CN115536900A - Preparation method of absorbable open porous polyester microspheres with biological activity - Google Patents
Preparation method of absorbable open porous polyester microspheres with biological activity Download PDFInfo
- Publication number
- CN115536900A CN115536900A CN202211201297.9A CN202211201297A CN115536900A CN 115536900 A CN115536900 A CN 115536900A CN 202211201297 A CN202211201297 A CN 202211201297A CN 115536900 A CN115536900 A CN 115536900A
- Authority
- CN
- China
- Prior art keywords
- microspheres
- polyester
- biological activity
- stirring
- absorbable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/36—After-treatment
- C08J9/40—Impregnation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/04—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof using blowing gases generated by a previously added blowing agent
- C08J9/06—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof using blowing gases generated by a previously added blowing agent by a chemical blowing agent
- C08J9/08—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof using blowing gases generated by a previously added blowing agent by a chemical blowing agent developing carbon dioxide
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
- C08J9/16—Making expandable particles
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2207/00—Foams characterised by their intended use
- C08J2207/10—Medical applications, e.g. biocompatible scaffolds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/20—Small organic molecules
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/30—Synthetic polymers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/50—Proteins
- C12N2533/54—Collagen; Gelatin
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Materials Engineering (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Cell Biology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method of absorbable open porous polyester microspheres with bioactivity, which comprises the following steps: s1, respectively dissolving polyester and a pore-forming agent in an organic solvent and deionized water, mixing the two solutions after the two solutions are completely dissolved, and stirring the two solutions at room temperature to form a primary emulsion; s2, slowly dropping the primary emulsion into an external water phase, and stirring until complete emulsification; s3, continuously stirring at room temperature until the organic solvent and the pore-forming agent are completely volatilized, forming dispersed microspheres in the water phase, and removing the supernatant; s4, collecting microspheres through suction filtration, and placing the microspheres in a mixed solution of sodium hydroxide and ethanol; and S5, washing the reacted microspheres with deionized water for multiple times, and freeze-drying to obtain the absorbable polyester porous microspheres. According to the invention, the cost is low, the operation is simple, the particle size of the prepared microsphere is controllable, and the scale production is easy.
Description
Technical Field
The invention relates to the technical field of high-molecular bioactive porous microspheres, in particular to a preparation method of an absorbable open type porous polyester microsphere with bioactivity.
Background
Polyester attracts more and more attention due to its good properties including excellent biocompatibility, biodegradability, non-toxicity, non-immunogenicity, shape controllability and good mechanical strength, has become one of the most common biomaterials for preparing microspheres, and is widely used in the fields of pharmaceutical industry, medical devices and the like. Currently, many polyester-based medical devices have obtained U.S. Food and Drug Administration (FDA) approval for drug delivery, microcarriers and tissue engineering.
The small cell carrier has been widely studied because of its convenient operation and high clinical safety, and can relieve pain of patients and repair complex tissue defects. However, most cell carriers have simple planar structures, and the bioactivity and cell adhesion are poor, so that the cell density is low, and the application effect is poor. Therefore, a three-dimensional carrier with good biocompatibility can effectively change this condition. The three-dimensional curved surface on the surface of the microsphere can well simulate the survival microenvironment of cells, improve the survival rate of the cells, and the microsphere has rich and various forms, thereby providing more choices for cell culture. And the microsphere structure is controllable, the large-scale production is easy, and favorable conditions are provided for the large-scale production of cells. Currently, the preparation of polyester integrated bio-fabrication platforms for the large-scale expansion and neuronal differentiation of human pluripotent stem cell-derived neural precursor cells has been investigated.
The smooth surface of most microspheres is not conducive to cell adhesion, resulting in a significant reduction in cell expansion efficiency. More and more research is being directed towards designing microspheres with rough surfaces. For example, a rough surface gel microsphere system is prepared by 3D digital light processing techniques. Cells cultured on this system exhibit high viability, attachment, proliferation, activity and differentiation potential. However, the specific surface area of smooth, hollow or rough microspheres is very limited, sufficient internal space cannot be provided for cell proliferation, cells can only adhere to the microsphere surface, so that the improvement is very limited, and cells only adhering to the microsphere surface easily die and fall off due to friction between microspheres or pressure during injection, resulting in a significant decrease in cell adhesion rate and cell activity.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the preparation method of the absorbable open type porous polyester microsphere with biological activity, which has the advantages of low cost, simple operation, controllable particle size of the prepared microsphere and easy scale production. To achieve the above objects and other advantages in accordance with the present invention, there is provided a method for preparing absorbable open porous polyester microspheres having biological activity, comprising:
s1, respectively dissolving polyester and a pore-foaming agent in an organic solvent and deionized water, mixing the two solutions after the two solutions are completely dissolved, and stirring at room temperature to form a primary emulsion;
s2, slowly dropping the primary emulsion into an external water phase, and stirring until complete emulsification;
s3, continuously stirring at room temperature until the organic solvent and the pore-forming agent are completely volatilized, forming dispersed microspheres in the water phase, and removing supernatant, wherein the pore-forming agent is ammonium bicarbonate, sodium chloride, gelatin, PEG (polyethylene glycol) or BSA (bovine serum albumin);
s4, collecting the microspheres through suction filtration, and placing the microspheres in a surface treating agent;
and S5, washing the reacted microspheres with deionized water for multiple times, and freeze-drying to obtain the absorbable polyester porous microspheres.
Preferably, the polyester comprises PLGA, PLA, PLCL, etc., and the polyester has a molecular weight of 1000 to 200000Da.
Preferably, the pore-forming agent is ammonium bicarbonate, sodium chloride, gelatin, PEG or BSA solution, and the concentration of the pore-forming solution is 0.1-30% (w/v).
Preferably, the organic solvent is dichloromethane, and the concentration of the organic solvent is 0.1-30% (w/v).
Preferably, in the step S1, the water-oil ratio of the pore-foaming agent to the polyester is 1 to 2-1 (v/v).
Preferably, in step S2, the external aqueous phase is water-soluble surfactant dissolved in deionized water, the water-soluble surfactant is PVA, and the concentration of the water-soluble surfactant is 0.01-10% (w/v).
Preferably, when the multiple emulsion is formed, the oil-water ratio is 1-1 (v/v).
Preferably, the surface treatment agent is a mixed solution of ethanol and sodium hydroxide, the concentration of the pore-foaming agent is 0.01-5M, and the volume ratio of the two solutions is 1. And (3) carrying out hydrolysis reaction on small holes on the surface of the polyester microsphere at the temperature of 10-40 ℃ to form 10-100 mu m big holes and 1-10 mu m small holes.
Preferably, the pore-forming agent is ammonium bicarbonate, sodium chloride, gelatin, PEG or BSA.
Compared with the prior art, the invention has the beneficial effects that: the formed open type porous polyester microspheres have uniform particle size, controllable pore diameter and good biocompatibility, the pore diameter of the microspheres is about 18 microns, the microspheres comprise macropores with the diameter of 10-60 microns and are used for cell adhesion and proliferation, and pores with the diameter of less than 10 microns are used for the in-and-out transportation of nutrient substances, oxygen and metabolic waste, so that extremely favorable conditions are provided for cell proliferation; during emulsification, the particle size and the form of the microspheres are controlled by adopting a stirring emulsification method, and a PVA (polyvinyl alcohol) aqueous solution with good biocompatibility is adopted, so that the microspheres have no cell toxic or side effect; the pore diameter of the microsphere is increased by combining NaOH and ethanol solution in the later stage, the defect that the pore diameter of the microsphere prepared only by an emulsion method is small can be overcome, the pore diameter of a macropore of the prepared microsphere meets the requirement of cell entry, the sphericity of the microsphere is good, the particle diameter is about 230 mu m, and the microsphere can be used as an excellent cell carrier to effectively increase the cell inoculation density and protect the cell activity.
Drawings
FIG. 1 is a flow chart of a method for preparing absorbable open porous polyester microspheres with bioactivity according to the invention;
FIG. 2 is a scanning electron microscope image of the open porous PLGA microspheres having biological activity according to the present invention;
fig. 3 is a scanning electron microscope image of the preparation method of the absorbable open porous polyester microsphere with bioactivity under different stirring conditions.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Referring to fig. 1 to 3, a method for preparing absorbable open porous polyester microspheres with bioactivity comprises the following steps:
s1, respectively dissolving polyester and a pore-foaming agent in an organic solvent and deionized water, mixing the two solutions after the two solutions are completely dissolved, and stirring at room temperature to form a primary emulsion;
s2, slowly dripping the primary emulsion into an external water phase, and stirring until complete emulsification;
s3, continuously stirring at room temperature until the organic solvent and the pore-forming agent are completely volatilized, forming dispersed microspheres in a water phase, and removing supernatant, wherein the pore-forming agent is ammonium bicarbonate or sodium chloride;
s4, collecting microspheres through suction filtration, and placing the microspheres in a surface treating agent;
and S5, washing the reacted microspheres with deionized water for multiple times, and freeze-drying to obtain the absorbable polyester porous microspheres.
Further, the polyester includes PLGA, PLA, PLCL, etc., and the molecular weight in the polyester is 1000 to 200000Da.
Further, the pore-foaming agent is NH 4 HCO 3 A solution, wherein the concentration of the porogenic solution is 0.1-30% (w/v).
Further, the organic solvent is dichloromethane, and the concentration of the organic solvent is 0.1-30% (w/v).
Further, in the step S1, the water-oil ratio of the pore-foaming agent to the polyester is 1 to 2-1 (v/v), the stirring speed is 50 to 10000rpm, and the stirring time is 1 to 30min.
Further, in the step S2, the external water phase is water-soluble surfactant dissolved in deionized water, the water-soluble surfactant is PVA, and the concentration of the water-soluble surfactant is 0.01-10% (w/v).
Further, when the multiple emulsion is formed, the oil-water ratio is 1-1 (v/v), the stirring speed is 50-10000rpm, and the stirring time is 10min-30h.
Further, the surface treatment agent is a mixed solution of ethanol and sodium hydroxide, the concentration of the sodium hydroxide solution is 0.01-5M, and the volume ratio of the two solutions is 1-1. And (3) carrying out hydrolysis reaction on small holes on the surface of the PLGA microsphere at the temperature of 10-40 ℃ to form 10-100 mu m big holes and 1-10 mu m small holes.
Further, the pore-forming agent is ammonium bicarbonate, sodium chloride, gelatin, PEG or BSA.
The method of the figure I is adopted to prepare the open type porous microspheres, and the required raw materials and sources are as follows: l-lactide (L-LA) and Glycolide (GA) were purchased from Jinan Dai handle & Tiger biological materials Ltd, jinan, china. Dichloromethane (DCM) and absolute ethanol were purchased from shanghai Linfeng Chemicals, ltd (shanghai, china). Stannous octoate (Sn (Oct) 2), polyvinyl alcohol (PVA), ammonium bicarbonate (NH 4HCO 3), sodium hydroxide (NaOH) was obtained from sigma-aldrich (missouri, usa).
Example 1
1) 150mgPLGA (50. Adding into 20ml dichloromethane, stirring to dissolve completely;
2) 5mL of 5wt% ammonium bicarbonate aqueous solution is prepared and added into the oil phase in the step 1), and the mixture is magnetically stirred at a high speed of 800rpm for 10min to form water-in-oil emulsion;
3) Preparing 1.5wt% PVA solution, adding the emulsion prepared in step 2) into 150mL PVA solution, stirring by magnetic stirring at a speed of 600rpm for 3h to completely emulsify.
4) The reactor is opened and stirring is continued at room temperature overnight to fully volatilize dichloromethane and fully volatilize NH3 and CO2 through the decomposition of ammonium bicarbonate, so that a connected pore structure can be formed inside and on the surface of the microsphere.
5) The PLGA microspheres were collected by suction filtration and washed 3 times with deionized water.
6) Mixing 25mL0.25M NaOH solution with ethanol 1, placing the microspheres prepared in the step 5) in the mixture, and continuing to react for 3min at room temperature.
7) And performing suction filtration, washing and centrifugation again to obtain porous PLGA microspheres, collecting the microspheres, and freeze-drying for 48 hours to obtain the open type porous microsphere cell carrier with the average particle size of 326 +/-42 mu m.
Example 2
The present embodiment takes the following steps:
1) 120mgPLGA (60. Adding into 15ml dichloromethane, stirring until it is fully dissolved;
2) 5mL of 5wt% ammonium bicarbonate aqueous solution is prepared and added into the oil phase in the step 1), and the mixture is magnetically stirred at a high speed of 800rpm for 10min to form water-in-oil emulsion;
3) Preparing 1.5wt% PVA solution, adding the emulsion prepared in step 2) into 150mL PVA solution, stirring by magnetic stirring at a speed of 800rpm for 3h to complete emulsification.
4) The reactor was opened and stirring continued at room temperature overnight to allow the dichloromethane to evaporate sufficiently and the NH3 and CO2 to evaporate by sufficient decomposition of ammonium bicarbonate, allowing the formation of a connected pore structure inside and on the surface of the microspheres.
5) The PLGA microspheres were collected by suction filtration and washed 3 times with deionized water.
6) Mix 25ml0.25m NaOH solution with ethanol 1, and put the microspheres prepared in step 5) in it, continue to react at room temperature for 3min.
7) And carrying out suction filtration, washing and centrifugation again to obtain porous PLGA microspheres, collecting the microspheres, and freeze-drying for 48 hours to obtain the open porous microsphere cell carrier with the average particle size of 223 +/-31 microns.
Example 3
The present embodiment takes the following steps:
1) 100mgPLGA (70. Adding into 10ml dichloromethane, stirring until it is fully dissolved;
2) 5mL of 5wt% ammonium bicarbonate aqueous solution is prepared and added into the oil phase in the step 1), and the mixture is magnetically stirred at a high speed of 800rpm for 10min to form water-in-oil emulsion;
3) Preparing 1.5wt% PVA solution, adding the emulsion prepared in step 2) into 150mL PVA solution, stirring by magnetic stirring at a speed of 1000rpm for 3h to completely emulsify.
4) The reactor was opened and stirring continued at room temperature overnight to allow the dichloromethane to evaporate sufficiently and the NH3 and CO2 to evaporate by sufficient decomposition of ammonium bicarbonate, allowing the formation of a connected pore structure inside and on the surface of the microspheres.
5) The PLGA microspheres were collected by suction filtration and washed 3 times with deionized water.
6) Mixing a 25mL0.25M NaOH solution with ethanol 1, placing the microspheres prepared in the step 5) in the mixture, and continuing to react for 3min at room temperature.
7) And carrying out suction filtration, washing and centrifugation again to obtain porous PLGA microspheres, collecting the microspheres, and freeze-drying for 48 hours to obtain the open porous microsphere cell carrier with the average particle size of 153 +/-27 microns.
Example 4
The present embodiment takes the following steps:
1) 80mgPLGA (80. Adding into 8ml dichloromethane, stirring until it is fully dissolved;
2) 4mL of 5wt% ammonium bicarbonate aqueous solution is prepared and added into the oil phase in the step 1), and the mixture is magnetically stirred at a high speed of 800rpm for 10min to form water-in-oil emulsion;
3) Preparing 1.5wt% PVA solution, adding the emulsion prepared in step 2) to 100mL PVA solution, stirring mechanically at a speed of 200rpm for 3h to complete the emulsification.
4) The reactor was opened and stirring continued at room temperature overnight to allow the dichloromethane to evaporate sufficiently and the NH3 and CO2 to evaporate by sufficient decomposition of ammonium bicarbonate, allowing the formation of a connected pore structure inside and on the surface of the microspheres.
5) The PLGA microspheres were collected by suction filtration and washed 3 times with deionized water.
6) Mixing 25mL0.25M NaOH solution with ethanol 1, placing the microspheres prepared in the step 5) in the mixture, and continuing to react for 3min at room temperature.
7) And carrying out suction filtration, washing and centrifugation again to obtain porous PLGA microspheres, collecting the microspheres, and freeze-drying for 48 hours to obtain the open porous microsphere cell carrier with the average particle size of 331 +/-25 microns.
Example 5
The present embodiment takes the following steps:
1) 50mgPLGA (90: 10). Adding into 5ml dichloromethane, stirring to dissolve completely;
2) 2mL of 5wt% ammonium bicarbonate aqueous solution is prepared and added into the oil phase in the step 1), and the mixture is magnetically stirred at a high speed of 800rpm for 10min to form water-in-oil emulsion;
3) Preparing 1.5wt% PVA solution, adding the emulsion prepared in step 2) to 50mL of PVA solution, stirring mechanically at a rate of 300rpm for 3h to complete emulsification.
4) The reactor was opened and stirring continued at room temperature overnight to allow the dichloromethane to evaporate sufficiently and the NH3 and CO2 to evaporate by sufficient decomposition of ammonium bicarbonate, allowing the formation of a connected pore structure inside and on the surface of the microspheres.
5) The PLGA microspheres were collected by suction filtration and washed 3 times with deionized water.
6) Mixing a 25mL0.25M NaOH solution with ethanol 1, placing the microspheres prepared in the step 5) in the mixture, and continuing to react for 3min at room temperature.
7) And carrying out suction filtration, washing and centrifugation again to obtain porous PLGA microspheres, collecting the microspheres, and freeze-drying for 48 hours to obtain the open porous microsphere cell carrier with the average particle size of 148 +/-16 microns.
The number of devices and the scale of the processes described herein are intended to simplify the description of the invention, and applications, modifications and variations of the invention will be apparent to those skilled in the art.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable in various fields of endeavor to which the invention pertains, and further modifications may readily be made by those skilled in the art, it being understood that the invention is not limited to the details shown and described herein without departing from the general concept defined by the appended claims and their equivalents.
Claims (9)
1. The preparation method of the absorbable open porous polyester microspheres with biological activity is characterized by comprising the following steps:
s1, respectively dissolving polyester and a pore-forming agent in an organic solvent and deionized water, mixing the two solutions after the two solutions are completely dissolved, and stirring the two solutions at room temperature to form a primary emulsion;
s2, slowly dropping the primary emulsion into an external water phase, and stirring until complete emulsification;
s3, continuously stirring at room temperature until the organic solvent and the pore-forming agent are completely volatilized, forming dispersed microspheres in the water phase, and removing the supernatant;
s4, collecting the microspheres through suction filtration, and placing the microspheres in a surface treating agent;
and S5, washing the reacted microspheres with deionized water for multiple times, and freeze-drying to obtain the absorbable polyester porous microspheres.
2. The method for preparing absorbable open porous polyester microspheres with biological activity as claimed in claim 1, wherein the polyester comprises PLGA, PLA, PLCL etc. and the molecular weight of the polyester is 1000-200000 Da.
3. The method for preparing absorbable porous polyester microspheres with biological activity as claimed in claim 2, wherein the pore-forming agent is ammonium bicarbonate, sodium chloride, gelatin, PEG or BSA solution, and the concentration of the pore-forming solution is 0.1-30% (w/v).
4. The method for preparing absorbable porous polyester microspheres with biological activity as claimed in claim 3, wherein the organic solvent is dichloromethane, and the concentration of the organic solvent is 0.1-30% (w/v).
5. The method for preparing absorbable open porous polyester microspheres with biological activity as claimed in claim 4, wherein in step S1, the water-oil ratio of the porogen and the polyester is 1-2-1 (v/v), the stirring speed is 50-10000rpm, and the stirring time is 1-30min.
6. The method for preparing absorbable open porous polyester microspheres with biological activity according to claim 5, wherein in step S2, the external aqueous phase is water-soluble surfactant dissolved in deionized water, the water-soluble surfactant is PVA, and the concentration of the water-soluble surfactant is 0.01-10% (w/v).
7. The method for preparing absorbable porous polyester microspheres with biological activity as claimed in claim 1, wherein the oil-water ratio is 1-1 (v/v), the stirring speed is 50-10000rpm, and the stirring time is 10min-30h during the formation of the multiple emulsion.
8. The method for preparing absorbable porous polyester microspheres with biological activity as claimed in claim 1, wherein the surface treatment agent is a mixed solution of ethanol and sodium hydroxide, the concentration of the sodium hydroxide solution is 0.01-5M, the volume ratio of the two solutions is 1.
9. The method for preparing absorbable porous polyester microspheres with biological activity as claimed in claim 1, wherein the pore-forming agent is ammonium bicarbonate, sodium chloride, gelatin, PEG or BSA.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211201297.9A CN115536900A (en) | 2022-09-29 | 2022-09-29 | Preparation method of absorbable open porous polyester microspheres with biological activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211201297.9A CN115536900A (en) | 2022-09-29 | 2022-09-29 | Preparation method of absorbable open porous polyester microspheres with biological activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115536900A true CN115536900A (en) | 2022-12-30 |
Family
ID=84731432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211201297.9A Pending CN115536900A (en) | 2022-09-29 | 2022-09-29 | Preparation method of absorbable open porous polyester microspheres with biological activity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115536900A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001078687A1 (en) * | 2000-04-18 | 2001-10-25 | Peptron Inc. | Injectable sustained release pharmaceutical composition and processes for preparing the same |
| CN101249077A (en) * | 2008-04-14 | 2008-08-27 | 西南交通大学 | Preparation of degradable pollutant polyalcohol stephanoporate microballoons and uses thereof |
| CN102728287A (en) * | 2012-06-07 | 2012-10-17 | 东南大学 | Preparation method of PLGA microsphere with porous surface |
| CN105664242A (en) * | 2016-02-03 | 2016-06-15 | 重庆科技学院 | Method for preparing PLGA microspheres with porous surfaces |
| CN112662005A (en) * | 2020-12-17 | 2021-04-16 | 北京科技大学 | Preparation and use method of polyester porous polymer microspheres |
| CN114634634A (en) * | 2022-03-22 | 2022-06-17 | 陈凌卉 | Biological function composite porous polyester microsphere and preparation method thereof |
-
2022
- 2022-09-29 CN CN202211201297.9A patent/CN115536900A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001078687A1 (en) * | 2000-04-18 | 2001-10-25 | Peptron Inc. | Injectable sustained release pharmaceutical composition and processes for preparing the same |
| CN101249077A (en) * | 2008-04-14 | 2008-08-27 | 西南交通大学 | Preparation of degradable pollutant polyalcohol stephanoporate microballoons and uses thereof |
| CN102728287A (en) * | 2012-06-07 | 2012-10-17 | 东南大学 | Preparation method of PLGA microsphere with porous surface |
| CN105664242A (en) * | 2016-02-03 | 2016-06-15 | 重庆科技学院 | Method for preparing PLGA microspheres with porous surfaces |
| CN112662005A (en) * | 2020-12-17 | 2021-04-16 | 北京科技大学 | Preparation and use method of polyester porous polymer microspheres |
| CN114634634A (en) * | 2022-03-22 | 2022-06-17 | 陈凌卉 | Biological function composite porous polyester microsphere and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zhang et al. | Inverse opal scaffolds for applications in regenerative medicine | |
| CN103361885B (en) | A kind of preparation method of antibacterial fibroin fiber film | |
| CN110538346B (en) | Preparation method of porous nano hydroxyapatite sustained-release gel | |
| CN101920043B (en) | Porous bracket with micro grooves on pore walls and preparation method thereof | |
| CN108283729B (en) | Injectable bone repair material with controllable magnesium ion release behavior and preparation method thereof | |
| Zhang et al. | Fabrication of hollow porous PLGA microspheres for controlled protein release and promotion of cell compatibility | |
| CN104140551A (en) | Preparation method of organic/inorganic composite porous scaffold material for bone tissue engineering | |
| CN114259571B (en) | Super-assembly preparation method of intelligent temperature-responsive nano motor | |
| CN105664242A (en) | Method for preparing PLGA microspheres with porous surfaces | |
| CN103800292A (en) | Preparation method of organic/inorganic hybrid nano fiber drug carrying microsphere | |
| CN113248772A (en) | Microfluidic preparation method of porous polyhydroxyalkanoate polymer microspheres, porous polymer microspheres prepared by microfluidic preparation method and application of porous polyhydroxyalkanoate polymer microspheres | |
| CN105344334A (en) | Preparation method for polyvinyl alcohol/silicon dioxide composite microspheres | |
| CN112870439A (en) | Nano fiber bone tissue engineering scaffold with core-shell-series crystal structure and preparation method thereof | |
| CN111269444A (en) | Crosslinked microsphere and preparation method and application thereof | |
| CN103709447A (en) | Magnetic cellulose composite microsphere, and preparation method and application thereof | |
| CN115536900A (en) | Preparation method of absorbable open porous polyester microspheres with biological activity | |
| CN110681323B (en) | Golf ball type degradable microsphere with micro-topological structure and preparation method thereof | |
| CN100418581C (en) | Method for preparation of polyester magnetic composite microsphere capable of being biodegraded | |
| KR101352411B1 (en) | Cell carrier for immunosuppression, and method for preparing the same | |
| CN114288262B (en) | Drug-loaded microsphere and preparation method and application thereof | |
| CN111909417B (en) | Preparation method of polylactic acid film with uniform pore on surface | |
| CN114042044B (en) | Trace polylactic acid/rifampicin drug-loaded microsphere and preparation method thereof | |
| Cheng et al. | Facile development of a hollow composite microsphere with porous surface for cell delivery | |
| CN103599075A (en) | Sustained release microspheres of polyethylene glycol-polylactic acid entrapped betamethasone dipropionate and preparation method thereof | |
| CN102949751A (en) | Preparation method for tissue engineering collagen-hyaluronic acid-chondroitin sulfate electrostatic spinning bracket |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |