated on microneedles template, vacuumize 0.5-
After 60min, unnecessary vaccine solution is reclaimed, continues to dry 0.5-60min in vacuum environment, treats that vaccine solution deposits to micropin top
End；Take highly concentrated solution 0.01-5ml be coated onto it is above-mentioned be loaded with the microneedles template of vaccine solution, vacuumize 1-300min again；It is cold
Dry 5-600min is freezed, is stripped after drying, is 15-25 DEG C in temperature, is sealed in the confined space under humidity 10%-30%RH
Dress, obtains microneedle patch；
The microneedle patch includes the soluble micropin needle body of soluble paster substrate and array distribution in paster substrate；
The micropin needle body is loaded with drug target on its top, and the micropin needle body prepares material including water miscible biodegradable
High polymer material；The stabilizer is one or more of in sucrose, russule ketone terpene, trehalose；The high polymer material is poly- second
It is one or more of in enol, chondroitin sulfate, hyaluronic acid；The animal vaccine is blue ear vaccine or rabies vaccine.
2. preparation method according to claim 1, it is characterised in that the microneedle patch is the side that the length of side is 2-50mm
Shape, 1-10000 micropin is shared, the spacing between adjacent micropin is 0.2-5mm.
3. preparation method according to claim 1, it is characterised in that the micropin needle body is shaped as cone or class circle
Taper, the micropin needle body length are 200-3000 μm, and bottom footpath is 100-1500 μm.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510131662.7A CN104706626B (en) | 2015-03-25 | 2015-03-25 | A kind of microneedle patch for being easy to animal vaccine to be administered and preparation method thereof |
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| CN201510131662.7A CN104706626B (en) | 2015-03-25 | 2015-03-25 | A kind of microneedle patch for being easy to animal vaccine to be administered and preparation method thereof |
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| CN105078880A (en) * | 2015-09-12 | 2015-11-25 | 北京化工大学 | Macromolecular soluble microneedle used for cutaneous penetration of polypeptide and protein medicines and preparation method of macromolecular soluble microneedle |
| KR101610598B1 (en) | 2015-09-21 | 2016-04-07 | 비엔엘바이오테크 주식회사 | FLEXIBLE MICRONEEDLE FOR DENTAL MATERIAL DELIVERY AND THE MANUFACTURING METHOD Of THE SAME |
| CN105726458B (en) * | 2016-01-29 | 2018-09-28 | 广州新济药业科技有限公司 | Responsive to temperature type solubility micropin and preparation method thereof |
| CN105596287B (en) * | 2016-02-04 | 2018-09-18 | 广州新济药业科技有限公司 | Active divergence type solubility micropin and preparation method thereof |
| CN106039552A (en) * | 2016-05-30 | 2016-10-26 | 北京化工大学 | Bubble-type microneedle and preparation method therefor |
| CN106422045A (en) * | 2016-09-05 | 2017-02-22 | 中国科学院理化技术研究所 | Flexible slow-release micro-needle patch and preparation method thereof |
| CN106474620A (en) * | 2016-09-22 | 2017-03-08 | 北京化工大学 | A kind of polymer micro needle of medicine controlled release, preparation method and microneedle patch |
| TWI633901B (en) * | 2017-05-16 | 2018-09-01 | 怡定興科技股份有限公司 | Medical beauty microneedle patch manufacturing method |
| CA3065371A1 (en) | 2017-06-13 | 2018-12-20 | Vaxxas Pty Limited | Quality control of substrate coatings |
| CN108379573B (en) * | 2018-03-26 | 2020-10-16 | 中国医学科学院生物医学工程研究所 | Pertussis vaccine microneedle array and preparation method thereof |
| CN110680909A (en) * | 2018-07-04 | 2020-01-14 | 辽宁成大生物股份有限公司 | Quick-release type-b haemophilus influenzae conjugate vaccine soluble microneedle patch and preparation method thereof |
| CN110840822B (en) * | 2018-07-26 | 2021-05-18 | 华中科技大学 | Method for preparing porous polymer microneedle and application thereof |
| CN110870943A (en) * | 2018-08-31 | 2020-03-10 | 中科微针（北京）科技有限公司 | Implantable two-section type microneedle patch and preparation method thereof |
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| CN114533649A (en) * | 2022-01-05 | 2022-05-27 | 华中科技大学同济医学院附属协和医院 | Separable microneedle array capable of drug delivery and in-situ labeling and preparation method thereof |
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