Polyhydroxyalkanoate microspheres as well as preparation method and application thereof

Abstract

The invention relates to a polyhydroxyalkanoate microsphere as well as a preparation method and application thereof. The preparation method of the polyhydroxyalkanoate microspheres comprises the following steps that 1, water, PHA and a composite surface active agent are mixed and subjected to ultrasonic dispersion, dispersion liquid is obtained, and the composite surface active agent at least comprises an ampholytic surface active agent and a non-ionic surface active agent; and 2) stirring the dispersion liquid at the temperature of 100-220 DEG C, then naturally cooling to room temperature, and filtering to obtain the PHA microspheres. The yield of the PHA microspheres prepared through the method is high, and no organic solvent is used, so that the method has the advantages of being environmentally friendly and green. In addition, the PHA microspheres prepared by the invention are relatively small in overall particle size, uniform in distribution, safe and non-toxic, and can be widely applied to the fields of medicines and daily chemical products.

Description

Technical Field

[0001] The invention relates to the field of polymer materials, and in particular to polyhydroxyalkanoate microspheres and a preparation method and application thereof. Background Art

[0002] Plastic microspheres were once very popular in the cosmetics industry, but they are tiny and difficult to degrade. They can escape the filtration and recycling system of urban sewage treatment systems and enter surface water bodies such as rivers, lakes and oceans, accumulating in the environment and causing environmental pollution. Eventually, they may even affect human health through the food chain. In view of the irreversible harm caused by plastic microspheres to the environment, various countries have successively issued relevant regulations to prohibit the use of plastic microspheres in cosmetics.

[0003] Polyhydroxyalkanoate (PHA) is a natural high molecular polymer synthesized by microorganisms through fermentation of various carbon sources. Compared with traditional plastics, it has good biocompatibility, biosafety and biodegradability. It is very suitable to replace traditional plastic microspheres in cosmetics and is expected to become a new generation of cosmetic materials.

[0004] At present, the commonly used methods for preparing PHA microspheres are mainly stirring emulsification and membrane emulsification. Among them, the stirring emulsification method is to dissolve PHA in an organic solvent to form an oil phase, then add the oil phase to the water phase, form an emulsion by stirring, and then evaporate the organic solvent to obtain PHA microspheres; the membrane emulsification method is to dissolve PHA in an organic solvent to form an oil phase and disperse it into the water phase through a microporous membrane to obtain a microemulsion, and then remove the organic solvent to obtain PHA microspheres. However, the above two methods for preparing PHA microspheres both use organic solvents, which not only harm the environment, but also the residual organic solvents in the PHA microspheres may also damage human health and affect the application of PHA microspheres in the fields of medicine and cosmetics; in addition, the yield of microspheres obtained using the above methods is low, which is easy to cause waste of raw materials and is not conducive to the application of PHA.

[0005] Based on this, there is an urgent need for a green, environmentally friendly and high-yield preparation method of PHA microspheres and a safe and harmless PHA microsphere. Summary of the invention

[0006] In order to overcome the above-mentioned defects of the prior art, one of the objectives of the present invention is to provide a method for preparing PHA microspheres.

[0007] Specifically, the present application provides a method for preparing PHA microspheres, comprising the following steps:

[0008] 1) Mix water, PHA and composite surfactant and disperse by ultrasound to obtain a dispersion.

[0009] Wherein, the composite surfactant comprises at least an amphoteric surfactant and a nonionic surfactant;

[0010] 2) Stirring the dispersion at a temperature of 100-220° C., then naturally cooling to room temperature, and filtering to obtain PHA microspheres.

[0011] In a specific embodiment, the amphoteric surfactant includes a betaine-type amphoteric surfactant.

[0012] The betaine type amphoteric surfactant includes one or more of alkyl betaine, alkyl amide betaine, sulfopropyl betaine and phosphate betaine.

[0013] The alkyl betaine includes one or more of dodecyl dimethyl betaine, tetradecyl dimethyl betaine, octadecyl dimethyl betaine, dodecyl dihydroxyethyl betaine, and octadecyl dihydroxyethyl betaine.

[0014] The alkyl amide betaine includes one or more of lauryl amide propyl betaine, cocoamidopropyl betaine, and stearyl amide propyl betaine.

[0015] The sulfopropyl betaine includes one or more of dodecyl sulfopropyl betaine, tetradecyl sulfopropyl betaine, hexadecyl sulfopropyl betaine, and octadecyl sulfopropyl betaine.

[0016] The phosphate betaine includes one or more of lauryl hydroxypropyl phosphate betaine and tetradecyl hydroxypropyl phosphate betaine.

[0017] The nonionic surfactant includes polyvinyl pyrrolidone.

[0018] The betaine-type surfactants in the present application are all amphoteric surfactants, which can produce a synergistic effect with nonionic surfactants. The combination of the two can not only fully disperse PHA in water, but also control the morphology of PHA microspheres, thereby promoting the agglomeration of PHA into spheres after melting.

[0019] In a specific embodiment, the nonionic surfactant further comprises polyvinyl alcohol and F127.

[0020] In a specific embodiment, the complex surfactant includes cocamidopropyl betaine and polyvinyl pyrrolidone, or the complex surfactant consists of cocamidopropyl betaine and polyvinyl pyrrolidone.

[0021] In a specific embodiment, the composite surfactant includes cocamidopropyl betaine, polyvinyl pyrrolidone, polyvinyl alcohol and F127, or the composite surfactant consists of cocamidopropyl betaine, polyvinyl pyrrolidone, polyvinyl alcohol and F127.

[0022] In a specific embodiment, the amount of PHA added in step 1) relative to water is 0.1-10wt%, preferably 0.2-5wt%, more preferably 0.3-1wt%, further preferably 0.3-0.4wt%, for example, 0.3wt%, 0.375wt%, 0.4wt%.

[0023] The total weight of the composite surfactant is 0.05-5wt% relative to water, preferably 0.1-0.5wt%, more preferably 0.10wt%, 0.15wt%, 0.2wt%, 0.25wt%, 0.3wt%, 0.35wt%, 0.4wt%, 0.45wt%, 0.5wt%. The addition ratio of the amphoteric surfactant to the nonionic surfactant is 1:1-1:10, preferably 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10.

[0024] In a specific embodiment, there is no particular limitation on the ultrasonic operation conditions in step 1), as long as the PHA can be evenly dispersed in water.

[0025] Preferably, the ultrasonic frequency is an energy level of 20 KHz or higher, more preferably, the ultrasonic frequency is 20 KHz-80 KHz;

[0026] Preferably, the ultrasonic time is 10 min-60 min; more preferably, the ultrasonic time is 20-40 min; further preferably, the ultrasonic time is 30 min.

[0027] In a specific embodiment, there is no particular limitation on the stirring at a temperature of 100-220° C. in step 2), and preferably, it is carried out in a hydrothermal reactor.

[0028] Preferably, the temperature of the hydrothermal reactor in step 2) is 100-220°C, more preferably, the heating temperature is 120-180°C, further preferably 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C, 165°C, 170°C, 175°C, 180°C, most preferably, the heating temperature is 130°C.

[0029] In a specific embodiment, the stirring rate and time in step 2) are not particularly limited. Preferably, the stirring rate is 500-1000 r / min, more preferably 500 r / min, 600 r / min, 700 r / min, 800 r / min, 900 r / min, and most preferably 800 r / min.

[0030] Preferably, the stirring time is 10 min-60 min; more preferably, the stirring time is 20-40 min; further preferably, the stirring time is 30 min.

[0031] The room temperature in step 2) is generally 20-30°C, and the highest temperature is not more than 40°C. Typical but non-limiting temperatures include 20°C, 25°C, 30°C, and 35°C.

[0032] In a specific embodiment, the polyhydroxyalkanoate may be a single polymer or a combination of two or more polymers, wherein each polymer may have one or more monomers (ie, the structural unit in the polymer may be one or more).

[0033] Specifically, any polymer contains a structural unit represented by the following general formula I:

[0034]

[0035] Formula I

[0036] In the general formula I, R represents C p H 2p+1 In the alkyl group shown in the figure, p represents an integer of 1 to 15, preferably, p is an integer of 1 to 10, and more preferably an integer of 1 to 8. Examples of R include linear or branched alkyl groups such as methyl, ethyl, propyl, n-butyl, isobutyl, tert-butyl, pentyl, and hexyl.

[0037] In Formula I, m is 1, 2 or 3.

[0038] When m=1, the general formula I represents a 3-hydroxyalkanoate structural unit; when m=2, the general formula I represents a 4-hydroxyalkanoate structural unit; when m=3, the general formula I represents a 5-hydroxyalkanoate structural unit. Among them, the 3-hydroxyalkanoate structural unit and the 4-hydroxyalkanoate structural unit are more common, such as the 3-hydroxybutyrate structural unit (sometimes referred to as 3HB) and the 4-hydroxybutyrate structural unit (sometimes referred to as 4HB).

[0039] Preferably, the polyhydroxyalkanoate comprises at least one poly(3-hydroxyalkanoate) (sometimes referred to as PHB).

[0040] Further, the poly(3-hydroxyalkanoate) is a poly(3-hydroxybutyrate) homopolymer containing only 3-hydroxybutyrate structural units, or a poly(3-hydroxybutyrate) copolymer containing 3-hydroxybutyrate structural units and other hydroxyalkanoate structural units. As other hydroxyalkanoic acids, 3-hydroxyalkanoic acid, 4-hydroxyalkanoic acid, 5-hydroxyalkanoic acid, etc. can be used. Among them, 3-hydroxyalkanoic acid, for example, can use one or more monomers selected from 3-hydroxyhexanoic acid (hereinafter also referred to as 3HH), 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxynonanoic acid, 3-hydroxydecanoic acid, 3-hydroxyundecanoic acid, 3-hydroxydodecanoic acid, 3-hydroxytridecanoic acid, 3-hydroxytetradecanoic acid, 3-hydroxypentadecanoic acid and 3-hydroxyhexadecanoic acid.

[0041] Furthermore, specific examples of poly(3-hydroxyalkanoates) include poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxypropionate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (abbreviated as P3HB3HV or PHBV), poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (abbreviated as P3HB3HV3HH), poly(3-hydroxybutyrate ... 3HB3HH or PHBH), poly (3-hydroxybutyrate-co-3-hydroxyheptanoate), poly (3-hydroxybutyrate-co-3-hydroxyoctanoate) (abbreviated as PHBO), poly (3-hydroxybutyrate-co-3-hydroxynonanoate), poly (3-hydroxybutyrate-co-3-hydroxydecanoate), poly (3-hydroxybutyrate-co-3-hydroxyundecanoate), poly (3-hydroxybutyrate-co-4-hydroxybutyrate) (abbreviated as: P3HB4HB or P34HB), etc.

[0042] Furthermore, there is no particular limitation on the weight average molecular weight of PHA. Preferably, the weight average molecular weight of PHA is 100,000 to 1,000,000; more preferably, 200,000 to 900,000; and even more preferably, 300,000 to 800,000.

[0043] In a specific embodiment, PHA is in the form of powder or a PHA filter cake obtained by pressing, filtering and washing. The filter cake-like PHA is easier to transport than the powder-like PHA, and can also be directly used as a raw material for preparing medicines, daily chemicals, etc.

[0044] Another technical purpose of the present invention is to provide PHA microspheres prepared by the preparation method, wherein the particle size of the PHA microspheres is less than 5 mm.

[0045] In a specific embodiment, among the PHA microspheres, PHA microspheres with a particle size less than 0.5 mm account for 1% of the total mass of the microspheres, PHA microspheres with a particle size less than 1 mm account for no less than 2% of the total mass of all PHA microspheres, and PHA microspheres with a particle size less than 3 mm account for no less than 13% of the total mass of all PHA microspheres.

[0046] In a specific embodiment, among the PHA microspheres, PHA microspheres with a particle size less than 0.5 mm account for 3% of the total mass of all PHA microspheres, PHA microspheres with a particle size less than 1 mm account for no less than 5% of the total mass of all PHA microspheres, and PHA microspheres with a particle size less than 3 mm account for no less than 25% of the total mass of all PHA microspheres.

[0047] Another technical purpose of the present invention is to provide a medicine or daily chemical product, which at least includes the PHA microspheres as described above.

[0048] Another technical purpose of the present invention is to provide the use of the PHA microspheres in the preparation of medicines or daily chemical products.

[0049] In a specific embodiment, the pharmaceutical dosage forms include but are not limited to suspensions, ointments, gels, wipes, and pastes; the daily chemical products include but are not limited to toiletries and cosmetics. Preferably, the daily chemical products include facial cleansers, shower gels, scrubs, toothpastes, sunscreens, eye shadows, blushers, liquid foundations and other products; the daily chemical products include liquids, emulsions, creams, solids, powders, gels and other forms.

[0050] Beneficial Effects

[0051] The present invention has the following technical advantages over the prior art:

[0052] 1. The present application realizes the preparation of PHA microspheres by using a water phase dispersion-heating and melting process. On the basis of adding a surfactant, the ultrasonic dispersion and heating and melting methods are combined, which can not only make PHA dispersed evenly in water, but also prevent PHA from aggregating into PHA microspheres larger than 5 mm.

[0053] 2. The amphoteric surfactant and nonionic surfactant added in the preparation of microspheres in this application can produce a synergistic effect, which can not only make the PHA powder fully dispersed in water, but also control the morphology of PHA microspheres, and promote the agglomeration of PHA into spheres after melting. Specifically, there is a synergistic effect between the betaine-type amphoteric surfactant and polyvinyl pyrrolidone used in this application, which is conducive to the formation of perfect PHA microspheres and the formation of PHA microspheres with smaller particle sizes; there is an optimal synergistic effect between the betaine-type amphoteric surfactant and polyvinyl pyrrolidone, polyvinyl alcohol and F127 composition, so that the PHA microspheres with a particle size of less than 1 mm are not less than 5% of the total mass of the microspheres. The small-particle PHA microspheres prepared in this application have a larger specific surface area and can absorb more active ingredients. When prepared into daily chemical products or medicines, they can not only enhance the efficacy of daily chemical products or medicines, but also make the product feel more delicate and comfortable, which is more conducive to the application of PHA microspheres in the field of medicines or daily chemical products.

[0054] 3. The entire process of the microsphere preparation method of the present application does not use organic solvents and will not cause environmental pollution. At the same time, the yield of PHA microspheres can reach 100%, of which PHA microspheres with a particle size of less than 1 mm can reach 5% of the total mass, solving the problem that the PHA microsphere production process in the prior art will cause environmental pollution and the yield of the obtained microspheres is low. In addition, since the present application does not use organic solvents in the entire process of microsphere preparation, it can ensure that the microspheres finally prepared do not contain any organic solvent residues, increase the safety of microspheres in various applications (including medicines and daily chemical products), thereby broadening the application range of the microsphere products of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] Figure 1 A photograph (A) and a particle size distribution diagram (B) of the PHA microspheres prepared in Example 1 of the present application are shown.

[0056] Figure 2 A photograph (A) and a particle size distribution diagram (B) of the PHA microspheres prepared in Example 2 of the present application are shown.

[0057] Figure 3 A photograph of the PHA microspheres prepared in Comparative Example 1 of the present application is shown.

[0058] Figure 4 A photograph of the PHA microspheres prepared in Comparative Example 2 of the present application is shown.

[0059] Figure 5 A photograph of the PHA microspheres prepared in Comparative Example 3 of the present application is shown.

[0060] Figure 6 A photograph of the PHA microspheres prepared in Comparative Example 4 of the present application is shown.

[0061] Figure 7 A photograph of the PHA microspheres prepared in Comparative Example 5 of the present application is shown.

[0062] Figure 8 A photograph of the PHA microspheres prepared in Comparative Example 6 of the present application is shown. DETAILED DESCRIPTION

[0063] The technical solution of the present application is described in detail below through specific embodiments so that those skilled in the art can better understand the present application, but the scope of the present application is not limited thereto.

[0064] Materials and Reagents

[0065] PHA (prepared by Beijing Blue Crystal Microbiology Technology Co., Ltd.);

[0066] Cocamidopropyl betaine (liquid type, CAB-35, 35wt%, Shandong Youso);

[0067] Polyvinylpyrrolidone (Product No. 932394, Beijing Bailingwei Technology Co., Ltd.);

[0068] Polyvinyl alcohol (Product No. 911172, Beijing Bailingwei Technology Co., Ltd.);

[0069] F127 (Product No. P2443, Sigma-Aldrich).

[0070] Example 1

[0071] Weigh 80 g of water, 0.3 g of PHA powder, 0.06 g of cocamidopropyl betaine (liquid type, 35 wt%), and 0.1 g of polyvinyl pyrrolidone, mix the above substances, and use ultrasonic dispersion to dissolve for 30 min to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130 ° C and 800 r / min for 30 min, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0072] Example 2

[0073] Weigh 80 g of water, 0.3 g of PHA powder, 0.06 g of cocamidopropyl betaine (liquid type, 35 wt%), 0.05 g of polyvinyl pyrrolidone, 0.05 g of polyvinyl alcohol, and 0.05 g of F127, mix the above substances, and use ultrasonic dispersion to dissolve for 30 min to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130 ° C and 800 r / min for 30 min, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0074] Embodiment 3-10

[0075] Example 3-10 provides a method for preparing PHA microspheres, and the steps are the same as those of Example 1-2, except that the amount of surfactant added relative to water, the ratio of amphoteric surfactant to nonionic surfactant, and the heating and melting temperature are different, as shown in Table 1:

[0076] Table 1

[0077]

[0078]

[0079] “-” means not added.

[0080] Comparative Example 1

[0081] Weigh 80 g of water, 0.3 g of PHA powder, 0.06 g of cocamidopropyl betaine (liquid type, 35 wt%), and 0.1 g of polyvinyl pyrrolidone, and mix the above substances to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130° C. and 800 r / min for 30 min, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0082] Comparative Example 2

[0083] Weigh 80 g of water, 0.3 g of PHA powder, and 0.06 g of cocamidopropyl betaine (liquid type, 35 wt%), mix the above substances, and use ultrasonic dispersion to dissolve for 30 min to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130 ° C and 800 r / min for 30 min, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0084] Comparative Example 3

[0085] Weigh 80 g of water, 0.3 g of PHA powder, and 0.1 g of polyvinyl pyrrolidone, mix the above substances, and use ultrasonic dispersion to dissolve for 30 minutes to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130°C and 800 r / min for 30 minutes, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0086] Comparative Example 4

[0087] Weigh 80 g of water and 0.3 g of PHA powder, mix the above substances, and use ultrasonic dispersion to dissolve for 30 minutes to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130°C and 800 r / min for 30 minutes, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0088] Comparative Example 5

[0089] Weigh 80 g of water, 0.3 g of PHA powder, 0.06 g of cocamidopropyl betaine (liquid type, 35 wt%), and 0.1 g of polyvinyl alcohol, mix the above substances, and use ultrasonic dispersion to dissolve for 30 min to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130 ° C and 800 r / min for 30 min, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0090] Comparative Example 6

[0091] Weigh 80 g of water, 0.3 g of PHA powder, 0.06 g of cocamidopropyl betaine (liquid type, 35 wt%), and 0.1 g of F127, mix the above substances, and use ultrasonic dispersion to dissolve for 30 min to obtain a dispersion; transfer the dispersion to a hydrothermal reactor, keep it warm at 130 ° C and 800 r / min for 30 min, then naturally cool to room temperature, and filter to obtain PHA microspheres.

[0092] Test example:

[0093] The PHA microspheres prepared in the above Examples 1-10 and Comparative Examples 1-6 were washed, dried, placed on A4 paper, and photographed with a mobile phone; a laboratory standard sieve (Hunan Lichen Instrument Technology Co., Ltd.) was used to perform particle size distribution statistics.

[0094] In these embodiments / comparative examples, Examples 1-10 selected cocamidopropyl betaine, the most common betaine-type surfactant, as an amphoteric surfactant to verify the synergistic effect between it and polyvinyl pyrrolidone; Comparative Example 1 did not perform ultrasonic operation relative to Example 1; Comparative Examples 2-3, 5-6 used different combinations of surfactants relative to Example 1, including the case where cocamidopropyl betaine and polyvinyl pyrrolidone were used alone (Comparative Examples 2 and 3), and also included the case where cocamidopropyl betaine was used in combination with other surfactants (Comparative Examples 5 and 6); Comparative Example 4 only performed the ultrasonic and heating operations relative to Example 1, and no surfactant was added, which was a blank control.

[0095] The results of Examples 1-2 and Comparative Examples 1-6 are as follows: Figure 1 , Figure 2 as well as Figure 3-8 As shown (Examples 3-10 show similar results to Examples 1-2, which are not shown here).

[0096] From the results, it can be seen that the PHA microspheres obtained in Examples 1-2 of the present application show good formation effect ( Figure 1 and Figure 2 ), not only a large number of PHA microspheres with smaller particle size were generated, but also the particle size distribution was relatively uniform ( Figure 1 A and Figure 2A). In Example 1, a combination of cocamidopropyl betaine and polyvinyl pyrrolidone was used as a surfactant. In the obtained PHA microspheres, the PHA microspheres with a particle size less than 0.5 mm accounted for 1% of the total mass of the microspheres, the PHA microspheres with a particle size less than 1 mm accounted for not less than 2% of the total mass of the microspheres, the PHA microspheres with a particle size less than 3 mm accounted for not less than 13% of the total mass of the microspheres, and the PHA microspheres with a particle size less than 5 mm accounted for 100% of the total mass of the microspheres ( Figure 1 B); Example 2: Based on the combination of cocamidopropyl betaine and polyvinyl pyrrolidone, polyvinyl alcohol and F127 are added. In the obtained PHA microspheres, the PHA microspheres with a particle size of less than 0.5 mm account for 3% of the total mass of the microspheres, the PHA microspheres with a particle size of less than 1 mm account for not less than 5% of the total mass of the microspheres, the PHA microspheres with a particle size of less than 3 mm account for not less than 25% of the total mass of the microspheres, and the PHA microspheres with a particle size of less than 5 mm account for 100% of the total mass of the microspheres ( Figure 2 B).

[0097] Examples 3-10 can obtain similar results to Examples 1-2, and the particle size of the obtained PHA microspheres is less than 5 mm, and the particle size distribution is relatively uniform. Among them, the PHA microspheres with a particle size less than 0.5 mm account for about 1-3% of the total mass of the microspheres, and the PHA microspheres with a particle size less than 3 mm account for about 13-25% of the total mass of the microspheres.

[0098] Compared with Example 1, the overall particle size of the PHA microspheres obtained in Comparative Example 1 is larger and the distribution is extremely uneven ( Figure 3 ), it can be seen that the ultrasonic dispersion and heating melting steps are indispensable, and the combination of the two can obtain PHA microspheres with small particle size and uniform distribution;

[0099] Compared with Examples 1-2, Comparative Example 2 used only cocamidopropyl betaine as a surfactant, and the obtained product was a larger block ( Figure 4 ), while Comparative Example 3 only used polyvinyl pyrrolidone as a surfactant, and the obtained product was a flocculent ( Figure 5 ); Comparative Example 5 used a combination of cocamidopropyl betaine and polyvinyl alcohol, and the obtained microspheres had uneven particle size distribution and formed block aggregates with significantly larger volume ( Figure 7 ); Comparative Example 6 used a combination of cocamidopropyl betaine and F127. Although the microspheres were dispersed more evenly, most of the microspheres had larger particle sizes ( Figure 8 ); Comparative Example 4 is a blank control without adding a surfactant. Under the condition of not adding a surfactant, effective microspheres cannot be formed ( Figure 6 ).

[0100] By comparing the results of the embodiments and the comparative examples, it can be seen that only when two surfactants, cocamidopropyl betaine and polyvinyl pyrrolidone, are present at the same time can PHA microspheres with a particle size of less than 5 mm be obtained, and cocamidopropyl betaine and polyvinyl pyrrolidone play a synergistic role in the preparation of PHA microspheres; in addition, on the basis of the combination of cocamidopropyl betaine and polyvinyl pyrrolidone, polyvinyl alcohol and F127 are further added, and in the prepared PHA microspheres, the percentage of PHA microspheres with a particle size of less than 1 mm in the total mass of the PHA microspheres is increased to more than 5%, that is, on the basis of the combined effect of cocamidopropyl betaine and polyvinyl pyrrolidone, the addition of polyvinyl alcohol and F127 composition can further increase the proportion of small-size microspheres in the total microspheres, therefore, compared with the simultaneous use of cocamidopropyl betaine and polyvinyl pyrrolidone, the simultaneous use of cocamidopropyl betaine, polyvinyl pyrrolidone, polyvinyl alcohol and F127 to prepare microspheres shows a better synergistic effect.

[0101] This application uses cocamidopropyl betaine as an example of an amphoteric surfactant used in combination with a nonionic surfactant, and confirms that a synergistic effect is produced between the two. Since betaine-type surfactants are all betaine derivatives, have similar structures and properties, and are all amphoteric surfactants, those skilled in the art can infer that other types of betaine-type amphoteric surfactants can also produce similar synergistic effects with nonionic surfactants, and obtain results similar to those of Examples 1-10.

[0102] In addition, the mass of the PHA microspheres and the PHA raw material was weighed, and the yield of the PHA microspheres was calculated using the following formula: yield (%) = mass of PHA microspheres / mass of PHA raw material × 100%.

[0103] The results show that the yield of PHA microspheres prepared in Examples 1 to 10 is 100%. Therefore, the method of the present application can fully utilize the raw materials and has advantages in the economic efficiency of microsphere preparation compared with the prior art.

Claims

1. A method for preparing PHA microspheres, the method comprising the following steps: 1) Mix water, PHA and composite surfactant and disperse by ultrasound to obtain a dispersion. Wherein, the composite surfactant comprises at least an amphoteric surfactant and a nonionic surfactant; 2) Stirring the dispersion at a temperature of 100-220° C., then naturally cooling to room temperature, and filtering to obtain PHA microspheres.

2. The method according to claim 1, wherein: The amphoteric surfactant includes a betaine-type amphoteric surfactant, and the nonionic surfactant includes polyvinyl pyrrolidone.

3. The method according to claim 2, wherein: The nonionic surfactants also include polyvinyl alcohol and F127.

4. The method according to claim 1, wherein: The PHA includes a polymer containing a structural unit represented by the following general formula I: In the general formula I, R represents C p H 2p+1 In the alkyl group shown, p represents an integer of 1-15; and m is 1, 2 or 3.

5. The method according to claim 1, wherein: In step 1), the amount of PHA added relative to water is 0.1-10 wt %.

6. The method according to any one of claims 1 to 5, wherein: The addition amount of the composite surfactant relative to water is 0.05-5wt%, wherein the addition ratio of the amphoteric surfactant to the nonionic surfactant is 1:1-1:

10.

7. The method according to claim 1, wherein: The stirring in step 2) is carried out in a hydrothermal reaction kettle at a temperature of 120-150°C.

8. PHA microspheres prepared by the method according to any one of claims 1 to 7, wherein the particle size of the PHA microspheres is less than 5 mm.

9. A medicine or daily chemical product, comprising at least the PHA microspheres according to claim 8.

10. Use of the PHA microspheres according to claim 8 in the preparation of medicines or daily chemical products.

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