CN111803450B - Nano-reinforced degradable polymer microsphere and preparation method and application thereof - Google Patents
Nano-reinforced degradable polymer microsphere and preparation method and application thereof Download PDFInfo
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- CN111803450B CN111803450B CN202010544353.3A CN202010544353A CN111803450B CN 111803450 B CN111803450 B CN 111803450B CN 202010544353 A CN202010544353 A CN 202010544353A CN 111803450 B CN111803450 B CN 111803450B
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- degradable polymer
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Abstract
The invention provides a nano-reinforced degradable polymer microsphere and a preparation method and application thereof, wherein the preparation method comprises the following steps: (1) dispersing the nano crystal whisker in the composite solution to obtain a solution A; (2) dissolving degradable macromolecules in a volatile solvent to obtain a solution B; (3) emulsifying the solution A and the solution B to obtain an emulsion; and stirring the emulsion, adding the emulsion into an aqueous solution containing a surfactant, performing ultrasonic treatment, and curing to obtain the water-based emulsion. According to the preparation method of the microsphere, the organic solvent is added into the internal water phase, and the interaction force of the nanowhiskers and the degradable macromolecules in the volatile organic solvent is regulated and controlled, so that the effect of regulating and controlling the uniform distribution of the nanowhiskers in the microsphere is achieved, the good dispersion effect of the nanowhiskers is achieved, the size of the degradation products of the macromolecule microsphere is regulated and controlled, and the immune inflammatory reaction of the microsphere after entering a human body is reduced.
Description
Technical Field
The invention belongs to the technical field of polymer microspheres, and particularly relates to a nano-reinforced degradable polymer microsphere and a preparation method and application thereof.
Background
Materials used for tissue repair and regeneration must be non-toxic to tissues, cells, etc., and should not cause excessive inflammatory immune responses after implantation. Thus, successful repair and regeneration of the tissue can be effectively ensured. Among these, macrophages are the key immune cells, and their interaction with the implant will influence the extent of the inflammatory response and will determine whether subsequent tissue repair and regeneration is successful.
The polymer microsphere generally refers to a polymer aggregate with a diameter ranging from nanometer to micrometer and a spherical shape. The polymer microsphere attracts the interests of more and more scientific workers due to the designability and the multifunctionality, and is widely researched and applied in the field of tissue repair and regeneration. The materials currently used in microspheres are mainly classified into inorganic materials, natural polymer materials and synthetic polymer materials. The degradable materials and non-degradable materials can be further classified according to their degradation properties. The artificially synthesized degradable high polymer material can be designed for biological response characteristics by changing the chemical composition, the material structure, the surface properties and the like of the raw materials. Polyesters are the most studied and widely used biodegradable synthetic polymeric materials, such as polylactic acid, polyglycolic acid, poly-epsilon-caprolactone, poly-beta-hydroxybutyric acid, poly-beta-hydroxyvaleric acid, and copolymers thereof. The copolymer of lactic acid-glycolic acid is a high molecular material approved by the U.S. food and drug administration for clinical application, and has good biocompatibility.
However, synthetic polymers such as copolymers of lactic acid and glycolic acid are degraded in vivo in the form of bulk degradation, and during the degradation, the synthetic polymers are broken into bulk particles, which are mainly phagocytosed by macrophages of proinflammatory type. But at the same time, the inflammatory differentiation of macrophages is promoted in the process, so that the local inflammatory effect is aggravated, and the repair and regeneration of bone defects are not facilitated. Whereas systems with low inflammatory response prepared in the prior art are ubiquitous 1) requiring external devices to coordinate regulation of inflammatory response; 2) the aim of regulating and controlling inflammatory reaction is achieved by means of local/targeted release of the medicament; 3) the preparation process is complex and difficult to industrialize.
The nano crystal whisker is a nano short fiber grown from high-purity single crystal, and the highly oriented structure of the crystal whisker ensures that the crystal whisker has high strength, high modulus and high elongation and can be used as a reinforcing material.
Disclosure of Invention
The invention aims to provide a degradable microsphere and a preparation method and application thereof, wherein nanowhiskers are used as reinforcing steel bars of polymer-based microspheres, the distribution and directional arrangement of the nanowhiskers in a polymer phase are regulated and controlled, and one or more composite microspheres with controllable degradation kinetics and small inflammatory reaction caused by the size of degraded fragments are obtained. The prepared microsphere has good biocompatibility and controllable degradation kinetics, the degradation product is not easy to cause inflammatory reaction, and the microsphere can be used as wound repair materials, food and drug materials and drug carrier materials.
The technical scheme adopted by the invention is as follows:
in a first aspect of the present invention, there is provided:
a method for preparing nano reinforced degradable polymer microspheres comprises the following steps:
(1) dispersing the nano crystal whisker in the composite solution to obtain a solution A;
(2) dissolving degradable macromolecules in a volatile solvent to obtain a solution B;
(3) emulsifying the solution A and the solution B to obtain an emulsion; and adding the emulsion into an aqueous solution containing a surfactant, stirring, carrying out ultrasonic treatment, and curing to obtain the nano reinforced degradable polymer microsphere.
Preferably, the step (3) further includes purifying the nano reinforced degradable polymer microsphere after curing, specifically, the purification includes washing and drying, and the purity of the nano reinforced degradable polymer microsphere can be further improved by the washing and drying method.
Preferably, the speed of dispersing in the step (1) is 200 to 20000rpm, and the dispersing time is 1min to 24 h.
Preferably, the emulsifying speed in the step (3) is 6000-20000 rpm, and the emulsifying time is 0.5-3 min.
Preferably, the rotation speed of the stirring in the step (3) is 200-1000 rpm, and the stirring time is 15-60 min.
Preferably, the ultrasonic frequency of the ultrasound in the step (3) is 20 to 25KHz, the power of the ultrasonic is 2 to 800W, and the ultrasound time is 10 to 180 min.
Preferably, the curing time in the step (3) is 6 to 10 hours.
Preferably, the drying mode is at least one selected from room temperature air drying, heat drying and freeze drying, and the drying time is 24-48 h.
Preferably, the nanowhisker in step (1) above includes, but is not limited to, at least one selected from the group consisting of silicon carbide, boron nitride, silicon nitride, cellulose, chitin, zinc oxide, tungsten carbide, calcium sulfate, alumina, potassium titanate, and titanium dioxide.
Preferably, the organic solvent in the step (1) is at least one selected from methanol, ethanol, diethyl ether, hexane, isopropanol and acetone.
Preferably, the volume ratio of the organic solvent to the water in the step (1) is (0.5-1.5): 1.
preferably, the mass-to-volume ratio of the nanowhiskers to the composite solution in the step (1) is (0.03-0.5): 1 g/mL.
Preferably, the degradable polymer in step (2) includes, but is not limited to, at least one selected from the group consisting of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, poly-3-hydroxyalkanoate, poly (3-hydroxybutyrate), poly-3-hydroxybutyrate-co-3-hydroxyvalerate, polytrimethylene carbonate and polybutylene succinate.
Preferably, the molecular weight of the degradable polymer is 3000-60000 dalton.
Preferably, the volatile solvent in the step (2) is at least one selected from the group consisting of ethyl acetate, dichloromethane, chloroform, and tetrahydrofuran.
Preferably, in the step (2), the mass-to-volume ratio of the degradable polymer to the volatile solvent is (0.025-0.3): 1 g/mL.
Preferably, the mass ratio of the nanowhiskers to the degradable polymer in the emulsion in the step (3) is (0.05-0.45): 1.
preferably, in the step (3), the surfactant is at least one selected from gelatin, methylcellulose and polyvinyl alcohol.
Preferably, the mass concentration of the surfactant-containing aqueous solution in the step (3) is 0.5% to 1.5%.
Preferably, the volume ratio of the emulsion to the surfactant-containing aqueous solution in the step (3) is (0.002-0.01): 1.
in a second aspect of the present invention, there is provided:
a nanometer reinforced degradable polymer microsphere is prepared by the preparation method of the nanometer reinforced degradable polymer microsphere.
Preferably, the particle size of the nano reinforced degradable polymer microsphere is 20 to 300 μm.
In a third aspect of the present invention, there is provided:
the application of the nano-reinforced degradable polymer microspheres in wound repair materials, food and drug materials and drug carrier materials is provided.
The invention has the beneficial effects that:
1. the preparation method of the microsphere is based on the traditional emulsion solvent volatilization method, and aims at different types of nano whiskers, the organic solvent is added into the internal water phase, and the interaction force of the nano whiskers and the degradable macromolecules in the volatile solvent is regulated and controlled, so that the effect of regulating and controlling the uniform distribution of the nano whiskers in the microsphere is achieved, the better nano whisker dispersion effect is achieved, the size of a degradation product of the macromolecule microsphere is regulated and controlled, and the immune inflammatory reaction of the microsphere after entering a human body is reduced.
2. Furthermore, aiming at an emulsion system containing different nano-whiskers, the invention regulates the distribution of the nano-whiskers in the microspheres and the curing and forming speed of the microspheres by using an ultrasonic means in the curing and forming process of the microspheres, achieves the effect of synergistically regulating the uniform distribution of the nano-whiskers in the microspheres with an organic solvent in an internal water phase, and further achieves the purpose of regulating and controlling the size of a degradation product.
3. The mass concentration ratio of the nano whiskers to the degradable high molecular polymer in the emulsion is far less than 1, so that the nano whiskers in the prepared high molecular microsphere can be uniformly distributed in the microsphere, have good interaction force with a degradable high molecular polymer chain segment, and can be used as a reinforcing steel bar of a polymer material, so that when the high molecular microsphere is degraded, the size and the distribution of degradation products are regulated, and the degradation products are not easy to activate immune cells such as macrophages or inflammation thereof.
4. The preparation method has the advantages of simple process, low requirement on equipment, industrialized raw materials, easily-obtained sources, low cost and easy realization of industrialization.
Drawings
FIG. 1 is a graph showing the secretion of TNF- α by co-culturing macrophages in vitro, prepared in examples 1 to 5 and comparative examples 1 to 4.
Detailed Description
In order to make the objects, technical solutions and technical effects of the present invention more clear, the present invention will be described in further detail with reference to specific embodiments. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. Those in examples or comparative examples or test examples, for which no specific conditions are indicated, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Example 1: a preparation method of nano-reinforced degradable polymer microspheres comprises the following steps:
(1) dispersing 150mg of nano zinc oxide crystal whisker into 2mL of hexane/water (volume ratio is 1.5: 1) composite solution, and stirring at 6000rpm for 5min to obtain solution A;
(2) dissolving 1.5g of poly 3-hydroxybutyrate-co-3-hydroxyvalerate in 10mL of ethyl acetate to obtain a solution B;
(3) emulsifying the solution A and the solution B at 15000rpm for 2min, adding the emulsion into 500mL of 1.0% methyl cellulose aqueous solution, stirring at 600rpm at room temperature for 60min, and performing ultrasonic treatment for 120 min; after 5h, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 36h to obtain the nano-reinforced degradable polymer microspheres.
Example 2: a preparation method of nano-reinforced degradable polymer microspheres comprises the following steps:
(1) dispersing 800mg of nano-cellulose whiskers in 3mL of ethanol/water (volume ratio is 0.5: 1) composite solution, and stirring at 200rpm for 24 hours to obtain solution A;
(2) dissolving 2g of polylactic acid-glycolic acid copolymer in 10mL of dichloromethane to obtain a solution B;
(3) emulsifying the solution A and the solution B at 15000rpm for 1.5min, adding the emulsion into 200mL of 1788 type polyvinyl alcohol aqueous solution with mass concentration of 0.5%, stirring at 200rpm at room temperature for 30min, and performing ultrasonic treatment for 60 min; after 10h, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 24h to obtain the nano-reinforced degradable polymer microspheres.
Example 3: a preparation method of nano-reinforced degradable polymer microspheres comprises the following steps:
(1) dispersing 450mg of nano chitin whisker in 5mL of acetone/water (volume ratio is 1.0: 1) composite solution, and stirring at 400rpm for 24 hours to obtain solution A;
(2) dissolving 1g of polycaprolactone in 10mL of chloroform to obtain a solution B;
(3) emulsifying the solution A and the solution B at 10000rpm for 3min, adding the emulsion into 400mL of methyl cellulose aqueous solution with the mass concentration of 1.2%, stirring at 400rpm, stirring at room temperature for 15min, and performing ultrasonic treatment for 30 min; after 8h, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 36h to obtain the nano-reinforced degradable polymer microspheres.
Example 4: a preparation method of nano-reinforced degradable polymer microspheres comprises the following steps:
(1) dispersing 150mg of nano calcium sulfate crystal whisker into 1mL of ethanol/water (volume ratio is 1.2: 1) composite solution, and stirring for 3min at 10000rpm to obtain solution A;
(2) dissolving 3g of polylactic acid in 10mL of dichloromethane to obtain a solution B;
(3) emulsifying the solution A and the solution B at 20000rpm for 0.5min, adding the emulsion into 300mL of aqueous solution of 124-type polyvinyl alcohol with mass concentration of 1.5%, stirring at 1000rpm for 30min at room temperature, and performing ultrasonic treatment for 180 min; after 8h, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 24h to obtain the nano-reinforced degradable polymer microspheres.
Example 5: a preparation method of nano-reinforced degradable polymer microspheres comprises the following steps:
(1) dispersing 50mg of nano silicon carbide whiskers in 0.3mL of methanol/water (volume ratio is 0.7: 1) composite solution, and stirring at 15000rpm for 1min to obtain a solution A;
(2) dissolving 0.25g of polylactic acid-glycolic acid copolymer in 10mL of tetrahydrofuran to obtain a solution B;
(3) emulsifying the solution A and the solution B at 6000rpm for 2min, adding the emulsion into 125mL of 0.8 mass percent gelatin aqueous solution, stirring at 300rpm for 45min at room temperature, and performing ultrasonic treatment for 10 min; and after 7h, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 48h to obtain the nano-reinforced degradable polymer microspheres.
Comparative example 1: a preparation method of polymer microspheres comprises the following steps:
(1) dispersing 800mg of nano-cellulose whiskers in 3mL of aqueous solution, and stirring at 200rpm for 24 hours to obtain a solution A;
(2) dissolving 2g of polylactic acid-glycolic acid copolymer in 10mL of dichloromethane to obtain a solution B;
(3) emulsifying the solution A and the solution B at 15000rpm for 1.5min, adding the emulsion into 200mL of 1788 type polyvinyl alcohol aqueous solution with mass concentration of 0.5%, stirring at 200rpm at room temperature for 30min, and performing ultrasonic treatment for 60 min; after 10h, stirring is stopped, the microspheres are washed with water and centrifuged (the centrifugation conditions are 1000rpm, 10min and 3 times each time), and the polymer microspheres are obtained after freeze drying for 24 h.
Comparative example 2: a preparation method of polymer microspheres comprises the following steps:
(1) dispersing 800mg of nano cellulose whiskers in 3ml of ethanol/water (volume ratio is 0.5: 1) composite solution, and stirring at 200rpm for 24 hours to obtain solution A;
(2) dissolving 2g of polylactic acid-glycolic acid copolymer in 10mL of dichloromethane to obtain a solution B;
(3) emulsifying the solution A and the solution B at 15000rpm for 1.5min, adding the emulsion into 200mL of 1788 type polyvinyl alcohol aqueous solution with the mass concentration of 0.5%, stirring at 200rpm for 10h at room temperature, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 24h to obtain the polymer microspheres.
Comparative example 3: a preparation method of polymer microspheres comprises the following steps:
(1) dispersing 800mg of nano-cellulose whiskers in 3mL of aqueous solution, and stirring at 200rpm for 24 hours to obtain a solution A;
(2) dissolving 2g of polylactic acid-glycolic acid copolymer in 10mL of dichloromethane to obtain a solution B;
(3) emulsifying the solution A and the solution B at 15000rpm for 1.5min, adding the emulsion into 200mL of 1788 type polyvinyl alcohol aqueous solution with the mass concentration of 0.5%, stirring at 200rpm for 10h at room temperature, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 24h to obtain the polymer microspheres.
Comparative example 4: a preparation method of polymer microspheres comprises the following steps:
(1) dissolving 2g of polylactic acid-glycolic acid copolymer in 10mL of dichloromethane to obtain a solution B;
(2) and adding the solution B into 200mL of 1788 type polyvinyl alcohol aqueous solution with the mass concentration of 0.5%, stirring at the rotating speed of 200rpm for 10 hours at room temperature, stopping stirring, washing the microspheres with water, centrifuging (the conditions of each centrifugation are 1000rpm, 10min and 3 times), and freeze-drying for 24 hours to obtain the polymer microspheres.
Test example: the nano-reinforced degradable polymer microspheres prepared in examples 1 to 5 and the polymer microspheres prepared in comparative examples 1 to 4 are subjected to in vitro cytotoxicity test and in vitro stem cell osteogenesis induced differentiation performance test respectively.
1. In vitro cytotoxicity assay
The evaluation method comprises the following steps: MTT reagent is selected in the test example to evaluate the cytotoxicity of the polymer microsphere. Washing the microspheres planted with the cells for 2-3 times by using sterile PBS (phosphate buffer solution); adding 70 mu L of tetramethyl azodicarbonamide and 700 mu L of serum-free culture solution into each hole, and then placing the hole plate in an incubator; after 4h, the well plates were removed from the incubator. Carefully taking out the microspheres, respectively putting the microspheres into 1.5mL centrifuge tubes, and adding 0.8mL of dimethyl sulfoxide into each centrifuge tube; after all scaffolds were completely dissolved, the absorbance of each well at 490nm was measured using a microplate reader.
The nano-reinforced degradable polymer microspheres prepared in examples 1 to 5 and the polymer microspheres prepared in comparative examples 1 to 4 were taken, and in vitro cytotoxicity evaluation and scoring were performed according to the above methods, with the results shown in table 1:
TABLE 1 evaluation scoring results of in vitro cytotoxicity test
| Example 1 | Example 2 | Example 3 | Example 4 | Example 5 | Comparative example 1 | Comparative example 2 | Comparative example 3 | Comparative example 4 | |
| |
0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
2. In vitro macrophage regeneration typing induction differentiation performance detection
In vitro experiments used the mouse peripheral macrophage cell line RAW 264.7(RAW) cells (Shanghai cell bank, Chinese academy of sciences). The cells were cultured in a cell culture chamber using two-cell culture medium alpha-MEM (3T3), and were digested with trypsin when the degree of cell fusion reached 90%, for subsequent cell experiments.
The in vitro stem cell osteogenesis induced differentiation performance test is respectively carried out on the nano reinforced degradable polymer microspheres prepared in the embodiments 1-5 and the polymer microspheres prepared in the comparative examples 1-4, and the test method of the microspheres in each embodiment or comparative example is as follows: 250 μ L of sterile agarose with a mass concentration of 1% was spread on the bottom of each well of the 24-well plate, and the microspheres were added before they were completely solidified, so that the microspheres were fixed on the well plate. The microspheres were then immersed in 70% by volume ethanol solution for 2h, followed by ethanol aspiration, washing 5 times with PBS and irradiation under uv light for 20 min. Subsequently, 500. mu.L of the culture solution was added to each well, and the well plate was placed in an incubator for 24 hours. The culture medium in the well plate and the culture medium on the surface of the microspheres were aspirated, and 250. mu.L of a cell (mouse peripheral macrophage) suspension (1X 10)6Number of cells/mL) was uniformly dropped on the microspheres. After the addition was complete, the well plate was placed in an incubator for 1h, and after most of the cells adhered to the microspheres, an additional 750 μ L of culture medium was added to each well. The cell-seeded scaffold material was further cultured in an atmosphere of carbon dioxide at a temperature of 37 ℃ and a volume concentration of 5%Culturing in a culture box. After the culture for 7 hours, the inflammatory response performance of the macrophages is detected by secreted tumor necrosis factor-alpha (TNF-alpha), an ELISA kit and an enzyme-linked immunosorbent assay are adopted for joint detection, the detection is repeated for 3 times each time, and the cytokine concentration and the cell number of each group are subjected to normalization treatment. The results are shown in FIG. 1.
And (4) analyzing results: as can be seen from Table 1, the polymeric microspheres obtained in both examples and comparative examples were not cytotoxic. As can be seen from FIG. 1, example 2 and comparative examples 1 to 4 are microspheres prepared based on polylactic acid-glycolic acid copolymer. The nano reinforced degradable polymer microsphere with uniformly dispersed nano whiskers is prepared in example 2, the polymer microsphere prepared in a manner of regulating and controlling in an organic solvent-free manner in comparative example 1, the polymer microsphere prepared in a manner of assisting in preparing the polymer microsphere without using an internal water solvent in comparative example 2, the polymer microsphere prepared in a manner of not using ultrasonic treatment in the preparation process in comparative example 3, the polymer microsphere without adding an organic solvent in the internal water solvent and without using ultrasonic treatment in the preparation process in comparative example 3, and the non-nano reinforced degradable polymer microsphere in comparative example 4. In the 5 groups of materials, the microspheres prepared in example 2 have the least TNF-alpha secretion after coculture with macrophages, and compared with comparative examples 1-4, the nano reinforced degradable polymer microspheres prepared in examples 1 and 3-5 have the relatively less TNF-alpha secretion after coculture with macrophages, which indicates that the inflammatory reaction tendency of macrophages on the nano reinforced degradable polymer microspheres with uniformly distributed nano whiskers is the lowest. Further shows that the uniform distribution of the nano-whiskers in the microspheres prepared by the method has better effect of relieving the inflammatory reaction of macrophages.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A method for preparing nano reinforced degradable polymer microspheres is characterized by comprising the following steps: the method comprises the following steps:
(1) dispersing the nano-whiskers in a composite solution to obtain a solution A, wherein the composite solution is an organic solvent/water composite solution, and the volume ratio of the organic solvent to the water is (0.5-1.5): 1; the mass-volume ratio of the nanowhiskers to the composite solution is (0.03-0.5): 1 g/mL;
(2) dissolving degradable high polymer in a volatile solvent to obtain a solution B, wherein the mass-volume ratio of the degradable high polymer to the volatile solvent is (0.025-0.3): 1 g/mL;
(3) and emulsifying the solution A and the solution B to obtain an emulsion, wherein the mass ratio of the nanowhiskers to the degradable macromolecules in the emulsion is (0.05-0.45): 1; adding the emulsion into an aqueous solution containing a surfactant, stirring, carrying out ultrasonic treatment, and curing to obtain nano reinforced degradable polymer microspheres; the nano whiskers are distributed inside the nano reinforced degradable polymer microsphere.
2. The method for preparing nano reinforced degradable polymer microsphere according to claim 1, wherein the method comprises the following steps: the organic solvent is selected from at least one of methanol, ethanol, diethyl ether, hexane, isopropanol and acetone.
3. The method for preparing nano reinforced degradable polymer microsphere according to claim 1, wherein the method comprises the following steps: the volatile solvent is at least one of ethyl acetate, dichloromethane, trichloromethane and tetrahydrofuran.
4. The method for preparing nano reinforced degradable polymer microsphere according to claim 1, wherein the method comprises the following steps: and (4) in the step (3), the ultrasonic frequency of the ultrasonic wave is 20-25 KHz, the power of the ultrasonic wave is 2-800W, and the ultrasonic time is 10-180 min.
5. The method for preparing nano reinforced degradable polymer microsphere according to claim 1, wherein the method comprises the following steps: and (4) curing for 6-10 h in the step (3).
6. The method for preparing nano reinforced degradable polymer microsphere according to claim 1, wherein the method comprises the following steps: the nano crystal whisker is selected from at least one of silicon carbide, boron nitride, silicon nitride, cellulose, chitin, zinc oxide, tungsten carbide, calcium sulfate, aluminum oxide, potassium titanate and titanium dioxide.
7. A nanometer reinforced degradable polymer microsphere is characterized in that: the nano reinforced degradable polymer microsphere is prepared by the preparation method of the nano reinforced degradable polymer microsphere of any one of claims 1 to 6.
8. An application of nano-reinforced degradable polymer microspheres in preparing wound repair materials is characterized in that: the nano reinforced degradable polymer microsphere is the nano reinforced degradable polymer microsphere in claim 7.
9. An application of nano-reinforced degradable polymer microspheres in the preparation of pharmaceutical materials is characterized in that: the nano reinforced degradable polymer microsphere is the nano reinforced degradable polymer microsphere in claim 7.
10. An application of nano-reinforced degradable polymer microspheres in preparation of drug carrier materials is characterized in that: the nano reinforced degradable polymer microsphere is the nano reinforced degradable polymer microsphere in claim 7.
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Address after: No. 1307, Guangzhou Avenue middle, Tianhe District, Guangzhou, Guangdong 510500 Patentee after: Institute of health medicine, Guangdong Academy of Sciences Address before: No. 1307, Guangzhou Avenue middle, Tianhe District, Guangzhou, Guangdong 510500 Patentee before: GUANGDONG INSTITUTE OF MEDICAL INSTRUMENTS |
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Effective date of registration: 20231120 Address after: No.10, shiliugang Road, Haizhu District, Guangzhou City, Guangdong Province 510000 Patentee after: Institute of biological and medical engineering, Guangdong Academy of Sciences Address before: No. 1307, Guangzhou Avenue middle, Tianhe District, Guangzhou, Guangdong 510500 Patentee before: Institute of health medicine, Guangdong Academy of Sciences |