CN104069585B - Detachable microneedle device and its manufacture method - Google Patents
Detachable microneedle device and its manufacture method Download PDFInfo
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- CN104069585B CN104069585B CN201410312539.0A CN201410312539A CN104069585B CN 104069585 B CN104069585 B CN 104069585B CN 201410312539 A CN201410312539 A CN 201410312539A CN 104069585 B CN104069585 B CN 104069585B
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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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Abstract
The present invention relates to medical and beauty treatment micropin technical field, particularly a kind of detachable microneedle device and its manufacture method, including micropin and substrate, micropin is detachably fastened on substrate, after micropin is pierced into skin, micropin and substrate are separated, micropin is stayed in skin.The beneficial effects of the invention are as follows：Micropin is made of the degradable micropin material of bio-compatible, is had enough mechanical strengths, can smoothly be pierced through skin, can stay in the degraded of skin internal programization；Active material can keep activity stabilized in the micropin of the degradable micropin material based on bio-compatible, be advantageous to the phase controllably discharge medicine in injection point position director；And micropin substrate can use flexible material, hard micropin can separate with the substrate of flexibility, after micropin is pierced into skin, peel off substrate, and the micropin after separating continues to keep in skin the controllably internal active material of dissolving release.
Description
Technical field
The present invention relates to medical and beauty treatment micropin technical field, particularly a kind of detachable microneedle device and its manufacturer
Method.
Background technology
Percutaneous dosing is due to that can avoid macromolecule from being degraded in intestines and stomach and easy to use, as medicine delivery
Effective way and be widely used.In the past in order that effective component subcutaneously play pharmacological action, used comprising drug effect into
The external preparation divided.As such external preparation, it is known to which liquor, ointment, cream preparation, tape preparation, patch, mud apply
Agent etc., by the way that they are partly coated with or attached, effective component percutaneous absorbtion, subcutaneously playing desired pharmacological action.
However, the external preparation of above-mentioned coating or attaching form has the disadvantage that：Due to the barriers function of skin, effective component can not
By fully percutaneous absorbtion, it is impossible to play desired pharmacological action.It is difficult especially when effective component is high-molecular compound
With percutaneous absorbtion, it is difficult to play desired pharmacological action in external preparation.And in use, due to perspiring, clean,
External pressure etc., effective component come off or disappeared before by percutaneous absorbtion sometimes.In recent years, added with the micro- of effective component
The microneedle array of pin is widely studied as the technology for solving above-mentioned external preparation shortcoming.For example, Publication No. 102580232A
Chinese patent disclose mainly by scheme of the fibroin albumen as the microneedle array of micropin raw material.By the way that micropin is pierced into skin
Top layer and/or keratoderma, so as to which the effective component in micropin is supplied to subcutaneous, the micropin part of piercing can be in subcutaneously quilt
Dissolve or be biodegradable so as to disappear.In addition, micropin is because pin portion is very thin, thus even if being pierced into skin surface and/or skin
Skin cuticula, pain or bleeding are not produced yet, and puncture and hinder rapid closing, thus be adapted as subcutaneously supplying effective component
Method.Such microneedle array need to carry out most suitable design according to skin symptom, it is necessary to develop provide it is various
Microneedle array.Need synthetically to have concurrently as the micropin that external preparation uses（1）It can tolerate to skin surface and/or skin keratin
The Strong degree of layer piercing,（2）In order to not produce pain or the fineness of bleeding in the part for being pierced into skin surface and/or keratoderma
With flexibility and（3）It is pierced into subcutaneous micropin part dissolubility in vivo or biological degradability etc..In the past, such micropin
Substrate using hard material as micropin, and micropin can not separate with substrate, hard after micropin is pierced into skin
Hard substrate must be pressed in skin surface, and after the completion of waiting drug injection, just peelable substrate, so brings not to user
It is suitable.
The content of the invention
The technical problems to be solved by the invention are：The substrate of existing micropin is integral with micropin, is pierced into micropin
After skin, hard substrate must be pressed in skin surface, and after the completion of waiting drug injection, just peelable substrate, so gives and use
Person brings discomfort, and the rate of release and drugloading rate of medicine whard to control.
The technical solution adopted for the present invention to solve the technical problems is：A kind of detachable microneedle device, including micropin
And substrate, micropin are detachably fastened on substrate, after micropin is pierced into skin, micropin and substrate are separated, micropin is stayed in skin
In skin.
Micropin is detachably fastened on substrate by binding agent, and binding agent is peelable type binding agent, soluble-type is glued
Tie agent or structural strength is less than the binding agent of micropin needle structure intensity.
Further limit, peelable type binding agent is the pressure sensitive adhesive of peelable type；Described soluble-type binding agent is egg
Viscose glue is can dissolve made of white or starch.
Further limit, the surface that binding agent is covered in substrate forms tack coat.
Further limit, there is needle tray on the surface of substrate, the bottom insertion needle tray of micropin, have between micropin and needle tray
Binding agent, the bonding force that micropin passes through binding agent are detachably fastened on substrate.
Or there is needle tray on the surface of substrate, the bottom insertion needle tray of micropin, micropin passes through between micropin and needle tray
Mechanical bonding force be detachably fastened on substrate.
Or there is needle tray on the surface of substrate, the bottom insertion needle tray of micropin, have between micropin and needle tray and bond
Agent, micropin are separably fixed by the mechanical bonding force between micropin and needle tray and the collective effect of the bonding force of binding agent
On substrate.
Further limit, micropin is haplotype micropin, and needle tray is corresponding with the shape of the bottom of each haplotype micropin.Or
Person, micropin are coplanar microneedle array, and needle tray is corresponding with the shape of the micropin base of coplanar microneedle array, multiple coplanar
Microneedle array insertion substrate forms different plane microneedle array.
Further limit, micropin is made up of biodegradable micropin material, added in biodegradable micropin material
Add the active material of one or more medical treatment or beautifying use.
Further limit, substrate is fabricated from a flexible material.
Further limit, flexible material be bio-compatibility flexible material, bio-compatibility flexible material be hydrogel,
Polyvinylpyrrolidone/polyvinyl acetate, triethyl citrate, structure edge acid tributyl, trimethyl citrate, above-mentioned biology are simultaneous
The plasticiser added in flexible material is the one or more in glycerine, castor oil, emulsifying agent T-80, polyethylene glycol 400
Mixture；Or flexible material is flexible polymer, flexible polymer is cellulose, polyester, polypropylene, makrolon, poly-
Styrene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, dimethyl silicone polymer, Kynoar,
One or more mixtures in acetate fiber, polyurethane.
Further limit, micropin is vertically or tiltedly fixed on substrate.
A kind of manufacture method of detachable microneedle device, has following steps：
1）Make micropin female mold；
2）The micropin material of liquid is filled up in the micropin groove of micropin female mold and is solidified；
3）There is the substrate of binding agent to be pressed in micropin female mold surface；
4）Make the micropin and base plate bonding in micropin female mold, and together depart from micropin female mold with substrate, obtain dividing
From the needle system that declines.
Further limit, step 2 is specially：Micropin female mold is pressed against on the flat board for the micropin material for scribbling liquid,
Make to fill up micropin body pre-polymer solution in the micropin groove of micropin female mold, flat board is removed after the solidification of micropin body pre-polymer solution,
The micropin after solidification is left in micropin female mold；Or directly the micropin material of liquid is coated in micropin female mold, Ran Houzai
It is pressed against using flat board in micropin female mold, makes to fill up micropin body pre-polymer solution, micropin body in the micropin groove of micropin female mold
Flat board is removed after pre-polymer solution solidification, the micropin after solidification is left in micropin female mold.
A kind of preparation method of detachable microneedle device, has following steps：
1）Make micropin female mold；
2）Micropin body pre-polymer solution is filled up in the micropin groove of micropin female mold and is solidified；
3）Micropin female mold is pressed against on viscosity transfer flat board, micropin is transferred on viscosity transfer flat board；
4）Micropin is transferred in transfer mold using viscosity transfer flat board, the depth of the micropin groove of the transfer mold is small
In the depth of the micropin groove of micropin female mold；
5）Micropin in transfer mold is transferred on the substrate for being carved with needle tray, micropin insertion needle tray, and with substrate together
Depart from micropin female mold, obtain detachable microneedle device.
The beneficial effects of the invention are as follows：Micropin is made of the degradable micropin material of bio-compatible, has enough machines
Tool intensity, skin can be smoothly pierced through, the degraded of skin internal programization can be stayed in；Active material can be based on the degradable of bio-compatible
Keep activity stabilized in the micropin of micropin material, be advantageous to the phase controllably discharge medicine in injection point position director；And micropin substrate
Flexible material can be used, hard micropin can separate with the substrate of flexibility, after micropin is pierced into skin, peel off substrate, and separate
Micropin afterwards, which continues to keep, controllably dissolves the internal active material of release in skin.
Brief description of the drawings
The present invention is further described with reference to the accompanying drawings and examples；
Fig. 1 is the micropin delivery process schematic diagram of the detachable microneedle device of the present invention；
Fig. 2 is the manufacturing process schematic diagram of the adhered separable microneedle device of the present invention；
Fig. 3 is the using process diagram of the adhered separable microneedle device of the present invention；
Fig. 4 is that the needle tray formula of the present invention separates the manufacturing process schematic diagram of microneedle device；
Fig. 5 is that the needle tray formula of the present invention separates the using process diagram of microneedle device；
Fig. 6 is the manufacturing process schematic diagram of the adhered separable microneedle device of multiple rows of assembling of the present invention；
Fig. 7 is the using process diagram of the adhered separable microneedle device of multiple rows of assembling of the present invention；
In figure, 1. micropins, 2. substrates, 3. binding agents, 4. skins, 5. micropin female molds, 6. flat boards, 7. viscosity shift flat
Plate, 8. transfer molds, 9. coplanar microneedle arrays, 10. microneedle array master molds, the micropin material of 11. liquid.
Embodiment
As shown in figure 1, a kind of detachable microneedle device, including micropin 1 and substrate 2, micropin 1 are detachably fastened to base
On plate 2, micropin 1 is made up of biodegradable micropin material, is added in biodegradable micropin material one or more
Medical treatment or the active material of beautifying use.After micropin 1 is pierced into skin 4, micropin 1 and substrate 2 are separated, micropin 1 is stayed in skin 4
It is interior.
Biodegradable micropin material may be selected from fibroin albumen, collagen, gelatin, hydrogel, carboxymethyl cellulose,
Hydroxypropyl methyl cellulose, chondroitin sulfate, glycogen, dextrin, amylose, hyaluronic acid, polylactic-co-glycolic acid,
Poly(D,L-lactide-co-glycolide, PVOH ester, polyacrylic acid, polypropylene, makrolon, polystyrene, polyethylene, polychlorostyrene
Ethene, ABS plastic（Acrylonitrile-butadiene-styrene copolymer）, dimethyl silicone polymer, Kynoar, acetate fiber,
Polyester, polyurethane, poly- dioxy ring ethyl ketone, PEG, poly- (lactic acid), polyacrylamide polymer, cycloolefin copolymer close
Thing, carboxymethyl chitosan, PLLA, 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, PGA, hydroxypropyl cellulose,
Wax, polyester, polyanhydride, polyamide, phosphorus based polymer, poly- (cyanoacrylate), polyurethane, poe, poly- dihydropyran,
One kind or combinations thereof in polyacetals, Biodegradable polymeric, polypeptide, carbohydrate.
The active material of medical treatment or beautifying use can be medicine or cosmetics molecule, including citric acid, protein, peptide, more
Sugar, antigen, immunogene, vaccine, antibody, enzyme, nucleic acid, aptamer, virus, bacterium, cell, hormone, antibiotic, cancer therapy drug,
Genetically engineered drug, natural products medicine, traditional Chinese medicine ingredients, nutritional ingredient, therapeutic agent, diagnosticum, and the combination of mentioned reagent.
Detachable microneedle device includes adhered separable microneedle device and needle tray formula separates microneedle device.Needle tray formula
Separable microneedle device is easier to separate with substrate 2 compared to adhered separable microneedle device, it is not necessary to as adhered separable
Microneedle device controls bonding force like that, and need not be moistened during disengaging.
The structure of adhered separable microneedle device is as follows：
The micropin 1 of adhered separable microneedle device is detachably fastened on substrate 2 by binding agent 3, and binding agent 3 is
Peelable type binding agent, soluble-type binding agent or structural strength are less than the binding agent of micropin needle structure intensity.Binding agent 3
The surface that substrate 2 can be completely covered on forms tack coat, only can also be locally lain in the FX of micropin 1.
Peelable type binding agent is the pressure sensitive adhesive of peelable type, such as organic silicon pressure-sensitive adhesive, pressure-sensitive acrylate
Stick.After being pierced into skin 4, to help micropin 1 to separate, moisture is coated on the surface of skin 4, moisture soaks peelable type binding agent,
The bonding force of substrate 2 and micropin 1 is reduced, then opening substrate 2 makes binding agent 3 depart from micropin 1.
Soluble-type binding agent is that viscose glue is can dissolve made of albumen or starch, as albumen viscose glue and paddy, wheat,
Amylan made of corn, potato.After being pierced into skin 4, the moisture dissolving soluble-type binding agent on the surface of skin 4 is coated in, so
After open substrate 2 and binding agent 3 is departed from micropin 1.
When being less than the binding agent of micropin needle structure intensity using structural strength, after being pierced into skin 4, by translating substrate 2,
The micropin 1 that can make vertically or tiltedly to fix on a substrate 2 is separated from substrate 2, stayed with the fracture of the bonding place of substrate 2, micropin 1
Release is wrapped in micropin 1 or is applied to the active material on the surface of micropin 1 in the skin 4, obliquely fixed on a substrate 2 micro-
Pin 1 is more easy to be broken in bonding place relative to the micropin 1 being vertically fixed on substrate 2.
Needle tray can also be designed with the surface of the substrate 2 of adhered separable microneedle device, is separated with needle tray formula
Microneedle device is compared, and does not have mechanical bonding force between micropin 1 and needle tray, the bottom insertion needle tray of micropin 1, micropin 1 and needle tray it
Between there is binding agent 3, the bonding force that micropin 1 passes through binding agent 3 is detachably fastened on substrate 2.
The structure that needle tray formula separates microneedle device is as follows：
Needle tray formula, which separates, has needle tray on the surface of the substrate 2 of microneedle device, the bottom insertion needle tray of micropin 1, micropin
1 is detachably fastened on substrate 2 by the mechanical bonding force between micropin 1 and needle tray, the mechanical bonding force of micropin 1 and needle tray
After being pierced into skin 4 less than micropin 1, skin 4 after being pierced into skin 4, opens substrate 2, substrate 2 is de- with micropin 1 to the resistance of micropin 1
From micropin 1 stays in slow mechanism dissolved release in skin 4 and is wrapped in interior medicine.
Can also carry out auxiliary fixation by binding agent between micropin 1 and needle tray, micropin 1 by micropin 1 and needle tray it
Between mechanical bonding force and the collective effect of bonding force of binding agent be detachably fastened on substrate 2.Micropin 1 and needle tray it
Between mechanical bonding force and binding agent bonding force collective effect be less than micropin 1 be pierced into skin 4 after, skin 4 is to micropin 1
Resistance, after being pierced into skin 4, substrate 2 is opened, substrate 2 departs from micropin 1, and micropin 1 stays in slow mechanism dissolved release parcel in skin 4
Medicine inside.
The micropin 1 that adhered separable microneedle device and needle tray formula separate microneedle device can be that haplotype micropin also may be used
To be coplanar microneedle array 9, coplanar microneedle array 9 includes multiple micropin needle bodies and connects the base of micropin needle body, micropin
Needle body and base are in the same plane.
As shown in Fig. 2 embodiment 1：
The manufacture method of adhered detachable micropin, there are following steps：
（1）The microneedle array master mold 10 of SU-8 materials is made using photoetching process；
a）Microneedle array base patterns are drawn with AUTOCAD, make mask plate, the microneedle substrate of microneedle array base patterns
300 μm of figure length, wide 200 μm, 500 μm of the gap between micropin,
b）Prepare a piece of K9 glass wafers, as substrate of glass, sputter one layer of 300 thick metal of nm on the glass substrate
Chromium（Cr）；
c）The thick BP212-37s positive photo glues of subsequent 2 microns of spin coating one layer, with step 1）The mask plate of making is exposed
Light, dry 5 min with 0.5% sodium hydroxide developing liquid developing, after 100 DEG C and obtain patterned photoresist mask；
d）Then corrosion crome metal is corroded with CR-14（Cr）, then remove photoresist mask with acetone and obtain Cr masks
Version, so as to which photoetching SU-8 Cr mask plates are transferred in substrate of glass；
e）SU-8 photoresists are spun in substrate of glass, thickness is 500 μm；
f）From the canted exposure of the substrate of glass back side after 90 DEG C of drying, slant light exposure angle is 15 degree, often exposes and once revolves afterwards
Turn 90 degree, canted exposure again, so dried altogether after canted exposure four times, then with developing liquid developing, obtain SU-8 micropin battle arrays
Array structure.
（2）Make micropin female mold 5；
The mixed liquor of PDMS performed polymers and crosslinking agent is spun coating in the microneedle array master mold 10 of the SU-8 materials prepared,
Polymerizing curable is dried in 90 degree of vacuum tank 30 minutes.Then slough SU-8 materials microneedle array master mold 10 obtain it is micro-
Pin female mold 5.
（3）The micropin material 11 of liquid is filled up in the micropin groove of micropin female mold 5 and is solidified；
A kind of micropin material 11 of liquid, such as maltose solution containing proportion more than 30% are spun coating on the plate 6, by micropin
Female mold 5 is pressed against on the flat board 6 for the micropin material 11 for scribbling liquid, makes to fill up micropin body in the micropin groove of micropin female mold 5
Pre-polymer solution, flat board 6 is removed after the solidification of micropin body pre-polymer solution, the micropin 1 after solidification is left in micropin female mold 5；
Or directly the micropin material 11 of liquid is spun coating in micropin female mold 5, as proportion be more than 20% silk fibroin protein solution,
Then reuse flat board 6 to be pressed against in micropin female mold 5, make to fill up micropin body prepolymer in the micropin groove of micropin female mold 5 molten
Liquid, flat board 6 is removed after the solidification of micropin body pre-polymer solution, the micropin 1 after solidification is left in micropin female mold 5.Solidification process
It can dry and complete in 20 degree to 90 degree vacuum drying ovens.
（4）The substrate 2 that surface has tack coat is pressed in micropin female mold 5；
In order that micropin 1 and the durable bond of substrate 2 in micropin female mold 5, can apply appropriate pressure, and simultaneously
Heating so that melted after the local heating of micropin 1, then cooled and solidified ensures micropin so as to the durable bond of binding agent 3 with substrate 2
1 can subsequently depart from substrate 2.
It is cloudy that the substrate 2 of adhesive layer containing one layer of peelable type bonding agent composition is pressed against the micropin filled with micropin 1
On mould 5.Substrate 2 can use bio-compatibility flexible material, and bio-compatibility flexible material is hydrogel, polyvinylpyrrolidine
Ketone/polyvinyl acetate, triethyl citrate（triethyl citrate）, structure edge acid tributyl（Tributyl
Citrate）, trimethyl citrate, the plasticiser added in above-mentioned bio-compatibility flexible material is glycerine, castor oil, emulsification
One or more mixtures in agent T-80, polyethylene glycol 400；Or substrate 2 can also use flexible polymer, flexibility is gathered
Compound is cellulose, polyester, polypropylene, makrolon, polystyrene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-benzene second
One or more mixtures in alkene copolymer, dimethyl silicone polymer, Kynoar, acetate fiber, polyurethane.
（5）The micropin 1 in micropin female mold 5 is bonded with substrate 2, and together depart from micropin female mold 5 with substrate 2, obtain
To adhered flexible separable microneedle device.
As shown in figure 3, the application method of above-mentioned adhered separable microneedle device：（1）Extruding substrate 2 is pierced into micropin 1
Skin 4；（2）After being pierced into skin 4, the moisture wetting peelable type binding agent on the surface of skin 4 is coated in, reduces substrate 2 and micropin 1
Bonding force, then opening substrate 2 makes peelable type binding agent depart from micropin 1；（3）Micropin 1 stays in slow mechanism dissolved in skin 4 and released
Put and be wrapped in interior medicine.
As shown in figure 4, embodiment 2：
Needle tray formula separates the manufacture method of microneedle device, has following steps：
（1）Make microneedle array master mold 10；
（2）Make micropin female mold 5；
（3）Micropin body pre-polymer solution is filled up in the micropin groove of micropin female mold 5 and is solidified；
（4）Micropin female mold 5 is pressed against on viscosity transfer flat board 7, micropin 1 is transferred on viscosity transfer flat board 7；
（5）Micropin 1 is transferred in transfer mold 8 using viscosity transfer flat board 7, the micropin groove of the transfer mold 8
Depth is less than the depth of the micropin groove of micropin female mold 5；
（6）Micropin 1 in transfer mold 8 is transferred on the substrate 2 for being carved with needle tray, micropin 1 is embedded in needle tray, and with substrate
2 together depart from micropin female mold 5, obtain the flexible detachable microneedle device of needle tray formula.
Manufacturing process（1）Extremely（4）It can refer to embodiment 1.
Manufacturing process（5）In the transfer mold 8 with shallower micropin groove the step of embodiment 1 can be used（1）With（2）Institute
The manufacture method stated is fabricated.
Manufacturing process（6）Middle utilize is laser-ablated in silica gel（PDMS）Made on surface corresponding with the bottom shape of micropin 1
Needle tray, using be used as connection micropin 1 substrate 2.
As shown in figure 5, needle tray formula separates the application method of microneedle device：（1）Extruding substrate 2 makes micropin 1 be pierced into skin
4；（2）Substrate 2 is opened upwards, because the adhesion of micropin 1 and the needle tray of substrate 2 is weaker, substrate 2 departs from micropin 1；（3）It is micro-
Pin 1 stays in slow mechanism dissolved release in skin 4 and is wrapped in interior medicine.
As shown in fig. 6, embodiment 3：
The manufacture method of the adhered separable microneedle device of multiple rows of assembling：（1）Use resolvability material such as fibroin egg
White and maltose material is prepared into coplanar microneedle array 9, and the thickness of coplanar microneedle array 9 is less than its width；（2）It is multiple same
Plane microneedle array 9 is vertically or tiltedly embedded in the needle tray of substrate 2, the shape of needle tray and the micropin base of coplanar microneedle array 9
Shape is corresponding, and is fixed with bonding agent to obtain different plane microneedle array.
As shown in fig. 7, the application method of the adhered separable microneedle device of multiple rows of assembling：（1）Extruding substrate 2 makes coplanar
Microneedle array 9 is pierced into skin 4；（2）Translation substrate 2 makes coplanar microneedle array 9 be broken in bonding part；（3）It is post-rift same flat
Face microneedle array 9 stays in slow mechanism dissolved in skin 4 and discharges medicine.
Claims (9)
1. a kind of preparation method of detachable microneedle device, it is characterized in that：With following steps：
1) micropin female mold (5) is made；
2) micropin body pre-polymer solution is filled up in the micropin groove of micropin female mold (5) and is solidified；
3) micropin female mold (5) is pressed against on viscosity transfer flat board (7), micropin (1) is transferred to viscosity transfer flat board (7)
On；
4) micropin (1) is transferred in transfer mold (8) using viscosity transfer flat board (7), the micropin groove of the transfer mold (8)
Depth be less than micropin female mold (5) micropin groove depth；
5) micropin (1) in transfer mold (8) is transferred on the substrate (2) for being carved with needle tray, micropin (1) insertion needle tray, and with
Substrate (2) together departs from transfer mold (8), obtains detachable microneedle device,
The detachable microneedle device, including micropin (1) and substrate (2), it is characterized in that：Described micropin (1) is separably solid
It is scheduled on substrate (2), after micropin (1) is pierced into skin, separation micropin (1) and substrate (2), micropin (1) is stayed in skin (4)
It is interior,
Described micropin (1) is detachably fastened on substrate (2) by binding agent (3), and binding agent (3) bonds for peelable type
Agent, soluble-type binding agent or structural strength are less than the binding agent of micropin needle structure intensity,
There is needle tray, the bottom insertion needle tray of micropin (1), micropin (1) has between needle tray on the surface of described substrate (2)
Binding agent (3), micropin (1) are detachably fastened on substrate (2) by the bonding force of binding agent (3)；
Or the detachable microneedle device, including micropin (1) and substrate (2), it is characterized in that：Described micropin (1) is separable
Ground is fixed on substrate (2), after micropin (1) is pierced into skin, separation micropin (1) and substrate (2), micropin (1) is stayed in skin
(4) in,
There is needle tray on the surface of described substrate (2), the bottom insertion needle tray of micropin (1), micropin (1) by micropin (1) with
Mechanical bonding force between needle tray is detachably fastened on substrate (2)；
Or the detachable microneedle device, including micropin (1) and substrate (2), it is characterized in that：Described micropin (1) is separable
Ground is fixed on substrate (2), after micropin (1) is pierced into skin, separation micropin (1) and substrate (2), micropin (1) is stayed in skin
(4) in,
There is needle tray, the bottom insertion needle tray of micropin (1), micropin (1) has between needle tray on the surface of described substrate (2)
Binding agent (3), micropin (1) are common by the bonding force of mechanical bonding force of the micropin (1) between needle tray and binding agent (3)
Effect is detachably fastened on substrate (2).
2. the preparation method of detachable microneedle device according to claim 1, it is characterized in that：Described peelable type is glued
Tie the pressure sensitive adhesive that agent is peelable type；Described soluble-type binding agent is that viscose glue is can dissolve made of albumen or starch.
3. the preparation method of detachable microneedle device according to claim 1, it is characterized in that：Described micropin (1) is
Haplotype micropin, needle tray are corresponding with the shape of the bottom of each haplotype micropin.
4. the preparation method of detachable microneedle device according to claim 1, it is characterized in that：Described micropin (1) is
Coplanar microneedle array (9), needle tray is corresponding with the shape of the base of coplanar microneedle array (9), multiple coplanar micropin battle arrays
Arrange (9) embedded substrate (2) and form different plane microneedle array.
5. the preparation method of detachable microneedle device according to claim 1, it is characterized in that：Described micropin (1) by
The degradable micropin material of bio-compatible is made, added in the degradable micropin material of bio-compatible one or more medical treatment or
The active material of beautifying use.
6. the preparation method of detachable microneedle device according to claim 1, it is characterized in that：Described substrate (2) by
Flexible material is made.
7. the preparation method of detachable microneedle device according to claim 6, it is characterized in that：Described flexible material is
Bio-compatibility flexible material, bio-compatibility flexible material are hydrogel, polyvinylpyrrolidone and polyvinyl acetate
Mixture, triethyl citrate, structure edge acid tributyl, trimethyl citrate, add in above-mentioned bio-compatibility flexible material
Plasticiser is one or more mixtures in glycerine, castor oil, emulsifying agent T-80, polyethylene glycol 400；
Or flexible material is flexible polymer, flexible polymer be cellulose, polyester, polypropylene, polystyrene, polyethylene,
One in polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, dimethyl silicone polymer, Kynoar, acetate fiber
Kind or a variety of mixtures.
8. the preparation method of detachable microneedle device according to claim 1, it is characterized in that：Described micropin (1) hangs down
It is fixed on directly or obliquely on substrate (2).
9. the preparation method of detachable microneedle device according to claim 7, it is characterized in that：Described polyester is poly- carbon
Acid esters or polyurethane.
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