CN104117137B - Unloaded medicine microneedle array and preparation method thereof in a kind of capsule-type - Google Patents
Unloaded medicine microneedle array and preparation method thereof in a kind of capsule-type Download PDFInfo
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- CN104117137B CN104117137B CN201410323437.9A CN201410323437A CN104117137B CN 104117137 B CN104117137 B CN 104117137B CN 201410323437 A CN201410323437 A CN 201410323437A CN 104117137 B CN104117137 B CN 104117137B
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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
- A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
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- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
Unloaded medicine microneedle array and preparation method thereof, belongs to technical field of medical instruments in a kind of capsule-type.The present invention is arranged in the needle point in substrate containing microneedle substrate and array；There is hollow structure, hollow structure runs through substrate inside needle point, forms " capsule " formula structure inside each needle point.The present invention can once complete the administration of particular area and skin site, compared with the solid microneedles of identical size, considerably increase drugloading rate, and pharmaceutical activity can be kept as far as possible, dosing techniques efficiency high, facilitate doctor and patient, mitigate patient suffering, and it is administered uniformly, the synchronization of drug diffusion onset time is realized, so as to effectively increase the effect of cutaneous penetration.Present invention also offers the method for preparing unloaded medicine microneedle array in capsule-type.
Description
Technical field
The present invention relates to a kind of microneedle array through skin transport medicine, belong to technical field of medical instruments.
Background technology
Skin is a preferable position of drug delivery.With being administered orally or the noninvasive administration mode such as topical administration
Compare, drug administration by injection has its irreplaceable advantage.By taking intravenous injection as an example, drug delivery directly can be entered blood by it, with
Blood circulation and arrive at focus, compared with being administered orally and being absorbed the drug using alimentary canal, there is faster speed and Geng Gao medicine
Utilization rate.Moreover, the burden to digestive system and unnecessary harm that it can also effectively avoid that oral drugs bring.Pass
Why the injection system of system can bring pain, be because the presence of human skin cuticula has obstructed the transdermal penetration of medicine,
This road barrier must be passed through by syringe, can just medicine is effectively absorbed.And because the size of conventional syringe limits
System, skin corium will be penetrated and cause pain nerve excited, so as to give people to bring sense of discomfort.However, patient generally because pain without
Like this effective and efficient injected s. c, particularly old man and child.
In order to transmit medicine, the even polypeptide of some macromoleculars, protein and DNA into human body by skin, just need
Want a kind of administering mode for the sense of discomfort for hindering and patient being mitigated that can overcome keratoderma.Conventional research is
Through having summed up by Medicine small molecule or by some outside energies, such as electric current or ultrasonic wave, to strengthen Medicated Permeation
Ability.
Painless administration can be realized using micropin technology, by the size Control to micropin, epidermis can be penetrated, more
Cross cuticula, without touching skin corium, so as to avoid the contact with nerve fibre and blood, it also avoid bleeding naturally or
It is pain.Micropin generally occurs in an array manner；One microneedle array can include tens of to hundreds of small projections, high
From 25 to 2000 micron, bottom is connected on a fixed pedestal degree.The manufacturing process of traditional micropin is typically by micro-
Electromechanical technology is completed.
Microneedle array is once placed in skin, and micropore of multiple diameters in micron level can be formed on skin, as oozing
Saturating path, drug molecule, compound and particulate can be transmitted.Transmission means caused by different micropin types
Also it is not quite similar.Common micropin type is divided to two major classes, solid class and middle empty class.Middle empty class is readily understood by, with traditional note
It is similar to penetrate syringe needle；There is a hole at the center of middle empty class micropin, is available for medicine by being permeated in export-oriented skin, and can realize continuous
The process of administration, material are usually metal or silicon.And solid class can be divided into three kinds according to the difference of transmission means：Penetrate patch
Types of Medicine, coating type and degradation-type.The main material for penetrating patch Types of Medicine micropin is silicon or stainless steel, and its transmission means is to pass through point
End punctures on skin, removes microneedle array after forming micropore, medicine is attached to form micropore in the form of gel or paster
Skin at, then be transmitted by spreading or being aided with other external strengths.Coating type micropin is then typically made of metal or silicon,
Transmission means and the difference of penetration type are that medicine is that microneedle surface is coated in a manner of coating, and micropin then is inserted into skin
Skin, it is to be sent into medicine by the dissolving of coating.The special character of degradation-type micropin is then its material, carbohydrate, starch chain, can
The acid and the material such as ketone of degraded may be used to make degradation-type micropin, and the key made be by medicine with it is degradable
Together, hardness and biofacies content needle-like all up to specification is made in material fusion, by the automatic degraded of micropin in vivo,
Release medicine internal.
From current clinical practice, undoubtedly the degradable more applicable clinical practice of the pin that declines, essentially consists in its good life
Thing compatibility feature；The micropin of metal or silicon materials, and micro-structural makes them inevitably break to fall in skin when in use,
So as to cause to damage to human body, this just greatly improves the micropin application risk of these materials.The degradable pin that declines can make up
These problems, more suitable for clinical practice.But the preparation of current degradable micropin relies on the characteristic of needle body shaping biomaterial, and
And need the medicine of delivering being merged with biomaterial, be so likely to affect medicinal property, and drugloading rate compared with
It is low, it is impossible to load the materials such as bacterium, stem cell of living.
The content of the invention
In view of the deficiencies of the prior art, the present invention provides unloaded medicine microneedle array and preparation method thereof in a kind of capsule-type,
It is set both to have kept degradable microneedle array function and performance, simple in construction, safe to use, personal convenience, cost are cheap, and
And drugloading rate can be increased, and can be used for the subcutaneous delivery of the materials such as stem cell, bacterium living.
To achieve the above object, technical scheme is as follows：
Unloaded medicine microneedle array in a kind of capsule-type, the microneedle array contains substrate and array is arranged in pin in substrate
Point；It is characterized in that：There is hollow structure, hollow structure runs through substrate inside needle point, is formed " capsule " inside each needle point
Formula structure；The base material of microneedle array uses degradable high polymer material.
In above-mentioned technical proposal, described degradation material is using fibroin albumen, polyvinyl alcohol, carboxymethyl cellulose, half
Lactose, methyl vinyl ether copolymer, polyvinylpyrrolidone, polyacrylic acid or hyaluronic acid.
The present invention another technical characteristic be：Described hollow structure accounts for the 1/5~4/5 of needle point whole height.Described
Needle point is shaped as pyramid or cone.
The preparation method of unloaded medicine microneedle array in a kind of capsule-type provided by the invention, it is characterised in that this method includes
Following steps：
1) microneedles template is made：Silicon material is prepared using the method for micro-nano processing technology, laser cutting or mechanical engraving
Material, the microneedles template of metal material；
2) mould is made：It is 8 by volume by polydimethylsiloxane prepolymer thing and curing agent:1 to 12:1 is mixed,
Stir and vacuumize；Then, the liquid dimethione for removing bubble is poured on microneedles template, as
In 70-85 °C of baking oven, 1-2 hour, that is, the dimethyl silicone polymer of solid-state is obtained, then it tears from microneedles template,
Form the dimethyl silicone polymer mould of the micropore with array-like；
3) again by degradation material and deionized water according to 1.5-20% mass volume ratio wiring solution-forming, poly- two are poured into
In methylsiloxane mould；
4) 5-10 minutes are vacuumized, or it is 30 minutes small to 1.5 with 2500g-3500gg dynamics centrifugation using centrifuge
When so that solution or colloid are sufficiently filled in the hole of dimethyl silicone polymer, then by the solution or colloid on mould top layer
Remove, normal temperature, which is stood, to be dried 10-30 hours, and dissolving or colloid drying and forming-film are attached to die surface, will solidify obtained film from
Separated on mould, that is, obtain unloaded medicine microneedle array in degradable capsule-type.
Present invention also offers another preparation method of unloaded medicine microneedle array in the capsule-type, it is characterised in that should
Method comprises the following steps：
1) microneedles template and typified form of metal material are prepared using the method for laser cutting or mechanical engraving；
2) mould is made：It is 8 by volume by polydimethylsiloxane prepolymer thing and curing agent:1 to 12:1 is mixed,
Stir and vacuumize, the liquid dimethione for removing bubble is poured on microneedles template, is subsequently placed in baking
In case, 1-2 hours are toasted at a temperature of 70 DEG C -85 DEG C, that is, obtain the dimethyl silicone polymer of solid-state, then poly- two by solid-state
Methylsiloxane is torn from microneedles template, forms the dimethyl silicone polymer mould with array-like micropore；
3) degradation material and deionized water are poured into according to 1.5-20% mass volume ratio wiring solution-forming or colloid
In dimethyl silicone polymer mould；
4) 5-10 minutes are vacuumized, or it is 30 minutes small to 1.5 with 2500g-3500gg dynamics centrifugation using centrifuge
When so that solution or colloid are sufficiently filled in the hole of dimethyl silicone polymer；By neck by the array in typified form
Position is alignd with array position in dimethyl silicone polymer mould, and typified form is buckled in into dimethyl silicone polymer die surface
In solution or colloid, and inwardly compress；Normal temperature, which is stood, dries 10-30 hours；First take out typified form, then from poly dimethyl silicon
The part of degradation material solidification is removed on oxygen alkane mould, that is, obtains unloaded medicine microneedle array in degradable capsule-type.
The present invention compared with prior art, has advantages below and high-lighting effect：1. the microneedle array of the present invention uses
Hollow structure, there is bigger drugloading rate relative to degradable solid microneedles, and more preferably keep pharmaceutical activity；2. the present invention's
Microneedle array introduces typified form and forms intact hollow structure, so as to a kind of new method as making hollow microneedles；3. this
The degradable hollow microneedle arrays of invention packaging medicine by way of capsule, can be used for living bacterium and stem cell etc. are with life
The subcutaneous delivery of the medicine of thing activity, this is that the current degradable pin that declines is irrealizable；4. the present invention has structure letter
The features such as list, small volume, cost are low, esy to use, safe and reliable.
Brief description of the drawings
Fig. 1 is the front view structure signal of dimethyl silicone polymer (PDMS) mould, microneedle array, typified form of the present invention
Figure.
Fig. 2 is the structural representation of unloaded medicine microneedle array in capsule-type.
Fig. 3 is the flow chart for making unloaded medicine microneedle array in capsule-type using bimodulus legal system.
Fig. 4 is that a kind of PDMS moulds of unloaded embodiment of medicine microneedle array, the front view structure of microneedles template are shown in capsule-type
It is intended to.
Fig. 5 is a kind of microneedles template structural representation of unloaded embodiment of medicine microneedle array in capsule-type.
Fig. 6 is a kind of typified form structural representation of unloaded embodiment of medicine microneedle array in capsule-type.
In figure：1- needle points；2- substrates；3- hollow structures；4- dimethyl silicone polymer moulds；5- typified forms；6- necks；
7- microneedles templates.
Embodiment
Described in detail below in conjunction with principle, structure and specific implementation of the accompanying drawing to the present invention.
Unloaded medicine microneedle array, is arranged in substrate containing substrate 2 and array in a kind of capsule-type provided by the invention
Needle point 1, there is hollow structure 3 inside each needle point, hollow structure runs through substrate 2, formation " capsule " formula knot from the inside of needle point 1
Structure.The base material of microneedle array uses degradable high polymer material, such as degradable high polymer material to use fibroin albumen, poly- second
Enol, carboxymethyl cellulose, galactolipin, methyl vinyl ether copolymer, polyvinylpyrrolidone, polyacrylic acid or hyalomitome
Acid.
The hollow structure of the present invention typically constitutes from the 1/5~4/5 of needle point whole height；Its needle point is shaped as pyramid or circle
Taper (as shown in Figure 2).
The preparation method of unloaded medicine microneedle array, this method specifically comprise the following steps in capsule-type provided by the invention：
1) microneedles template is made：Silicon material is prepared using the method for micro-nano processing technology, laser cutting or mechanical engraving
Material, the microneedles template of metal material；
2) mould is made：It is 8 by volume by polydimethylsiloxane prepolymer thing and curing agent:1 to 12:1 is mixed,
Stir and vacuumize；Then, the liquid dimethione for removing bubble is poured on microneedles template, as
In 70-85 °C of baking oven, 1-2 hour, that is, the dimethyl silicone polymer of solid-state is obtained, then it tears from microneedles template,
Form the dimethyl silicone polymer mould of the micropore with array-like；
3) again by degradation material and deionized water according to 1.5-20% mass volume ratio wiring solution-forming, poly- two are poured into
In methylsiloxane mould；
4) 5-10 minutes are vacuumized, or it is 30 minutes small to 1.5 with 2500g-3500gg dynamics centrifugation using centrifuge
When so that solution or colloid are sufficiently filled in the hole of dimethyl silicone polymer, then by the solution or colloid on mould top layer
Remove, normal temperature, which is stood, to be dried 10-30 hours, and dissolving or colloid drying and forming-film are attached to die surface, will solidify obtained film from
Separated on mould, that is, obtain unloaded medicine microneedle array in degradable capsule-type.
The preparation method of unloaded medicine microneedle array in another capsule-type provided by the invention, this method include following step
Suddenly：
1) microneedles template and typified form of metal material are prepared using the method for laser cutting or mechanical engraving；
2) mould is made：It is 8 by volume by polydimethylsiloxane prepolymer thing and curing agent:1 to 12:1 is mixed,
Stir and vacuumize, the liquid dimethione for removing bubble is poured on microneedles template, is subsequently placed in baking
In case, 1-2 hours are toasted at a temperature of 70 DEG C -85 DEG C, that is, obtain the dimethyl silicone polymer of solid-state, then poly- two by solid-state
Methylsiloxane is torn from microneedles template, forms the dimethyl silicone polymer mould with array-like micropore；
3) degradation material and deionized water are poured into according to 1.5-20% mass volume ratio wiring solution-forming or colloid
In dimethyl silicone polymer mould；
4) 5-10 minutes are vacuumized, or it is 30 minutes small to 1.5 with 2500g-3500gg dynamics centrifugation using centrifuge
When so that solution or colloid are sufficiently filled in the hole of dimethyl silicone polymer；By neck by the array in typified form
Position is alignd with array position in dimethyl silicone polymer mould, and typified form is buckled in into dimethyl silicone polymer die surface
In solution or colloid, and inwardly compress；Normal temperature, which is stood, dries 10-30 hours；First take out typified form, then from poly dimethyl silicon
The part of degradation material solidification is removed on oxygen alkane mould, that is, obtains unloaded medicine microneedle array in degradable capsule-type.
Accompanying drawing of the present invention uses the microneedle array of 3*3 structures, and the structure of microneedle array and the preparation method of microneedle array are tight
It is close to link together.It typically for the shape of micropin, can suitably set, can readily be pierced into skin, be pierced into body
It is interior to can dissolve and do not cause pain or bleeding, preferably rectangular pyramid.Micropin without rib is when being pierced into skin, due to skin
Elasticity, it will produce resistance from all directions, finally overcome resistance to enter in skin, cause tearing property to damage to skin, and have
The micropin of rib is after skin is contacted, and because pressure will produce shearing force to skin at rib, opens skin along the shearing of rib direction, reduces resistance
It it also avoid pullling the violent of skin while power, so as to reduce wound.
Fig. 1 is the dimethyl silicone polymer mould of unloaded medicine microneedle array, microneedle array, the master of typified form in capsule-type
Depending on structural representation.Three modules can be according to the concaveconvex structure perfect adaptation on surface together.Wherein, microneedles template 7 is with determining
The both sides of pattern plate 5 have neck 6, available for the thickness of determination substrate, while also make micropin accurate positioning in manufacturing process.
Fig. 3 is the flow chart for making unloaded medicine microneedle array in capsule-type using bimodulus legal system.Use silicon materials or metal
Other non-degradable materials such as material produce microneedles template and typified form, and PDMS moulds are made using microneedles template, then will
The material wiring solution-forming or colloid of the selected degradable micropin of making, are poured into PDMS moulds, through centrifuging after a while
After buckle typified form, microneedle array is obtained after drying.
Fig. 4 is main view (section) structural representation of the PDMS moulds of unloaded medicine microneedle array in capsule-type, microneedles template.
Ensure that liquid PDMS being capable of fully wrapped around microneedles template.
Fig. 5 is the microneedles template structural representation of unloaded medicine microneedle array in capsule-type.By metal material etc. it is other it is non-can
Degraded material makes through laser cutting parameter.
Fig. 6 is the typified form structural representation of unloaded medicine microneedle array in capsule-type.By metal material etc. it is other it is non-can
Degraded material makes through laser cutting parameter.
By degradable formula hollow microneedles are compared with hollow microneedles before in the present invention, hollow microneedles are typically adopted before
With non-degradable material, there is a hole at the center of needle point, is available for medicine by being permeated in export-oriented skin, it is possible to achieve successive administration
Process, can be used continuously；It is disposable and hollow microneedles use degradation material, enter human body equivalent to by skin
Medicament capsule.
Because micropin inner space is big, different pharmaceutical can be stored, also stores the medicine of larger particles, while can also be used
In stem cell, the subcutaneous delivery of live bacterial cell.
The drug release mode of degradable hollow microneedle arrays in the present invention, degradation material before can using with
Medicine mixes, and after microneedle array is pierced into skin, degradable needle point can dissolve within a certain period of time after running into body fluid
To discharge medicine；Can also be that medicine is stored in the hollow structure of microneedle array, because the size of micropin is in micron order, medicine
Thing solution can be adsorbed in hollow structure by capillarity, while is sealed using diaphragm seal, and microneedle array is pierced into
After skin, degradable needle point can dissolve within a certain period of time after running into body fluid, so as to the medicine that will be stored in hollow structure
Release；Also can be combined together using two methods.These delivering release designs can be according to the application demand of different pharmaceutical
To design, to meet the demand of different clinical applications.
Embodiment 1：
(1) stainless steel material needle mould plate is prepared using laser cutting method.
(2) PDMS moulds are made using microneedles template.It is 10 by volume by PDMS prepolymers and curing agent：1 is mixed
Close, stir and vacuumize；Then, the liquid dimethione for removing bubble is poured on microneedles template, extremely
Dried 1.5 hours in 80 DEG C of baking oven, that is, obtain the dimethyl silicone polymer of solid-state, then it tears from microneedles template,
Form the dimethyl silicone polymer mould of the micropore with array-like.；
(3) silk fibroin protein solution of mass volume ratio 8% is poured into dimethyl silicone polymer mould；
(4) vacuumize 5 minutes, the silk fibroin protein solution on mould top layer is removed, normal temperature, which is stood, to be dried 20 hours, fibroin egg
White solution drying and forming-film is attached to die surface, and the film that solidification obtains is separated from mould, that is, obtained in fibroin albumen
Empty microneedle array.
Embodiment 2：
(1) stainless steel material needle mould plate and typified form are prepared using laser cutting method.
(2) PDMS moulds are made using microneedles template.It is 10 by volume by PDMS prepolymers and curing agent：1 is mixed
Close, stir and vacuumize；Then, the liquid dimethione for removing bubble is poured on microneedles template, extremely
Dried 1.5 hours in 80 DEG C of baking oven, that is, obtain the PDMS oxygen alkane of solid-state, then it tears from microneedles template, form band
There are the PDMS moulds of the micropore of array-like.；
(3) polyethylene solution of mass volume ratio 15% is poured into PDMS moulds；
(4) vacuumize 5 minutes.By neck by array position pair in the array position in typified form and PDMS moulds
Together, typified form is buckled in the polyethylene solution of PDMS die surfaces, and inwardly compressed.Normal temperature, which is stood, dries hour.First take out
Typified form, then removed from PDMS moulds polyethylene solidification part for the hollow microneedles battle array of polythene material
Row.
In the present invention microneedle array can deliver it is various can intramuscular injection medicine, macromolecular drug, DNA, vaccine, also may be used
To deliver cell, bacterium, special material medicine etc..
Claims (5)
1. unloaded medicine microneedle array in a kind of capsule-type, the microneedle array contains substrate (2) and array is arranged in substrate
Needle point (1)；It is characterized in that：There is hollow structure (3), hollow structure (3) passes through inside needle point (1) inside each needle point (1)
Substrate (2) is worn, forms " capsule " formula structure；The needle point (1) and the hollow structure (3) are in rectangular pyramid；Microneedle array
Base material use degradable high polymer material, the size of the micropin of the microneedle array is made in micron order, drug solution by capillary
With absorption in the hollow structure, while carry out sealing the hollow structure using diaphragm seal；Described degradable macromolecule
Material is using fibroin albumen, polyvinyl alcohol, carboxymethyl cellulose, galactolipin, methyl vinyl ether copolymer, polyvinylpyrrolidine
Ketone, polyacrylic acid or hyaluronic acid.
2. unloaded medicine microneedle array in a kind of capsule-type as claimed in claim 1, it is characterised in that：Described hollow structure accounts for
The 1/5~4/5 of needle point whole height.
3. unloaded medicine microneedle array in a kind of capsule-type as claimed in claim 1, it is characterised in that：The shape of described needle point
For pyramid or cone.
A kind of 4. preparation method of unloaded medicine microneedle array in capsule-type as claimed in claim 1, it is characterised in that this method bag
Include following steps：
1) microneedles template is made：Silicon materials, gold are prepared using the method for micro-nano processing technology, laser cutting or mechanical engraving
Belong to the microneedles template of material；
2) mould is made：It is 8 by volume by polydimethylsiloxane prepolymer thing and curing agent:1 to 12:1 is mixed, fully
Stir and vacuumize；Then, the liquid dimethyl silicone polymer for removing bubble is poured on microneedles template, as 70-
In 85 DEG C of baking oven, 1-2 hours, that is, the dimethyl silicone polymer of solid-state is obtained, then it tears from microneedles template, formed
The dimethyl silicone polymer mould of micropore with array-like；
3) again by degradation material and deionized water according to 1.5-20% mass volume ratio wiring solution-forming, it is poured into poly dimethyl
In silicone mold；
4) 5-10 minutes are vacuumized, or are centrifuged 30 minutes to 1.5 hours with 2500g-3500g dynamics using centrifuge, are made
Obtain solution or colloid be sufficiently filled in the hole of dimethyl silicone polymer, then remove the solution on mould top layer or colloid,
Normal temperature, which is stood, to be dried 10-30 hours, and solution or colloid drying and forming-film are attached to die surface, will solidify obtained film from mould
Separate, that is, obtain unloaded medicine microneedle array in degradable capsule-type.
A kind of 5. preparation method of unloaded medicine microneedle array in capsule-type as claimed in claim 1, it is characterised in that this method bag
Include following steps：
1) microneedles template and typified form of metal material are prepared using the method for laser cutting or mechanical engraving；
2) mould is made：It is 8 by volume by polydimethylsiloxane prepolymer thing and curing agent:1 to 12:1 is mixed, fully
Stir and vacuumize, the liquid dimethyl silicone polymer for removing bubble is poured on microneedles template, is subsequently placed in baking oven
In, 1-2 hours are toasted at a temperature of 70 DEG C -85 DEG C, that is, obtain the dimethyl silicone polymer of solid-state, then the poly- diformazan by solid-state
Radical siloxane is torn from microneedles template, forms the dimethyl silicone polymer mould with array-like micropore；
3) degradation material and deionized water are poured into poly- two according to 1.5-20% mass volume ratio wiring solution-forming or colloid
In methylsiloxane mould；
4) 5-10 minutes are vacuumized, or are centrifuged 30 minutes to 1.5 hours with 2500g-3500g dynamics using centrifuge, are made
Obtain solution or colloid is sufficiently filled in the hole of dimethyl silicone polymer；By neck by the array position in typified form with
In dimethyl silicone polymer mould array position align, by typified form be buckled in dimethyl silicone polymer die surface solution or
In person's colloid, and inwardly compress；Normal temperature, which is stood, dries 10-30 hours；First take out typified form, then from dimethyl silicone polymer mould
The part of degradation material solidification is removed on tool, that is, obtains unloaded medicine microneedle array in degradable capsule-type.
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| CN104888284B (en) * | 2015-05-07 | 2017-12-22 | 苏州大学 | Hollow fibroin albumen micropin delivery system of swelling type and preparation method thereof |
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