A kind of preparation method of Biodegradable high molecular porous microsphere
Technical field
The present invention relates to a kind of preparation methods of Biodegradable high molecular porous microsphere, belong to biological medical polymer material
Field.
Background technique
Biodegradable high molecular microballoon is more and more widely used in terms of medicine sustained and controlled release.It is hollow micro-
Ball can both wrap up hydrophilic drug, while can also load hydrophobic drug.The drug of package passes through diffusion or microballoon
Degradation is discharged into medium in a controlled manner, realizes the slow/controlled release of drug.
The Biodegradable high molecular microballoon of conventional emulsification method preparation is usually fine and close tiny balloon, is dissolved in organic solvent
Biodegradable high molecular forms stable emulsion droplet under the action of surfactant, raw with the volatilization of organic solvent in microballoon
Object degraded macromolecular forms fine and close spherical shell, is washed to remove the surfactant of microsphere surface absorption, obtains tiny balloon.
For hydrophobic drug, the fine and close shell of microballoon has become the obstacle of its quick release, is discharged into diffusion way
Drug in medium is difficult to drug concentration needed for meeting treatment, meanwhile, the release behavior degraded by microballoon is even more to be difficult to control
The burst size and rate of pharmacy object.The porous structure on microballoon shell surface is conducive to regulate and control the burst size of wrapped up hydrophobic drug
And rate.Therefore, preparing porous Biodegradable high molecular microballoon will be for the control of hydrophobic drug release with important
Meaning.
Summary of the invention
Goal of the invention: the microballoon spherical shell prepared for existing emulsion process is fine and close, is difficult to effectively control releasing for hydrophobic drug
The problem of putting, the present invention provide a kind of preparation method of Biodegradable high molecular porous microsphere.
Technical solution: a kind of preparation method of Biodegradable high molecular porous microsphere of the present invention, including walk as follows
It is rapid:
(1) biodegradated polymer materal and hydrophilic pore high molecular material are dissolved in low boiling point organic solvent, institute
Biodegradable high molecular/pore Polymer Solution is obtained to be added drop-wise in water under agitation;
(2) by the heating stirring of mixed solution obtained by step (1), after organic solvent volatilization, centrifugal treating acquired solution, so
After remove supernatant, wash thus obtained microsphere;
(3) microballoon after washing is freeze-dried to get Biodegradable high molecular porous microsphere.
Wherein, biodegradated polymer materal can be selected from Poly L-lactide (PLLA), poly- (DL- lactide) (PDLLA), gather
At least one of (lactide coglycolide) copolymer (PLGA).Pore high molecular material can be husky for polyethylene glycol and/or pool Lip river
Nurse.Low boiling point organic solvent can be methylene chloride and/or chloroform.
Preferably, in step (1), the mass ratio of biodegradated polymer materal and pore high molecular material is 20:1~5:
1。
More preferably, the volume ratio of Biodegradable high molecular/pore Polymer Solution and water is 1:10~1:5.
In above-mentioned steps (2), heating stirring condition is preferred are as follows: mixed solution obtained by step (1) is warming up to 30~45 DEG C,
Stirring 5~24 hours.Further, the condition of centrifugal treating are as follows: the centrifugal treating 3~10 under the revolving speed of 2000~12000rpm
Minute.
The utility model has the advantages that the preparation method of Biodegradable high molecular porous microsphere of the invention, organic using can both be dissolved in
Solvent has water-soluble or hydrophilic high molecular material as pore-foaming agent again, makes biodegradated polymer materal can be on no surface
It is emulsified in the case where activating agent, forms stable emulsion droplet, by the volatilization of organic solvent, obtained microballoon, then freeze microballoon
Dry, the hole on final Biodegradable high molecular porous microsphere surface obtained is the through-hole through spherical shell, so as to effectively adjust
Control the burst size and rate of wrapped up hydrophobic drug;Moreover, the resulting Biodegradable high molecular porous microsphere table of the present invention
The aperture of face through-hole and density can be adjusted by Biodegradable high molecular and the high molecular ratio of pore, so as to fit extensively
For various types of hydrophobic drug.
Detailed description of the invention
Fig. 1 is the SEM photograph of Biodegradable high molecular porous microsphere made from embodiment 1;
Fig. 2 is the SEM photograph of Biodegradable high molecular porous microsphere made from embodiment 3.
Specific embodiment
Technical solution of the present invention is described further with reference to the accompanying drawings and examples.
Embodiment 1
PLLA Biodegradable high molecular and polyethylene glycol are dissolved in methylene chloride, gained PLLA/ according to the mass ratio of 20:1
Polyglycol solution is slowly dropped in distilled water under agitation with the volume ratio of 1:5, and mixed solution is warming up to 30 DEG C,
Stirring 5 hours is centrifuged 3 minutes under the revolving speed of 2000rpm after methylene chloride volatilization, removes supernatant, and thus obtained microsphere steams
Distilled water is washed 3 times, up to PLLA Biodegradable high molecular porous microsphere after freeze-drying.
Its scanning electron microscope (SEM) photograph such as Fig. 1, it can be seen that the hole on PLLA Biodegradable high molecular porous microsphere surface is through ball
The through-hole of shell.
Embodiment 2
PDLLA Biodegradable high molecular and poloxamer are dissolved in chloroform, gained PDLLA/ according to the mass ratio of 5:1
Poloxamer solution is slowly dropped in distilled water under agitation with the volume ratio of 1:10, and mixed solution is warming up to 45
DEG C, it stirs 24 hours, after chloroform volatilization, is centrifuged 10 minutes under the revolving speed of 12000rpm, removes supernatant, gained is micro-
Ball is washed with distilled water 3 times, up to PDLLA Biodegradable high molecular porous microsphere after freeze-drying;The hole on its surface is also to pass through
The through-hole of logical spherical shell.
Embodiment 3
PLGA Biodegradable high molecular and polyethylene glycol are dissolved in methylene chloride, gained PLGA/ according to the mass ratio of 10:1
Polyglycol solution is slowly dropped in distilled water under agitation with the volume ratio of 1:8, and mixed solution is warming up to 40 DEG C,
Stirring 15 hours is centrifuged 5 minutes under the revolving speed of 8000rpm after methylene chloride volatilization, removes supernatant, and thus obtained microsphere is used
Distillation water washing 3 times, up to PLGA Biodegradable high molecular porous microsphere after freeze-drying.
Its scanning electron microscope (SEM) photograph such as Fig. 2, it can be seen that the hole on PLGA Biodegradable high molecular porous microsphere surface be also through
The through-hole of spherical shell;Moreover, the density in microsphere surface pore size and hole made from the present embodiment with exist in embodiment 1 it is obvious poor
Different, this is generated by the proportional difference between Biodegradable high molecular and pore macromolecule, i.e., Biodegradable high molecular is porous micro-
The aperture of ball surface through-hole and density can be adjusted by Biodegradable high molecular and the high molecular ratio of pore.
Embodiment 4
PLGA Biodegradable high molecular and poloxamer are dissolved in chloroform according to the mass ratio of 8:1, PLGA/ is moored into Lip river
Husky nurse solution is slowly dropped in distilled water under agitation with the volume ratio of 1:10, and mixed solution is warming up to 35 DEG C, is stirred
It mixes 20 hours, after chloroform volatilization, is centrifuged 10 minutes under the revolving speed of 5000rpm, remove supernatant, thus obtained microsphere steams
Distilled water is washed 3 times, up to PLGA Biodegradable high molecular porous microsphere after freeze-drying;The hole on its surface is to penetrate through leading to for spherical shell
Hole.
Embodiment 5
PLLA Biodegradable high molecular and polyethylene glycol are dissolved in methylene chloride according to the mass ratio of 15:1, PLLA/ is gathered
Ethylene glycol solution is slowly dropped in distilled water under agitation with the volume ratio of 1:6, and mixed solution is warming up to 42 DEG C, is stirred
It mixes 7 hours, after methylene chloride volatilization, is centrifuged 10 minutes under the revolving speed of 3000rpm, remove supernatant, thus obtained microsphere steams
Distilled water is washed 3 times, up to PLLA Biodegradable high molecular porous microsphere after freeze-drying;The hole on its surface is to penetrate through leading to for spherical shell
Hole.