Water-phase green preparation method and application of polyester microspheres

Abstract

The invention relates to the technical field of polymer synthesis, and discloses a water-phase green preparation method and application of polyester microspheres, dicarboxylic acid and glutaraldehyde are dissolved in a polyvinylpyrrolidone aqueous solution, then tert-butyl isocyanide is added, the mixture is sealed and stirred for a corresponding reaction time, after the reaction is finished, a reaction solution is transferred to a centrifugal tube for centrifugation, and the polyester microspheres are obtained. And pouring out supernatant liquid, adding the same amount of ultrapure water, dispersing again, and centrifuging to obtain the polyester microspheres. According to the preparation method, the polyester microspheres are prepared in a water phase through suspension polymerization for the first time, and compared with a traditional preparation method, the reaction condition is mild, operation is easy, normal-temperature reaction can be conducted in air, no catalyst or organic solvent is needed, no by-product is generated, and the concept of green development is better met.

Description

Technical Field

[0001] The invention relates to the technical field of polymer synthesis, and in particular to an aqueous phase green preparation method and application of polyester microspheres. Background Art

[0002] Multicomponent reactions (MCRs) refer to methods that use three or more reactants to directly synthesize a single final product with a complex structure and containing all raw material fragments through a "one-pot method". The Passerini three-component reaction (P-3CR) is a mature multi-component reaction based on isocyanates, in which carboxylic acid, aldehyde (or ketone) and isocyanate are combined to form an α-acyloxyimide core structure, and then the polymerization method of obtaining ester-amide polymers through modular condensation reaction is called Passerini three-component polymerization (Passerini Three-Component Polymerization, P-3CP). When two of the Passerini three components are difunctional monomers, linear structure polymers can be obtained under appropriate conditions. Since each monomer has a unique backbone or side group, changes in the raw material structure can adjust the properties of the polymer product. At present, P-3CP is mostly used to prepare polyamides with ester side chains, polyesters with amide side chains, and poly (ester-amide).

[0003] Polyester microspheres are microspheres composed of polyester substances, with diameters usually ranging from nanometers to hundreds of micrometers, and can be modified as needed. In the biomedical field, they can be used for drug delivery, cell culture, biological separation and other applications. The traditional method for preparing polyester microspheres is to first prepare polyester through ring-opening polymerization, and then prepare microspheres through the polymer balling route. The preparation process requires reaction conditions such as argon environment, high temperature, catalysts and organic solvents, and cannot be prepared directly in the aqueous phase through emulsion, suspension, and dispersion polymerization. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide an aqueous green preparation method and application of polyester microspheres.

[0005] In order to achieve the above object, the technical solution of the present invention is: an aqueous green preparation method of polyester microspheres, comprising the following steps:

[0006] (1) Dissolve monomer 1 and monomer 2 in a stabilizer aqueous solution, add monomer 3, seal and stir to react; the structural formulas of monomer 1, monomer 2 and monomer 3 are shown in formula (I), formula (II) and formula (III) respectively:

[0007]

[0008] In formula (I), R1 is selected from substituted or unsubstituted alkyl, alkyl containing functional groups, wherein, when substituted, the substituent is selected from halogen; the number of carbon atoms in the alkyl is less than or equal to 20; in formula (II), R2 is selected from unsubstituted alkyl, the number of carbon atoms in the alkyl is less than or equal to 20; in formula (III), R3 is selected from substituted or unsubstituted alkyl, wherein, when substituted, the substituent is selected from halogen; the number of carbon atoms in the alkyl is less than or equal to 20;

[0009] (2) After the reaction is completed, the reaction solution is transferred to a centrifuge tube and centrifuged. The supernatant is discarded and then an equal amount of ultrapure water is added and centrifuged. After multiple centrifugations, the polyester microspheres are washed and dried to obtain.

[0010] Furthermore, the functional group is selected from any one or more of phenyl, alkenyl, bio-based isosorbide, furanyl, disulfide, and Boc-L glutamate.

[0011] Further, in step (1), the structural formula of monomer 1 is any one of formula (a) to formula (m), the structural formula of monomer 2 is formula (p), and the structural formula of monomer 3 is formula (q),

[0012]

[0013]

[0014]

[0015] Furthermore, in step (1), the molar ratio of monomer 1, monomer 2 and monomer 3 is 1:1:2.1, and the concentration of monomer 1 is 0.1 mol / L-1.2 mol / L.

[0016] Furthermore, the concentration of the stabilizer aqueous solution in step (1) is 1wt%-60wt%.

[0017] Furthermore, the stabilizer in the stabilizer aqueous solution in step (1) is one of potassium persulfate, sodium lauryl sulfate, polyvinyl alcohol, polyvinyl pyrrolidone (PVP), and carboxymethyl cellulose.

[0018] Furthermore, in step (1), the stirring speed is 200-800 rpm, the reaction time is 24-72h, and the reaction temperature is 0-80°C.

[0019] Furthermore, the centrifugal speed in step (2) is 10000r / min.

[0020] Another technical solution of the present invention is: polyester microspheres prepared by the aqueous green preparation method of polyester microspheres.

[0021] Another technical solution of the present invention is: the use of the polyester microspheres in drug delivery, medical cosmetic injections, bone tissue engineering scaffolds or tissue culture.

[0022] Beneficial effects of the present invention: The present invention utilizes Passerini three-component polymerization (P-3CP) in water phase to prepare polyester microspheres. It is the first time that polyester microspheres are prepared by suspension polymerization in water phase. The synthesis is carried out in one step at room temperature and in water phase, without the need for a catalyst, without by-products, simple operation and mild reaction conditions. The prepared microspheres have a smooth surface and good sphericity, good dispersibility, high roundness and good applicability. The particle size and distribution of polyester microspheres synthesized by P-3CP can be controlled by monomer concentration, stabilizer concentration and the like. The main chain structure of the microspheres can be regulated by different reaction monomers, and polyester microspheres with corresponding functions can be synthesized by reacting monomers containing different functional groups to meet various needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a scanning electron microscope image of the polyester microspheres prepared in Example 1;

[0024] Figure 2 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 1;

[0025] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 2;

[0026] Figure 4 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 3;

[0027] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 4;

[0028] Figure 6 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 5;

[0029] Figure 7 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 6;

[0030] Figure 8 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 7;

[0031] Fig. 9 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 8;

[0032] Fig.10 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 9;

[0033] Fig.11 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 10;

[0034] Fig.12 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 11;

[0035] Fig.13 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 12;

[0036] Fig.14 This is the hydrogen nuclear magnetic resonance spectrum of the polyester microspheres prepared in Example 13. DETAILED DESCRIPTION

[0037] The present invention discloses a water-phase green preparation method and application of polyester microspheres. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve the purpose. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application described herein without departing from the content, spirit and scope of the present invention to realize and apply the technology of the present invention.

[0038] Various raw materials involved in the present invention were purchased from the market or prepared according to references. The sources and purity of some reagents and the models of instruments used are shown in Tables 1 and 2.

[0039] Table 1 Source and purity of reagents

[0040]

[0041]

[0042] Isosorbide-succinic acid preparation reference: MD Zenner, SA Madbouly, JS Chem, MR Kessler, Chem Sus Chem. 2015, 8, 448-51.

[0043] Table 2 Instruments and equipment

[0044] Instrument Name model factory Heating magnetic stirrer RCT Basic Germany IKA Group Electronic analytical balance BT-423S Sartorius Instruments Ltd. Nuclear Magnetic Resonance Spectrometer BRUKERAVANCE400MHZ Bruker Scanning electron microscopy JSM-7500F China Beijing Jieoulu Technology and Trade Co., Ltd. Desktop high speed centrifuge TG16-WS China Shanghai-Heng Scientific Instrument Co., Ltd. Laser particle size analyzer ZS90 Malvern

[0045] The present invention will be further described below in conjunction with embodiments:

[0046] Example 1

[0047] Dissolve malonic acid (1mmol, 104.06mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction is completed, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. The polyester microspheres are washed with ultrapure water and then dispersed and stored in ultrapure water. The scanning electron microscope image of the polyester microspheres is Figure 1 , using deuterated chloroform for H NMR spectrum detection, the spectrum is Figure 2 The average particle size measured by a laser particle size analyzer is 1756 nm and the dispersion coefficient is 0.155.

[0048] Example 2

[0049] Glutaric acid (1mmol, 132.24mg) and glutaraldehyde (1mmol, 0.194mL) were dissolved in 50wt% PVP aqueous solution (2mL), tert-butyl isocyanide (2.1mmol, 0.242mL) was added, and the mixture was sealed and stirred at a speed of 400r / min for 48h. After the reaction, the reaction solution was transferred to a centrifuge tube, centrifuged at 10000r / min for 15min, the supernatant was poured out, an equal amount of ultrapure water was added, and the mixture was dispersed and centrifuged again. After three centrifugations, polyester microspheres were obtained, and the polyester microspheres were washed and dispersed and stored in ultrapure water. The polyester microspheres were detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum was as follows: Figure 3 The average particle size measured by a laser particle size analyzer is 1833 nm and the dispersion coefficient is 0.140.

[0050] Example 3

[0051] Adipic acid (1mmol, 146.14mg) and glutaraldehyde (1mmol, 0.194mL) were dissolved in 50wt% PVP aqueous solution (2mL), tert-butyl isocyanide (2.1mmol, 0.242mL) was added, and the mixture was sealed and stirred at a speed of 400r / min for 48h. After the reaction, the reaction solution was transferred to a centrifuge tube, centrifuged at 10000r / min for 15min, the supernatant was poured out, an equal amount of ultrapure water was added, and the mixture was dispersed and centrifuged again. After three centrifugations, polyester microspheres were obtained, and the polyester microspheres were washed and dispersed and stored in ultrapure water. The polyester microspheres were detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum was as follows: Figure 4 The average particle size measured by a laser particle size analyzer is 2022nm and the dispersion coefficient is 0.263.

[0052] Example 4

[0053] Dissolve suberic acid (1mmol, 174.2mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction is completed, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Figure 5 The average particle size measured by a laser particle size analyzer is 2391nm and the dispersion coefficient is 0.193.

[0054] Example 5

[0055] Dissolve sebacic acid (1mmol, 204.3mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at 400r / min for 48h. After the reaction, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Figure 6 The average particle size measured by a laser particle size analyzer is 1127nm and the dispersion coefficient is 0.056.

[0056] Example 6

[0057] Dissolve dodecanedioic acid (1mmol, 230.3mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Figure 7 The average particle size measured by a laser particle size analyzer is 950nm and the dispersion coefficient is 0.210.

[0058] Example 7

[0059] Dissolve tetradecanedioic acid (1mmol, 258.35mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Figure 8 The average particle size measured by a laser particle size analyzer is 515 nm and the dispersion coefficient is 0.168.

[0060] Example 8

[0061] Dissolve 2,5-furandicarboxylic acid (1mmol, 156.03mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Fig. 9 The average particle size measured by a laser particle size analyzer is 1016 nm and the dispersion coefficient is 0.452.

[0062] Example 9

[0063] Fumaric acid (1mmol, 116.07mg) and glutaraldehyde (1mmol, 0.194mL) were dissolved in 50wt% PVP aqueous solution (2mL), tert-butyl isocyanide (2.1mmol, 0.242mL) was added, and the mixture was sealed and stirred at a speed of 400r / min for 48h. After the reaction, the reaction solution was transferred to a centrifuge tube, centrifuged at 10000r / min for 15min, the supernatant was poured out, an equal amount of ultrapure water was added, and the mixture was dispersed and centrifuged again. After three centrifugations, polyester microspheres were obtained, and the polyester microspheres were washed and dispersed and stored in ultrapure water. The polyester microspheres were detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum was as follows: Fig.10 The average particle size measured by a laser particle size analyzer is 1559 nm and the dispersion coefficient is 0.188.

[0064] Example 10

[0065] Dissolve 3,3'-dithiodipropionic acid (1mmol, 210.27mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at 400r / min for 48h. After the reaction, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Fig.11 The average particle size measured by a laser particle size analyzer is 1323 nm and the dispersion coefficient is 0.292.

[0066] Embodiment 11

[0067] Dissolve isosorbide-succinic acid (1mmol, 346mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction is completed, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Fig.12 The average particle size measured by a laser particle size analyzer is 1738nm and the dispersion coefficient is 0.216.

[0068] Example 12

[0069] Dissolve terephthalic acid (1mmol, 166.13mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at a speed of 400r / min for 48h. After the reaction is completed, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Fig.13 The average particle size measured by a laser particle size analyzer is 1304 nm and the dispersion coefficient is 0.468.

[0070] Example 13

[0071] Dissolve Boc-L-glutamic acid (1mmol, 247.25mg) and glutaraldehyde (1mmol, 0.194mL) in 50wt% PVP aqueous solution (2mL), add tert-butyl isocyanide (2.1mmol, 0.242mL), and stir at 400r / min for 48h. After the reaction, transfer the reaction solution to a centrifuge tube, centrifuge at 10000r / min for 15min, pour out the supernatant, add an equal amount of ultrapure water, and disperse and centrifuge again. After centrifugation three times, polyester microspheres are obtained. After washing, the polyester microspheres are dispersed and stored in ultrapure water. The polyester microspheres are detected by nuclear magnetic resonance hydrogen spectrum using deuterated chloroform, and the spectrum is Fig.14 The average particle size measured by a laser particle size analyzer is 1719 nm and the dispersion coefficient is 0.357.

[0072] The dynamic light scattering (DLS) test results of the reactants and the obtained polyester microspheres of Examples 1-13 are shown in Table 3.

[0073] Table 3 DLS results of reactants and polyester microspheres of Examples 1-13

[0074]

[0075] Characterization test results of polyester microspheres prepared in Examples 1-13

[0076] Figure 2-14 No -COOH peak was observed in the H NMR spectra, indicating that the carboxylic acid groups were consumed in the P-3CP process. Characteristic peaks of amide (-NH) were observed at 4.5-5.0 ppm, the proton peak of -CH3 was at 1.1-1.5 ppm, and the characteristic peak of -CH was at 5.0-6.0 ppm, indicating that the amide side groups and the polyester main chain were successfully formed.

[0077] From Examples 1-7, it can be seen that the method of preparing polyester microspheres using the Passerini three-component polymerization reaction in aqueous phase has a certain versatility, and carboxylic acids with different carbon atoms, such as malonic acid and tetradecanedioic acid, can react. And the particle size and distribution of polyester microspheres prepared by different carboxylic acid reactions are significantly different.

[0078] It can be seen from Examples 8-13 that the method for preparing polyester microspheres using the Passerini three-component polymerization reaction in water phase can introduce different functional groups into the microspheres to meet different needs.

[0079] In summary, the method of the present invention has certain versatility, and can use reactants with specific functional groups to prepare polyester microspheres with specific functions. The polyester microspheres prepared by the present invention have a wide range of particle sizes and can be used in many aspects such as medical injection, drug delivery, cell culture, etc.

[0080] The above-described embodiments are only preferred solutions of the present invention and are not intended to limit the present invention in any form. Other variations and modifications are possible without exceeding the technical solutions described in the claims.

Claims

1. A water-phase green preparation method for polyester microspheres, characterized in that: The following steps are involved: (1) Dissolve monomer 1 and monomer 2 in a stabilizer aqueous solution, add monomer 3, seal and stir to react; the structural formulas of monomer 1, monomer 2 and monomer 3 are shown in formula (I), formula (II) and formula (III) respectively: In formula (I), R1 is selected from substituted or unsubstituted alkyl, alkyl containing functional groups, wherein, when substituted, the substituent is selected from halogen; the number of carbon atoms in the alkyl is less than or equal to 20; in formula (II), R2 is selected from unsubstituted alkyl, the number of carbon atoms in the alkyl is less than or equal to 20; in formula (III), R3 is selected from substituted or unsubstituted alkyl, wherein, when substituted, the substituent is selected from halogen; the number of carbon atoms in the alkyl is less than or equal to 20; (2) After the reaction is completed, the reaction solution is transferred to a centrifuge tube and centrifuged. The supernatant is discarded and then an equal amount of ultrapure water is added and centrifuged. After multiple centrifugations, the polyester microspheres are washed and dried to obtain.

2. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: The functional group is selected from any one or more of phenyl, alkenyl, bio-based isosorbide, furanyl, disulfide, and Boc-L-glutamic acid.

3. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: The structural formula of the monomer 1 in step (1) is any one of formulas (a) to (m), the structural formula of the monomer 2 is formula (p), and the structural formula of the monomer 3 is formula (q).

4. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: In step (1), the molar ratio of monomer 1, monomer 2 and monomer 3 is 1:1:2.1, and the concentration of monomer 1 is 0.1 mol / L-1.2 mol / L.

5. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: The concentration of the stabilizer aqueous solution in step (1) is 1wt%-60wt%.

6. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: The stabilizer in the stabilizer aqueous solution in step (1) is one of potassium persulfate, sodium lauryl sulfate, polyvinyl alcohol, polyvinyl pyrrolidone and carboxymethyl cellulose.

7. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: In step (1), the stirring speed is 200-800 rpm, the reaction time is 24-72 h, and the reaction temperature is 0-80°C.

8. The aqueous green preparation method of polyester microspheres according to claim 1, characterized in that: The centrifugal speed in step (2) is 10000r / min.

9. Polyester microspheres prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the polyester microspheres according to claim 9 in drug delivery, medical cosmetic injection, bone tissue engineering scaffold or tissue culture.

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