CN105126243B - Microneedle injection bullet and preparation method thereof and microneedle injection equipment - Google Patents
Microneedle injection bullet and preparation method thereof and microneedle injection equipment Download PDFInfo
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- CN105126243B CN105126243B CN201510556515.4A CN201510556515A CN105126243B CN 105126243 B CN105126243 B CN 105126243B CN 201510556515 A CN201510556515 A CN 201510556515A CN 105126243 B CN105126243 B CN 105126243B
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- microneedle
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
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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
- A61M2037/0023—Drug applicators 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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- General Health & Medical Sciences (AREA)
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- Media Introduction/Drainage Providing Device (AREA)
Abstract
The present invention relates to the microneedle injection technical fields of cutaneous penetration, especially a kind of microneedle injection bullet and preparation method thereof and microneedle injection equipment, the microneedle injection bullet, including microneedle array film and substrate, microneedle array film includes film substrate and the positive microneedle array of film substrate, have on substrate and the perforation hole array of microneedle array alignment, the film substrate of microneedle array film are fixed on substrate, the through hole of each micropin insertion perforation hole array of microneedle array.The mating microneedle injection equipment with above-mentioned microneedle injection bullet, including microneedle injection bullet and micropin propulsion device, micropin propulsion device is by each micropin of microneedle array and microneedle array thin film separation and is pressed into skin.The beneficial effects of the invention are as follows：When snapping into row injection using microneedle injection, by by micropin and microneedle array thin film separation so that for micropin completely into skin, the drug that micropin is included is completely dissolved release, achievees the purpose that accurately control micropin dosage.
Description
Technical field
The present invention relates to the microneedle injection technical field of cutaneous penetration, the microneedle injection bullet of especially a kind of cutaneous penetration and
Preparation method and microneedle injection equipment.
Background technology
Cutaneous penetration refers in drugs through skin surface administration.Drug passes through the barrier of skin layers, through capillary
It is absorbed into body circulation and generates whole body or local therapeutic effects.This Transdermal delivery systems in principle be subcutaneously injected or vein
Input administration be same class medication administration method, but compared with conventional injection administering mode have it is more painless, it is more safe and stable and
The good advantage of patient compliance.In cutaneous penetration technology, drug is by the concentration gradient of drug as driving force, diffusion
Enter blood flow through skin and generate drug effect, diffusion rate is depended on across the concentration gradient of cuticula and the size of drug molecule
And hydrophily.But since skin is very low to the permeability of most drugs, skin can be effectively passed through by Passive diffusion
The drug for playing drug effect is seldom.To promote drug transdermal permeability, people start to make keratoderma generate using mechanical means
Micropore and rupture.Wherein microneedle cutaneous technology is proved to be the most effective cutaneous penetration based on mechanical means.Micropin is saturating
Skin medicine-feeding technology combines the dual drug release advantage being subcutaneously injected with percutaneous plaster, and by a kind of band, there are many devices of microspike
The micropore wound that skin causes skin minimum degree is acted on, drug can increase the permeability of drug by the micropore created,
Prodigious facilitation is played in infiltration especially for macromolecular drug.It is made when using soluble biodegradable material
When making micropin, drug and biomolecule can be mixed into micropin itself.In application process, soluble microneedle configuration is in skin
Interior quick dissolving, to discharge drug and biomolecule, so the waste with tip is not present.
Dissolvable micropin penetrate skin method at present usually there are two types of, one is hand beating penetrate, one is based on bullet
The automatic needle inserter of spring, the automatic blood sampler used when taking a blood sample similar to finger tip.The maximum that micropin is penetrated to skin is patted with hand
The disadvantage is that dynamics is different when everyone uses, lead to the significant difference of the depth penetrated, even same person, as
The dynamics pricked every time is variant and causes depth of needle different.Although automatic needle inserter based on spring can improve inserting needle
Repeatability, but still cannot solve the difference brought by skin difference.Due to the patch substrate of ining succession of patch micropin, one
Point microneedle drug rest on skin surface with the substrate of patch, do not dissolved and absorbed by human body, due to individual's skin thickness and
The difference of skin elasticity, the ratio that when use stays in top half in the micropin needle body that cannot be dissolved of skin surface is different,
Cause when per injection can absorbed micropin dose be different, so it is difficult to accurately controlling the dosage of micropin.
Invention content
The technical problem to be solved by the present invention is to：In existing microneedle cutaneous technology, it is difficult to accurately control note
Dosage when penetrating.
The technical solution adopted by the present invention to solve the technical problems is：A kind of microneedle injection bullet, including microneedle array are thin
Film and substrate, microneedle array film include film substrate and the positive microneedle array of film substrate, are had and micropin battle array on substrate
The perforation hole array of column alignment, the film substrate of microneedle array film are fixed on substrate, each micropin insertion of microneedle array
Penetrate through the through hole of hole array.
It further limits, which further includes cover board, and cover board is located at the back side of microneedle array film, cover board and base
Plate connects, and constitutes the shell of microneedle array film, and microneedle array film is sandwiched between cover board and substrate, has on cover board and base
The perforation hole array of perforation hole array alignment on plate.
It further limits, there is connection structure, microneedle injection bullet to be mounted on by the connection structure on cover board on cover board
At the injection port of micropin propulsion device.
It further limits, the micropin of microneedle array film is that can dissolve micropin, the active medicament in micropin.It can dissolve
Micropin includes at least one soluble polymeric object, and soluble polymeric object can be selected from hyaluronic acid, fibroin albumen, collagen, bright
Glue, hydrogel, carboxymethyl cellulose, hydroxypropyl methyl cellulose, chondroitin sulfate, glycogen, dextrin, amylose, sulfuric acid are soft
Ossein, Poly(D,L-lactide-co-glycolide, polyethanol ester, polyvinyl alcohol, polyacrylic acid, gathers polylactic-co-glycolic acid
Propylene, polystyrene, polyethylene, polyvinyl chloride, ABS plastic (acrylonitrile-butadiene-styrene copolymer), gathers makrolon
Dimethyl siloxane, Kynoar, acetate fiber, polyester, polyurethane, poly- dioxy ring ethyl ketone, poly(ethylene glycol), polylactic acid,
Polyacrylamide polymer, cyclic olefin copolymer, carboxymethyl chitosan, Poly L-lactic acid, alginic acid, glucan, sulfuric acid
Glucan, hydroxypropyl methyl cellulose, chitin, polyvinylpyrrolidone, lactose, galactolipin, trehalose, sucrose, maltose,
Glucan, glucosides, fructose, chitosan, agarose, D-sorbite, mannitol or xylitol, phosphatidyl choline, gather proteoglycans
Lactide, polyglycolide, hydroxypropyl cellulose, wax, polyester, polyanhydride, polyamide, phosphorus based polymer, poly- (cyanoacrylate),
One kind in polyurethane, polyorthoester, poly- dihydropyran, polyacetals, Biodegradable polymeric, polypeptide, carbohydrate
Or the arbitrary combination of above-mentioned polymer.There are at least one active agents in micropin, active agents can be medicine or non-
Curative drug, such as cosmetics molecule, active agents can be selected from citric acid, protein, peptide, polysaccharide, antigen, immunogene, vaccine,
Antibody, enzyme, nucleic acid, aptamer, virus, bacterium, cell, hormone, antibiotic, anticancer drug, genetically engineered drug, natural products
The combination of drug, traditional Chinese medicine ingredients, nutritional ingredient, therapeutic agent, diagnosticum and mentioned reagent.
The mating microneedle injection equipment with above-mentioned microneedle injection bullet, including microneedle injection bullet and micropin propulsion device, micropin
Propulsion device is by each micropin of microneedle array and microneedle array thin film separation and is pressed into skin.
It further limits, microneedle injection bullet is mounted on the injection port of micropin propulsion device, and micropin propulsion device is based on height
It calms the anger the micropin propulsion device of body, the micropin propulsion device based on high pressure gas applies high pressure gas to the back side of microneedle injection bullet
Body pushes micropin to be detached from microneedle array film, is pressed into skin by high pressure gas.Alternatively, micropin propulsion device is based on micro- lance
Micropin propulsion device, micro- lance array is inserted into the back side of microneedle injection bullet based on the micropin propulsion device of micro- lance, passes through micro- lance
Micro- lance of array pushes micropin to be detached from microneedle array film, is pressed into skin.
Wherein, the micropin propulsion device based on high pressure gas has injecting cavity, high pressure chest, high-pressure air source, valve train, gas
Valve jacket mechanism and cocking mechanism, high-pressure air source are passed through high pressure gas to high pressure chest, and high pressure chest passes through valve train with injecting cavity
It communicates, cocking mechanism controls the needle of air valve knocking gear strike valve train, so that valve train is quickly opened, before injecting cavity
End opening, the opening are mounted on the opening as injection port, microneedle injection bullet, and the high pressure gas into injecting cavity pushes micropin
It is detached from microneedle array film, is pressed into skin.
It further limits, micropin propulsion device is in pistol shape, the gentle valve jacket mechanism of injecting cavity, high pressure chest, valve train
Positioned at the body of a gun part of micropin propulsion device, length of the gentle valve jacket mechanism of injecting cavity, high pressure chest, valve train along body of a gun part
Degree direction is arranged in order, and injecting cavity is located at the front end of body of a gun part, and valve train includes valve opening and air valve needle, valve opening and high pressure
Chamber communicates, and there is exhaust outlet, exhaust outlet to be communicated with injecting cavity by being vented gas circuit, air valve needle is movably linearly installed in valve opening
There is sealing cooperation, the rear end of air valve needle to expose valve opening in valve opening, between air valve needle and valve opening, air valve needle passes through forward movement
Mode open between air valve needle and valve opening seal cooperation, make the high pressure gas in high pressure chest pass through exhaust outlet and exhaust gas circuit enter
Injecting cavity, air valve needle is moved backward by spring to be resetted, and keeps the sealing mated condition between air valve needle and valve opening, air valve
Knocking gear includes impact block and propelling spring, and cocking mechanism discharges impact block, impact block is made to be beaten under the promotion of propelling spring
Hit the rear end of the needle of valve train.
Wherein, the micropin propulsion device based on micro- lance includes on elastic outer cover, micro- lance substrate and micro- one side end face of lance substrate
Micro- lance array, micro- lance array is aligned with the microneedle array of microneedle injection bullet, another side end face of micro- lance substrate and elastic outer cover
It is connected, for the opening of elastic outer cover as injection port, microneedle injection bullet is mounted on the opening of elastic outer cover, and micro- lance array indentation is micro-
Needle injection bomb, and micropin is pushed to be detached from microneedle array film, it is pressed into skin.
It further limits, microneedle injection bullet further includes cover board, and cover board is located at the back side of microneedle array film, cover board and substrate
Connection constitutes the shell of microneedle array film, and microneedle array film is sandwiched between cover board and substrate, has on cover board and substrate
On the alignment of perforation hole array perforation hole array, have on cover board or substrate and the lifting moving of micro- lance substrate be oriented to
Guide frame.
A kind of preparation method of above-mentioned microneedle injection bullet, step specific as follows：
A, micropin body pre-polymer solution is filled up in micropin female mold and is cured, and microneedle array film is made；
B, surface had into the film substrate that microneedle array film after hardening is pasted in the transfer base substrate pressing of pressure sensitive adhesive
The back side be detached from former for gluing microneedle array film；
C, microneedle array film is transferred to substrate using transfer base substrate, and microneedle array is aligned with perforation hole array,
Micropin is set to be embedded in the through hole of substrate, the end face of substrate is coated with viscose glue, and microneedle array film passes through viscose glue and substrate bonding
It is fixed；
D, pressure sensitive adhesive and microneedle array film are detached from, obtain microneedle injection bullet described in claim 1.
A kind of preparation method of the microneedle injection bullet with cover board, step specific as follows：
A, micropin body pre-polymer solution is filled up in micropin female mold and is cured, and microneedle array film is made；
B, surface had into the film substrate that microneedle array film after hardening is pasted in the transfer base substrate pressing of pressure sensitive adhesive
The back side be detached from former for gluing microneedle array film；
C, microneedle array film is transferred to substrate using transfer base substrate, and microneedle array is aligned with perforation hole array,
Micropin is set to be embedded in the through hole of substrate, the end face of substrate is coated with viscose glue, and microneedle array film passes through viscose glue and substrate bonding
It is fixed；
D, pressure sensitive adhesive and microneedle array film are detached from, obtain microneedle injection bullet described in claim 1；
E, by cover plate lid at the back side of microneedle array film, while the perforation hole array of the perforation hole array of cover board and substrate
It is aligned by position mark.
The beneficial effects of the invention are as follows：When snapping into row injection using microneedle injection, by the way that micropin is thin with microneedle array
UF membrane so that for micropin completely into skin, the drug that micropin is included is completely dissolved release, reach accurately control micropin to
The purpose of pharmaceutical quantities.
Description of the drawings
Present invention will be further explained below with reference to the attached drawings and examples；
Fig. 1 is the preparation process schematic diagram of the microneedle injection bullet of the embodiment of the present invention 1；
Fig. 2 is the structural schematic diagram of the microneedle injection bullet of the embodiment of the present invention 2；
Fig. 3 is the electromicroscopic photograph schematic diagram of the master mold mold for preparing micropin female mold of the present invention；
Fig. 4 is the electromicroscopic photograph schematic diagram of the micropin female mold of the present invention；
Fig. 5 is the single unit system schematic diagram of the microneedle injection equipment based on high pressure gas in the embodiment of the present invention 3；
Fig. 6 is the single unit system schematic diagram of the microneedle injection equipment based on micro- lance in the embodiment of the present invention 4；
Fig. 7 is the process chart one of the microneedle injection equipment based on micro- lance in the embodiment of the present invention 4；
Fig. 8 is the process chart two of the microneedle injection equipment based on micro- lance in the embodiment of the present invention 4；
In figure, 1. microneedle array films, 2. substrates, 3. micropin female molds, 4. transfer base substrates, 5. viscose glues, 6. cover boards, 61.
Connection structure, 62. guide posts, 7. injecting cavities, 8. high pressure chests, 9. gascollecting cap cylinders, 10. air valve needles, 11. impact blocks, 12. promote
Spring, 13. cocking mechanisms, 14. safety-valves, 15. elastic outer covers, 16. micro- lance substrates
Specific implementation mode
Embodiment 1：
As shown in Figure 1, a kind of microneedle injection bullet, including microneedle array film 1 and substrate 2, microneedle array film 1 include thin
Film substrate and the positive microneedle array of film substrate, have on substrate 2 and the perforation hole array of microneedle array alignment, microneedle array
The film substrate of film 1 is fixed on a substrate 2, the through hole of each micropin insertion perforation hole array of microneedle array.
The micropin of microneedle array film 1 is that can dissolve micropin, and can dissolve micropin includes at least one soluble polymeric object, can
Dissolving polymer can be selected from fibroin albumen, collagen, gelatin, hydrogel, carboxymethyl cellulose, hydroxypropyl methyl cellulose,
Chondroitin sulfate, glycogen, dextrin, amylose, hyaluronic acid, chondroitin sulfate, polylactic-co-glycolic acid, polylactic acid-
Co-glycolic acid, polyvinyl alcohol, polyacrylic acid, polypropylene, makrolon, polystyrene, polyethylene, is gathered polyethanol ester
Vinyl chloride, ABS plastic (acrylonitrile-butadiene-styrene copolymer), dimethyl silicone polymer, Kynoar, acetic acid are fine
Dimension, polyester, polyurethane, poly- dioxy ring ethyl ketone, poly(ethylene glycol), polylactic acid, polyacrylamide polymer, cycloolefin copolymer close
Object, carboxymethyl chitosan, Poly L-lactic acid, alginic acid, glucan, dextran sulfate, hydroxypropyl methyl cellulose, chitin,
Polyvinylpyrrolidone, lactose, galactolipin, trehalose, sucrose, maltose, glucan, glucosides, fructose, chitosan, agarose,
D-sorbite, mannitol or xylitol, proteoglycans, phosphatidyl choline, polylactide, polyglycolide, hydroxypropyl cellulose,
Wax, polyanhydride, polyamide, phosphorus based polymer, poly- (cyanoacrylate), polyurethane, polyorthoester, poly- dihydropyran, gathers polyester
The arbitrary combination of one kind or above-mentioned polymer in acetal, Biodegradable polymeric, polypeptide, carbohydrate.
It can be medicine or non-therapeutic drug to have at least one active agents, active agents in micropin, such as changed
Cosmetic molecule, active agents can be selected from citric acid, protein, peptide, polysaccharide, antigen, immunogene, vaccine, antibody, enzyme, nucleic acid, fit
Gamete, virus, bacterium, cell, hormone, antibiotic, anticancer drug, genetically engineered drug, natural products drug, traditional Chinese medicine ingredients,
The combination of nutritional ingredient, therapeutic agent, diagnosticum and mentioned reagent.
The preparation method of the microneedle injection bullet, step specific as follows：
A, interior in the micropin slot of micropin female mold 3 to fill up micropin body pre-polymer solution and cure, it is thin that microneedle array is made
Film 1；
Wherein, micropin body pre-polymer solution can be containing 5% hyaluronic acid, hepatitis B vaccine and it is suitable for the assistants of vaccine
The water-soluble polymers of agent (Th1 types adjuvant).Step A is specific as follows：Micropin female mold 3 is prepared first；Then by micropin body
Pre-polymer solution covers in the micropin female mold 3 with needle tray；The 20 minutes gas completely removed in needle tray is placed in a vacuum
Bubble so that micropin body pre-polymer solution enters in the needle tray, the micropin body pre-polymerization of 3 surface residual of recycling micropin female mold
Object solution；The female mold that micropin body pre-polymer solution has been added is positioned over dry solidification in 4 DEG C~20 DEG C of dry environment, is obtained
To microneedle array film 1.
Micropin female mold 3 is prepared by the following procedure step and is prepared,
1, prepare master mold mold, there are the micropin of 400 (20X20 rows) tetrahedroids, the height of micropin in the surface of master mold mold
About 500 microns, about 300 microns of bottom diameter.(aciculiform is as shown in Figure 3)；
2,50 grams of prepolymerized dimethyl silicone polymer and the mixture of 5 grams of crosslinking agent is taken to be poured on master mold mold,
Temperature is to be placed 60 minutes at 90 DEG C, by the dimethyl silicone polymer and master mold mould separating after solidification, inverts female mold, obtains
Surface has the female mold (as shown in Figure 4) of needle tray compatible with micropin on master mold mold；
B, surface had into the film base that microneedle array film 1 after hardening is pasted in the pressing of transfer base substrate 4 of pressure sensitive adhesive
The back side at bottom is detached from former for gluing microneedle array film 1；
Surface has the preparation method of the transfer base substrate 4 of pressure sensitive adhesive as follows：
A kind of pressure sensitive adhesive is prepared first, and this pressure sensitive adhesive is containing a variety of preparation solution mixing provided by Dow corning company
It is prepared.By 7646 viscose glues of DOW CORNING/7652 viscose glues of DOW CORNING/toluene solvant according to mass ratio be 7：3：10 ratio mixing
Stir 5 hours；
Then, each into the mixed liquor after stirring is 1 in mass ratio：200 addition DOW CORNING SYL-OFF SL 7028 are crosslinked
9250 anchorage additives of agent and DOW CORNING SYL-OFF SL；
Subsequently, with mixed solution in again in mass ratio be 1：200 addition DOW CORNING SYL-OFF 4000 are catalyzed
Agent continues to stir a hour；
Finally, by with pressure-sensitive sol solution be spun on the substrate 2 of PET materials with 3000 (revolutions per second) rotating speeds, by spin coating
There is the transfer base substrate 4 of pressure-sensitive sol solution to be placed in 150 DEG C of baking oven to dry 1 minute, is prepared into surface and turns with pressure sensitive adhesive
Move substrate 4.
C, microneedle array film 1 is transferred to substrate 2 using transfer base substrate 4,2 thickness of substrate is 0.6mm, and by micropin battle array
Row are aligned with perforation hole array, so that micropin is embedded in the through hole of substrate 2, the end face of substrate 2 is coated with viscose glue 5, microneedle array
Film 1 is adhesively fixed by viscose glue 5 and the end face of substrate 2；
D, pressure sensitive adhesive and microneedle array film 1 are detached from.
Embodiment 2：
As shown in Fig. 2, a kind of microneedle injection bullet is compared with embodiment 1, which further includes cover board 6, cover board 6
Positioned at the back side of microneedle array film 1, cover board 6 is connect with substrate 2, constitutes the shell of microneedle array film 1, cover board 6 and substrate 2
Connection type be threadedly coupled or dovetail groove clamping, microneedle array film 1 is sandwiched between cover board 6 and substrate 2, on cover board 6
With the perforation hole array being aligned with the perforation hole array on substrate 2, each through hole of the perforation hole array of cover board 6 and substrate 2
Size is the same, and merging after the perforation hole array consistency from top to bottom of cover board 6 and substrate 2 becomes cylinder array, each circle of cylinder array
There are one micropins for folder all as sandwich in cylinder.
There is connection structure 61, microneedle injection bullet to be mounted on by the connection structure 61 on cover board 6 and be pushed away in micropin on cover board 6
Into at the injection port of device.
The preparation method of the microneedle injection bullet, step specific as follows：
A, interior in the micropin slot of micropin female mold 3 to fill up micropin body pre-polymer solution and cure, it is thin that microneedle array is made
Film 1；Micropin body pre-polymer solution can configuring by the hyaluronic acid of different molecular weight, by molecular weight be 80K~800KDa
Mixing hyaluronan molecule amount hyaluronic acid dissolving in deionized water, the mass fraction of the hyaluronic acid of solution is
20%, then 8wt% vitamin Cs are added to the configuration for the hyaluronic acid for being mixed with different molecular weight, other additions are active
The preparation of the hyaluronic acid for being mixed with different molecular weight of ingredient can refer to embodiment.
B, surface had into the film base that microneedle array film 1 after hardening is pasted in the pressing of transfer base substrate 4 of pressure sensitive adhesive
The back side at bottom is detached from former for gluing microneedle array film 1；
C, microneedle array film 1 is transferred to substrate 2 using transfer base substrate 4, and by microneedle array and penetrates through hole array pair
Together, micropin is made to be embedded in the through hole of substrate 2, the end face of substrate 2 is coated with viscose glue 5, microneedle array film 1 by viscose glue 5 with
The end face of substrate 2 is adhesively fixed；
D, pressure sensitive adhesive and microneedle array film 1 are detached from；
E, cover board 6 is covered at the back side of microneedle array film 1, while the through hole of the perforation hole array and substrate 2 of cover board 6
Array is aligned by position mark.
Embodiment 3：
A kind of microneedle injection equipment includes the microneedle injection bullet and micropin propulsion device of embodiment 1 and embodiment 2, micropin
Injection bomb is mounted on the injection port of micropin propulsion device, and micropin propulsion device is the micropin propulsion device based on high pressure gas, base
Apply high pressure gas to the back side of microneedle injection bullet in the micropin propulsion device of high pressure gas, pushes micropin de- by high pressure gas
From microneedle array film 1, it is pressed into skin, passes completely through biological barrier, such as skin, tissue or cell membrane, the micropin after
Start to dissolve wrapped up drug, drug is degraded completely into skin to be absorbed, to reach the dosage for accurately controlling micropin
Purpose.
As shown in figure 5, being somebody's turn to do the micropin propulsion device based on high pressure gas has injecting cavity 7, high pressure chest 8, high-pressure air source, gas
Valve system, air valve knocking gear and cocking mechanism 13, high-pressure air source are passed through high pressure gas, high pressure chest 8 and injecting cavity to high pressure chest 8
7 are communicated by valve train, and cocking mechanism 13 controls the needle of air valve knocking gear strike valve train, keeps valve train quick
It opens, the front opening of injecting cavity 7, the opening is as injection port, and microneedle injection bullet is mounted on the opening, into injecting cavity 7
High pressure gas push micropin to be detached from microneedle array film 1, be pressed into skin.The company of the cover board 6 of microneedle injection bullet in the attached drawing
Binding structure 61 is the screwed pipe of the rear end of cover board 6, and there is external screw thread, microneedle injection bullet to pass through the external screw thread and injection on screwed pipe
The open-top screw thread of chamber 7 connects.
Micropin propulsion device is in pistol shape, and the gentle valve jacket mechanism of injecting cavity 7, high pressure chest 8, valve train is pushed away positioned at micropin
Into the body of a gun part of device, the gentle valve jacket mechanism of injecting cavity 7, high pressure chest 8, valve train along body of a gun part length direction according to
Secondary arrangement, injecting cavity 7 are located at the front end of body of a gun part.
Valve train includes valve opening and air valve needle 10, and valve opening is communicated with high pressure chest 8, has exhaust outlet, exhaust outlet in valve opening
It is communicated with injecting cavity 7 by being vented gas circuit, air valve needle 10 is movably linearly mounted in valve opening, between air valve needle 10 and valve opening
Coordinate with sealing, valve opening is exposed in the rear end of air valve needle 10, air valve needle 10 opened by way of forward movement air valve needle 10 with
Cooperation is sealed between valve opening, so that the high pressure gas in high pressure chest 8 is passed through exhaust outlet and is vented gas circuit and is entered injecting cavity 7, air valve needle 10
It is moved backward and is resetted by spring, keep the sealing mated condition between air valve needle 10 and valve opening.
Air valve knocking gear includes impact block 11 and propelling spring 12, and cocking mechanism 13 discharges impact block 11, makes impact block
11 hit the rear end of the needle of valve train under the promotion of propelling spring 12.
High-pressure air source is the gascollecting cap cylinder 9 of built-in liquefied carbon dioxide.The gascollecting cap cylinder 9 of liquefied carbon dioxide passes through
Screw thread is connect with high pressure chest 8, and there are one safety-valves 14 for connecting place tool.
When preparing the micropin of transmitting microneedle injection bullet, the safety-valve 14 of gascollecting cap cylinder 9, gascollecting cap cylinder 9 are opened
High pressure gas is filled into high pressure chest 8, the trigger of cocking mechanism 13 is detained, discharges impact block 11, the propelling spring 12 of compression is hit
It hits block 11 and hits air valve needle 10, air valve needle 10 is knocked forward slip, opens and seals cooperation, high pressure between air valve needle 10 and valve opening
Gas enters injecting cavity 7 by exhaust outlet and exhaust gas circuit, and it is thin that the high pressure gas that moment is poured pushes micropin to be detached from microneedle array
Film 1, micropin project, and submerge skin completely, and dissolving release is wrapped in the active agents inside micropin.
Embodiment 4：
Micropin propulsion device is the micropin propulsion device based on micro- lance, based on the micropin propulsion device of micro- lance to microneedle injection
Micro- lance array is inserted at the back side of bullet, is pushed micropin to be detached from microneedle array film 1 by micro- lance of micro- lance array, is pressed into skin.
As shown in Fig. 6,7 and 8, the micropin propulsion device based on micro- lance includes elastic outer cover 15, micro- lance substrate 16 and micro- lance
Micro- lance array on 16 1 side end face of substrate, elastic outer cover 15 are in dome-shaped, and micro- lance of micro- lance array is micron-sized cylinder,
A diameter of 500 microns, micro- lance array is aligned with the microneedle array of microneedle injection bullet, and every micro- lance is directed at one and is clipped in cylinder array
In micropin bullet, another side end face of micro- lance substrate 16 is connected with elastic outer cover 15, and the opening of elastic outer cover 15 is as injection
Mouthful, microneedle injection bullet is mounted on the opening of elastic outer cover 15, and micro- lance array is pressed into microneedle injection bullet, and it is micro- to push micropin to be detached from
Needle array film 1 is pressed into skin.
Microneedle injection bullet further includes cover board 6, and cover board 6 is located at the back side of microneedle array film 1, and cover board 6 is connect with substrate 2,
The shell of microneedle array film 1 is constituted, microneedle array film 1 is sandwiched between cover board 6 and substrate 2, is had on cover board 6 and substrate
The perforation hole array of perforation hole array alignment on 2, there is on the cover board 6 or substrate 2 lifting to micro- lance substrate 16 to move
The dynamic guide frame being oriented to.In the figure, guide frame is guide post 62.
Elastic outer cover 15 is pressed with finger, elastic outer cover 15 can depress micro- lance array, and micro- lance array is pressed into microneedle injection
Bullet, and micropin is pushed to be detached from microneedle array film 1, it is pressed into skin, elastic outer cover 15 is then restored from deformation, and micro- lance battle array is driven
Row leave skin and are returned to original position, and micropin stays in the body, and dissolving release is wrapped in interior active agents.
Claims (6)
1. a kind of microneedle injection equipment, it is characterized in that：Including microneedle injection bullet and micropin propulsion device, micropin propulsion device will be micro-
The each micropin and microneedle array thin film separation of needle array are simultaneously pressed into skin,
Microneedle injection bullet includes microneedle array film and substrate, and microneedle array film includes that film substrate and film substrate are positive
Microneedle array, has on substrate and the perforation hole array of microneedle array alignment, the film substrate of microneedle array film are fixed on base
On plate, the through hole of each micropin insertion perforation hole array of microneedle array,
The microneedle injection bullet is mounted on the injection port of micropin propulsion device, and micropin propulsion device is based on the micro- of high pressure gas
Needle propulsion device, the micropin propulsion device based on high pressure gas apply high pressure gas to the back side of microneedle injection bullet, pass through high pressure
Gas push micropin is detached from microneedle array film, is pressed into skin,
The micropin propulsion device based on high pressure gas has injecting cavity, high pressure chest, high-pressure air source, valve train, air valve
Knocking gear and cocking mechanism, high-pressure air source are passed through high pressure gas to high pressure chest, and high pressure chest passes through valve train phase with injecting cavity
Logical, cocking mechanism controls the needle of air valve knocking gear strike valve train, so that valve train is quickly opened, the front end of injecting cavity
Opening, the opening are mounted on the opening as injection port, microneedle injection bullet, and the high pressure gas into injecting cavity pushes micropin de-
From microneedle array film, it is pressed into skin.
2. microneedle injection equipment according to claim 1, it is characterized in that：The micropin propulsion device is in pistol shape, note
Penetrate the body of a gun part that the gentle valve jacket mechanism of chamber, high pressure chest, valve train is located at micropin propulsion device, injecting cavity, high pressure chest, gas
Length direction of the gentle valve jacket mechanism of valve system along body of a gun part is arranged in order, and injecting cavity is located at the front end of body of a gun part,
Valve train includes valve opening and air valve needle, and valve opening is communicated with high pressure chest, and there is exhaust outlet, exhaust outlet to pass through exhaust in valve opening
Gas circuit is communicated with injecting cavity, and air valve needle is movably linearly mounted in valve opening, has sealing cooperation between air valve needle and valve opening,
Valve opening is exposed in the rear end of air valve needle, and air valve needle is opened by way of forward movement seals cooperation between air valve needle and valve opening, make
High pressure gas in high pressure chest enters injecting cavity by exhaust outlet and exhaust gas circuit, and air valve needle is moved backward by spring and answered
Position keeps the sealing mated condition between air valve needle and valve opening,
Air valve knocking gear includes impact block and propelling spring, and cocking mechanism discharges impact block, makes impact block in propelling spring
Push the rear end of the needle of lower strike valve train.
3. microneedle injection equipment according to claim 1, it is characterized in that：Further include cover board, it is thin that cover board is located at microneedle array
The back side of film, cover board and substrate connection, constitute the shell of microneedle array film, microneedle array film be sandwiched in cover board and substrate it
Between, there is the perforation hole array being aligned with the perforation hole array on substrate on cover board.
4. microneedle injection equipment according to claim 3, it is characterized in that：There is connection structure, micropin on the cover board
Injection bomb is mounted on by the connection structure on cover board at the injection port of micropin propulsion device.
5. a kind of preparation method of microneedle injection bullet, it is characterized in that：Microneedle injection bullet includes microneedle array film and substrate, micropin
Array film includes film substrate and the positive microneedle array of film substrate, has the through hole with microneedle array alignment on substrate
The film substrate of array, microneedle array film is fixed on substrate, and each micropin insertion perforation hole array of microneedle array is passed through
Through-hole,
Step specific as follows：
A, micropin body pre-polymer solution is filled up in micropin female mold and is cured, and microneedle array film is made；
B, surface had into the back of the body that the transfer base substrate of pressure sensitive adhesive presses the film substrate for pasting microneedle array film after hardening
Face is detached from former for gluing microneedle array film；
C, microneedle array film is transferred to substrate using transfer base substrate, and microneedle array is aligned with perforation hole array, made micro-
Needle is embedded in the through hole of substrate, and the end face of substrate is coated with viscose glue, and microneedle array film is fixed by viscose glue and substrate bonding；
D, pressure sensitive adhesive and microneedle array film are detached from, obtain microneedle injection bullet described in claim 1.
6. a kind of preparation method of microneedle injection bullet, it is characterized in that：Microneedle injection bullet includes microneedle array film and substrate, micropin
Array film includes film substrate and the positive microneedle array of film substrate, has the through hole with microneedle array alignment on substrate
The film substrate of array, microneedle array film is fixed on substrate, and each micropin insertion perforation hole array of microneedle array is passed through
Through-hole,
The microneedle injection bullet further includes cover board, and cover board is located at the back side of microneedle array film, cover board and substrate connection, constitutes micropin
The shell of array film, microneedle array film are sandwiched between cover board and substrate, are had and the through hole battle array on substrate on cover board
The perforation hole array of column alignment,
Step specific as follows：
A, micropin body pre-polymer solution is filled up in micropin female mold and is cured, and microneedle array film is made；
B, surface had into the back of the body that the transfer base substrate of pressure sensitive adhesive presses the film substrate for pasting microneedle array film after hardening
Face is detached from former for gluing microneedle array film；
C, microneedle array film is transferred to substrate using transfer base substrate, and microneedle array is aligned with perforation hole array, made micro-
Needle is embedded in the through hole of substrate, and the end face of substrate is coated with viscose glue, and microneedle array film is fixed by viscose glue and substrate bonding；
D, pressure sensitive adhesive and microneedle array film are detached from, obtain microneedle injection bullet described in claim 1；
E, by cover plate lid at the back side of microneedle array film, while the perforation hole array of cover board and the perforation hole array of substrate pass through
Position mark is aligned.
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| US11040103B2 (en) | 2016-04-15 | 2021-06-22 | Admbioscience Inc. | Method for manufacturing nucleic acid film and apparatus for injecting medicine using nucleic acid film |
| US11241563B2 (en) * | 2016-12-22 | 2022-02-08 | Johnson & Johnson Consumer Inc. | Microneedle arrays and methods for making and using |
| KR102539625B1 (en) * | 2016-12-22 | 2023-06-05 | 오하이오 스테이트 이노베이션 파운데이션 | Interpenetrating microstructures for cargo delivery based on nanochannels |
| BR112020025907A8 (en) | 2018-06-29 | 2022-07-26 | Currahee Holding Company Inc | THREE-DIMENSIONAL MICROFLUID DEVICES FOR THE RELEASE OF ACTIVE PRINCIPLES |
| CN109303976A (en) * | 2018-11-07 | 2019-02-05 | 何坛明 | A kind of microneedle configuration that medicaments uniformity distribution imports |
| CN109298180A (en) * | 2018-11-19 | 2019-02-01 | 中南大学 | A method of detection salmonella typhimurium |
| CN112569465B (en) * | 2020-12-29 | 2022-07-19 | 华东理工大学 | Preparation method of microneedle patch |
| CN115737531A (en) * | 2022-11-29 | 2023-03-07 | 华中科技大学 | Method for preparing microneedle array by double-permeation micro-perfusion method, microneedle array and application |
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