CN1586704A - Method for preparing polylactic porous microball - Google Patents
Method for preparing polylactic porous microball Download PDFInfo
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- CN1586704A CN1586704A CN 200410052981 CN200410052981A CN1586704A CN 1586704 A CN1586704 A CN 1586704A CN 200410052981 CN200410052981 CN 200410052981 CN 200410052981 A CN200410052981 A CN 200410052981A CN 1586704 A CN1586704 A CN 1586704A
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Abstract
The preparation process of porous polylactic acid microball includes the following steps: dissolving polylactic acid in solvent dichloromethane and adding bad solvent via mixing; dissolving PVA in deionized water to prepare solution, and under stirring, pouring the polylactic acid solution into the PVA solution; volatilizing organic solvent, filtering and washing to obtain the porous polylactic acid microball. The said process is simple and has mild condition, and the obtained porous polylactic acid microball may be used widely in controlled medicine releasing system, micro cell carrier in cell engineering and adhered microball rack in tissue engineering.
Description
Technical field
The present invention relates to prepare the method for porous polylactic acid microball.
Background technology
PLA has good physical and mechanical properties, avirulence, easy absorbability in processing forming, biological degradability and the body, and therefore important use value arranged in a plurality of fields, especially as the carrier of tissue engineering material and drug delivery and controlled release.In biomedical materials field, adopt various process technologies, PLA can be prepared to bar, nail, suture, medicine microcarrier and the microballoon etc. of inner tight, or the support of loose and porous inner surface, nonwoven and hollow microsphere etc.Wherein, microballoon is with the popularity of the polytropy of the particularity of its structure, performance, application and in biomedical materials field crucial status is arranged.For example, can in multiple treatment of diseases, play a significant role as the carrier of embedding, transmission and the controlled release of medicine, gene, polypeptide and albumen; The microballoon that the surface is modified through specificity can improve the culture density of cell as the microcarrier in the cell engineering, keeps the normal physiological function of cell; The microcarrier of compound cell can be injected directly into defect, carries out tissue repair; By the further assembling between microballoon and integrated, can obtain three-dimensional porous rack, be used for the regeneration of cell guiding and tissue.
The preparation method of solid microsphere mainly contains phase separation method, emulsification-solvent evaporation method, freezing and spray-on process etc.Wherein the application of emulsification-solvent evaporation method is the most extensive.Emulsification-solvent evaporation method be with polymer dissolution in organic solvent, under agitation in the aqueous solution, carry out emulsification then, along with the volatilization of solvent, polymer microballoon slowly forms.Because the drop of organic solvent can shrink in the solvent evaporates process, the microballoon of therefore emulsification usually-solvent evaporation method preparation is solid microsphere.As implants in vivo such as drug carrier system or cell carrier, the degraded of microballoon can produce a large amount of acidic materials, mainly is lactic acid.Local high concentration acidity easily causes the aseptic inflammation reaction of peripheral organs and tissue, produces the red and swollen even downright bad of tissue.Therefore, when guaranteeing the microballoon function, the consumption that as far as possible reduces PLA is one of best solution.Porous microsphere can reduce the content of PLA in the microballoon significantly under the situation that guarantees medicine carrying amount and support overall mechanical strength.At present, the preparation method of porous microsphere mainly contains quick removal solvent method, pore-foaming agent method and two emulsion methods etc.The operating process of these methods and implementing process more complicated, influence factor is more, and the loose structure of microballoon is wayward, so the repeatability of gained porous microsphere and the difficult assurance of quality.
Summary of the invention
The purpose of this invention is to provide the method for preparing porous polylactic acid microball that a kind of operating process and implementing process are simple, can control microsphere porous structure.
The method for preparing porous polylactic acid microball of the present invention may further comprise the steps:
1) PLA is dissolved in the methylene chloride, adds poor solvent then, mix, the bulking value concentration of PLA in the mixed solvent of carrene and poor solvent is 3～8%; The volume ratio of carrene and poor solvent is 10: 0～8: 2 in the mixed solvent;
2) polyvinyl alcohol is dissolved in the deionized water, be prepared into bulking value concentration and be 0.3～0.8% solution, low whipping speed is under 300～800 rev/mins of situations, and PLA solution is poured in the poly-vinyl alcohol solution, and the volume ratio of water and organic facies is 5: 1～10: 1;
3) vapor away organic solvent under 10～40 ℃, filter, washing obtains porous polylactic acid microball.
Among the present invention, said poor solvent can be n-hexane, normal heptane, normal octane, isooctane or n-dodecane.
The inventive method operating procedure is simple, implementation condition is gentle.Prepare porous polylactic acid microball with emulsification-solvent evaporation method with the molten method that combines that is separated that causes, can regulate and control the particle size of polylactic acid microsphere, the porosity of microballoon and the size of internal capillary by the mixed proportion of mixing speed, PLA concentration, polyethylene of dispersing agent determining alcohol, good solvent carrene and poor solvent and the ratio of organic facies and water.The inventive method provides a kind of new method of simple possible for the preparation porous polylactic acid microball.The gained porous polylactic acid microball can be widely used in cell microcarrier in medicine controlled releasing system, the cell engineering and the microballoon adhesion type support in the organizational project.
Description of drawings
Fig. 1 is that the particle diameter of example 1 porous polylactic acid microball distributes;
Fig. 2 is the configuration of surface and the internal structure of example 1 porous polylactic acid microball; Fig. 2 a, Fig. 2 b are the configuration of surface stereoscan photograph of porous polylactic acid microball, and multiplication factor is respectively 100 times and 230 times; Fig. 2 c is the cross sectional photograph of porous polylactic acid microball; Fig. 2 d is the internal structure photo of porous polylactic acid microball;
Fig. 3 is that the particle diameter of example 2 porous polylactic acid microball distributes;
Fig. 4 is the configuration of surface and the internal structure of example 2 porous polylactic acid microball; Fig. 4 a, Fig. 4 b are the configuration of surface stereoscan photograph of porous polylactic acid microball, and multiplication factor is respectively 50 times and 150 times; Fig. 4 c is the cross sectional photograph of porous polylactic acid microball; Fig. 4 d is the internal structure photo of porous polylactic acid microball;
Fig. 5 is that the particle diameter of example 3 porous polylactic acid microball distributes;
Fig. 6 is the configuration of surface and the internal structure of example 3 porous polylactic acid microball; Fig. 6 a, Fig. 6 b are the configuration of surface stereoscan photograph of porous polylactic acid microball, and multiplication factor is respectively 100 times and 180 times; Fig. 6 c is the cross sectional photograph of porous polylactic acid microball; Fig. 6 d is the internal structure photo of porous polylactic acid microball;
Fig. 7 is the configuration of surface and the internal structure of example 4 PLLA porous microspheres; Fig. 7 a is the configuration of surface of PLLA porous microsphere; Fig. 7 b is the cross sectional photograph of PLLA porous microsphere;
Fig. 8 is the configuration of surface and the internal structure of example 5 PLLA porous microspheres; Fig. 8 a is the configuration of surface of PLLA porous microsphere; Fig. 8 b is the cross sectional photograph of PLLA porous microsphere;
The specific embodiment
Example 1: the 0.5g PLA is dissolved in the 9ml carrene, adds 1ml.N-hexane mixes, and is standby.Adding bulking value concentration is 0.8% polyvinyl alcohol water solution 100ml in the beaker of 200ml.Start and stir, mixing speed is 500 rev/mins, pours the carrene/hexane solution of PLA into.Temperature is 25 ℃, stirs 24h, makes the organic solvent volatilization fully.After stopping to stir, microballoon is suspended in solution surface, filters, and uses the deionized water cyclic washing, collects the back in 35 ℃ of following vacuum drying 3 days.Yield is 98%, and microballoon number average bead diameter d=290 micron is seen Fig. 1; Apparent density is 0.2891g/cm
3, inner average pore size is 16 ± 3 microns, sees Fig. 2 a～Fig. 2 d.
Example 2: the 0.5g PLA is dissolved in the 9ml carrene, adds the 1ml normal octane, mix, standby.Adding bulking value concentration is 0.8% polyvinyl alcohol water solution 100ml in the beaker of 200ml.Start and stir, mixing speed is 300 rev/mins, pours the carrene/hexane solution of PLA into.Temperature is 25 ℃, stirs 24 hours, makes the organic solvent volatilization fully.After stopping to stir, microballoon is suspended in solution surface, filters, and uses the deionized water cyclic washing, collects the back in 35 ℃ of following vacuum drying 3 days.Yield is 97.7%, and microsphere average grain diameter d=471 micron is seen Fig. 3; Apparent density is 0.2136g/cm
3, inner average pore size is 24 ± 4 microns, sees Fig. 4 a～Fig. 4 d.
Example 3: the 0.5g PLA is dissolved in the 8ml carrene, adds the 2ml n-hexane, mix, standby.Adding bulking value concentration is 0.8% polyvinyl alcohol water solution 100ml in the beaker of 200ml.Start and stir, mixing speed is 500 rev/mins, pours the carrene/hexane solution of PLA into.Temperature is 25 ℃, stirs 24 hours, makes the organic solvent volatilization fully.After stopping to stir, microballoon is suspended in solution surface, filters, and uses the deionized water cyclic washing, collects back 35 ℃ of following vacuum drying 3 days.Yield is 99%, and microsphere average grain diameter d=413 micron is seen Fig. 5; Apparent density is 0.1726g/cm
3, inner average pore size is 30 ± 5 microns, sees Fig. 6 a～Fig. 6 d.
Example 4 is dissolved in the 0.5g PLLA in the 9ml carrene, adds the 1ml n-hexane, mixes, and is standby.Adding bulking value concentration is 0.8% polyvinyl alcohol water solution 100ml in the beaker of 200ml.Start and stir, mixing speed is 500 rev/mins, pours the carrene/hexane solution of PLLA into.Temperature is 25 ℃, stirs 24 hours, makes the organic solvent volatilization fully.After stopping to stir, visible microballoon is suspended in solution surface, filters, and uses the deionized water cyclic washing, collects back 35 ℃ of following vacuum drying 3 days.See Fig. 7 a, Fig. 7 b.
Example 5 is dissolved in the 0.5g PLLA in the 9ml carrene, adds the 1ml n-dodecane, mixes, and is standby.Adding bulking value concentration is 0.8% polyvinyl alcohol water solution 100ml in the beaker of 200ml.Start and stir, mixing speed is 500 rev/mins, pours the carrene/n-dodecane solution of PLLA into.Temperature is 25 ℃, stirs 24 hours, makes the organic solvent volatilization fully.After stopping to stir, microballoon is suspended in solution surface, filters, and uses the deionized water cyclic washing, collects back 35 ℃ of following vacuum drying 3 days.See Fig. 8 a, Fig. 8 b.
Claims (2)
1. method for preparing porous polylactic acid microball, this method may further comprise the steps:
1) PLA is dissolved in the methylene chloride, adds poor solvent then, mix, the bulking value concentration of PLA in the mixed solvent of carrene and poor solvent is 3～8%; The volume ratio of carrene and poor solvent is 10: 0～8: 2 in the mixed solvent;
2) polyvinyl alcohol is dissolved in the deionized water, be prepared into bulking value concentration and be 0.3～0.8% solution, low whipping speed is under 300～800 rev/mins of situations, and PLA solution is poured in the poly-vinyl alcohol solution, and the volume ratio of water and organic facies is 5: 1～10: 1;
3) vapor away organic solvent under 10～40 ℃, filter, washing obtains porous polylactic acid microball.
2. the method for preparing porous polylactic acid microball according to claim 1, said poor solvent are n-hexane, normal heptane, normal octane, isooctane or n-dodecane.
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