CN110075365A - A kind of hydrogel containing hydrophilic medicament takes bolt bracket preparation method - Google Patents
A kind of hydrogel containing hydrophilic medicament takes bolt bracket preparation method Download PDFInfo
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- CN110075365A CN110075365A CN201910361799.XA CN201910361799A CN110075365A CN 110075365 A CN110075365 A CN 110075365A CN 201910361799 A CN201910361799 A CN 201910361799A CN 110075365 A CN110075365 A CN 110075365A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/045—Gelatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/145—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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Abstract
The present invention provides a kind of hydrogels for containing hydrophilic medicament to take bolt bracket and preparation method thereof, including taking bolt bracket and being coated on the hydrogel layer for taking bolt rack surface；The hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking；The inner aqueous phase of the W/O/W type nano-emulsion is hydrophilic medicament solution, and oil is mutually emulsifier, and outer aqueous phase includes gelatin, photoinitiator, polyvinylpyrrolidone and the lauryl sodium sulfate of methacrylation.The present invention is not under the premise of influencing the flexibility and the planning function of metallic support, after hydrogel tunic encounters blood, realize swelling rapidly, to accelerate discharging rapidly for internal drug, the hydrophilic medicament of release can efficiently penetrate tissue resorption, the availability of local organization is improved, and then realizes inhibition thrombosis and promotes the clinical treatment purpose of thrombolysis.
Description
Technical field
The invention belongs to the field of medical instrument technology more particularly to a kind of hydrogel for containing hydrophilic medicament to take bolt bracket
And preparation method thereof.
Background technique
With since 2015, machinery takes the relevant five big randomized clinical result of study of bolt treatment acute ischemic cerebral apoplexy
It continuously delivers, bracket takes bolt technology to be recommended as the clinical first line therapy technology that intracranial vessel occlusion is opened by guide.With
Simple intravenous thrombolysis compares, and bracket takes bolt to may be implemented to occlude quickly leading to again for big blood vessel, so that apoplexy patient obtains more preferably
Prognosis, while not increasing bleeding risk.
Bracket takes bolt as a kind of invasive surgical procedure, takes bolt efficiency to improve, metallic support needs to have one
Fixed radial support power realizes the recycling of thrombus by cutting, attaching and the clamping to thrombus.Therefore inevitable, it is above-mentioned
Need whole process in open state during rack restoring, stent wire can generate apparent scraping to vascular wall and act on.Early period
Research shows that taking bolt to operate on the bracket in normal lumina, damage is mainly limited to endodermis and interior elastic plate, scanning electron microscope
Display is with the focal loss of endothelial cell for main feature；And taking bolt to operate on the bracket in Stenosis, damage can be involved
Inner membrance, middle film even damage (the J Neurointerv Surg.2018 of tube wall holostrome；10:1085-1091).Once intravascular
Film endothelial cell destroys extensively or vessel wall damage is serious, causes collagenous fibres over-exposure, by triggering exogenous cruor pathway,
It can induce new life thrombosis.
Different with American-European crowd, asian population Intracranial Atherosclerosis lesion disease incidence can be up to 33%~50%,
In the case where blood vessel has lesion even severe stenosis, when taking that bracket passes through Stenosis with compressive state during bolt, tool
There are higher radial support power, more easy damaged vascular wall；Likewise, wire is inevitably to existing after bracket release
Thrombosis cutting, causes thrombi to tear.Fibre composition either inside vascular wall collagenous fibres or thrombus is exposed to
After blood constituent, new coagulant can be used as, on the basis of existing thrombus, further sprawling forms fresh thrombus；
Finally, metallic support, although having good bio-compatible performance in hematological system, et al. Ke and recycling are grasped repeatedly
Make, the Hemodynamic characteristics that operating time is too long in addition and the lesion part stasis of blood is stagnant, metallic support as exogenous foreign matter,
The potential risk of newborn thrombosis is unavoidably had on surface.
Therefore, it is current take bolt stent in the treatment narrow on the basis of intracranial vessel occlusion lesion have again occlusion rate it is high,
The technological deficiency of vessel wall damage weight, then occlude mainly based on the formation of secondary fresh thrombus.
Summary of the invention
The purpose of the present invention is to provide a kind of hydrogels for containing hydrophilic medicament to take bolt bracket and preparation method thereof, this
Hydrogel in invention takes bolt bracket to be able to suppress the formation of new thrombus and promotes thrombolysis.
The present invention provides a kind of hydrogel for containing hydrophilic medicament and takes bolt bracket, including takes bolt bracket and be coated on described
Take the hydrogel layer of bolt rack surface；
The hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking；
The inner aqueous phase of the W/O/W type nano-emulsion is hydrophilic medicament solution, and oil is mutually soybean oil and emulsifier, outer aqueous phase
Gelatin, photoinitiator, polyvinylpyrrolidone and lauryl sodium sulfate including methacrylation.
Preferably, emulsifier is Tween-80 and Arlacel-80；
The mass ratio of the Tween-80 and Arlacel-80 is (1~3): 1；
The mass ratio of the soybean oil and emulsifier is 1:(1~5).
Preferably, in the outer aqueous phase, the mass fraction of the gelatin of methacrylation is 5~20%；It is described light-initiated
The mass fraction of agent is 0.5~2%；The mass fraction of the polyvinylpyrrolidone is 0.1~2%；The dodecyl sulphur
The mass fraction of sour sodium is 0.1~1%.
Preferably, the mass concentration of the hydrophilic medicament solution is (0.01~1) μ g/ μ L.
Preferably, the mass ratio of the inner aqueous phase and oily phase is (0.05~0.2): (0.8~0.95)；
The inner aqueous phase is (2~3) with the quality summation of oily phase and the mass ratio of outer aqueous phase: 1.
The present invention provides the preparation method that a kind of hydrogel for containing hydrophilic medicament takes bolt bracket, comprising the following steps:
A) under agitation, inner aqueous phase is added dropwise in oil-phase solution, obtains w/o type nanometer colostrum；Inner aqueous phase is parent
Aqueous pharmaceutical solution；
B) under stirring conditions, the w/o type nanometer colostrum is added dropwise in outer aqueous phase solution, obtains W/O/W type and receives
Rice milk；Oily is mutually emulsifier, and outer aqueous phase includes the gelatin, photoinitiator, polyvinylpyrrolidone and 12 of methacrylation
Sodium alkyl sulfate；
C bolt bracket) will be taken to be immersed in the W/O/W type nano-emulsion, carry out being crosslinked under ultraviolet light after taking-up anti-
It answers, the hydrogel for obtaining containing hydrophilic medicament takes bolt bracket.
Preferably, described to take bolt bracket before being immersed in the W/O/W type nano-emulsion, first carry out abrasive Flow polishing and/
Or carboxylated surface processing.
Preferably, the step C) in impregnate time be 30~120s.
Preferably, the step C) in ultraviolet light wavelength be 365nm；
The exposure intensity of the ultraviolet light is 500~700mW/cm2；
The irradiation time of the ultraviolet light is 100~200s；
The spot diameter of the ultraviolet light is 1.2cm.
It preferably, further include drying after the ultraviolet irradiation step；
The temperature of the drying is 35~40 DEG C；
The time of the drying is 0.5~4 hour.
The present invention provides a kind of hydrogels for containing hydrophilic medicament to take bolt bracket, including takes bolt bracket and be coated on institute
State the hydrogel layer for taking bolt rack surface；The hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking；The W/O/W type
The inner aqueous phase of nano-emulsion is hydrophilic medicament solution, and oil is mutually emulsifier, and outer aqueous phase includes that the gelatin of methacrylation, light draw
Send out agent, polyvinylpyrrolidone and lauryl sodium sulfate.The methacryl that the present invention passes through building load hydrophilic medicament
Gelatin hydrogel (GelMA) solution of change is increased stickiness by the way that PVP is added, is implemented in combination with using GelMA hydrogel physically encapsulation
Drug is fixed in hydrogel, it is further that hydrogel is uniform and stable in metal support surface, polymeric membrane is formed after dry,
Form package load liquid medicine gel takes bolt bracket.Premise of the present invention in the flexibility and the planning function for not influencing metallic support
Under, after hydrogel tunic encounters blood, realize swelling rapidly, to accelerate discharging rapidly for internal drug, release it is hydrophilic
Property drug can efficiently penetrate tissue resorption, improve the availability of local organization, and then realize inhibition thrombosis and promote blood
The clinical treatment purpose of bolt dissolution.The experimental results showed that the present invention in hydrogel layer swelling ratio up to 212.50%, through more
After secondary conveying release, hydrogel layer is still uniformly attached to the surface for taking bolt bracket, has preferable adhesion.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
The embodiment of invention for those of ordinary skill in the art without creative efforts, can also basis
The attached drawing of offer obtains other attached drawings.
Fig. 1 is the grain size distribution of w/o type nanometer colostrum in the embodiment of the present invention 1；
Fig. 2 is the SEM figure of product surface hydrogel coating in the embodiment of the present invention 1；
Fig. 3 is the picture of the W/O/W type nano-emulsion in embodiment 1 and comparative example 1~2；
Fig. 4 is the vitro release curve for taking bolt bracket of hydrogel coating in the embodiment of the present invention 1；
Fig. 5 be in the embodiment of the present invention 1 and comparative example 3 hydrogel coating take bolt bracket to discharge through repeatedly conveying after change
Change figure.
Specific embodiment
The present invention provides a kind of hydrogel for containing hydrophilic medicament and takes bolt bracket, including takes bolt bracket and be coated on described
Take the hydrogel layer of bolt rack surface；
The hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking；
The inner aqueous phase of the W/O/W type nano-emulsion is hydrophilic medicament solution, and oil is mutually emulsifier, and outer aqueous phase includes methyl
Acrylated gelatin, photoinitiator, polyvinylpyrrolidone and lauryl sodium sulfate.
In the present invention, described that bolt bracket is taken to take bolt bracket for commonly used in the art, the present invention does not have special limit to it
System, in the present invention it is possible to take bolt bracket using material for stainless steel.
In the present invention, the hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking, the thickness of the hydrogel layer
Preferably 20~100 μm, suitable thickness can be selected within the range of value according to actual demand.
In the present invention, the inner aqueous phase is hydrophilic medicament solution, and the hydrophilic medicament is preferably thrombolytic drug, this
Invention does not have special limitation to the type of the thrombolytic drug, using the common thrombolytic drug of those skilled in the art,
Specifically, in the present invention, bovine serum albumin(BSA) (BSA) or ADAMTS13 protein powder can be used.It is close in the inner aqueous phase
The mass concentration of aqueous pharmaceutical preferably (0.01~0.1) mg/ μ L, more preferably (0.02~0.08) mg/ μ L, most preferably
(0.04~0.06) mg/ μ L.
In the present invention, the oil mutually preferably includes soybean oil and emulsifier, and the emulsifier is preferably Arlacel-80 and spits
The mass ratio of temperature -80, the soybean oil and emulsifier is preferably 1:(1~5), more preferably 1:(2~4), most preferably 1:3；
The mass ratio of the Tween-80 and Arlacel-80 is preferably (1~3): 1, more preferably 2:1.
In the present invention, the outer aqueous phase be hydrogel solution, preferably include methacrylation gelatin (GelMA),
Photoinitiator, polyvinylpyrrolidone and lauryl sodium sulfate (SDS), in the outer aqueous phase, the gelatin of methacrylation
Mass fraction be preferably 5~20%, more preferably 10~15%；The mass fraction of the photoinitiator is 0.5~2%, more
Preferably 1~1.5%；The mass fraction of the polyvinylpyrrolidone is 0.1~2%, more preferably 1~1.5%；Described ten
The mass fraction of sodium dialkyl sulfate is 0.1~1%, more preferably 0.5~0.6%.
The present invention does not have special limitation to the type of the photoinitiator, is using photoinitiator commonly used in the art
Can, specifically, in the present invention, the photoinitiator of 2959 model of Igracure, the MA of the GelMA strand can be used
Rate is preferably 40~80%, and more preferably 50~60%.
In the present invention, the mass ratio of the inner aqueous phase and oily phase is preferably (0.05~0.2): (0.8~0.95), more excellent
It is selected as 0.11:0.89；The inner aqueous phase is preferably 1:(2~3 with the quality summation of oily phase and the mass ratio of outer aqueous phase), more preferably
For 1:2.5.
The present invention also provides the preparation methods that a kind of hydrogel for containing hydrophilic medicament takes bolt bracket, including following step
It is rapid:
A) under agitation, inner aqueous phase is added dropwise in oil-phase solution, obtains w/o type nanometer colostrum；Inner aqueous phase is parent
Aqueous pharmaceutical solution；
B) under stirring conditions, the w/o type nanometer colostrum is added dropwise in outer aqueous phase solution, obtains W/O/W type and receives
Rice milk；Oily is mutually emulsifier, and outer aqueous phase includes the gelatin, photoinitiator, polyvinylpyrrolidone and 12 of methacrylation
Sodium alkyl sulfate；
C bolt bracket) will be taken to be immersed in the W/O/W type nano-emulsion, carry out being crosslinked under ultraviolet light after taking-up anti-
It answers, the hydrogel for obtaining containing hydrophilic medicament takes bolt bracket.
The present invention preferably first prepares inner aqueous phase solution, oil-phase solution and outer aqueous phase solution respectively,
Inner aqueous phase solution: hydrophilic medicament is added in deionized water and is configured to inner aqueous phase solution, the hydrophilic medicament
Preferably hydrophilic thrombolytic drug, specifically, in an embodiment of the present invention, can be bovine serum albumin(BSA) (BSA) or
ADAMTS13 protein powder.The mass concentration of hydrophilic medicament is preferably (0.01~0.1) mg/ μ L in the inner aqueous phase, more excellent
It is selected as (0.02~0.08) mg/ μ L, most preferably (0.04~0.06) mg/ μ L；
Oil-phase solution: emulsifier is mixed with soybean oil, is configured to oil-phase solution, and the emulsifier is preferably Tween-80
And Arlacel-80, the mass ratio of the soybean oil and emulsifier is preferably 1:(1~5), more preferably 1:(2~4), most preferably
1:3；The mass ratio of the Tween-80 and Arlacel-80 is preferably (1~3): 1, more preferably 2:1.
Outer aqueous phase solution: by gelatin (GelMA), photoinitiator, the polyvinylpyrrolidone and 12 of methacrylation
Sodium alkyl sulfate (SDS) is configured to solution with deionized water, and the photoinitiator is preferably Igracure 2959；The outer water
Xiang Zhong, the mass fraction of the gelatin of methacrylation are preferably 5~20%, and more preferably 10~15%；The photoinitiator
Mass fraction be 0.5~2%, more preferably 1~1.5%；The mass fraction of the polyvinylpyrrolidone is 0.1~2%,
More preferably 1~1.5%；The mass fraction of the lauryl sodium sulfate is 0.1~1%, more preferably 0.5~0.6%.Outside
Aqueous phase solution needs to be protected from light when configuring, using and storing.
After preparing above-mentioned three kinds of solution, the present invention first takes inner aqueous phase solution, will under conditions of room temperature, magnetic agitation
Oil-phase solution is instilled dropwise in inner aqueous phase solution, and the transparent liquid crystal with layer structure is formed between two-phase, continues that oil is added dropwise
Phase solution after dripping, balances 2 hours under conditions of room temperature, magnetic agitation, obtains w/o type nanometer colostrum.
In the present invention, the mass ratio of the inner aqueous phase and oily phase is preferably (0.05~0.2): (0.8~0.95), more excellent
It is selected as 0.11:0.89；The speed of the magnetic agitation is preferably 50~200rpm, more preferably 100~150rpm, the oil phase
The rate of addition of solution is preferably 20~200 μ L/min, more preferably 50~150 μ L/min, most preferably 100~120 μ L/
min。
After obtaining w/o type nanometer colostrum, the present invention preferably be protected from light, room temperature and under conditions of magnetic agitation, by the W/O
Type nanometer colostrum is added drop-wise to dropwise in outer aqueous phase solution, is balanced 15~30min, is obtained W/O/W type nano-emulsion.
In the present invention, the ratio between the quality of the w/o type nanometer colostrum and the volume of the outer aqueous phase solution preferably 1:
(2~3), more preferably 1:2.5；The speed of the magnetic agitation is preferably 600~800rpm, more preferably 700~750rpm；
The rate of addition of the outer aqueous phase solution is preferably 20~200 μ L/min, more preferably 50~150 μ L/min, and most preferably 100
~120 μ L/min.
The W/O/W type nano-emulsion that the present invention is prepared is the nano-emulsion-aquogel system for containing hydrophilic medicament.
After obtaining W/O/W type nano-emulsion, the present invention will take bolt bracket to be immersed in the W/O/W type nano-emulsion, take out
Cross-linking reaction is carried out under conditions of ultraviolet light later, the hydrogel for obtaining containing hydrophilic medicament takes bolt bracket.
The present invention preferably takes bolt bracket to be first surface-treated to described, to enhance hydrogel in the patch of metal support surface
Attached property, the surface treatment for taking bolt bracket can be abrasive Flow polishing or surface carboxylation processing or the two joint
Pretreatment, abrasive Flow polishing and surface carboxylation processing used in the present invention are surface well known to those skilled in the art
Processing technique, details are not described herein by the present invention.
The present invention preferably by it is described take bolt bracket to be immersed in the W/O/W type nano-emulsion after, be slowly rotated by 360 °,
So that it is stopped at least time of 30s or more in the W/O/W type nano-emulsion, makes metal surface and the nano-emulsion for taking bolt bracket
Between come into full contact with, the time of the immersion is preferably 30~120s, more preferably 60~80s.
After the completion of immersion, bolt bracket will be taken to be slowly withdrawn after immersion, carries out photo-crosslinking under the irradiation of ultraviolet light,
Every exposed 30s~50s will take bolt bracket to overturn 90 °, until taking bolt bracket to turn over 360 ° for described, that is, think that crosslinking is completed.
In the present invention, the wavelength of the ultraviolet light is preferably 365nm；The exposure intensity of the ultraviolet light is preferably 500
~700mW/cm2, more preferably 600W/cm2；Preferably 100~200s between the irradiation of the ultraviolet light, more preferably 120~
160s；During photo-crosslinking, spot diameter 1.2cm is kept.
In order to which the hydrogel wrapping layer of metal support surface reaches certain thickness, the present invention repeat above-mentioned immersion,
The step of photo-crosslinking, until hydrogel layer reaches required thickness.
After the hydrogel layer reaches required thickness, the present invention preferably will take bolt bracket to be dried, and be aquagel membrane
It is tightly attached to metal support surface.
In the present invention, the drying is preferably dried, and the temperature of the drying is preferably 35~40 DEG C, yet more preferably
36~37 DEG C；The time of the drying is preferably 0.5~4 hour, and more preferably 1~2 hour.
The present invention provides a kind of hydrogels for containing hydrophilic medicament to take bolt bracket, including takes bolt bracket and be coated on institute
State the hydrogel layer for taking bolt rack surface；The hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking；The W/O/W type
The inner aqueous phase of nano-emulsion is hydrophilic medicament solution, and oil is mutually emulsifier, and outer aqueous phase includes that the gelatin of methacrylation, light draw
Send out agent, polyvinylpyrrolidone and lauryl sodium sulfate.The methacryl that the present invention passes through building load hydrophilic medicament
Gelatin hydrogel (GelMA) solution of change is increased stickiness by the way that PVP is added, is implemented in combination with using GelMA hydrogel physically encapsulation
Drug is fixed in hydrogel, it is further that hydrogel is uniform and stable in metal support surface, polymeric membrane is formed after dry,
Form package load liquid medicine gel takes bolt bracket.Premise of the present invention in the flexibility and the planning function for not influencing metallic support
Under, after hydrogel tunic encounters blood, realize swelling rapidly, to accelerate discharging rapidly for internal drug, release it is hydrophilic
Property drug can efficiently penetrate tissue resorption, improve the availability of local organization, and then realize inhibition thrombosis and promote blood
The clinical treatment purpose of bolt dissolution.The experimental results showed that the present invention in hydrogel layer swelling ratio up to 212.50%, through more
After secondary conveying release, hydrogel layer is still uniformly attached to the surface for taking bolt bracket, has preferable adhesion.
In order to further illustrate the present invention, with reference to embodiments to a kind of hydrophilic medicament of containing provided by the invention
Hydrogel takes bolt bracket and preparation method thereof to be described in detail, but cannot be understood as the limit to the scope of the present invention
It is fixed.
Embodiment 1
Prepare the stock solution of each phase of W/O/W type nano-emulsion
Inner aqueous phase: accurately weighed 20mg ADAMTS13 protein powder, with 890uL deionized water wiring solution-forming, (blank group makes
Use deionized water as inner aqueous phase).
Oily phase: accurately weighed 2.28g Arlacel-80,4.55g Tween-80, with 2.28g soybean oil wiring solution-forming.
Outer aqueous phase: (control group uses SDS's by accurately weighed 100mg GelMA, 10mg Igracure 2959,6mg SDS
Deionized water solution is as outer aqueous phase), with 1000uL deionized water wiring solution-forming.Outer aqueous phase is needed when preparing, using and storing
It is protected from light.
It prepares w/o type nanometer colostrum: 890 μ L being taken to carry medicine inner aqueous phase solution, under room temperature, magnetic agitation (50rpm), Xiang Qi
In instill oil-phase solution dropwise, form the transparent liquid crystal with layer structure between two-phase, continuation is dripped dropwise under this condition
Enter oil-phase solution 0.11g, i.e. w/o type colostrum total amount is 10.0g, balances 2h with this condition.
Preparation W/O/W type nano-emulsion: taking 1000 μ L outer aqueous phase solution, be protected from light, under room temperature, magnetic agitation (600rpm),
It is all in outside aqueous phase solution to be added dropwise to 0.40g W/O single emulsion, it then balances 15 minutes, 10mg polyvinylpyrrolidone is added
(PVP), the nano-emulsion-aquogel system for containing ADAMTS13 can be obtained.
Take the metallic support that pretreatment finishes, in room temperature, be protected from light under, be immersed in the W/O/W for preparing and be kept in dark place in advance
It in type nano-emulsion stock solution, and is slowly rotated by 360 °, it is made to stop the time of 60s in stock solution, enable stock solution can be with metal
Surface comes into full contact with.It is slowly withdrawn, static a period of time, drains the extra stock solution being stained on bracket, be then in wavelength
365nm, 600mW/cm2Irradiation causes photo-crosslinking, every exposed 30s overturning under the ultraviolet light of (keeping spot diameter 1.2cm)
90 °, until turning over 360 °, crosslinking is completed.Then metallic support is obtained into hydrogel coating as 1h dry in 37 DEG C of baking ovens
Take bolt bracket.
Obtain with hydrogel coating take bolt bracket dry after weight only increase 1.6mg (metallic support weight be
12.5mg), only 40 μm of coating layer thickness (stent wire is with a thickness of 80 μm), bracket conveying, compression and release mechanicalness are not influenced
Energy, and can be realized 212.5% swelling ratio.
Structured testing is carried out to obtained w/o type nanometer colostrum, as a result as shown in FIG. 1, FIG. 1 is in the embodiment of the present invention 1
The grain size distribution of w/o type nanometer colostrum, have Fig. 1 it is found that nano-emulsion w/o type structure partial size be 581.9nm, particle diameter distribution compared with
Uniformly (PDI < 0.3), and determining albumen drugloading rate is 2.14mg/mL.
The detection of SEM Electronic Speculum is carried out to the hydrogel coating of product surface, as a result as shown in Fig. 2, Fig. 2 is the embodiment of the present invention
The SEM figure of product surface hydrogel coating in 1.In Fig. 2, A and B are that sample is lyophilized after GelMA+PVP (outer aqueous phase solution) is crosslinked；
C and D is that sample is lyophilized after GelMA+PVP+ nano-emulsion (W/O/W type nano-emulsion) is crosslinked, the freeze-drying GelMA+PVP+ of D display amplification
A large amount of particles (arrow) in nano-emulsion sample, the BSA particle as inside nano-emulsion, and table after the common GelMA amplification that B is shown
Face is then relatively smooth.Illustrate that the hydrogel coating in the present embodiment has successfully coated hydrophilic medicament.
Vitro release test is carried out to the product in the present embodiment, as a result as shown in figure 4, Fig. 4 is the embodiment of the present invention 1
The vitro release curve for taking bolt bracket of middle hydrogel coating.Release in vitro is studies have shown that nano-emulsion microballoon is swollen in GelMA
Afterwards 1,3,5,10 minute, the release rate of BSA can achieve 30.54%, 43.51%, 53.60% and 72.71% respectively.BSA
Practical drugloading rate is 0.823mg/mL.
Comparative example 1
Hydrogel coating, which is prepared, according to the method in embodiment 1 takes bolt bracket, unlike, using spitting in this comparative example
Temperature -80 replaces the SDS in outer aqueous phase.
Comparative example 2
Hydrogel coating, which is prepared, according to the method in embodiment 1 takes bolt bracket, unlike, lecithin is used in this comparative example
Rouge replaces the SDS in outer aqueous phase.
Fig. 3 is the picture of the W/O/W type nano-emulsion in embodiment 1 and comparative example 1~2, and from the left side, two figures, which is followed successively by, compares
Example 1 (Tween-80) and comparative example 2 (lecithin), two figure of the right are respectively (SDS) and addition before PVP is added in embodiment 1
After PVP (SDS+PVP).As seen from Figure 2, when Tween 80 is as emulsifier, surface flotation oil film；Lecithin is used as cream
When agent, solutions turbid；The two emulsifying effectiveness is poor, fails to reduce surface tension, does not play the effect of surfactant
Fruit can not form stable nano-emulsion system.And SDS be used as emulsifier when, solution is able to maintain the nano-emulsion system of W/O/W.Most
Latter column are to be added to PVP on the basis of SDS is as emulsifier as stickiness reinforcing agent, it is found that the characteristic of lotion does not occur
Change, is still able to maintain good nano-emulsion system.
Comparative example 3
Hydrogel coating, which is prepared, according to the method in embodiment 1 takes bolt bracket, unlike, it is not added in this comparative example
Polyvinylpyrrolidone PVP.
Taking in bolt bracket and comparative example 3 in embodiment 1 is taken bolt bracket repeatedly to be discharged by the present invention, as a result as schemed
Shown in 5, it is added to PVP in the hydrogel coating in embodiment 1, after stent collapses to be entered to conveyer and are folded, is discharged again
When, the part hydrogel of metal support surface is scraped by conveyer, and hydrogel total amount can be declined, and surface is not only
It is sliding, it is easy Endovascular in vivo and falls off, may cause blocking.Such case shows the most aobvious in repeated multiple times repeat
It writes.The GelMA hydrogel coating for being added to PVP then has better adhesion, makes metallic support bar surface relative smooth, coating
Thickness can also be bigger, to obtain higher drugloading rate；After taking in conveyer and discharging again, cradling piece surface can be remained with more
More hydrogels, and morphologic change is smaller, and enough thickness can be also maintained after swelling.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of hydrogel for containing hydrophilic medicament takes bolt bracket, including takes bolt bracket and be coated on and described take bolt rack surface
Hydrogel layer；
The hydrogel layer is made by W/O/W type nano-emulsion through photo-crosslinking；
The inner aqueous phase of the W/O/W type nano-emulsion is hydrophilic medicament solution, and oil is mutually soybean oil and emulsifier, and outer aqueous phase includes
Gelatin, photoinitiator, polyvinylpyrrolidone and the lauryl sodium sulfate of methacrylation.
2. hydrogel according to claim 1 takes bolt bracket, which is characterized in that emulsifier is Tween-80 and Arlacel-80；
The mass ratio of the Tween-80 and Arlacel-80 is (1~3): 1；
The mass ratio of the soybean oil and emulsifier is 1:(1~5).
3. hydrogel according to claim 1 takes bolt bracket, which is characterized in that in the outer aqueous phase, methacrylation
Gelatin mass fraction be 5~20%；The mass fraction of the photoinitiator is 0.5~2%；The polyvinylpyrrolidone
Mass fraction be 0.1~2%；The mass fraction of the lauryl sodium sulfate is 0.1~1%.
4. hydrogel according to claim 1 takes bolt bracket, which is characterized in that the quality of the hydrophilic medicament solution is dense
Degree is (0.01~1) μ g/ μ L.
5. hydrogel described in any one takes bolt bracket according to claim 1~4, which is characterized in that the inner aqueous phase and oil
The mass ratio of phase is (0.05~0.2): (0.8~0.95)；
The inner aqueous phase is (2~3) with the quality summation of oily phase and the mass ratio of outer aqueous phase: 1.
6. the preparation method that a kind of hydrogel for containing hydrophilic medicament takes bolt bracket, comprising the following steps:
A) under agitation, inner aqueous phase is added dropwise in oil-phase solution, obtains w/o type nanometer colostrum；Inner aqueous phase is hydrophily
Drug solution；
B) under stirring conditions, the w/o type nanometer colostrum is added dropwise in outer aqueous phase solution, obtains W/O/W type nano-emulsion；
Oily is mutually emulsifier, and outer aqueous phase includes gelatin, photoinitiator, polyvinylpyrrolidone and the dodecyl sulphur of methacrylation
Sour sodium；
C bolt bracket) will be taken to be immersed in the W/O/W type nano-emulsion, cross-linking reaction is carried out after taking-up under ultraviolet light, obtain
Bolt bracket is taken to the hydrogel for containing hydrophilic medicament.
7. preparation method according to claim 6, which is characterized in that described that bolt bracket is taken to be immersed in the W/O/W type
Before nano-emulsion, abrasive Flow polishing and/or carboxylated surface processing are first carried out.
8. preparation method according to claim 6, which is characterized in that the step C) in impregnate time be 30~
120s。
9. preparation method according to claim 6, which is characterized in that the step C) in ultraviolet light wavelength be 365nm；
The exposure intensity of the ultraviolet light is 500~700mW/cm2；
The irradiation time of the ultraviolet light is 100~200s；
The spot diameter of the ultraviolet light is 1.2cm.
10. preparation method according to claim 6, which is characterized in that further include doing after the ultraviolet irradiation step
It is dry；
The temperature of the drying is 35~40 DEG C；
The time of the drying is 0.5~4 hour.
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| CN114403968A (en) * | 2021-12-30 | 2022-04-29 | 杭州唯强医疗科技有限公司 | Intracavity occluder and processing method thereof |
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