Device and method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology
Polylactic acid microspheres containing stereocomplex crystals are prepared using microfluidic technology, which solves the problems of uneven size and poor morphology of microspheres in the existing technology, and achieves controllable size of microspheres and improved performance, especially the improvement of melting point and modulus.
Patent Information
- Application Number
- CN202410981585.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-07-22
- Publication Date
- 2025-09-23
- Estimated Expiration
- 2044-07-22
AI Technical Summary
The microspheres obtained by the existing preparation methods of polylactic acid microspheres are non-uniform in size and poor in morphology. In addition, when L-polylactic acid is used as the raw material, the homogeneous crystals formed have a low melting point, insufficient modulus and insufficient hydrolysis resistance.
Microfluidic technology is used to prepare polylactic acid microspheres containing stereocomposite crystals using microfluidic devices and microinjection pumps. The design of a dual-channel injection tube and a droplet size adjustment tube is used to control the mixing of droplets to form stereocomposite crystals. Combined with the use of surfactants and volatile solvents, microspheres of uniform size are prepared.
The prepared polylactic acid microspheres have controllable size and uniform particle size, higher melting point, modulus and better hydrolysis resistance, and the content of stereocomplex crystals is adjustable.
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Figure CN118904223B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of preparation of polylactic acid microspheres, and in particular to a device and method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology. Background Art
[0002] Polylactic acid (PLA), a bio-based polyester, has a wide range of applications in food, medicine, and agriculture due to its excellent biodegradability and biocompatibility. Microspheres made from PLA, with their adjustable size, large surface area, and excellent dispersibility, have been used in cutting-edge fields such as cosmetics, drug delivery, and embolization therapy.
[0003] Generally, polylactic acid (PLA) microspheres are prepared using a homogeneous emulsification-solvent evaporation technique. However, existing methods for preparing PLA microspheres result in relatively dispersed microspheres with poor morphology. Furthermore, currently common PLA microspheres are all made from left-handed polylactic acid (PLLA), which forms homogeneous crystals during solvent evaporation and crystallization. Homogeneous crystals have a low melting point and poor modulus and hydrolysis resistance. Summary of the Invention
[0004] In view of the shortcomings of the existing technology, based on the microfluidic technology developed in recent years, the present invention proposes a device and method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology. The specific technical solution is as follows:
[0005] A device for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology, the device comprising a microfluidic device, a microinjection pump, a syringe, a droplet size adjustment tube and an evaporating dish;
[0006] The microfluidic device includes a glass substrate, an oil-phase injection needle, an aqueous-phase injection needle, a dual-channel injection tube, and a square tube; the square tube and the droplet size adjustment tube are connected at their ends, and both are fixed to the glass substrate; the evaporating dish is placed below the droplet size adjustment tube to collect polylactic acid droplets;
[0007] The dual-channel injection tube is centrally inserted into the square tube; the dual-channel injection tube is a dual-channel capillary tube drawn and polished to form a tapered structure at the end, and the diameter of a single channel at the end of the tapered structure of the dual-channel injection tube is 50-300 μm; the water-phase injection needle is inserted into the square tube and fixed at the intersection of the square tube and the dual-channel injection tube; the two oil-phase injection needles are respectively inserted and fixed in the two channels of the dual-channel injection tube;
[0008] There are three microinjection pumps and three syringes, and the syringes are arranged on the microinjection pumps in a one-to-one correspondence. The three microinjection pumps are respectively used to pump a surfactant solution as an aqueous phase, a L-polylactic acid solution as an oil phase 1, and a D-polylactic acid solution as an oil phase 2; the outlet of the syringe pumping the aqueous phase is connected to the aqueous phase injection needle; and the two syringes pumping the oil phase are respectively connected to the two oil phase injection needles;
[0009] The droplet size adjustment tube is a polytetrafluoroethylene microtube with bends.
[0010] Furthermore, the bends of the droplet size adjustment tube are any one of sinusoidal, triangular, square and spiral, or the cross section of the droplet size adjustment tube along the droplet flow direction is a variable cross section.
[0011] Furthermore, the droplet size adjustment tube has no less than 2 bends.
[0012] A method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology, the method is implemented based on the above-mentioned preparation device, and the method comprises the following steps:
[0013] Step 1: dissolving L-polylactic acid and D-polylactic acid in a volatile organic solvent to prepare an oil phase 1 and an oil phase 2, each with a mass percentage of 5 to 15 wt%, respectively; dissolving a surfactant in deionized water to obtain an aqueous phase with a mass percentage of 1 to 5 wt%;
[0014] Step 2: The aqueous phase is loaded into the corresponding syringe, and the aqueous phase is injected into the square tube through the aqueous phase injection needle using a micro-injection pump for pumping the aqueous phase; the oil phase 1 and the oil phase 2 are loaded into the corresponding syringes respectively, and the oil phase 1 and the oil phase 2 are injected into the dual-channel injection tube through two oil phase injection needles using a micro-injection pump for pumping the oil phase; at the outlet of the dual-channel injection tube, polylactic acid droplets are obtained due to shearing action;
[0015] Step 3: Collect the prepared polylactic acid droplets through the droplet size adjustment tube and place them in a room temperature air environment to completely evaporate the organic solvent to obtain polylactic acid microspheres; then wash the polylactic acid microspheres with deionized water multiple times and freeze-dry to obtain polylactic acid microspheres of uniform size.
[0016] Furthermore, the organic solvent is dichloromethane or chloroform.
[0017] Furthermore, the surfactant is polyvinyl alcohol, polysorbate and polyvinyl pyrrolidone.
[0018] Furthermore, the flow rate of the oil phase in the dual-channel injection tube is 0.5 to 1 mL / h, and the flow rate of the water phase in the square tube is 2.5 to 7.5 mL / min.
[0019] Furthermore, in the step three, the volatilization time is prolonged, and the content of stereocomplex crystals in the formed polylactic acid microspheres is increased.
[0020] Furthermore, the first oil phase is prepared by dissolving L-polylactic acid in dichloromethane to obtain a 10 wt% solution, and the second oil phase is prepared by dissolving D-polylactic acid in dichloromethane to obtain a 10 wt% solution.
[0021] Furthermore, the flow rate of the oil phase in the dual-channel injection tube is 0.5 mL / h, and the flow rate of the water phase in the square tube is 7.5 mL / min.
[0022] The beneficial effects of the present invention are as follows:
[0023] The apparatus of the present invention for preparing polylactic acid microspheres containing stereocomplex crystals produces polylactic acid microspheres of controllable size, uniform particle size, and monodispersity. Furthermore, the polylactic acid microspheres containing stereocomplex crystals produced by the apparatus of the present invention have a higher melting point, higher modulus, and better hydrolysis resistance than existing polylactic acid microspheres, and the content of stereocomplex crystals in the polylactic acid microspheres is adjustable. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1 Schematic diagram of the structure of a device for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to an embodiment of the present invention.
[0025] Figure 2 This is a magnified image of the dual-channel injection tube under a microscope.
[0026] Figure 3 Schematic diagrams of droplet size adjustment tubes with different cross-sectional shapes.
[0027] Figure 4 Wide-angle X-ray diffraction patterns of microspheres collected for droplet size adjustment tubes with different square wave numbers.
[0028] Figure 5 Wide-angle X-ray diffraction patterns of microspheres at different volatilization rates.
[0029] Figure 6 This is the differential scanning calorimetry test results of stereostructured crystalline microspheres and homogeneous crystalline microspheres.
[0030] Figure 7 This is a comparison chart of the moduli of stereostructured crystalline microspheres and homogeneous crystalline microspheres.
[0031] Figure 8This is a statistical diagram of the size distribution of polylactic acid microspheres.
[0032] In the figure, 1 is a glass substrate, 2 is a dual-channel injection tube, 3 is a square tube, 4 is an aqueous phase injection needle, 5 is an oil phase injection needle, 6 is a droplet size adjustment tube, 7 is a microinjection pump, 8 is a syringe, 9 is an injection microtube, and 10 is an evaporating dish. DETAILED DESCRIPTION
[0033] The present invention will be described in detail below with reference to the accompanying drawings and preferred embodiments, and the purpose and effects of the present invention will become more apparent. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.
[0034] like Figure 1 As shown, the device of this embodiment for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology includes a glass substrate 1, a dual-channel injection tube 2, a square tube 3, an aqueous phase injection needle 4, an oil phase injection needle 5, a droplet size adjustment tube 6, a microinjection pump 7, a syringe 8, an injection microtube 9 and an evaporating dish 10.
[0035] The microfluidic device comprises a glass substrate 1, a dual-channel injection tube 2, a square tube 3, an aqueous injection needle 4, and an oil-phase injection needle 5. The dual-channel injection tube 2 is inserted into the square tube 3. The dual-channel injection tube 2 is a dual-channel capillary tube drawn and polished to form a tapered end. The diameter of each channel of the tapered end of the dual-channel injection tube is 50-300 μm. The square tube 3 and the droplet size adjustment tube 6 are connected at their ends and both are fixed to the glass substrate 1. An evaporating dish 10 is placed below the droplet size adjustment tube 6 to collect polylactic acid droplets containing stereocomplex crystals. The aqueous injection needle 4 is inserted into the square tube 3 and fixed at the junction of the square tube 3 and the dual-channel injection tube 2. Two oil-phase injection needles 5 are inserted and fixed in the two channels of the dual-channel injection tube 2, respectively.
[0036] There are three microinjection pumps 7 and three syringes 8. The three syringes 8 are arranged on the three microinjection pumps 7 in a one-to-one correspondence. The three microinjection pumps 7 are respectively used to pump the surfactant solution as the water phase, the left-handed polylactic acid solution as the oil phase one, and the right-handed polylactic acid solution as the oil phase two; the outlet of the syringe for pumping the water phase is connected to the water phase injection needle 4; the two syringes for pumping the oil phase are respectively connected to the two oil phase injection needles 5.
[0037] Among them, the surfactant solution as the aqueous phase is a polyvinyl alcohol aqueous solution with a mass percentage of 1 to 5wt% formed by dissolving polyvinyl alcohol in deionized water; the left-handed polylactic acid solution as the oil phase one is a solution of 5 to 15wt% obtained by dissolving left-handed polylactic acid in dichloromethane, preferably a solution of 10wt%; the right-handed polylactic acid solution as the oil phase two is a solution of 5 to 15wt% obtained by dissolving right-handed polylactic acid in dichloromethane, preferably a solution of 10wt%.
[0038] like Figure 1 and Figure 2 As shown, the water phase injection needle 4 in this embodiment is a syringe needle, which is connected to the corresponding syringe through the injection microtube 9. The oil phase injection needle 5 is a slender flat stainless steel needle, so it can be directly connected to the corresponding syringe. Figure 3 As shown, the bends of the droplet size adjustment tube may be sinusoidal, triangular, square, or spiral, or the cross-section of the droplet size adjustment tube along the droplet flow direction may be variable. As droplets flow through the flow channels of droplet size adjustment tubes of varying shapes, secondary flow within the droplets causes varying degrees of mixing, forming different concentrations of stereocomplex crystals. Thus, the concentration of stereocomplex crystals can be adjusted by adjusting the shape and number of bends in the droplet size adjustment tube.
[0039] As another embodiment, this embodiment provides a method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology. The method is implemented based on the above-mentioned preparation device and includes the following steps:
[0040] Step 1: dissolving L-polylactic acid and D-polylactic acid in a volatile organic solvent to prepare an oil phase 1 and an oil phase 2, each with a mass percentage of 5 to 15 wt%, respectively; dissolving a surfactant in deionized water to obtain an aqueous phase with a mass percentage of 1 to 5 wt%;
[0041] Step 2: The aqueous phase is loaded into a corresponding syringe, and the aqueous phase is injected into the square tube through an aqueous phase injection needle using a micro-injection pump for pumping the aqueous phase; the oil phase 1 and the oil phase 2 are respectively loaded into corresponding syringes, and the oil phase 1 and the oil phase 2 are injected into a dual-channel injection tube through two oil phase injection needles using a micro-injection pump for pumping the oil phase; at the outlet of the dual-channel injection tube, polylactic acid droplets are obtained due to shearing action; wherein, the flow rate of the oil phase in the dual-channel injection tube is 0.5-1 mL / h, and the flow rate of the aqueous phase in the square tube is 2.5-7.5 mL / min.
[0042] Step 3: Collect the prepared polylactic acid droplets through the droplet size adjustment tube and place them in a room temperature air environment to completely evaporate the organic solvent to obtain polylactic acid microspheres; then wash the polylactic acid microspheres with deionized water multiple times and freeze-dry to obtain polylactic acid microspheres of uniform size.
[0043] Example 1
[0044] (1) Weigh 0.4 g each of left-handed poly (lactic acid) (PLLA) and right-handed poly (lactic acid) (PDLA) and dissolve them in 4 g of dichloromethane to form the oil phase. Draw the solution into a 10 mL syringe and secure the syringe to a microinjection pump.
[0045] (2) Weigh 1.5 g of polyvinyl alcohol and dissolve it in 30 g of deionized water at 40°C with stirring to form the aqueous phase. Draw the solution into a 30 mL syringe and secure the syringe to the microinjection pump. For the droplet size adjustment tube 6, use a square-wave-shaped tube.
[0046] (3) The flow rate of the oil phase microinjection pump was set to 0.5 mL / h, and the flow rate of the water phase microinjection pump was set to 7.5 mL / min. Polylactic acid droplets were prepared by shearing. The polylactic acid droplets were collected by a level adjustment tube and placed in an air environment at room temperature to allow the dichloromethane to completely evaporate. The microspheres were then washed multiple times with deionized water and freeze-dried to obtain polylactic acid microspheres of uniform size with an average diameter of 265 μm.
[0047] In order to study the effect of the number of square waves of the droplet size adjustment tube 6 on the content of stereocomposite crystals, experiments were carried out using droplet size adjustment tubes 6 with 1 square wave, 3 square waves, and 5 square waves. The content of stereocomposite crystals was characterized by wide-angle X-ray diffraction. The results are shown in Figure 2. Figure 4 As the number of square waves increases, the diffraction peak of the homogeneous crystal gradually weakens, while the diffraction peak of the stereocomplex crystal gradually strengthens, proving that the content of stereocomplex crystals in the microspheres can be regulated by adjusting the number of square waves in the flow channel.
[0048] Furthermore, in order to verify the effect of volatilization time on the content of stereocomplex crystals in the formed polylactic acid microspheres, 30, 60, 120, 300, and 600 polylactic acid microspheres were placed in the evaporating dish, and the wide-angle X-ray diffraction patterns of the microspheres at different volatilization rates were obtained, as shown in FIG. Figure 5 As shown, from Figure 5 As can be seen from the figure, as the number of PLA microspheres increases, the rate of organic solvent evaporation slows down, the degree of mixing of L- and D-PLA molecules within the droplets increases, and the content of stereocomplex crystals in the formed PLA microspheres decreases. Therefore, extending the evaporation time can increase the content of stereocomplex crystals in the formed PLA microspheres.
[0049] Comparative Example 1
[0050] (1) Weigh 0.8 g of poly (L-lactic acid) (PLLA) and dissolve it in 4 g of dichloromethane to form the oil phase. Draw the solution into a 10 mL syringe and secure the syringe to a microinjection pump.
[0051] (2) Weigh 1.5 g of polyvinyl alcohol and dissolve it in 30 g of deionized water at 40°C with stirring to form the aqueous phase. Draw the solution into a 30 mL syringe and secure the syringe to the microinjection pump. For the droplet size adjustment tube 6, use a square-wave-shaped tube.
[0052] (3) The flow rate of the oil phase microinjection pump was set to 0.5 mL / h, and the flow rate of the water phase microinjection pump was set to 7.5 mL / min. Polylactic acid droplets were prepared by shearing. The polylactic acid droplets were collected by a level adjustment tube and placed in an air environment at room temperature to allow the dichloromethane to completely evaporate. The microspheres were then washed multiple times with deionized water and freeze-dried to obtain polylactic acid microspheres of uniform size.
[0053] The heat changes of the microspheres obtained in Example 1 and Comparative Example 1 during the heating process were measured using a differential scanning calorimeter. The results are as follows: Figure 6 As shown, from Figure 6 It can be seen that the melting point of polylactic acid microspheres containing stereocomplex crystals is 221.7°C, while the melting point of polylactic acid microspheres with homogeneous crystals is 173.1°C. The formation of stereocomplex crystals significantly increases the melting point of polylactic acid microspheres.
[0054] The compression modulus of the polylactic acid microspheres obtained in Example 1 and Comparative Example 1 was tested. Figure 7 As shown, from Figure 7 It can be seen that the compression modulus of the polylactic acid microspheres containing stereocomposite crystals is 565.1 MPa, while the compression modulus of the polylactic acid microspheres with homogeneous crystals is 1068.0 MPa. The formation of stereocomposite crystals significantly increases the melting point of the polylactic acid microspheres.
[0055] Example 2
[0056] Steps (1) and (2) were the same as in Example 1. In step (3), the flow rate of the oil phase microinjection pump was set to 0.5 mL / h, and the flow rate of the water phase microinjection pump was set to 2.5 mL / min. Finally, the average diameter of the microspheres obtained was 768 μm.
[0057] Example 3
[0058] Steps (1) and (2) were the same as in Example 1. In step (3), the flow rate of the oil phase microinjection pump was set to 1 mL / h, and the flow rate of the water phase microinjection pump was set to 7.5 mL / min. Finally, the average diameter of the microspheres obtained was 363 μm.
[0059] Example 4
[0060] Steps (1) and (2) were the same as in Example 1. In step (3), the flow rate of the oil phase microinjection pump was set to 1 mL / h, and the flow rate of the water phase microinjection pump was set to 2.5 mL / min. Finally, the average diameter of the microspheres obtained was 947 μm.
[0061] Example 5
[0062] Steps (1) and (2) were the same as in Example 1. In step (3), the flow rate of the oil phase microinjection pump was set to 0.5 mL / h, and the flow rate of the water phase microinjection pump was set to 5 mL / min. Finally, the average diameter of the microspheres obtained was 410 μm.
[0063] Example 6
[0064] Steps (1) and (2) were the same as in Example 1. In step (3), the flow rate of the oil phase microinjection pump was set to 1 mL / h, and the flow rate of the water phase microinjection pump was set to 5 mL / min. Finally, the average diameter of the microspheres obtained was 561 μm.
[0065] The relationship between the size of the microspheres obtained in Examples 1 to 6 and the flow rates of the water and oil phases is shown in Table 1.
[0066] Table 1 Relationship between microsphere size and water and oil phase flow rate
[0067]
[0068] As can be seen from Table 1, the size of the final polylactic acid microspheres can be adjusted by adjusting the flow rates of the water phase and the oil phase. The standard deviation of the microsphere sizes of Examples 1 to 6 is small. Figure 8 It can be seen that the size distribution of the microspheres is concentrated and the monodispersity is good.
[0069] Example 7
[0070] Steps (1) and (2) were the same as in Example 1, except that the surfactant in step (2) was replaced with polyvinylpyrrolidone. In step (3), the flow rate of the oil phase microinjection pump was set to 0.5 mL / h, and the flow rate of the water phase microinjection pump was set to 7.5 mL / min.
[0071] Example 8
[0072] Steps (1) and (2) were the same as in Example 1, except that the surfactant in step (2) was replaced with polysorbate. In step (3), the flow rate of the oil phase microinjection pump was set to 0.5 mL / h, and the flow rate of the water phase microinjection pump was set to 7.5 mL / min.
[0073] Example 9
[0074] Steps (1) and (2) are the same as in Example 1, wherein the organic solvent in step (1) is replaced by chloroform. In step (3), the flow rate of the oil phase microinjection pump is set to 0.5 mL / h, and the flow rate of the water phase microinjection pump is set to 7.5 mL / min.
[0075] Those skilled in the art will understand that the foregoing descriptions are merely preferred embodiments of the invention and are not intended to limit the invention. Although the invention has been described in detail with reference to the foregoing examples, those skilled in the art will still be able to modify the technical solutions described in the foregoing examples or substitute equivalents for some of the technical features therein. Any modifications, equivalent substitutions, etc. made within the spirit and principles of the invention shall be included within the scope of protection of the invention.
Claims
1. A method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology, characterized in that: The method is achieved by using a device for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology. The device includes a microfluidic device, a microinjection pump, a syringe, a droplet size adjustment tube, and an evaporating dish. The microfluidic device includes a glass substrate, an oil-phase injection needle, an aqueous-phase injection needle, a dual-channel injection tube, and a square tube. The square tube and the droplet size adjustment tube are connected at their ends and both are fixed on the glass substrate. The evaporating dish is placed below the droplet size adjustment tube and is used to collect polylactic acid droplets. The dual-channel injection tube is centrally inserted into the square tube; the dual-channel injection tube is a dual-channel capillary tube drawn and polished to form a tapered structure at the end, and the diameter of a single channel at the end of the tapered structure of the dual-channel injection tube is 50-300 μm; the water-phase injection needle is inserted into the square tube and fixed at the intersection of the square tube and the dual-channel injection tube; the two oil-phase injection needles are respectively inserted and fixed in the two channels of the dual-channel injection tube; There are three microinjection pumps and three syringes, and the syringes are arranged on the microinjection pumps in a one-to-one correspondence. The three microinjection pumps are respectively used to pump a surfactant solution as an aqueous phase, a L-polylactic acid solution as an oil phase 1, and a D-polylactic acid solution as an oil phase 2; the outlet of the syringe pumping the aqueous phase is connected to the aqueous phase injection needle; and the two syringes pumping the oil phase are respectively connected to the two oil phase injection needles; The method comprises the following steps: Step 1: dissolving L-polylactic acid and D-polylactic acid in a volatile organic solvent to prepare an oil phase 1 and an oil phase 2, each with a mass percentage of 5 to 15 wt%. Dissolving a surfactant in deionized water to obtain an aqueous phase with a mass percentage of 1 to 5 wt%. Step 2: The aqueous phase is loaded into the corresponding syringe, and the aqueous phase is injected into the square tube through the aqueous phase injection needle using a micro-injection pump for pumping the aqueous phase; the oil phase 1 and the oil phase 2 are loaded into the corresponding syringes respectively, and the oil phase 1 and the oil phase 2 are injected into the dual-channel injection tube through two oil phase injection needles using a micro-injection pump for pumping the oil phase; at the outlet of the dual-channel injection tube, polylactic acid droplets are obtained due to shearing action; Step 3: Collect the prepared polylactic acid droplets through the droplet size adjustment tube and place them in a room temperature air environment to completely evaporate the organic solvent to obtain polylactic acid microspheres; then wash the polylactic acid microspheres with deionized water multiple times and freeze-dry to obtain polylactic acid microspheres of uniform size.
2. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 1, characterized in that: The droplet size adjustment tube is a polytetrafluoroethylene microtube with bends.
3. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 2, characterized in that: The bends of the droplet size adjustment tube are any one of sinusoidal, triangular, square and spiral, or the cross section of the droplet size adjustment tube along the droplet flow direction is a variable cross section.
4. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 2, characterized in that: The droplet size adjustment tube has no less than 2 bends.
5. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 1, characterized in that: The organic solvent is dichloromethane or chloroform.
6. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 1, characterized in that: The surfactants are polyvinyl alcohol, polysorbate and polyvinyl pyrrolidone.
7. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 1, characterized in that: The flow rate of the oil phase in the dual-channel injection tube is 0.5-1 mL / h, and the flow rate of the water phase in the square tube is 2.5-7.5 mL / min.
8. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 1, characterized in that: In the step three, the volatilization time is prolonged, and the content of stereocomplex crystals in the formed polylactic acid microspheres is increased.
9. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 1, characterized in that: The first oil phase is prepared by dissolving L-polylactic acid in dichloromethane to obtain a 10 wt% solution, and the second oil phase is prepared by dissolving D-polylactic acid in dichloromethane to obtain a 10 wt% solution.
10. The method for preparing polylactic acid microspheres containing stereocomplex crystals based on microfluidic technology according to claim 7, characterized in that: The flow rate of the oil phase in the dual-channel injection tube was 0.5 mL / h, and the flow rate of the water phase in the square tube was 7.5 mL / min.
Citation Information
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