A method for preparing high molecular weight ppdo based on a high flux microchannel reactor

Abstract

The application discloses a method for preparing high molecular weight PPDO based on a high-flux micro-channel reactor and belongs to the technical field of polymer synthesis. The method is as follows: (1) PDO-containing organic solution is mixed with a catalyst and stirred uniformly; (2) the solution obtained in the step (1) is added to a high-flux micro-channel reactor, and polymerization reaction is carried out at 120-180 DEG C and 5-40 MPa; (3) a crude product is separated, crystallized, washed, purified, and then dried to obtain high molecular weight PPDO. The method can significantly improve the molecular weight of the PPDO, and the distribution is more uniform. Compared with a traditional preparation method, the performance is significantly improved. The molecular weight and distribution of the prepared PPDO are significantly improved, and the high molecular weight and narrow distribution of the PPDO are more helpful to improve the mechanical properties and biodegradability of medical materials.

Description

Technical Field

[0001] This invention belongs to the field of polymer synthesis technology, specifically relating to a method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor. Background Technology

[0002] Poly(p-dioxanone) (PPDO) has significant applications in medical materials due to its excellent biocompatibility and biodegradability, particularly in surgical sutures, drug delivery carriers, and tissue engineering scaffolds. However, the properties of PPDO largely depend on its molecular weight and molecular weight distribution. Preparing PPDO with high molecular weight and uniform distribution has been a key research focus in this field. Currently, PPDO synthesis mainly relies on the following methods: melt polymerization and solution polymerization. Melt polymerization involves melting p-dioxanone (PDO) under high temperature conditions and then carrying out the polymerization reaction. While melt polymerization of PPDO offers advantages such as high efficiency and solvent-free operation, it also has some drawbacks.

[0003] First, high temperatures can lead to thermal degradation, affecting the polymer's molecular weight and properties. Second, the rapid reaction rate makes molecular weight control difficult, and heat accumulation during polymerization can cause localized overheating, affecting reaction stability. Melt polymerization also struggles to achieve high molecular weight and high crystallinity, and its applicability to high-temperature-sensitive monomers and catalysts is limited. Furthermore, inhomogeneity can occur during the reaction, leading to unstable polymer quality, and the high equipment requirements increase production costs. In summary, while melt polymerization has advantages in industrial production, its control precision and stability remain challenges. Solution polymerization uses organic solvents as a medium, mixing a PDO solution with a catalyst for the reaction. This method can control reaction uniformity to some extent. However, solution polymerization of PPDO presents challenges in controlling molecular weight. Because the reaction rate is difficult to control precisely during polymerization, it often results in lower polymer molecular weights and a wider molecular weight distribution. This wide distribution means significant differences in polymer chain length, affecting its mechanical properties and application stability. Moreover, lower molecular weights can lead to poorer mechanical strength in PPDO, limiting its application in some high-performance fields. Currently, in the continuous preparation of PPDO, achieving high molecular weight and uniform molecular weight distribution while improving production efficiency and reducing energy consumption remains a bottleneck for technological development. Summary of the Invention

[0004] To address the aforementioned shortcomings in the existing technology, this invention provides a method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor. This method can significantly increase the molecular weight of PPDO and achieve a more uniform distribution, resulting in a significant performance improvement compared to the traditional batch method.

[0005] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is as follows: The purpose of this invention is to provide a method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor, comprising the following steps: (1) Mix the PDO-containing organic solution with the catalyst and stir until homogeneous; (2) The solution obtained in step (1) is added to a high-throughput microchannel reactor and polymerized at 120~180℃ and 10~15MPa. (3) Separate the crude product, crystallize, wash and purify, and then dry to obtain high molecular weight PPDO.

[0006] Further, in step (1), the concentration of the organic solution containing PDO is 50~100wt%; the solvent used is toluene, xylene, N,N-dimethylformamide, or N,N-dimethylacetamide.

[0007] Furthermore, in step (1), the amount of catalyst added is 0.5 to 1% of the mass of PDO.

[0008] Furthermore, the catalyst is an organometallic catalyst or an organic acid catalyst.

[0009] Furthermore, the organometallic catalyst is one of stannous octoate and triethylaluminum; the organic acid catalyst is one of chlorosulfonic acid, benzenesulfonic acid and methanesulfonic acid.

[0010] Furthermore, the high-throughput microchannel reactor used in step (2) comprises several stacked reaction modules; the equivalent characteristic size of the reaction module is 0.5~5 mm, and its operating environment is 120~180℃, 5~30MPa.

[0011] Furthermore, the reaction module of the high-throughput microchannel reactor has a reaction channel, which is a closed curve structure composed of relatively arranged arc-shaped segments. The channel is symmetrically distributed and has a reduced cross-section in the middle, thereby creating localized acceleration and circulation during fluid flow, improving the mass transfer efficiency and reaction uniformity of the reactants (see...). Figure 2 ).

[0012] Further, in step (2), the solution obtained in step (1) is added to the high-throughput microchannel reactor at a flow rate of 10~50 mL / min.

[0013] Furthermore, in step (2), the polymerization reaction temperature is 150~180℃, the pressure is 12~15MPa, and the reaction time is 0.15~24h.

[0014] The beneficial effects of this invention are: 1. This invention uses a closed high-throughput microchannel reactor to prepare PPDO, which can avoid the influence of external environmental humidity and seasonal changes, and ensure the repeatability of the viscosity of the obtained product and the stability of the final product performance.

[0015] 2. The reaction system of this invention has high flexibility and heat transfer performance. Therefore, it can not only avoid the disadvantage of existing technologies where the viscosity increases too quickly and stirring is impossible, resulting in the final product being only in large blocks, but also obtain PPDO in the form of small blocks, granules or powder by adjusting the pressure and temperature and selecting different types of catalysts as needed.

[0016] 3. This invention solves the problem of uneven reaction in traditional batch processes. Continuous operation reduces energy consumption and environmental pollution, achieving green production. Simultaneously, the microchannel reactor supports continuous operation, significantly improving production efficiency. Compared to traditional batch operations, microchannel technology reduces production downtime and equipment cleaning time, meeting the needs of industrial production.

[0017] 4. This invention is green and environmentally friendly. It reduces waste emissions through a highly efficient solvent recovery system and significantly reduces energy consumption through the efficient heat transfer characteristics of microchannels. The solvent recovery technology used in the reaction system can significantly reduce waste liquid discharge, conforming to the principles of green chemistry and significantly reducing environmental impact.

[0018] 5. This invention improves safety by using a low-volume microchannel reactor, eliminating the need for large-scale reaction vessels and effectively reducing chemical reaction risks. It meets safety production requirements. The process can be seamlessly scaled up from pilot-scale to large-scale production without requiring additional equipment modifications, saving costs. This invention, centered on a high-throughput microchannel reactor, provides a novel, efficient, stable, and environmentally friendly method for PPDO preparation, possessing significant industrial application value and widespread potential.

[0019] 6. The method of the present invention can significantly increase the molecular weight of PPDO and make its distribution more uniform. Compared with the traditional batch method, the performance is significantly improved. The molecular weight and distribution of the obtained PPDO are significantly improved, and the high molecular weight and narrow distribution of PPDO are more conducive to improving the mechanical properties and biodegradability of medical materials. Attached Figure Description

[0020] Figure 1 GPC curve of PPDO prepared for this invention; Figure 2 This is a schematic diagram of the reaction channel. Detailed Implementation

[0021] The specific embodiments of the present invention are described below to enable those skilled in the art to understand the present invention. However, it should be understood that the present invention is not limited to the scope of the specific embodiments. For those skilled in the art, various changes are obvious as long as they are within the spirit and scope of the present invention as defined and determined by the appended claims. All inventions utilizing the concept of the present invention are protected.

[0022] Example 1 A method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor includes the following steps: (1) Mix a 50wt% PDO toluene solution with stannous octoate, wherein the amount of stannous octoate added is 0.5% of the mass of PDO, and stir until homogeneous; (2) The solution obtained in step (1) is added to a high-throughput microchannel reactor at a flow rate of 10 mL / min. The reaction module of the reactor is a reaction channel with a heart-shaped structure. Then, the polymerization reaction is carried out at 120 °C and 10 MPa. (3) After the reaction is completed, the solvent and unreacted PDO monomer are removed by a continuous separator, and the crude product is separated. The crude product is cooled to room temperature and crystallized under constant temperature conditions. Then, residual impurities are removed by washing to ensure high purity. (4) The crystallized product is dried at 60°C for 6-8 hours to obtain high-purity, high-molecular-weight PPDO particles that can be directly used for subsequent processing.

[0023] Example 2 A method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor includes the following steps: (1) Mix a toluene solution of PDO with a concentration of 80wt% with stannous octoate, wherein the amount of stannous octoate added is 1% of the mass of PDO, and stir until homogeneous; (2) The solution obtained in step (1) is added to a high-throughput microchannel reactor at a flow rate of 50 mL / min. The reaction module of the reactor is a reaction channel with a heart-shaped structure. Then, the polymerization reaction is carried out at 180 °C and 15 MPa. (3) After the reaction is completed, the solvent and unreacted PDO monomer are removed by a continuous separator, and the crude product is separated. The crude product is cooled to room temperature and crystallized under constant temperature conditions. Then, residual impurities are removed by washing to ensure high purity. (4) The crystallized product is dried at 60°C for 6-8 hours to obtain high-purity, high-molecular-weight PPDO particles that can be directly used for subsequent processing.

[0024] Example 3 A method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor includes the following steps: (1) Mix a 65wt% xylene solution of PDO with a catalyst, the catalyst being triethylaluminum, and the amount of catalyst added being 0.8% of the mass of PDO, and stir until homogeneous; (2) The solution obtained in step (1) is added to a high-throughput microchannel reactor at a flow rate of 30 mL / min. The reaction module of the reactor is a reaction channel with a heart-shaped structure. Then, the polymerization reaction is carried out at 150 °C and 12 MPa. (3) After the reaction is completed, the solvent and unreacted PDO monomer are removed by a continuous separator, and the crude product is separated. The crude product is cooled to room temperature and crystallized under constant temperature conditions. Then, residual impurities are removed by washing to ensure high purity. (4) The crystallized product is dried at 60°C for 6-8 hours to obtain high-purity, high-molecular-weight PPDO particles that can be directly used for subsequent processing.

[0025] Comparative Example 1 PPDO was prepared by conventional polymerization method, specifically: PDO monomer and stannous octoate catalyst were added to a conventional reactor and polymerization was carried out under the same conditions as in Example 1. After the reaction was completed, the PPDO sample was obtained by separation, crystallization, washing and drying.

[0026] Test case 1. The performance of PPDO prepared according to the embodiments of the present invention and traditional PPDO was tested. The results are shown in Table 1. The specific testing process is as follows: (1) Number average molecular weight (Mn) and molecular weight distribution (PDI) were determined by gel permeation chromatography (GPC) at a temperature of 35°C. The mobile phase was HPLC-grade chloroform (CHCl3) and the flow rate was 1.0 mL / min. The results were calibrated using polystyrene standard samples.

[0027] (2) Tensile strength, elongation at break and Young's modulus were tested using an electronic universal testing machine. The specimens were prepared and tested in accordance with GB / T1040.2-2006.

[0028] (3) In vitro degradation performance: The sample was placed in PBS buffer (pH 7.4) and degraded under constant temperature shaking at 37℃. Samples were taken, washed, vacuum dried and weighed periodically. The change in sample mass was recorded. The time when the sample mass loss reached 50% of the initial mass was defined as the in vitro degradation 50% mass time.

[0029] Table 1. Performance comparison of PPDO prepared by microfluidics with that of traditional PPDO

[0030] 2. The PPDO prepared in the embodiments of the present invention was subjected to performance and GPC testing, and the results are shown in Table 2 and... Figure 1 .

[0031] Table 2. Performance of PPDO prepared by this invention

[0032] From Table 1, Table 2 and Figure 1 The test results show that, compared with traditional PPDO, the PPDO prepared by the high-throughput microchannel reactor of this invention exhibits significant advantages in terms of number-average molecular weight (Mn), molecular weight distribution (PDI), tensile strength, elongation at break, Young's modulus, and in vitro degradation half-mass time. This is because the high-throughput microchannel reactor has higher heat and mass transfer efficiency and a more uniform residence time distribution, effectively reducing problems such as local overheating, local concentration fluctuations, and uneven reaction in traditional batch polymerization, thus facilitating the acquisition of PPDO with higher molecular weight and narrower molecular weight distribution. Furthermore, the higher molecular weight and narrower molecular weight distribution help improve the inter-chain interactions and overall structural uniformity of the polymer, resulting in superior mechanical strength, ductility, and modulus. Simultaneously, the optimized molecular structure leads to a longer 50% mass loss time during in vitro degradation, indicating that it maintains both degradability and better stability, making it more suitable for applications such as medical sutures, tissue engineering scaffolds, and biodegradable implant materials.

[0033] Finally, it should be noted that the above specific embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to examples, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method for preparing high molecular weight PPDO based on a high-throughput microchannel reactor, characterized in that, Includes the following steps: (1) Mix the PDO-containing organic solution with the catalyst and stir until homogeneous; (2) The solution obtained in step (1) is added to a high-throughput microchannel reactor and polymerized at 120~180℃ and 5~40MPa. (3) Separate the crude product, crystallize, wash and purify, and then dry to obtain high molecular weight PPDO.

2. The method according to claim 1, characterized in that, In step (1), the concentration of the organic solution containing PDO is 50~100wt%; the solvent used is toluene, xylene, N,N-dimethylformamide, or N,N-dimethylacetamide.

3. The method according to claim 1, characterized in that, In step (1), the amount of catalyst added is 0.5 to 1% of the mass of PDO.

4. The method according to claim 3, characterized in that, The catalyst is an organometallic catalyst or an organic acid catalyst.

5. The method according to claim 4, characterized in that, The organometallic catalyst is one of stannous octoate and triethylaluminum; the organic acid catalyst is one of chlorosulfonic acid, benzenesulfonic acid and methanesulfonic acid.

6. The method according to claim 1, characterized in that, The high-throughput microchannel reactor used in step (2) comprises several stacked reaction modules; the equivalent characteristic size of the reaction module is 0.5~5 mm, and its operating environment is 120~180℃, 5~30MPa.

7. The method according to claim 1 or 6, characterized in that, The high-throughput microchannel reactor has a reaction module with microscale flow channels. The reaction channel of the reaction module is a closed curve structure composed of oppositely arranged arc segments, which are symmetrically distributed and have a narrowing cross section in the middle, so that the fluid forms a circulating turbulent flow during the flow process.

8. The method according to claim 1, characterized in that, In step (2), the solution obtained in step (1) is added to the high-throughput microchannel reactor at a flow rate of 10~50 mL / min.

9. The method according to claim 1, characterized in that, In step (2), the polymerization reaction temperature is 150~180℃, the pressure is 12~15MPa, and the reaction time is 0.15~24h.

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