CN107595812A - The mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate - Google Patents
The mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate Download PDFInfo
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- CN107595812A CN107595812A CN201710993543.1A CN201710993543A CN107595812A CN 107595812 A CN107595812 A CN 107595812A CN 201710993543 A CN201710993543 A CN 201710993543A CN 107595812 A CN107595812 A CN 107595812A
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Abstract
Present invention relates to the mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate, kernel is the mesopore bioactive glass microballoon for loading medicine, outer layer is macromolecule PEG and PLA PEG integuments, PEG the and PLA PEG integuments of mesopore bioactive glass microsphere surface are uneven, and single some parts of mesopore bioactive glass microsphere surface are enclosed with PEG and PLA PEG layers, some parts do not wrap up PEG and PLA PEG layers.
Description
Technical field
Present invention relates to the mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate.
Background technology
The method replicated using three-dimensional ordered macroporous carbon template combination sol-gel process and block copolymer template, system
Standby small size single dispersing carries medicine mesopore bioactive glass microballoon（MBGMs）/ ethylene glycol lactic acid copolymer（PEG-PLA）Nanometer is micro-
Ball, and optimization formulation and technique, it is emerging pharmaceutical technology.
Bioactivity glass (BG) causes people widely to be closed after professor Hench by the U.S. in 1971 has found
Note.Compared with traditional biological activity glass, mesopore bioactive glass (MBG) shows more preferable bone remoulding ability and biofacies
Capacitive.MBG has mesoporous phase (2 ~ 50 nm), larger specific surface area and a pore volume, and abundant surface silanol group can then provide compared with
More avtive spot, so as to reach higher drug loading.Researcher releases also by experimental study extension MBG in medicine
Put and the application of biomedical sector.MBG is as the advantage of pharmaceutical carrier：Carrier has nontoxicity, lived without physiology in itself
Property and more preferable biological degradability, biocompatibility；The integrality of medicines structure can be kept after drug assemble；Mesopore molecular sieve
The abundant silicone hydroxyl in surface can make drug molecule be easy to equably load to as the avtive spot with drug molecule interaction
Have an effect on the surface in duct and duct so that drug molecule is firmly loaded into duct.By adjust assembling condition and
The parameters of mesopore molecular sieve, not only can with the size of regulating drug assembling amount, meanwhile, can effectively control drug molecule
Rate of release, so as to reach the purpose for making medicament slow release or controlled release.But up to the present sieve piperazine card using MBG as carrier
Because Atrigel does not have correlative study also.2017, team of Ji Li armies reports could using three-dimensional ordered macroporous carbon template
Highly monodispersed magnetic MBGMs is synthesized with accurate control.And by itself and the compound preparation magnetic of PEG-PLA block copolymers
MBGMs/PEG-PLA composite nano-microspheres, while the medicines such as arsenic trioxide, Anastrozole and brufen are have studied in MBGMs/
Load and release behavior in this new material of PEG-PLA nanoparticles, determine that the nanoparticle is adapted to carrying medicament.Research
It was found that the release behavior of medicine can pass through the hydrophilic and hydrophobic and thickness control of polymer covering layer.PEG-PLA hydrophilic and hydrophobic because
The two molecular weight it is different and different, therefore medicine can be controlled by using the PEG-PLA clads with different molecular weight
Release behavior.
But the release behavior of PEG-PLA clads control medicine receives PEG-PLA concentration, molecular weight, coating thickness
Deng the influence of many factors, therefore, in laboratory need to find a kind of PEG-PLA clads control medicine that can quickly adjust
The method of rate of release, in favor of studying under different pharmaceutical rate of release, Ropivacaine mesopore bioactive glass nanometer is micro-
The property of ball.
The content of the invention
In view of this, in order to solve the above problems, the present invention provides a kind of mesoporous life of quick adjustment drug releasing rate
Thing activity glass nanoparticle.
The mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate, kernel are the mesoporous life for loading medicine
Thing activity glass microballoon, outer layer are macromolecule PEG and PLA-PEG integument, it is characterized in that, mesopore bioactive glass microballoon table
PEG the and PLA-PEG integuments in face are uneven, and single some parts of mesopore bioactive glass microsphere surface are enclosed with
PEG and PLA-PEG layers, some parts do not wrap up PEG and PLA-PEG layers.
Further, the nm of mesopore bioactive glass microsphere diameter 400 after macromolecule PEG and PLA-PEG is wrapped up.
Further, Ropivacaine microsphere encapsulation rate is 60-80%.
Further, the nm-300 nm of nuclear diameter 200 in mesopore bioactive glass microballoon.
Further, by the PEG and PLA-PEG in integument, macromolecule integument either PEG or PLA- is replaced with
PEG or PLA-PEG-PLA.
PEG and PEG-PLA clads are fine and close and surface porosities, when the speed of its release internal drug is wrapped up with it
The concentration of solution（Molecular weight）It is relevant with integument thickness.In order to obtain the integument of different rate of release, conventional art needs
Adjustment solution molecule amount repeatedly is repeatedly carried out wrapping up.Often obtain once the integument of different rate of release, it is necessary to carry out
The technique for once completely making-carrying medicine-parcel outer layer from microballoon.It is and undesirable（Rate of release）Experiment product can only
Abandon, lose time and medicine.And the chloroform used when wrapping up is poisonous, the work of integument thickness is adjusted using multiple parcel
Skill, it is dangerous to experimenter.Using the integument of structure in the application, you can quick regulation integument rate of release.Work as needs
When configuring the integument of different rate of release, only the PEG and PLA-PEG of mesopore bioactive glass microsphere surface need to be caused to wrap up
Layer is uneven, and single mesopore bioactive glass microsphere surface is locally enclosed with PEG and PLA-PEG layers, part does not wrap up PEG
With PLA-PEG layers.The now speed of the control internal drug release of integument, depending on situation is wrapped up on surface（There is integument
Local insoluble drug release is slow, and fast without the thin place release of integument or integument, therefore the rate of release of single particulate obtains
Change）, change parcel situation（Integument is uneven, part is enclosed with PEG and PLA-PEG layers, part is not wrapped up）It can make
Make the integument of different rate of release.
Brief description of the drawings
Fig. 1 is the structural representation of the present invention.
Embodiment
Step 1：The preparation of SiO2 colloid crystal templates
The preparation of single dispersing SiO2 microballoons：Method using St ber passes through ethyl orthosilicate（TEOS）Basic hydrolysis process system
Standby single dispersing SiO2 microsphere suspension liquids.251.2 g absolute ethyl alcohols are weighed, 118.25 g deionized waters and 34 g NH3H2O are put
In conical flask, after being well mixed under magnetic stirring, 27.7 g TEOS are added, continues the h of magnetic agitation 3, obtains SiO2
The suspension of grain.
The preparation of SiO2 colloid crystal templates：First by the suspension of SiO2 particles obtained above by rotary evaporation with except
Unnecessary solvent is removed, is then placed in Flat bottom container, is centrifuged off unnecessary solvent, forms the unordered SiO2 colloids of bulk
Crystal template, then sintered under 1000 DEG C of high temperature and SiO2 colloid crystal templates are made.
Step 2：The preparation of anti-Colloidal crystals carbon template
SiO2 colloids crystal template obtained above is immersed in urotropine（Methenamine）Phenol as crosslinking agent
Urea formaldehyde（PF）（M methenamines:mPF=1:10）Ethanol solution in.After alcohol solvent volatilization, it will be wrapped in PF's
SiO2 colloid crystal templates are put into box atmosphere furnace, are warming up to 1000oC under nitrogen protection（Programming rate is 3oC/min）Make
PF completes carbonisation, so as to obtain SiO2/C composites.Quality is immersed in after above-mentioned composite material surface is polished smooth
Fraction is to remove SiO2 in 40% hydrofluoric acid, and with deionized water, soaking flushing is to remove the HF of residual repeatedly afterwards, after drying i.e.
Obtain ordered big hole carbon template
Step 3：MBGs preparation
Si75Ca25-MBGs（Si/Ca = 75:25, mol ratio）Preparation process, it is described in detail below.By 2.7 g TEOS,
1.18 g Ca (NO3) 24H2O, 4.2 g F127 and the M HNO3 of 0.08 g 2 are added in the mixed liquor of 8 g absolute ethyl alcohols
Stirring, stirs 3 h at room temperature.Ordered big hole carbon template in step 2 is immersed into gained colloidal sol and is put into vacuum drying chamber 50
DEG C carry out sol-gel process, after collosol and gel drying after, in Muffle furnace at 600 DEG C sintering remove template, produce
MBGs.Then gained MBGs is ground into uniform powder, it is standby.
Step 4：Load of the medicine in MBGs
The saturated solution of medicine in MBGs need to be loaded in by preparing first, be loaded to using perfusion in MBGs, be embodied
Method is as follows：With the MBGs powder of certain density drug solution infiltration known quality, it is placed in vacuum drying chamber, vacuum
Under the conditions of make its rapid draing, completion once irrigates the cycle.Perfusion is repeated several times and can adjust its drugloading rate, most rear bearing medicine is completed
Afterwards, it is placed in drying box, it is standby.Record perfusion number, calculates theoretical drugloading rate.
Step 5：The preparation of complex microsphere
Select PEG (6000,10000,20000) and PLA-PEG（15000）It is anti-using chloroform for MBGs Surface coating material
Answer solvent.MBGs and load medicine-MBGs powder are uniformly dispersed first, are laid in smooth bright and clean and enough surface strength plane
On, then another smooth bright and clean and enough hardness surface is pressed in MBGs and carried and is pressurizeed on medicine-MBGs powder, adjust
Moulding pressure.Planar pressing surfaces are made from diamond, ceramics or glass, but hard alloy can not be used to make.Then exist dropwise
MBGs and the chloroformic solution that PEG and PLA-PEG is added dropwise around medicine-MBGs powder is carried, wetting, keep under normal temperature being vented to chlorine
Imitative volatilization finishes.After first time chloroform volatilizees, repeat to be added dropwise PEG and PLA-PEG chloroformic solution to being covered to complete.
Such as Fig. 1, kernel 1 is MBGs or carries medicine-MBGs, PEG and PLA-PEG integument 2 because when wrapping up from each other
Squeezed tight, so as to cause deep mixed breach 21 on the surface of integument 2.And some parts of single nanoparticle surface are wrapped up
There are PEG and PLA-PEG clads 2, some parts 22 not to wrap up PEG and PLA-PEG clads 2.
Claims (5)
1. the quickly mesopore bioactive glass nanoparticle of adjustment drug releasing rate, kernel is the mesoporous biological for loading medicine
Activity glass microballoon, outer layer are macromolecule PEG and PLA-PEG integument, it is characterized in that, mesopore bioactive glass microsphere surface
PEG and PLA-PEG integuments be uneven, and single some parts of mesopore bioactive glass microsphere surface are enclosed with PEG
PEG and PLA-PEG layers are not wrapped up with PLA-PEG layers, some parts.
2. the mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate as claimed in claim 1, its feature
For：Wrap up the nm of mesopore bioactive glass microsphere diameter 400 after macromolecule PEG and PLA-PEG.
3. the mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate as claimed in claim 2, its feature
For：Ropivacaine microsphere encapsulation rate is 60-80%.
4. the mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate as claimed in claim 3, its feature
For：The nm-300 nm of nuclear diameter 200 in mesopore bioactive glass microballoon.
5. the mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate as claimed in claim 4, its feature
For：By the PEG and PLA-PEG in integument, macromolecule integument either PEG or PLA-PEG or PLA-PEG- is replaced with
PLA。
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| CN201710993543.1A CN107595812A (en) | 2017-10-23 | 2017-10-23 | The mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate |
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| CN201710993543.1A CN107595812A (en) | 2017-10-23 | 2017-10-23 | The mesopore bioactive glass nanoparticle of quick adjustment drug releasing rate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110237269A (en) * | 2019-07-20 | 2019-09-17 | 扬州大学 | A kind of mesopore bioactive glass/PLA-b-PEG/PEG double shells medicine-carried system and preparation method thereof |
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- 2017-10-23 CN CN201710993543.1A patent/CN107595812A/en not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110237269A (en) * | 2019-07-20 | 2019-09-17 | 扬州大学 | A kind of mesopore bioactive glass/PLA-b-PEG/PEG double shells medicine-carried system and preparation method thereof |
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Application publication date: 20180119 |