A medical glycolide-lactide copolymer and a preparation method thereof
By using continuous production with twin-screw extruders and online purification technology, the problems of long production cycles, low efficiency, and solvent residue in batch polymerization have been solved, enabling the efficient, stable, and green preparation of PLGA.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- TIANJIN PRIME TECHNOLOGY CO LTD
- Filing Date
- 2026-03-25
- Publication Date
- 2026-06-05
AI Technical Summary
The existing batch polymerization method for producing PLGA has the disadvantages of long production cycle, low efficiency, poor batch stability and organic solvent residue risk, resulting in unstable product quality and biosafety hazards.
Continuous production is achieved using a twin-screw extruder, combined with online purification and granulation. Rapid and uniform mixing and polymerization are achieved through strong shear and efficient heat transfer, integrating the reaction, devolatilization and granulation processes, and avoiding the use of organic solvents.
Significantly shortens production cycle, improves batch stability, ensures product quality consistency, eliminates organic solvent residue, and achieves green and efficient production.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical materials technology, and in particular to a medical-grade glycolide-lactide copolymer and its preparation method. Background Technology
[0002] Poly(lactic-co-glycolic acid) copolymer (PLGA) is a key medical polymer material renowned for its excellent biocompatibility and biodegradability. In the human body, this material can be gradually degraded through hydrolysis into endogenous lactic acid and glycolic acid, and ultimately metabolized into water and carbon dioxide. Due to its superior properties, PLGA is widely used in drug delivery systems, tissue engineering scaffolds, and absorbable medical devices, and is one of the most important biodegradable medical polymer materials approved by the U.S. Food and Drug Administration.
[0003] Currently, the traditional batch polymerization process is commonly used in the industrial production of medical-grade PLGA. This method typically includes the following steps: First, lactide, glycolide monomers, and catalyst are added to a reactor; then, a ring-opening polymerization reaction is carried out at high temperature for 12 to 24 hours; after the reaction, the high-viscosity polymer melt is cooled and solidified to form a hard block solid; finally, in order to remove residual unreacted monomers and small molecule impurities, the block solid must be crushed and dissolved in organic solvents such as dichloromethane, and then precipitated in unsuitable solvents such as ethanol for purification. The purified product also needs to be filtered and dried under vacuum for a long time.
[0004] However, this traditional batch polymerization process has the following drawbacks: (1) The production cycle is extremely long and the efficiency is low. Due to the extremely high viscosity of the polymer after polymerization, the post-processing, especially the dissolution-precipitation purification step, becomes extremely time-consuming. The dissolution process of the polymer alone often takes 3 to 4 days, resulting in an overall production cycle of about one week for a single batch of products, which seriously restricts the production efficiency.
[0005] (2) Poor batch-to-batch stability. The batch reactor exhibits a significant scale-up effect, meaning that as the reactor volume increases, the heat and mass transfer efficiency inside decreases sharply, leading to uneven temperature gradients within the reaction system. This not only causes uneven polymer molecular weight distribution (PDI) and copolymer composition at different locations within the same batch of product, but also results in significant differences in product quality between different batches, making it difficult to guarantee the stability and consistency of product performance.
[0006] (3) There are biosafety risks. Traditional processes rely on the extensive use of organic solvents to dissolve and precipitate the product for purification. This inevitably results in trace amounts of organic solvent residues in the final medical-grade product. For medical devices and drug carriers that are directly implanted or come into contact with the human body, these residual solvents pose a potential biosafety hazard and increase the risks of clinical application.
[0007] Therefore, there is an urgent need to develop a new PLGA preparation method to overcome the problems of long production cycle, poor batch stability and solvent residue risk of existing batch polymerization methods, so as to achieve efficient, stable and green production of medical-grade PLGA. Summary of the Invention
[0008] This invention provides a medical-grade glycolide-lactide copolymer and its preparation method, which solves the defects of the existing technology of preparing medical-grade PLGA by traditional batch polymerization, such as extremely long production cycle, low efficiency, unstable product quality between batches, and the need to use organic solvents for purification, which leads to biosafety risks. It can integrate the polymerization reaction, online purification and granulation process into one, thereby realizing efficient, stable and green continuous production of medical-grade PLGA.
[0009] This invention provides a method for preparing medical-grade glycolide-lactide copolymer, comprising the following steps: A mixture containing glycolide, lactide, initiator, and catalyst is fed into a twin-screw extruder at a shear rate of 50-80 s. -1 The extrusion polymerization reaction is carried out at a temperature of 160-190℃; the residence time of the mixture in the twin-screw extruder is controlled to be 20-50 min.
[0010] The method for preparing medical-grade glycolide and lactide copolymers provided by this invention innovatively employs a twin-screw extruder as a continuous reactor for extrusion polymerization. Utilizing the powerful shearing action and efficient heat transfer and mixing capabilities within the twin-screw extruder, materials such as glycolide and lactide can achieve molecular-level uniform mixing and rapid, controllable polymerization reactions in a very short time. This drastically shortens the polymerization reaction time, which typically lasts over ten hours in traditional processes, to 20-50 minutes, fundamentally solving the problems of long production cycles and low efficiency, while ensuring stable product quality across batches. If the residence time of the mixture in the twin-screw extruder is less than 20 minutes, the monomer conversion rate will be low, or the mixture may even flow out before reacting. Conversely, if the residence time is greater than 50 minutes, the product will degrade.
[0011] According to the method for preparing medical-grade glycolide-lactide copolymer of the present invention, the aspect ratio (L / D) of the twin-screw extruder is (40-60):1. Such an aspect ratio ensures that the mixture has a sufficiently long residence time in the twin-screw extruder to complete the efficient conversion from monomer to high molecular weight copolymer.
[0012] According to the preparation method of the medical-grade glycolide-lactide copolymer of the present invention, the feeding speed of the twin-screw extruder is controlled at 3-5 kg / h, and the screw speed is controlled at 120-150 rpm. This combination of parameters further ensures that the mixture has sufficient reaction time to achieve a high conversion rate, thereby obtaining the desired molecular weight.
[0013] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the twin-screw extruder includes a barrel and a screw assembly. The screw assembly is installed in the barrel and includes a screw, at least one kneading block and at least one reverse mixing element. The kneading block and the reverse mixing element are detachably installed on the screw and are spaced apart along the length direction of the barrel.
[0014] In this invention, the kneading block, through its powerful shearing action, forces radial dispersion and micro-mixing of materials, ensuring uniform contact between the catalyst and monomer at the molecular level, thereby effectively initiating and maintaining a homogeneous polymerization reaction. Meanwhile, the reverse mixing element, by generating localized backflow or remixing, artificially extends the actual residence time of materials in specific reaction zones, solving the problem of incomplete reaction caused by excessively short residence time in continuous extrusion processes. This modular and customizable screw configuration allows for the construction of clearly defined strong mixing zones and long residence reaction zones within the extruder, achieving high conversion rates typically only achievable in traditional batch reactors within a very short equipment length and time.
[0015] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the number of the kneading block and the reverse mixing element are each independently 1-3.
[0016] According to the preparation method of medical-grade glycolide-lactide copolymer of the present invention, the twin-screw extruder further includes a feeder, which is installed at one end of the barrel.
[0017] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the screw assembly includes a screw, three kneading blocks and one reverse mixing element. The three kneading blocks and the one reverse mixing element are mounted on the screw. The three kneading blocks are spaced apart along the length of the cylinder. The reverse mixing element is mounted between two of the kneading blocks, near one end of the feeder.
[0018] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the screw assembly includes a screw, a kneading block and three reverse mixing elements, wherein the kneading block and the three reverse mixing elements are spaced apart along the length direction of the cylinder.
[0019] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the screw assembly includes a screw, three kneading blocks and one reverse mixing element, wherein the three kneading blocks and one reverse mixing element are spaced apart along the length direction of the cylinder.
[0020] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the screw assembly includes a screw, two kneading blocks and two reverse mixing elements, wherein the two reverse mixing elements and the two kneading blocks are spaced apart along the length direction of the cylinder 2.
[0021] According to the preparation method of the medical glycolide-lactide copolymer of the present invention, the molar ratio of lactide and glycolide is (50-85):(15-50).
[0022] According to the preparation method of the medical glycolide-lactide copolymer of the present invention, the initiator is selected from one or more of dodecyl alcohol, butanol, lactic acid and glycolic acid; preferably, the amount of the initiator is 0.1-1% of the sum of the mass of the lactide and the glycolide.
[0023] According to the preparation method of the medical-grade glycolide-lactide copolymer of the present invention, the catalyst is selected from one or more of stannous octoate, tri-n-butylmethoxytin and dioctyltin dilaurate; preferably, the amount of the catalyst is 0.01-0.1% of the sum of the mass of the lactide and the glycolide.
[0024] According to the preparation method of the medical-grade glycolide-lactide copolymer of the present invention, after the extrusion polymerization reaction, the reaction product is subjected to devolatilization treatment under a vacuum of -0.09 MPa to -0.1 MPa.
[0025] This invention utilizes the structural features of a screw extruder to directly and efficiently remove residual unreacted monomers online in a molten state. This solution not only fundamentally solves the biosafety risks posed by residual organic solvents in the final medical product, achieving green purification and ensuring that the product is completely free of toxic solvents such as dichloromethane, significantly improving the biosafety of the material in the implant, but also seamlessly integrates the purification steps that originally took several days with the extrusion process, greatly simplifying the process and shortening the production cycle, enabling continuous production integrating reaction and purification.
[0026] According to the method for preparing medical-grade glycolide-lactide copolymer of the present invention, the twin-screw extruder further includes a vacuum device, which is installed at the end of the barrel opposite to the feeder. After the extrusion polymerization reaction is completed, the vacuum device is turned on, and the vacuum degree of the barrel is controlled at -0.09 MPa to -0.1 MPa for devolatilization treatment.
[0027] The method for preparing medical-grade glycolide-lactide copolymer according to the present invention further includes: granulating the reaction product after devolatilization treatment.
[0028] According to the preparation method of medical glycolide-lactide copolymer of the present invention, the equipment for implementing the preparation method of the present invention includes a twin-screw extruder, a conveying device and a pelletizer. One end of the conveying device is connected to the end of the barrel away from the feeder, and the other end is connected to the pelletizer. The reaction product can be conveyed to the pelletizer through the conveying device.
[0029] According to a second aspect of the present invention, the present invention also provides a medical glycolide-lactide copolymer, which is prepared by the above-described preparation method.
[0030] According to the medical glycolide-lactide copolymer of the present invention, the number average molecular weight of the medical glycolide-lactide copolymer is 40-100 kDa (preferably 45-95 kDa), the molecular weight distribution coefficient is less than 1.8 (preferably 1.4-1.6), the residual amount of lactide monomer is less than 0.3% (preferably 0.15-0.25%), and the residual amount of glycolide monomer is less than 0.5% (preferably 0.04-0.07%).
[0031] The method for preparing medical-grade glycolide-lactide copolymers provided by this invention integrates reaction, devolatilization, and granulation steps into a single process, revolutionarily shortening the traditional batch polymerization production cycle from a week to minutes, thereby significantly reducing energy consumption and labor costs. This method not only fundamentally solves the problem of batch instability through continuous processing, achieving excellent batch stability, but also utilizes high-vacuum online devolatilization technology to eliminate organic solvent contamination, enabling the efficient and environmentally friendly preparation of high-quality products with narrower molecular weight distributions and no yellowing. Attached Figure Description
[0032] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0033] Figure 1This is a diagram of the equipment used in the preparation method of the medical PLGA5050 provided in Embodiment 1 of the present invention.
[0034] Figure 2 This is a diagram of the equipment used in the preparation method of the medical PLGA5050 provided in Embodiment 2 of the present invention.
[0035] Figure 3 This is a diagram of the equipment used in the preparation method of medical PLGA8515 provided in Embodiment 3 of the present invention.
[0036] Figure 4 This is a diagram of the equipment used in the preparation method of medical PLGA7525 provided in Embodiment 4 of the present invention.
[0037] 1: Feeder; 2: Cylinder; 3: Conveying device; 4: Pelletizer; C: Conveying zone; M: Kneading block; R: Reverse mixing element. Detailed Implementation
[0038] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.
[0039] The kneading blocks and reverse mixing elements used in the following examples and comparative examples are from Microtech Corporation.
[0040] Example 1 This embodiment provides a method for preparing medical PLGA5050, the method being based on... Figure 1 The equipment shown is implemented, which includes a co-rotating twin-screw extruder (L / D=56), a conveyor 3, and a pelletizer 4, as shown. Figure 1 As shown, the twin-screw extruder includes a feeder 1, a barrel 2, and a screw assembly. One end of the barrel 2 is connected to the feeder 1, and the other end is connected to a conveyor 3. The end of the conveyor 3 facing away from the barrel 2 is connected to a pelletizer 4. The screw assembly is installed inside the barrel 2. The screw assembly includes a screw, three kneading blocks, and one reverse mixing element. The three kneading blocks and the reverse mixing element are mounted on the screw. The three kneading blocks are spaced apart along the length of the barrel 2, and the reverse mixing element is installed between two of the kneading blocks, near the end of the feeder 1. In the figure, C represents the conveying zone, M represents a detachable kneading block, and R represents a detachable reverse mixing element. The entire feed port is placed in a nitrogen-protected glove box. A vacuum device is connected to the tail of the barrel 2.
[0041] The preparation method includes the following steps: Step 1: Mix 1.35 kg D, L-lactide, 1.09 kg glycolide, 14 mL dodecanol and 1 mL stannous octoate evenly and then transfer the mixture to feeder 1.
[0042] Step 2: Set the feeding speed of feeder 1 of the twin-screw extruder to 5 kg / h, the speed of the twin-screw extruder to 150 rpm, and the shearing speed to approximately 78 s. -1 The temperature of the twin-screw extruder was set to 180℃. The mixed material was transferred through feeder 1 into the twin-screw extruder. Under the push of the screws, the polymerization reaction was completed in the extruder. Two-stage vacuum pumps were activated at the tail of the extruder for devolatilization treatment, and the vacuum degree was maintained at -0.098 MPa. The average residence time of the material was 35 minutes. A receiving device was placed at the extruder outlet, and PLGA5050 was obtained after natural cooling.
[0043] Three parallel experiments were conducted using this method, and the test results are as follows: Test result 1: The product is white in color, with a number average molecular weight of 45.6 kDa and a molecular weight distribution coefficient of 1.45 (significantly better than the 1.80~2.20 of batch polymerization). The residual lactide monomer is 0.19%, and the residual glycolide monomer is 0.07% (the monomer residue is significantly lower than the 0.5%~2% of batch polymerization). The material takes only 40 minutes from feeding to discharge.
[0044] Test result 2: The product is white in color, with a number-average molecular weight of 46.6 kDa, a molecular weight distribution coefficient of 1.46, a lactide monomer residue of 0.17%, and a glycolide monomer residue of 0.05%.
[0045] Test result 3: The product is white in color, with a number-average molecular weight of 45.6 kDa, a molecular weight distribution coefficient of 1.45, a lactide monomer residue of 0.19%, and a glycolide monomer residue of 0.05%.
[0046] Comparative Example 1 This embodiment provides a method for preparing medical PLGA5050, which differs from Embodiment 1 in that the preparation method is carried out in a reaction vessel.
[0047] The preparation method includes the following steps: Step 1: Add 1.35 kg D,L-lactide, 1.09 kg glycolide, 14 mL dodecanol and 1 mL stannous octoate to the reaction vessel and react at 180 °C for 12 h under nitrogen protection.
[0048] Step 2: Add 5 kg of dichloromethane to the reactor and dissolve it until the system is clear (dissolve for at least 48 h). Transfer the solution to a large amount of cooled anhydrous ethanol to precipitate the precipitate. Repeat this process three times and then vacuum dry at 40 °C for 48 h.
[0049] Three parallel tests were performed according to the preparation method, and the test results are as follows: Test result 1: The product is pale yellow in color, with a number-average molecular weight of 43.7 kDa, a molecular weight distribution coefficient of 1.91, a lactide monomer residue of 0.35%, and a glycolide monomer residue of 0.10%.
[0050] Test result 2: The product is pale yellow in color, with a number-average molecular weight of 35.9 kDa, a molecular weight distribution coefficient of 1.99, a lactide monomer residue of 0.38%, and a glycolide monomer residue of 0.14%.
[0051] Test result 3: The product is pale yellow in color, with a number-average molecular weight of 44.8 kDa, a molecular weight distribution coefficient of 1.97, a lactide monomer residue of 0.32%, and a glycolide monomer residue of 0.15%.
[0052] Comparative analysis revealed that traditional batch polymerization takes at least 6 days to obtain the same amount of dried product due to time-consuming post-processing (dissolution, precipitation, and drying), and the product PDI > 1.9, with batch-to-batch Mw fluctuations of ±10%.
[0053] Example 2 This embodiment provides a method for preparing medical PLGA5050, the method being based on... Figure 2 The device shown is implemented in this way, and the only difference between this device and Embodiment 1 is that the screw assembly includes a screw, a kneading block and three reverse mixing elements. The kneading block and the three reverse mixing elements are spaced apart along the length of the cylinder 2 from one end of the feeder 1 to one end of the conveying device 3.
[0054] The preparation method includes the following steps: Step 1: Mix 1.35 kg D,L-lactide, 1.09 kg glycolide, 7 mL dodecanol and 1 mL stannous octoate thoroughly and then transfer the mixture to the feeder.
[0055] Step 2: Set the feed rate of the twin-screw extruder feeder to 3 kg / h, the twin-screw extruder speed to 120 rpm, and the shear rate to approximately 63 s. -1The twin-screw extruder was set to a zone temperature of 190℃. The mixed material was transferred through a feeder into the twin-screw extruder, where the polymerization reaction was completed under the drive of the screws. A two-stage vacuum pump was activated at the tail of the extruder for devolatilization, maintaining a vacuum level of -0.098 MPa. The average residence time of the material was 50 minutes. A receiving device was placed at the extruder outlet, and PLGA5050 was obtained after natural cooling.
[0056] Test results: The product is white in color, with a number-average molecular weight of 91.1 kDa and a molecular weight distribution coefficient of 1.48 (significantly better than the 1.80~2.20 of batch polymerization). The residual lactide monomer is 0.23%, and the residual glycolide monomer is 0.05% (the residual monomer is significantly lower than the 0.5%~2% of batch polymerization).
[0057] Example 3 This embodiment provides a method for preparing medical PLGA8515, the method being based on... Figure 3 The device shown is implemented in this way. The only difference between this device and Example 1 is that this device is a co-rotating twin-screw extruder (L / D=40). The screw assembly includes a screw, three kneading blocks and one reverse mixing element. The three kneading blocks and one reverse mixing element are spaced apart along the length of the barrel 2 from one end of the feeder 1 to one end of the conveying device 3.
[0058] The preparation method includes the following steps: Step 1: Mix 2.0 kg D,L-lactide, 0.28 kg glycolide, 13 mL dodecanol and 0.9 mL stannous octoate thoroughly and then transfer the mixture to the feeder; Step 2: Set the feed rate of the twin-screw extruder feeder to 4 kg / h, the twin-screw extruder speed to 140 rpm, and the shear rate to approximately 73 s. -1 The twin-screw extruder was set to a zone temperature of 160℃. The mixed material was transferred through a feeder into the twin-screw extruder, where polymerization was completed under the drive of the screws. A two-stage vacuum pump was activated at the tail of the extruder for devolatilization, maintaining a vacuum level of -0.098 MPa. The average residence time was 40 minutes. A receiving device was placed at the extruder outlet, and PLGA8515 was obtained after natural cooling.
[0059] Test results: The product is white in color, with a number-average molecular weight of 47.9 kDa and a molecular weight distribution coefficient of 1.47 (significantly better than the 1.80~2.20 of batch polymerization). The residual lactide monomer is 0.21%, and the residual glycolide monomer is 0.04% (the monomer residue is significantly lower than the 0.5%~2% of batch polymerization). The material takes only 40 minutes from feeding to discharge.
[0060] Example 4 This embodiment provides a method for preparing medical PLGA7525, the method being based on... Figure 4 The device shown is implemented in this way. The only difference between this device and Example 1 is that the L / D of the co-rotating twin-screw extruder is 50, and the screw assembly includes a screw, two kneading blocks and two reverse mixing elements. The two reverse mixing elements and the two kneading blocks are alternately arranged along the length of the barrel 2 from one end of the feeder 1 to one end of the conveying device 3.
[0061] The preparation method includes the following steps: Step 1: Mix 1.8 kg D,L-lactide, 0.48 kg glycolide, 10 mL dodecanol and 0.9 mL stannous octoate thoroughly and then transfer the mixture to the feeder; Step 2: Set the feed rate of the twin-screw extruder feeder to 4.5 kg / h, the twin-screw extruder speed to 145 rpm, and the shear rate to approximately 76 s. -1 The twin-screw extruder was set to a zone temperature of 175℃. The mixed material was transferred through a feeder into the twin-screw extruder, where polymerization was completed under the drive of the screws. A two-stage vacuum pump was activated at the tail of the extruder for devolatilization, maintaining a vacuum level of -0.098 MPa. The average residence time was 38 minutes. A receiving device was placed at the extruder outlet, and PLGA7525 was obtained after natural cooling.
[0062] Test results: The product is white in color, with a number-average molecular weight of 65.2 kDa, a molecular weight distribution coefficient of 1.51, a lactide monomer residue of 0.18%, and a glycolide monomer residue of 0.05%.
[0063] Comparative Example 2 This comparative example provides a method for preparing medical PLGA, which differs from Example 1 in that the feeding speed is 8 kg / h, the extruder speed is 200 rpm, and the residence time is 10 min.
[0064] Test results: The product is white in color, with a number-average molecular weight of 17.8 kDa, a molecular weight distribution coefficient of 1.37, a lactide monomer residue of 40%, and a glycolide monomer residue of 17%.
[0065] Comparative Example 3 This comparative example provides a method for preparing medical PLGA, which differs from Example 1 in that the feeding speed is 2 kg / h, the extruder speed is 30 rpm, and the residence time is 70 min.
[0066] Test results: The product is pale yellow in color, with a number-average molecular weight of 30.8 kDa, a molecular weight distribution coefficient of 1.69, a lactide monomer residue of 0.21%, and a glycolide monomer residue of 0.07%.
[0067] Comparative Example 4 This comparative example provides a method for preparing a medical PLGA, which differs from Example 1 in that: no reverse element is added and the residence time is 25 minutes.
[0068] Test results: The product is white in color, with a number-average molecular weight of 29.8 kDa, a molecular weight distribution coefficient of 1.44, a lactide monomer residue of 17%, and a glycolide monomer residue of 9%.
[0069] Comparative Example 5 This comparative example provides a method for preparing medical PLGA, which differs from Example 1 in that vacuum devolatilization is not performed.
[0070] Test results: The product is white in color, with a number-average molecular weight of 43.6 kDa, a molecular weight distribution coefficient of 1.45, a lactide monomer residue of 1.9%, and a glycolide monomer residue of 0.87%.
[0071] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A method for preparing a medical-grade glycolide-lactide copolymer, characterized in that, Includes the following steps: A mixture containing glycolide, lactide, initiator, and catalyst is fed into a twin-screw extruder at a shear rate of 50-80 s. -1 The extrusion polymerization reaction is carried out at a temperature of 160-190℃; the residence time of the mixture in the twin-screw extruder is controlled to be 20-50 min.
2. The method for preparing medical-grade glycolide-lactide copolymer according to claim 1, characterized in that, The length-to-diameter ratio (L / D) of the twin-screw extruder is (40-60):
1.
3. The method for preparing medical-grade glycolide-lactide copolymer according to claim 1 or 2, characterized in that, The feeding speed of the twin-screw extruder is controlled at 3-5 kg / h, and the screw speed is controlled at 120-150 rpm.
4. The method for preparing the medical-grade glycolide-lactide copolymer according to any one of claims 1-3, characterized in that, The twin-screw extruder includes a barrel and a screw assembly. The screw assembly is installed in the barrel and includes a screw, at least one kneading block, and at least one reverse mixing element. The kneading block and the reverse mixing element are detachably mounted on the screw and are spaced apart along the length of the barrel.
5. The method for preparing medical-grade glycolide-lactide copolymer according to claim 4, characterized in that, The number of each of the kneading block and the reverse mixing element is independently 1-3.
6. The method for preparing the medical-grade glycolide-lactide copolymer according to any one of claims 1-5, characterized in that, The molar ratio of lactide to glycolide is (50-85):(15-50).
7. The method for preparing the medical-grade glycolide-lactide copolymer according to any one of claims 1-6, characterized in that, The initiator is selected from one or more of dodecyl alcohol, butanol, lactic acid, and glycolic acid; preferably, the amount of the initiator is 0.1-1% of the sum of the masses of the lactide and the glycolide; And / or, the catalyst is selected from one or more of stannous octoate, tri-n-butylmethoxytin, and dioctyltin dilaurate; preferably, the amount of the catalyst is 0.01-0.1% of the sum of the masses of the lactide and the glycolide.
8. The method for preparing the medical-grade glycolide-lactide copolymer according to any one of claims 1-7, characterized in that, After the extrusion polymerization reaction, the reaction product is subjected to devolatilization treatment under a vacuum of -0.09 MPa to -0.1 MPa.
9. A medical-grade glycolide-lactide copolymer, characterized in that, It is prepared by the preparation method according to any one of claims 1-8.
10. The medical-grade glycolide-lactide copolymer according to claim 9, characterized in that, The medical-grade glycolide-lactide copolymer has a number-average molecular weight of 40-100 kDa, a molecular weight distribution coefficient of less than 1.8, a lactide monomer residue of less than 0.3%, and a glycolide monomer residue of less than 0.5%.