CN104706626A - Microneedle patch convenient for administrating animal vaccine and preparation method of microneedle patch - Google Patents
Microneedle patch convenient for administrating animal vaccine and preparation method of microneedle patch Download PDFInfo
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- CN104706626A CN104706626A CN201510131662.7A CN201510131662A CN104706626A CN 104706626 A CN104706626 A CN 104706626A CN 201510131662 A CN201510131662 A CN 201510131662A CN 104706626 A CN104706626 A CN 104706626A
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- vaccine
- microneedle patch
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- micropin
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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
Abstract
The invention belongs to the technical field of administration equipment and particularly relates to a microneedle patch convenient for administrating animal vaccine and a preparation method of the microneedle patch. The microneedle patch comprises a soluble patch substrate and soluble microneedle bodies in array distribution on the patch substrate, wherein the microneedle bodies carry a targeted medicine at the top ends. The preparation material of the microneedle bodies comprises a water soluble degradable macromolecular material. Compared with the prior art, the microneedle patch convenient for administrating animal vaccine provided by the invention does not cause fear responses of animals when a vaccine is inoculated, is easy to administrate and convenient to operate, and inoculating personnel needs not to be trained; the vaccine inoculating work can be completed by a single person, so that the efficiency is high; the animal is not marked in an extra manner when the vaccine is inoculated; the microneedle patch is used at one time, so that the probability of cross infection is avoided; the material used is biodegradable and free of medical wastes; the microneedle patch is simple and economic in preparation method, free of cold preservation or vacuum storage and the like and convenient to transport.
Description
Technical field
The invention belongs to administration device technical field, specifically, relate to and be a kind ofly convenient to microneedle patch of animal vaccine administration and preparation method thereof.
Background technology
Vaccine is the important weapon controlling a certain infectious disease.Animal vaccine belongs to the category of veterinary biologics, and veterinary biologics is according to immunology principle, utilizes a class material prepared by microorganism, parasite and metabolite thereof or immunne response product.This kind of material specializes in the use of the diagnosis of the corresponding disease of animal, treatment or prevention.The invention of animal vaccine well prevents with popularization, controls zoonotic Occurrence & epidemic, for the sound development of China's animal husbandry makes a great contribution.
The traditional methods of administration of animal vaccine is parental injection.Use the intramuscular injection of syringe be by medicine by the entry needle that thrusts skin drug conveying to muscular tissue, absorbed by human body after diffusion, cause immunoreation.During conventional injection mode vaccinate, a lot of problem can be there is: fear reaction due to what inject that the pain that causes causes animal, cause injection inconvenience; Cause the injury of skin and muscle during injection or cause skin infection; The danger of broken needle is had during injection; There is the probability of cross infection; Need for avoiding cross infection syringe needle to change, the biologic garbage that disposable syringe brings causes environmental pollution and the wasting of resources; The action need of specification gives training operator; Many people are generally needed to coordinate during injection, inefficiency; Labelling etc. to be carried out to the animal of having injected for avoiding confusion after having injected.
Method of vaccination alternative at present mainly contains transdermal administration technology.Transdermal administration is in skin surface administration, make medicine with close to constant speed by skin layers, enter body circulation through capillary absorbance and produce whole body or local therapeutic effects.Transdermal vaccine administration belongs to non-invasive vaccine administration, depends on the percutaneous diffusion of medicine.Due to the cuticular protection of skin surface and barrier action, the efficiency of drug percutaneous diffusion is very low, has the efficacy data of administration abundant not for vaccine.
Summary of the invention
For solving the problems of the technologies described above, the invention provides and a kind ofly be convenient to microneedle patch of animal vaccine administration and preparation method thereof.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, described microneedle patch comprises the paster substrate of solubility and the array distribution micropin needle body in the suprabasil solubility of paster; Described micropin needle body is loaded with drug target on its top, and the material of preparing of this micropin needle body comprises by water miscible biodegradable macromolecular material.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, described macromolecular material is one or more in polyvinyl alcohol, poly-carboxymethyl cellulose, chondroitin sulfate, PLGA, fibroin, dextrin, hyaluronic acid, gelatin.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, described animal vaccine is blue ear vaccine, swine Fever Vaccine, foot-and-mouth disease vaccine, dog cough vaccine, dog hexavaccine, rabies vaccine, Bovine Ephemeral Fever vaccine, Anthrax vaccine, cattle brucella vaccine, one or more in sheep pox Seedling, pseudorabies vaccines, hog cholera lapinised virus vaccine, pig lung plague attenuated vaccine, pig erysipelas aluminium hydroxide vaccine, piglet red dysentery vaccine, Streptococcus suis aluminium hydroxide vaccine, mycoplasma pneumoniae of swine vaccine.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, described material of preparing also comprises stabilizing agent, and this stabilizing agent is one or more in sucrose, glucose, Russula ketone terpene, trehalose, chitosan.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, the medicine carrying mode of described drug target be medicine is spread upon micropin needle body top appearance, mix on micropin needle body top or concentrate on micropin needle body top.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, described microneedle patch is the length of side is the square of 2-50mm, and total 1-10000 micropin, the spacing between adjacent micropin is 0.2-5mm.
A kind of microneedle patch being convenient to animal vaccine administration of the present invention, the shape of described micropin needle body is that taper shape or class are conical, and this micropin needle body length is 200-3000 μm, and footpath, the end is 100-1500 μm.
A kind of preparation method being convenient to the microneedle patch of animal vaccine administration of the present invention, described preparation method comprises the following steps: the macromolecular material of 5%-50%, the stabilizing agent of 0%-50% are mixed with the water of surplus by mass percentage, stirring and dissolving at 40 DEG C-100 DEG C; Dissolve evacuation completely and remove bubble, obtain the highly concentrated solution of macromolecular material/sugar, sealing; By measuring requirement, the vaccine solution of compound concentration scope 0.1-1000mg/ml; Getting vaccine solution 0.01-5ml is coated on microneedles template, after evacuation 0.5-60min, reclaims unnecessary vaccine solution, continues, at the dry 0.5-60min of vacuum environment, to treat that vaccine solution deposits to micropin top; Get highly concentrated solution 0.01-5ml to be coated onto and to be above-mentionedly loaded with on the microneedles template of vaccine solution, evacuation 1-300min again; Lyophilization 5-600min, the demoulding after dry, encapsulates in the confined space under temperature is 15-25 DEG C, humidity 10%-30%RH, obtains microneedle patch.
Compared with prior art, what the microneedle patch being convenient to animal vaccine administration of the present invention can not cause animal when vaccination fears reaction, is easy to administration, easy to operate, does not need inoculation staff training; Singlely can complete vaccination work, efficiency is high; Do not need when completing vaccination additionally to carry out labelling to animal; Single use, avoids the probability of cross infection; Material therefor is biodegradable, produces without medical waste; Manufacture method simple economy; Product is without the need to stored refrigerated or vacuum preservation etc.; Convenient transportation.
Accompanying drawing explanation
Fig. 1: microneedles template schematic diagram; Fig. 2: microneedle patch preparation flow figure; Fig. 3: microneedle patch schematic diagram; Fig. 4: microneedle patch side schematic view; Fig. 5: microneedle patch microgram; Fig. 6: microneedle patch pricks Corii Sus domestica experiment microgram.
Detailed description of the invention
Below in conjunction with specific embodiment, the microneedle patch being convenient to animal vaccine administration of the present invention is described further, but protection scope of the present invention is not limited to this.
Embodiment 1
Be convenient to a microneedle patch for animal vaccine administration, described microneedle patch comprises solubility microneedle substrate and solubility micropin needle body; Described solubility micropin needle body is loaded with drug target, and it is prepared material and comprises by the degradable macromolecular material of water-soluble biological; The polyvinyl alcohol of described macromolecular material to be weight average molecular weight be 2000-300000; Described material of preparing also comprises stabilizing agent, and this stabilizing agent is sucrose; The medicine carrying mode of described drug target is most advanced and sophisticated medicine carrying; Described microneedle patch is the length of side is the square of 10mm, and have 100 micropins, the spacing between adjacent micropin is 0.5mm; The shape of described micropin needle body is that taper shape or class are conical, and this micropin needle body length is 700 μm, and footpath, the end is 500 μm.
A kind of preparation method being convenient to the microneedle patch of animal vaccine administration of the present invention, described preparation method comprises the following steps: get 50mg Sulforhodamine (aubergine, redness is highlighted, the model drug in this, as solubility micropin under fluorescence irradiates) prepare the Sulforhodamine solution of 1mg/ml; Get 18g polyvinyl alcohol, 12g sucrose, the mixing of 30g water, heated and stirred at 90 DEG C, after dissolving completely, evacuation removes bubble, and obtained polyvinyl alcohol mass fraction is 30%, and sucrose quality fraction is the highly concentrated solution of 20%; Sulforhodamine solution is coated on microneedles template, after evacuation 15min, reclaims unnecessary Sulforhodamine solution, continue, at the dry 20min of vacuum environment, to treat that Sulforhodamine solution deposition is to micropin top; Highly concentrated solution is covered (note: paster substrate can be shaped with the hypomere one piece of micropin needle body) on the above-mentioned microneedles template being loaded with Sulforhodamine solution, reclaim unnecessary highly concentrated solution, again after evacuation 1h, be positioned in 20 DEG C of fume hood dryings, transferred on the paster of thickness 1mm after curing molding, lyophilization 5h dewaters again, is 20 DEG C in temperature, encapsulate in confined space under humidity 20%RH, obtain microneedle patch.
The microneedle patch obtained in the present embodiment clearly can observe 100 needle bodies under an optical microscope, and each micropin in single paster has sharp keen tip, coniform in class, size uniformity; Each micropin needle body front end has aubergine medicine to pile up, and top color is the darkest, and part and base part do not have aubergine medicine below at micropin tip.Clearly can observe micro needlepoint end portion and have shiny red fluorescence under fluorescence microscope, other parts of needle body and micropin base part redfree fluorescence.Above optical microscope and fluorescence microscope to phenomenon show, model Sulforhodamine solution has loaded with micropin needle body tip portion well, and other parts of needle body and micropin base part there is no medicine.
Embodiment 2
Be convenient to a microneedle patch for animal vaccine administration, described microneedle patch comprises solubility microneedle substrate and solubility micropin needle body; Described solubility micropin needle body is loaded with drug target, and it is prepared material and comprises by the degradable macromolecular material of water-soluble biological; The polyvinyl alcohol of described macromolecular material to be weight average molecular weight be 2000-300000; Described material of preparing also comprises stabilizing agent, and this stabilizing agent is Russula ketone terpene; The medicine carrying mode of described drug target is most advanced and sophisticated medicine carrying; Described microneedle patch is the length of side is the square of 10mm, and have 100 micropins, the spacing between adjacent micropin is 0.7mm; The shape of described micropin needle body is that taper shape or class are conical, and this micropin needle body length is 700 μm, and footpath, the end is 500 μm.
A kind of preparation method being convenient to the microneedle patch of animal vaccine administration of the present invention, described preparation method comprises the following steps: get pig blue-ear disease vaccine and vaccine adjuvant prepares the vaccine solution that vaccine quality percent is 0.5%; Get 18g polyvinyl alcohol, 12g Russula ketone terpene, the mixing of 30g water, heated and stirred at 90 DEG C, after dissolving completely, evacuation removes bubble, and obtained polyvinyl alcohol mass fraction is 30%, and Russula ketone terpene mass fraction is the highly concentrated solution of 20%; Vaccine solution is coated on microneedles template, after evacuation 60min, reclaims unnecessary vaccine solution, continue, at the dry 60min of vacuum environment, to treat that vaccine solution deposits to micropin top; Highly concentrated solution is covered above-mentioned being loaded with on the microneedles template of vaccine solution (note: paster substrate can be shaped with the hypomere one piece of micropin needle body), reclaim unnecessary highly concentrated solution, again after evacuation 5h, be positioned in 20 DEG C of fume hood dryings, transferred on the paster of thickness 1mm after curing molding, lyophilization 5h dewaters again, is 25 DEG C in temperature, encapsulate in confined space under humidity 30%RH, obtain microneedle patch.Through comparing, relative to sucrose, glucose, trehalose and chitosan, adopt isolated Russula ketone terpene from smelly Russula to be stabilizing agent, its vaccine activity of obtained microneedle patch at least will exceed 12.4%, but its cost at least exceeds 4 times, also should not routinize at present.
The age being about 20kg with 10 body weight, wherein 5 as experimental subject vaccination, does not inoculate as a control group for other 5 the female pigs of about 7 weeks for experimental subject.By the blue-ear disease vaccine microneedle patch obtained in the present embodiment by the left buttocks being pressed in pig, make micropin vertically thrust porcine skin during pressing, compressing time 2 minutes as far as possible, the vaccine on soluble vaccine micropin top is discharged in porcine skin completely, completes percutaneous dosing.Above-mentioned administration is repeated once after two weeks.And obtain serum in second time administration the previous day from pigtail vein haemospasia, measure the titre for specific IgG 1 antibody of blue-ear disease vaccine in serum by ELISA method.Experimental result is, the average titer titre of specific IgG 1 antibody in the experiment pig serum that matched group is inoculated by the blue-ear disease vaccine microneedle patch of above-mentioned preparation is 6log2, and the average titer titre of matched group specific IgG 1 antibody is 0log2.The administration success being used for pig blue-ear disease vaccine by soluble high-molecular microneedle patch of the present invention is described, Be very effective.
Embodiment 3
Be convenient to a microneedle patch for animal vaccine administration, described microneedle patch comprises solubility microneedle substrate and solubility micropin needle body; Described solubility micropin needle body is loaded with drug target, and it is prepared material and comprises by the degradable macromolecular material of water-soluble biological; The polyvinyl alcohol of described macromolecular material to be weight average molecular weight be 2000-300000; Described material of preparing also comprises stabilizing agent, and this stabilizing agent is trehalose; The medicine carrying mode of described drug target is most advanced and sophisticated medicine carrying; Described microneedle patch is the length of side is the square of 10mm, and have 100 micropins, the spacing between adjacent micropin is 0.6mm; The shape of described micropin needle body is that taper shape or class are conical, and this micropin needle body length is 600 μm, and footpath, the end is 500 μm.
A kind of preparation method being convenient to the microneedle patch of animal vaccine administration of the present invention, described preparation method comprises the following steps: get rabies vaccine and vaccine adjuvant prepares the vaccine solution that vaccine quality percent is 0.5%; Get 18g polyvinyl alcohol, 12g trehalose, the mixing of 30g water, heated and stirred at 90 DEG C, after dissolving completely, evacuation removes bubble, and obtained polyvinyl alcohol mass fraction is 30%, and trehalose mass fraction is the highly concentrated solution of 20%; Vaccine solution is coated on microneedles template, after evacuation 15min, reclaims unnecessary vaccine solution, continue, at the dry 20min of vacuum environment, to treat that vaccine solution deposits to micropin top; Highly concentrated solution is covered above-mentioned being loaded with on the microneedles template of vaccine solution (note: paster substrate can be shaped with the hypomere one piece of micropin needle body), reclaim unnecessary highly concentrated solution, again after evacuation 1h, be positioned in 20 DEG C of fume hood dryings, transferred on the paster of thickness 1mm after curing molding, lyophilization 0.5h dewaters again, is 15 DEG C in temperature, encapsulate in confined space under humidity 10%RH, obtain microneedle patch.
The age being about 10kg with 5 body weight the female dog of about 7 weeks for experimental subject.By the rabies vaccine microneedle patch that obtains in the present embodiment by the left lower abdomen being pressed in dog, make micropin vertically thrust skin during pressing, compressing time 2 minutes as far as possible, the vaccine on soluble vaccine micropin top is discharged in dog skin completely, completes percutaneous dosing.Above-mentioned administration is repeated once after two weeks.And obtain serum in second time administration the previous day from vein haemospasia, to measure in serum for streptococcic specific IgG 1 antibody average titer.Experimental result is, the average titer titre of specific IgG 1 antibody in the experimental dog serum that matched group is inoculated by the rabies vaccine microneedle patch of above-mentioned preparation is 4log2, and the average titer titre of matched group specific IgG 1 antibody is 0log2.Illustrate by soluble high-molecular microneedle patch of the present invention for rabies vaccine administration success, Be very effective.
Compliance test result
1, micropin tuerculoderma
Prepare the smooth fresh porcine skin do not lost hair or feathers in advance, get the above-mentioned obtained polyvinyl alcohol micropin paster loading with fluorescent sample medicine Sulforhodamine solution, micropin tip alignment Corii Sus domestica top layer is vertically thrust, with the back side of hands pressing microneedle patch, the time of pressing is 2min, then the microneedle patch after effect is taken off, can Corii Sus domestica after optical microscope and the effect of fluorescence microscopy Microscopic observation.Can be observed under an optical microscope, pig skin surfaces after effect has 100 pin holes red clearly, other partial skin surfaces are intact, the aubergine model drug Sulforhodamine solution that the solubility micropin needle body top that red pin hole is microneedle patch is loaded with is stayed, show that the solubility micropin needle body of microneedle patch can pierce through Corii Sus domestica top layer effectively, the model drug Sulforhodamine solution loaded with in subcutaneous dissolving and by solubility micropin top is discharged among Corii Sus domestica.Same, can be observed under fluorescence microscope, pig skin surfaces after effect has 100 pin holes clearly sending red fluorescence, other parts display black, illustrate that the aubergine model drug Sulforhodamine solution loaded with on the solubility micropin needle body top that the pin hole of red fluorescence is microneedle patch is stayed, show that the solubility micropin needle body of microneedle patch can pierce through Corii Sus domestica top layer effectively, the model drug Sulforhodamine solution loaded with in subcutaneous dissolving and by solubility micropin top is discharged among Corii Sus domestica.
2, the subcutaneous dissolution kinetics of micropin
200 microneedle patch are prepared, each microneedle patch area 1cm according to the step in embodiment 1
2there are 10 × 10 micropins, needle body length 700 μm, spacing 0.5mm; The quality that each microneedle patch loads with model drug Sulforhodamine solution is 0.2mg.Every ten microneedle patch one group, 20 groups altogether.According to the tuerculoderma step in embodiment 2, above-mentioned microneedle patch is inserted the Corii Sus domestica of same experimental conditions, often organize micropin compressing time different, take off after 1 group of compressing time 10s, 2 groups of compressing times are 20s, and 3 groups of compressing times are 30s, the like, the 20th group of compressing time is 200s.After skin experiment, after detecting every a slice administration porcine skin on effective administration rate, the medicine namely skin deposited accounts for the percentage ratio of the total drug loading of microneedle patch, and result is as shown in table 1.
Table 1: effective administration rate of different compressing time
| 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, what the microneedle patch being convenient to animal vaccine administration of the present invention can not cause animal when vaccination fears reaction, is easy to administration, easy to operate, does not need inoculation staff training; Singlely can complete vaccination work, efficiency is high; Do not need when completing vaccination additionally to carry out labelling to animal; Single use, avoids the probability of cross infection; Material therefor is biodegradable, produces without medical waste; Manufacture method simple economy; Product is without the need to stored refrigerated or vacuum preservation etc.; Convenient transportation.
Claims (8)
1. be convenient to a microneedle patch for animal vaccine administration, it is characterized in that, described microneedle patch comprises the paster substrate of solubility and the array distribution micropin needle body in the suprabasil solubility of paster; Described micropin needle body is loaded with drug target on its top, and the material of preparing of this micropin needle body comprises water miscible biodegradable macromolecular material.
2. a kind of microneedle patch being convenient to animal vaccine administration according to claim 1, it is characterized in that, described macromolecular material is one or more in polyvinyl alcohol, poly-carboxymethyl cellulose, chondroitin sulfate, PLGA, fibroin, dextrin, hyaluronic acid, gelatin.
3. a kind of microneedle patch being convenient to animal vaccine administration according to claim 1, it is characterized in that, described animal vaccine is blue ear vaccine, swine Fever Vaccine, foot-and-mouth disease vaccine, dog cough vaccine, dog hexavaccine, rabies vaccine, Bovine Ephemeral Fever vaccine, Anthrax vaccine, cattle brucella vaccine, one or more in sheep pox Seedling, pseudorabies vaccines, hog cholera lapinised virus vaccine, pig lung plague attenuated vaccine, pig erysipelas aluminium hydroxide vaccine, piglet red dysentery vaccine, Streptococcus suis aluminium hydroxide vaccine, mycoplasma pneumoniae of swine vaccine.
4. a kind of microneedle patch being convenient to animal vaccine administration according to claim 1, is characterized in that, described material of preparing also comprises stabilizing agent, and this stabilizing agent is one or more in sucrose, Russula ketone terpene, glucose, trehalose, chitosan.
5. a kind of microneedle patch being convenient to animal vaccine administration according to claim 1, is characterized in that, the medicine carrying mode of described drug target be medicine is spread upon micropin needle body top appearance, mix on micropin needle body top or concentrate on micropin needle body top.
6. a kind of microneedle patch being convenient to animal vaccine administration according to claim 1, is characterized in that, described microneedle patch is the length of side is the square of 2-50mm, and total 1-10000 micropin, the spacing between adjacent micropin is 0.2-5mm.
7. a kind of microneedle patch being convenient to animal vaccine administration according to claim 1, is characterized in that, the shape of described micropin needle body is that taper shape or class are conical, and this micropin needle body length is 200-3000 μm, and footpath, the end is 100-1500 μm.
8. be convenient to the preparation method of the microneedle patch of animal vaccine administration as claimed in claim 1 for one kind, it is characterized in that, described preparation method comprises the following steps: the macromolecular material of 5%-50%, the stabilizing agent of 0%-50% are mixed with the water of surplus by mass percentage, stirring and dissolving at 40 DEG C-100 DEG C; Dissolve evacuation completely and remove bubble, obtain highly concentrated solution, sealing; By measuring requirement, the vaccine solution of compound concentration scope 0.1-1000mg/ml; Getting vaccine solution 0.01-5ml is coated on microneedles template, after evacuation 0.5-60min, reclaims unnecessary vaccine solution, continues, at the dry 0.5-60min of vacuum environment, to treat that vaccine solution deposits to micropin top; Get highly concentrated solution 0.01-5ml to be coated onto and to be above-mentionedly loaded with on the microneedles template of vaccine solution, evacuation 1-300min again; Lyophilization 5-600min, the demoulding after dry, encapsulates in the confined space under temperature is 15-25 DEG C, humidity 10%-30%RH, obtains microneedle patch.
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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 |
| CN105596287A (en) * | 2016-02-04 | 2016-05-25 | 广州新济药业科技有限公司 | Active separation-type soluble microneedle and preparation method thereof |
| CN105726458A (en) * | 2016-01-29 | 2016-07-06 | 广州新济药业科技有限公司 | Temperature-sensitive soluble microneedle 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 |
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| CN108379573A (en) * | 2018-03-26 | 2018-08-10 | 中国医学科学院生物医学工程研究所 | A kind of 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 |
| CN110840822A (en) * | 2018-07-26 | 2020-02-28 | 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 |
| US10980991B2 (en) | 2015-09-21 | 2021-04-20 | B&L Biotech, Inc. | Flexible microneedle for dental material delivery and method of manufacturing the same |
| CN113368033A (en) * | 2021-06-09 | 2021-09-10 | 中国人民解放军军事科学院军事医学研究院 | Heat-stable soluble microneedle vaccine patch based on animal gelatin and preparation method thereof |
| CN113874067A (en) * | 2019-03-29 | 2021-12-31 | 瓦克萨斯私人有限公司 | High density microprojection array patch for vaccines |
| 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 |
| US11828584B2 (en) | 2017-06-13 | 2023-11-28 | Vaxxas Pty Limited | Quality control of substrate coatings |
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| US10980991B2 (en) | 2015-09-21 | 2021-04-20 | B&L Biotech, Inc. | Flexible microneedle for dental material delivery and method of manufacturing the same |
| CN105726458A (en) * | 2016-01-29 | 2016-07-06 | 广州新济药业科技有限公司 | Temperature-sensitive soluble microneedle and preparation method thereof |
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| 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 |
| CN105596287A (en) * | 2016-02-04 | 2016-05-25 | 广州新济药业科技有限公司 | Active separation-type soluble microneedle and preparation method thereof |
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| 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 |
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| CN113368033A (en) * | 2021-06-09 | 2021-09-10 | 中国人民解放军军事科学院军事医学研究院 | Heat-stable soluble microneedle vaccine patch based on animal gelatin and preparation method thereof |
| 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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