A method for preparing biodegradable polyhydroxyalkanoate microspheres

Abstract

The present invention belongs to the technical field of chemical polyhydroxyalkanoates, and discloses a method for preparing polyhydroxyalkanoate microspheres and a product prepared by the method. The polyhydroxyalkanoate microspheres disclosed by the present invention include the following steps: using a special dissolution, emulsification and solidification process, wherein the dissolution process is to place the polyhydroxyalkanoate in an ester solvent and seal and heat it to a temperature above its melting point, and then keep it warm at 50-80°C. Among them, the emulsification process is to mix water and polyhydroxyalkanoate solution under heating conditions of 60-70°C, through high shear stirring, high pressure homogenization, ultrasonic homogenization, SPG (Shirasu Porous Glass) membrane or microfluidics to form a relatively stable emulsion or suspension. Among them, the solidification process is to rapidly cool the above emulsion so that the polyhydroxyalkanoate microspheres are irreversibly precipitated from the emulsion droplets, thereby quickly fixing the spherical droplet shape of the emulsion. The average particle size of the polyhydroxyalkanoate microspheres disclosed by the present invention is 0.1-100 microns, and the 60-day freshwater biodegradation rate is 76%.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical polyhydroxyalkanoate, and relates to a method for preparing polyhydroxyalkanoate microspheres and a product prepared by the method. Background Art

[0002] Microspheres refer to colloidal materials with particle sizes ranging from nanometers to micrometers and shapes of spheres, near-spheres or other regular geometric bodies. Their morphologies have diverse characteristics, such as solid, hollow, porous, core-shell structure, Janus structure and Colloidosomes structure. Their special particle size and composition structure often provide new functions beyond the bulk material. Among them, polymer (plastic) microspheres are usually used as a functional additive and are widely used in daily chemical products such as cosmetics and personal care, providing functions such as scrubbing, cleaning, smoothness, spreading, skin feel, oil control and light lines. After use, these polymer microspheres eventually flow into natural waters, forming microplastic pollution, which harms the environment and human health. Therefore, many countries have banned the deliberate addition of polymer microspheres to daily chemical products in the form of regulations, such as the EU Chemicals Agency's ban on plastic microparticles Annex XV, the United States' "Microbead-Free Waters Act of 2015" and China's "Guidelines for Industrial Structure Adjustment (2019)".

[0003] At present, cellulose and inorganic materials are often used as functional substitutes for polymer microspheres, but there are still some difficult to overcome problems, such as unstable quality, weak functionality, poor lubricity, poor lipophilicity, etc. Polyhydroxyalkanoates are natural materials synthesized by microorganisms, with excellent fresh / seawater degradability, lipophilicity, biocompatibility and biometabolism properties. They can meet the EU plastic microparticle ban's degradable material exemption clause, so they are very potential substitutes for polymer microspheres.

[0004] However, the original polyhydroxyalkanoate powder synthesized by microorganisms mainly meets the needs of biodegradable plastic masterbatch, hot melt adhesive, pressure-sensitive adhesive, etc., and has not been optimized for daily chemical applications. The main problems are large powder particles, wide particle size distribution, low sphericity, and difficult porosity adjustment. Figure 1 The figure shows the particle size distribution of a polyhydroxyalkanoate powder product, with an average particle size of 20um and a maximum particle size greater than 200um. If directly applied to cosmetics, it will bring poor skin feel.

[0005] Therefore, polyhydroxyalkanoate microspheres used in daily chemical products need to undergo secondary processing of the original powder material, among which the emulsification process is usually a processing method that is easy to control the particle size, porosity, and sphericity. Polyhydroxyalkanoates are affected by their crystallization properties and have poor solubility. They are insoluble in common alcohol and ester low-toxic solvents, which is the biggest obstacle to the emulsification process.

[0006] Chinese patent CN115023469A discloses a soluble polyhydroxyalkanoate copolymer, wherein when the content of 3-hydroxycaproic acid in the copolymer component is less than 16 mol%, the copolymer is insoluble in ethyl acetate, acetone, acetonitrile and other strong polar solvents, and when the content of 3-hydroxycaproic acid is greater than 16 mol%, the copolymer is soluble in ethyl acetate. At this time, the polyhydroxyalkanoate has a lower glass transition temperature and crystallinity, good pressure sensitivity and hot viscosity, and is therefore not conducive to meeting the functions of daily chemical additives such as smoothness, spreading, skin feel, and oil control.

[0007] The document Eng. Life Sci., 2018 Jan, Vol. 18, Page 20-28 proposed that non-halogen solvents such as ethylene carbonate, methanol, propanol, glacial acetic acid, dimethyl sulfoxide, and dimethylformamide have certain solubility for polyhydroxyalkanoates. However, this series of solvents are both toxic and miscible with water, making it difficult to prepare spherical particles by emulsification.

[0008] Chinese patents CN114601964A and CN115192769A disclose a method for preparing polyhydroxyalkanoic acid microspheres, which are used for in vivo implantation of stents, surgical membranes and in vivo filling materials. The method prepares microspheres through oil-water two phases, and uses dichloromethane and chloroform as organic solvents. Halogen-containing organic solvents have strong physiological toxicity and environmental destructiveness. Both domestic and foreign legislation has been passed to restrict the use of halogen-containing organic solvents in production, so this method can only be used in experimental research. Summary of the invention

[0009] The present invention aims to solve at least one of the technical problems existing in the above-mentioned prior art. To this end, the present invention provides a method for preparing polyhydroxyalkanoate microspheres, which adopts a special dissolution, emulsification and solidification process to improve the controllability of the microsphere morphology, and uses a slightly soluble or partially water-soluble ester solvent to avoid the use of toxic halogen-containing solvents.

[0010] Another object of the present invention is to provide polyhydroxyalkanoate microspheres prepared by the above preparation method, wherein the microspheres have good biodegradability.

[0011] The technical solution of the present invention is as follows:

[0012] The present invention provides a method for preparing polyhydroxyalkanoate microspheres, which comprises the following steps:

[0013] S1: preparing the oil phase: dissolving the polyhydroxyalkanoate in one or a mixed solvent, adding the solvent into a high pressure reactor, stirring and heating, and filtering to obtain a clear polymer slurry after the polymer is completely dissolved.

[0014] S2: preparing the aqueous phase: adding a certain amount of the above-mentioned solvent, dispersant and dispersant aid into deionized water, and stirring to obtain an aqueous phase solution.

[0015] S3 Oil-water emulsification: Heat the above aqueous solution to maintain solvent reflux, then gradually add the above-configured oil solution into the aqueous solution, and disperse with a homogenizer and mechanical stirring. After the addition is completed, keep stirring to obtain a stable polyhydroxyalkanoate emulsion system.

[0016] S4 preparation of microspheres: the polyhydroxyalkanoate emulsion is rapidly cooled to obtain a microsphere suspension, and then the suspension is evaporated to recover the solvent, and then centrifuged and washed, and finally freeze-dried or spray-dried to obtain polyhydroxyalkanoate spherical micropowder.

[0017] The S1 oil phase preparation also mixes a plasticizer and a pore-forming agent into the polymer slurry.

[0018] The polyhydroxyalkanoic acid ester used in the S1 to prepare the oil phase is selected from one or more of poly-3-hydroxybutyrate (PHB), 3-hydroxybutyric acid and 3-hydroxyvaleric acid copolymer (PHBV), 3-hydroxybutyric acid and 3-hydroxyhexanoic acid copolymer (PHBHHx), 3-hydroxybutyric acid and 4-hydroxybutyric acid copolymer (P34HB), 3-hydroxybutyric acid, 3-hydroxyhexanoic acid and 3-hydroxyvaleric acid copolymer (PHBVHHx) or polyhydroxyhexanoate (PHHx).

[0019] The organic solvent for preparing the oil phase in S1 is selected from one or more of the following organic solvents: dimethyl carbonate, diethyl carbonate, ethylene carbonate, propylene carbonate, methyl acetate, ethyl acetate, propyl acetate, methyl formate, ethyl formate and propyl formate. Preferably, the organic solvent is slightly soluble or partially soluble in water or a mixed solvent, and its water solubility at room temperature is 0 to 10 g / 100 ml of water.

[0020] The plasticizer used in S1 to prepare the oil phase is selected from at least one of dioctyl adipate, tributyl acetyl citrate, and triacetin, and the porogen is selected from at least one of polyvinyl ether, pentaerythritol, ammonium bicarbonate, and urea.

[0021] The plasticizer for preparing the oil phase in S1 is selected from one or more of the following plasticizers: dioctyl adipate, tributyl acetyl citrate and triacetin, and the porogen is selected from one or more of the following porogens: polyvinyl ether, pentaerythritol, ammonium bicarbonate and urea. The solvent for preparing the water phase in S2 is selected from at least one of dimethyl carbonate, diethyl carbonate, ethylene carbonate, propylene carbonate, methyl acetate, ethyl acetate, propyl acetate, methyl formate, ethyl formate and propyl formate. Preferably, the solvent or mixed solvent is slightly soluble or partially soluble in water, and its water solubility at room temperature is 0 to 10 g / 100 ml of water.

[0022] The dispersant for preparing the aqueous phase in S2 is selected from one or more of the following dispersants: alkyl sodium sulfate, alkyl polyoxyethylene ether sodium sulfate, alkylphenol polyoxyethylene ether sodium sulfate, alkyl benzene sulfonate sodium, alkyl trimethyl ammonium chloride, alkylphenol polyoxyethylene ether, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, castor oil polyoxyethylene ether, polyoxyethylene sorbitan fatty acid ester and sorbitan fatty acid ester.

[0023] The dispersant aid for preparing the aqueous phase in S2 is selected from one or more of the following dispersants: methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, polyvinyl pyrrolidone, polyvinyl ether, polyvinyl ether / propylene ether copolymer, polyvinyl alcohol and gelatin.

[0024] The heating and dissolving temperature of the oil phase prepared in S1 is greater than the melting point of the corresponding hydroxy fatty acid ester, preferably 100-200°C, more preferably 100-150°C to completely dissolve the polyhydroxy fatty acid ester, and the concentration of the polyhydroxy fatty acid ester in the oil phase is 0-30%.

[0025] The aqueous phase solution prepared by S2 can be stirred at 5000 rpm-10000 rpm using an Ultra-Turrax T25 homogenizer.

[0026] The S3 oil-water emulsification is to heat the water phase solution to above 50°C and below the cloud point temperature of the emulsifier (such as 80°C), and more preferably 60-70°C; the oil phase solution is gradually added to the water phase solution within 5-10 minutes, and dispersed by a homogenizer and mechanical stirring at a speed of 5000rpm-20000rpm for the homogenizer and 500-2000rpm for the mechanical stirring. After the addition is completed, stirring is maintained for 20-60 minutes to obtain a stable polyhydroxyalkanoate emulsion system.

[0027] The step S4 of preparing microspheres is to rapidly cool the polyhydroxyalkanoate emulsion to below 30°C, preferably 0-20°C, more preferably 0-10°C, at a cooling rate of 10-100°C / min, and maintain the temperature for 0-60min, until the polyhydroxyalkanoate solidifies to obtain a suspension of microspheres.

[0028] The polyhydroxyalkanoate prepared according to the method of Example 1 was subjected to a biodegradation experiment. The typical degradation rate of the product was 76% in 60 days, which can effectively prevent the pollution of microplastics to the environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0030] Figure 1Particle size distribution of a polyhydroxyalkanoate powder product

[0031] Figure 2 Optical electron microscopic observation results of degradable polyhydroxyalkanoate microsphere dispersion (according to the method of Example 1)

[0032] Figure 3 Scanning electron micrograph of degradable polyhydroxyalkanoate microspheres (according to the method of Example 1).

[0033] Figure 4 Scanning electron microscopy photograph of degradable polyhydroxyalkanoate microspheres (according to the method of Example 2).

[0034] Figure 5 Scanning electron microscopy photograph of degradable polyhydroxyalkanoate microspheres (according to the method of Example 3).

[0035] Figure 6 Biodegradation percentage change curve of degradable polyhydroxyalkanoate microspheres (prepared according to the method of Example 1). DETAILED DESCRIPTION

[0036] It should be understood that, without departing from the scope or spirit of the present invention, those skilled in the art can envision other various embodiments and can modify them according to the teachings of this specification. Therefore, the following specific embodiments are not restrictive. Unless otherwise specified, all numbers used in this specification and claims to represent quantity and physicochemical properties should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise specified, the numerical parameters listed in the above description and the attached claims are approximate values, and those skilled in the art can use the teachings disclosed herein to seek the desired properties to obtain, and appropriately change these approximate values. The use of the numerical range represented by endpoints includes all numbers within the range and any range within the range, for example, 1, 2, 3, 4 and 5 include 1, 1.1, 1.3, 1.5, 2, 2.75, 3, 3.80, 4 and 5, etc.

[0037] Example 1

[0038] A method for preparing polyhydroxyalkanoate microspheres comprises the following steps:

[0039] 20g of poly 3-hydroxybutyric acid-3-hydroxycaproate (wherein the 3-hydroxycaproic acid content is 10 mol%) powder is dissolved in a mixed solvent of 190g of dimethyl carbonate and 190g of propyl acetate, added to an autoclave, stirred and heated at a temperature of 130°C, and after the polyhydroxyalkanoate powder is completely dissolved, 400g of oil phase is obtained by filtration. The polyhydroxyalkanoate concentration is 5wt%.

[0040] 20 g of dimethyl carbonate, 20 g of ethyl acetate, 5 g of hydroxypropyl methylcellulose and 10 g of Tween-20 were added to deionized water, and stirred at 5000 rpm using an Ultra-Turrax T25 homogenizer to obtain 400 g of an aqueous phase solution.

[0041] The above aqueous solution was heated to 60°C and kept under reflux, and then the above-configured oil phase solution was gradually added to the aqueous solution within 5 minutes, and dispersed by a homogenizer and mechanical stirring at a speed of 5000 rpm for the homogenizer and 1000 rpm for the mechanical stirring. After the addition was completed, stirring was maintained for 20 minutes to obtain a stable polyhydroxyalkanoate emulsion system.

[0042] The polyhydroxyalkanoate emulsion was rapidly cooled to 5°C at a cooling rate of 30°C / min and maintained for 30 minutes. The obtained microsphere suspension was then evaporated to recover the carbonate solvent, and then centrifuged and washed twice at 8000 rpm. The precipitate was freeze-dried to obtain 18.2 g of white powder with a yield of 91%.

[0043] Figure 2 This is the result of optical microscope observation of the polyhydroxyalkanoate powder prepared in this example after ultrasonic redispersion. Figure 3 According to the scanning electron microscope photograph of the polyhydroxyalkanoate powder prepared in this embodiment, the average particle size is 2.4 microns, the coefficient of variation of the particle size is 42%, the sphericity is 100%, and the smoothness is 100%.

[0044] Example 2

[0045] A method for preparing polyhydroxyalkanoate microspheres comprises the following steps:

[0046] 40g of poly 3-hydroxybutyric acid-3-hydroxycaproate (wherein the 3-hydroxycaproic acid content is 10 mol%) powder is dissolved in 360g of diethyl carbonate, added to a high temperature reactor, stirred and heated at 130°C, and after the polyhydroxyalkanoate powder is completely dissolved, 400g of oil phase is obtained by filtration. The polyhydroxyalkanoate concentration is 10wt%.

[0047] 40 g of diethyl carbonate, 5 g of hydroxypropyl methylcellulose and 10 g of Tween-28 were added to deionized water, and stirred at 5000 rpm using an Ultra-Turrax T25 homogenizer to obtain 400 g of an aqueous phase solution.

[0048] The above aqueous solution was heated to 60°C and kept under reflux, and then the above-configured oil phase solution was gradually added to the aqueous solution within 8 minutes, and dispersed by a homogenizer and mechanical stirring at a speed of 8000 rpm for the homogenizer and 1000 rpm for the mechanical stirring. After the addition was completed, stirring was maintained for 30 minutes to obtain a stable polyhydroxyalkanoate emulsion system.

[0049] The polyhydroxyalkanoate emulsion was rapidly cooled to 5°C at a cooling rate of 30°C / min and maintained for 60 minutes. The obtained microsphere suspension was then evaporated to recover the carbonate solvent, and then centrifuged and washed twice at 8000 rpm. The precipitate was freeze-dried to obtain 18.7 g of white powder with a yield of 93.5%.

[0050] Figure 4 The scanning electron microscope photograph of the polyhydroxyalkanoate microspheres prepared according to this example shows that the average particle size is 4.9 microns, the coefficient of variation of the particle size is 35%, the sphericity is 100%, and the smoothness is 100%.

[0051] Example 3

[0052] A method for preparing polyhydroxyalkanoate microspheres comprises the following steps:

[0053] 80g of poly 3-hydroxybutyrate-3-hydroxyvalerate (wherein the 3-hydroxyvaleric acid content is 5mol%) powder is dissolved in 320g of at least one of the above solvents, added into a high temperature reactor, stirred and heated at 150°C, and after the polyhydroxyalkanoate powder is completely dissolved, 10g of triacetin is added, and 400g of oil phase is obtained by filtration. The polyhydroxyalkanoate concentration is 20wt%.

[0054] 40 g of diethyl carbonate, 5 g of polyvinyl alcohol and 10 g of Tween-28 were added to deionized water, and stirred at 5000 rpm using an Ultra-Turrax T25 homogenizer to obtain 400 g of an aqueous phase solution.

[0055] The above aqueous solution was heated to 70°C and kept under reflux, and then the above-configured oil phase solution was gradually added to the aqueous solution within 10 minutes, and dispersed by a homogenizer and mechanical stirring at a speed of 10000 rpm for the homogenizer and 2000 rpm for the mechanical stirring. After the addition was completed, stirring was maintained for 30 minutes to obtain a stable polyhydroxyalkanoate emulsion system.

[0056] The polyhydroxyalkanoate emulsion was rapidly cooled to 10°C at a cooling rate of 30°C / min and maintained for 60 minutes. The obtained microsphere suspension was then evaporated to recover the carbonate solvent, and then centrifuged and washed twice at 8000 rpm. The precipitate was freeze-dried to obtain 17.9 g of white powder with a yield of 89.5%.

[0057] Figure 5 The scanning electron microscope photograph of the degradable polyhydroxyalkanoate microspheres prepared according to this example shows that the average particle size is 9.0 microns, the coefficient of variation of the particle size is 32%, the sphericity is 100%, and the smoothness is 100%.

[0058] The samples of Examples 1 to 3 above were added to the following concealer formula:

[0059]

[0060]

[0061] The average particle size of nylon micronized wax is 12um, the sphericity is 50%, and the smoothness is 40%. The average particle size of polyethylene micronized wax is 8um, the sphericity is 70%, and the smoothness is 70%.

[0062] The polyhydroxyalkanoate microspheres prepared in Example 1 have a smaller particle size and extremely high sphericity, which makes the formula have excellent lubricity, but the spacing effect it provides is slightly lower, which makes the spreadability and hiding power of the formula slightly lower. The polyhydroxyalkanoate microspheres prepared in Example 2 have a more suitable particle size and extremely high sphericity, which makes the lubricity, spreadability and hiding power of the formula excellent. The polyhydroxyalkanoate microspheres prepared in Example 3 have a larger particle size and particle size distribution, which reduces the spreadability and lubricity of the formula, but has excellent hiding power and uniformity. Compared with the nylon micropowder and polyethylene micropowder in the comparative example, the particle size and morphology of the polyhydroxyalkanoic acid microspheres can provide better spreadability, hiding power, uniformity and lubricity, and the formula performance is more balanced.

[0063] The polyhydroxyalkanoate microspheres prepared according to the method of Example 1 were subjected to a freshwater biodegradation experiment. The test method was GB / T21801-2008 Rapid Biodegradability of Chemicals: Respirometry Test. The product degradation rate was 76% in 60 days, which can effectively avoid the pollution of microplastics to the environment. Figure 6 Biodegradation percentage change curve of degradable polyhydroxyalkanoate microspheres (microspheres prepared according to the method of Example 1).

[0064] Although the above-mentioned specific embodiments contain many specific details for the purpose of illustration, it will be understood by those skilled in the art that many variations, modifications, substitutions and changes of these details are within the scope of the invention protected by the claims. Therefore, the disclosure described in the specific embodiments does not impose any limitation on the invention protected by the claims. The proper scope of the present invention shall be defined by the claims and their appropriate legal equivalents. All cited references are incorporated herein in their entirety by reference.

Claims

1. A method for preparing biodegradable polyhydroxyalkanoate microspheres, characterized in that: The method comprises the following steps: S1: preparing an oil phase: dissolving a polyhydroxyalkanoate in an organic solvent, heating and stirring, and filtering to obtain a clear polymer slurry after the polyhydroxyalkanoate is completely dissolved; S2: preparing the aqueous phase: adding a certain amount of the same organic solvent as that used in preparing the oil phase in S1, as well as a dispersant and a dispersant aid into deionized water, and stirring to obtain an aqueous phase solution; S3 oil-water emulsification: heating the aqueous phase solution to 50-80° C. and keeping the temperature, then adding the oil phase to the aqueous phase solution, stirring to obtain a polyhydroxyalkanoate emulsion system; S4: preparing microspheres: rapidly cooling the polyhydroxyalkanoate emulsion system to obtain a microsphere suspension, then evaporating the suspension to recover the solvent, centrifuging and washing, and finally freeze-drying or spray-drying to obtain polyhydroxyalkanoate microspheres; The polyhydroxyalkanoate used in preparing the oil phase in S1 is selected from one or more of the following polyhydroxyalkanoates: poly-3-hydroxybutyrate, copolymer of 3-hydroxybutyric acid and 3-hydroxyvaleric acid, copolymer of 3-hydroxybutyric acid and 3-hydroxyhexanoic acid, copolymer of 3-hydroxybutyric acid and 4-hydroxybutyric acid, copolymer of 3-hydroxybutyric acid, 3-hydroxyhexanoic acid and 3-hydroxyvaleric acid, or polyhydroxyhexanoate; The organic solvent used in S1 to prepare the oil phase and S2 to prepare the water phase is selected from one or more of the following organic solvents: dimethyl carbonate, diethyl carbonate, ethylene carbonate, propylene carbonate, methyl acetate, ethyl acetate, propyl acetate, methyl formate, ethyl formate and propyl formate.

2. The preparation method according to claim 1, characterized in that: The organic solvent is slightly soluble or partially soluble in water, and its water solubility at room temperature is 0-10g / 100ml water.

3. The preparation method according to claim 1, characterized in that: The dispersant for preparing the aqueous phase in S2 is selected from one or more of the following dispersants: alkyl sodium sulfate, alkyl polyoxyethylene ether sodium sulfate, alkylphenol polyoxyethylene ether sodium sulfate, alkyl benzene sulfonate sodium, alkyl trimethyl ammonium chloride, alkylphenol polyoxyethylene ether, fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ether, castor oil polyoxyethylene ether, polyoxyethylene sorbitan fatty acid ester and sorbitan fatty acid ester.

4. The preparation method according to claim 1, characterized in that: The dispersing aid S2 for preparing the aqueous phase is selected from one or more of methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, polyvinyl pyrrolidone, polyvinyl ether, polyvinyl ether / propylene ether copolymer, polyvinyl alcohol and gelatin.

5. The preparation method according to claim 1, characterized in that: A plasticizer and a pore-forming agent are mixed into the polyhydroxyalkanoate emulsion system.

6. The preparation method according to claim 5, characterized in that: The plasticizer used in S1 to prepare the oil phase is selected from one or more of the following plasticizers: dioctyl adipate, acetyl tributyl citrate and triacetin, and the porogen is selected from one or more of the following porogens: polyvinyl ether, pentaerythritol, ammonium bicarbonate and urea.

7. The preparation method according to claim 1, characterized in that: The heating and dissolving temperature of the oil phase prepared in S1 is greater than the melting point of the corresponding hydroxy fatty acid ester.

8. The preparation method according to claim 7, characterized in that: The heating and dissolving temperature of the oil phase prepared by S1 is 100-200°C.

9. The preparation method according to claim 8, characterized in that: The heating and dissolving temperature of the oil phase prepared by S1 is 100-150°C.

10. The preparation method according to claim 3 or 4, characterized in that: The aqueous phase prepared in S2 is stirred at 5000 rpm to 10000 rpm using an Ultra-Turrax T25 homogenizer.

11. The preparation method according to claim 1, characterized in that: The S3 oil-water emulsification is to heat the water phase solution to above 50°C and below 80°C; the oil phase is gradually added to the water phase solution within 5 to 10 minutes, and dispersed by a homogenizer and mechanical stirring, with a homogenizer speed of 5000rpm to 20000rpm and a mechanical stirring speed of 500 to 2000rpm. After the addition is completed, stirring is maintained for 20 to 60 minutes to obtain a stable polyhydroxyalkanoate emulsion system.

12. The preparation method according to claim 11, characterized in that: The S3 oil-water emulsification is to heat the water phase solution to 60-70°C.

13. The preparation method according to claim 1, characterized in that: The step S4 of preparing microspheres is to rapidly cool the polyhydroxyalkanoate emulsion to below 30°C at a cooling rate of 10-100°C / min and maintain the temperature for 0-60min until the polyhydroxyalkanoate solidifies to obtain a suspension of microspheres.

14. The preparation method according to claim 13, characterized in that: The S4 method for preparing microspheres is to rapidly cool the polyhydroxyalkanoate emulsion to 0-20°C.

15. The preparation method according to claim 14, characterized in that: The S4 method for preparing microspheres is to rapidly cool the polyhydroxyalkanoate emulsion to 0-10°C.

16. A polyhydroxyalkanoate microsphere prepared according to the preparation method according to any one of claims 1 to 15, characterized in that: The average particle size of the microspheres is 0.1 to 100 microns.

17. The polyhydroxyalkanoate microspheres according to claim 16, characterized in that: Its freshwater biodegradation rate is greater than or equal to 70% in 60 days.

18. The polyhydroxyalkanoate microspheres according to claim 17, characterized in that: Its freshwater biodegradation rate is greater than or equal to 75% in 60 days.

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