Porous structure polymer material and preparation method thereof
The preparation of porous polymer materials by freeze-drying solves the problem of uneven micropores in low-inner-diameter polyurethane neural scaffolds in existing technologies, achieving a highly efficient open-pore microporous structure and improving the nerve repair effect.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-29
- Publication Date
- 2026-04-14
AI Technical Summary
Existing polyurethane neural scaffold extrusion molding processes are not suitable for low-diameter structures. Sodium chloride replacement efficiency is low and residues remain, leading to uneven micropores and closed pores, which affects repair efficiency.
Porous polymer materials were prepared by freeze-drying, which utilizes the sublimation of organic solvents under frozen conditions to form micropores. By selecting appropriate organic solvents and solvent ratios as well as freeze-drying temperatures, open-pore microporous structures were formed.
This invention achieves uniform pore size in a low-diameter polyurethane neural scaffold, increases the number and quality of micropores, reduces material density, and improves neural repair efficiency.
Smart Images
Figure CN121851682A_ABST
Abstract
Description
Technical Field
[0001] This application relates to the field of porous polymer technology, specifically to a porous polymer material and its preparation method. Background Technology
[0002] Neural scaffolds are a type of tissue engineering material used to promote nerve repair. Currently, polyurethane is a commonly used material for neural scaffolds due to its good biocompatibility and high mechanical strength. Typically, polyurethane neural scaffolds also need to have a porous structure to facilitate substance exchange and improve repair efficiency. Existing polyurethane neural scaffolds are generally manufactured into hollow tubular structures using extrusion molding. To create pores, sodium chloride is added to the polyurethane material before extrusion molding. After extrusion molding, the sodium chloride is removed through water displacement, and the moisture is further removed through drying. Summary of the Invention
[0003] However, the current method of using sodium chloride as a pore-forming agent and extrusion molding to prepare polyurethane neural scaffolds still has the following shortcomings: (1) The current extrusion molding process is not suitable for polyurethane neural scaffolds with low inner diameter, such as 1-3 mm inner diameter; (2) Using sodium chloride to prepare micropores has problems such as low replacement efficiency, sodium chloride inability to replace in closed-cell structures, sodium chloride residue, uneven micropores, and few open-cell micropores.
[0004] To address the aforementioned technical problems in the prior art, this application provides a porous polymer material and a method for preparing the same.
[0005] The technical solution adopted in this application is as follows: A porous polymer material, the raw material components of which include: polyurethane and organic solvent; The melting point of the organic solvent is -70℃ to 20℃; The organic solvent is compatible with the polyurethane at 20°C; The polyurethane and the organic solvent are mixed and dissolved, and then freeze-dried under vacuum to produce the porous polyurethane material.
[0006] Preferably, the organic solvent has a melting point of -40°C to 15°C.
[0007] Preferably, the organic solvent is selected from good solvents of the polyurethane.
[0008] Preferably, the organic solvent is selected from a combination of good and bad solvents of the polyurethane in a weight ratio of 8-20:1.
[0009] Preferably, the weight ratio of the polyurethane to the organic solvent is 1:0.1-10.
[0010] Preferably, the molecular structure of the polyurethane includes at least one first block and at least one second block, the first block and the second block are arranged alternately, and adjacent first blocks and second blocks are connected by urethane bonds; The first block is formed from an aliphatic polyester diol or an alicyclic polyester diol; The second block is formed from polyether diol.
[0011] A method for preparing a porous polymer material according to any of the above embodiments includes: mixing and dissolving the polyurethane and the organic solvent, shaping it into a certain shape, freezing it, and performing freeze-vacuum drying to obtain the porous polymer material.
[0012] Preferably, the freezing temperature is 2°C or more lower than the melting point of the organic solvent.
[0013] Preferably, the temperature of the freeze-drying is not lower than the freezing temperature and is lower than the melting point of the organic solvent.
[0014] Preferably, after the freeze-drying and molding process, the method further includes: heating to above 0°C for drying or drying in an environment of 20-60°C for 1-24 hours.
[0015] In summary, this application has the following beneficial effects: 1. This application uses a freeze-drying method to prepare a porous polymer with many open micropores - porous polyurethane. In the frozen state, the polyurethane solution is frozen, and the organic solvent occupies a certain volume space of the polyurethane polymer chain. The organic solvent directly sublimates, and the positions occupied by the organic solvent form micropores, which makes the polyurethane form abundant micropores. Moreover, since it is the sublimation of organic solvent, the micropores formed are basically open pores.
[0016] 2. Further investigation revealed that adding a small amount of poor polyurethane solvent to the organic solvent is more conducive to the formation of micropores, resulting in a greater number of micropores and a lower density of polyurethane. Attached Figure Description
[0017] Appendix Figure 1 This is a SEM image of the porous polyurethane structure from Example 1.
[0018] Appendix Figure 2 This is a SEM image of the porous polyurethane structure in Comparative Example 1. Detailed Implementation
[0019] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be described in detail below.
[0020] Throughout this specification, unless otherwise specified, the terminology used herein should be understood as having the meaning commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. In the event of any conflict, this specification shall prevail.
[0021] This application proposes a porous polymer material, the raw material components of which include: polyurethane and organic solvent; the melting point of the organic solvent is -70℃ to 20℃; Organic solvents are compatible with polyurethane at 20°C. This means that at 20°C, at least 100g of polyurethane and 100g of organic solvent can be mixed to form a transparent and homogeneous state, and no abnormalities such as layering or precipitation will occur when the mixture is left at room temperature for one week.
[0022] Polyurethane and organic solvents are mixed and dissolved, then freeze-dried to produce a porous polyurethane material. During freeze-drying, the mixture of polyurethane and organic solvent freezes, and the organic solvent sublimates directly, creating voids in the volume space of the polyurethane polymer chains occupied by the organic solvent, thus forming open-pore micropores.
[0023] Considering the cost and low-temperature control of vacuum freeze-drying equipment, in a preferred embodiment of this application, the melting point of the organic solvent is -40℃ to 15℃. The higher the melting point of the organic solvent, the lower the requirements for the vacuum freeze-drying equipment, and the lower the cost of the equipment. For example, if the melting point of the organic solvent is -55℃, the temperature during vacuum freeze-drying must be below -55℃, such as -58℃ or -60℃. If the melting point of the organic solvent is -35℃, the temperature during vacuum freeze-drying must be below -35℃, such as -38℃ or -40℃.
[0024] In a preferred embodiment of this application, the organic solvent is selected from good solvents for polyurethane. For example, good solvents for polyurethane include chloroform, 1,2-dichloroethane, DMF, DMAc, 1,1,2-trichloroethane, 1,1,1-trichloroethane, N-methylpyrrolidone, nitromethane, acetonitrile, etc., or one or a combination of two or more of these solvents.
[0025] In a preferred embodiment of this application, the organic solvent may also be selected from a combination of good and bad solvents for polyurethane. Specifically, the weight ratio of good to bad solvent is 8-20:1. More preferably, the weight ratio of good to bad solvent is 10-20:1, for example, the weight ratio may be 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, etc. Specifically, the bad solvent may be a low-polarity or non-polar organic solvent, such as n-decane, n-dodecane, diheptane, dioctyl ether, etc., or a combination of two or more of them, and the melting point of the bad solvent may be -40℃ to 15℃. Adding a small amount of bad solvent to the organic solvent will not affect the solubility of polyurethane by the organic solvent at room temperature or the compatibility between the organic solvent and polyurethane at room temperature. During freeze-drying, the unsuitable solvent forms incompatible regions with the polyurethane polymer chains at the microscopic level. After the unsuitable solvent sublimates, these incompatible regions can form pores, resulting in open micropores within the polyurethane, further increasing the number and / or size of these pores. If the content of the unsuitable solvent in the organic solvent is high, for example, if the weight ratio of good solvent to unsuitable solvent is 6:1, it will affect the solubility of the polyurethane in the organic solvent. This will cause the solution, after being uniformly mixed with the polyurethane and left at room temperature for 2 days, to become turbid. If cooled to 0°C (where the melting point of the organic solvent is below 0°C, such as -10°C), turbidity will occur directly.
[0026] In a preferred embodiment of this application, the weight ratio of polyurethane to organic solvent is 1:0.1-10. More preferably, the weight ratio of polyurethane to organic solvent is 1:0.3-5. For example, the weight ratio can be 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.8, 1:1, 1:1.2, 1:1.5, etc.
[0027] In a preferred embodiment of this application, the molecular structure of polyurethane includes at least one first block and at least one second block, the first block and the second block are arranged alternately, and adjacent first blocks and second blocks are connected by urethane bonds; The first block is formed from an aliphatic polyester diol or an alicyclic polyester diol; The second block is formed from polyether diol.
[0028] In this application, the average molecular weight range of aliphatic polyester diols, alicyclic polyester diols, and aliphatic polyether diols can be 200-200,000, or further, the average molecular weight range can be 400-100,000. To improve the biocompatibility of the neural scaffold, the aliphatic polyester diol can be polylactic acid (PLA), polycaprolactone (PCL), polyglycolic acid (PGA), polybutylene succinate (PBS), polybutylene terephthalate (PBAT), etc., and can be one or a combination of two or more of these, such as PLA-b-PCL block copolymers and PGA-b-PCL block copolymers. Due to the cycloalkyl groups in their molecular structure, alicyclic polyester diols can improve the mechanical strength of the polyurethane neural scaffold. For example, the alicyclic polyester diol can be polycyclohexanediol adipate diol, polycyclohexanediol succinate diol, etc. Polyether diols can be polyethylene glycol, such as PEG400 (400 represents the average molecular weight, and so on), PEG600, PEG800, PEG1000, PEG1200, etc.
[0029] In this application, adjacent first and second blocks are linked by urethane bonds. Therefore, an aliphatic polyether diol can be pre-reacted with a diisocyanate monomer (such as IPDI, HDI, TDI, MDI, HMDI, etc.) to prepare a polyurethane prepolymer with -NCO end groups. The -NCO content in the polyurethane prepolymer can be 3-10 wt%, or further, the -NCO content in the polyurethane prepolymer can be 3-8 wt%. The polyurethane prepolymer is then subjected to an addition reaction with an aliphatic polyester diol and / or an alicyclic polyester diol to obtain a polyurethane polymer material.
[0030] Another aspect of this application proposes a method for preparing a porous polymer material according to any of the above embodiments, comprising: mixing and dissolving polyurethane and an organic solvent, shaping it into a certain shape, freezing it, and performing freeze-vacuum drying to obtain a porous polymer material.
[0031] In the above preparation method, setting it to a certain shape means that, according to the needs of the final porous polyurethane structure, the polyurethane and organic solvent solution can be molded and set to different shapes such as thin sheet, thick sheet, cylindrical, cylindrical, and conical.
[0032] In a preferred embodiment of this application, the freezing temperature is 2°C or more lower than the melting point of the organic solvent. A freezing temperature 2°C or more lower than the melting point of the organic solvent, such as 2°C, 3°C, or 4°C lower, ensures the freezing of the mixture of polyurethane and the organic solvent.
[0033] In a preferred embodiment of this application, the freeze-vacuum drying temperature is not lower than the freezing temperature and is lower than the melting point of the organic solvent. During freeze-vacuum drying, the lower the temperature, the slower the organic solvent sublimates. More preferably, the freeze-vacuum drying temperature is 1°C or more lower than the melting point of the organic solvent, for example, 2°C lower. By controlling the freeze-vacuum drying temperature within the above range, for example, if the melting point of the organic solvent is -35°C and the freezing temperature is -40°C, the freeze-vacuum drying temperature can be -38°C to -37°C.
[0034] In a preferred embodiment of this application, after freeze-vacuum drying molding, the process further includes: heating to above 0°C for drying or drying in an environment of 20-60°C for 1-24 hours. After freeze-vacuum drying molding, a large number of stable micropores have formed inside the polyurethane, and the remaining small amount or residual organic solvent can be removed at a higher temperature. This can improve the organic solvent removal rate, increase work efficiency, and reduce costs.
[0035] The polyurethane material of this application can be used in neural scaffolds. For example, a solution of polyurethane and organic solvent can be formed into a cylindrical shape, and after freeze-drying, the organic solvent can be removed, resulting in a polyurethane neural scaffold containing numerous micropores.
[0036] The technical solution of this application will be described in detail below with reference to embodiments and comparative examples.
[0037] The polyurethanes in the following embodiments and comparative examples were prepared according to the following methods, but are only examples and do not represent a limitation of the present invention.
[0038] PEG400 and IPDI were added to a dry container at a molar ratio of 0.7:1. Nitrogen gas was purged, and then 0.15% by weight of PEG400 and IPDI and dibutyltin dilaurate were added. The mixture was stirred at room temperature for 1 hour, and then heated to 70°C and reacted for another hour to obtain a polyurethane prepolymer.
[0039] The aforementioned polyurethane prepolymer and PCL glycol with an average molecular weight of 12000 were added to a reaction vessel at a -NCO to -OH molar ratio of 0.99:1. The mixture was heated to 80°C and reacted for 5 hours. After cooling, crude polyurethane was obtained. The crude polyurethane was dissolved in acetone to prepare a 25 wt% solution, which was then added to 20 times its volume of methanol for precipitation. The precipitate was collected and dried overnight under vacuum at 50°C to obtain polyurethane.
[0040] Example 1 Polyurethane and 1,1,2-trichloroethane were mixed in a weight ratio of 1:1 and dissolved evenly at room temperature. The mixture was then added to a mold and shaped into a thin plate. The plate was frozen at -42°C and then transferred to a freeze-drying equipment. The plate was freeze-dried at -41 to -40°C. After molding, the plate was demolded to obtain a porous polyurethane with dimensions of 10cm × 5cm × 1mm.
[0041] Appendix Figure 1 The image shown is an SEM image of the porous polyurethane structure from Example 1, which reveals a rich array of open pores.
[0042] Example 2 The difference between Example 2 and Example 1 is that in Example 1, 1,1,2-trichloroethane was replaced with a mixed solvent consisting of 1,1,2-trichloroethane and n-decane in a weight ratio of 20:1. The remaining steps remained unchanged.
[0043] Example 3 The difference between Example 3 and Example 1 is that in Example 1, 1,1,2-trichloroethane was replaced with a mixed solvent consisting of 1,1,2-trichloroethane and n-decane in a weight ratio of 15:1. The remaining steps remained unchanged.
[0044] Example 4 The difference between Example 3 and Example 1 is that in Example 1, 1,1,2-trichloroethane was replaced with a mixed solvent consisting of 1,1,2-trichloroethane and n-decane in a weight ratio of 10:1. The remaining steps remained unchanged.
[0045] Example 5 Polyurethane and 1,1,1-trichloroethane were mixed at a weight ratio of 1:1.4 and dissolved evenly at room temperature. The mixture was then added to a mold and shaped into a cylinder. The cylinder was frozen at -38°C and then transferred to a freeze-drying equipment. The mixture was freeze-dried at -36 to -35°C. After molding, the mixture was demolded to obtain a porous polyurethane structure with an inner diameter of 6 mm, an outer diameter of 8 mm, and a length of 10 cm.
[0046] Example 6 Polyurethane and 1,4-dioxane were mixed at a weight ratio of 1:1.5 and dissolved evenly at room temperature. The mixture was then added to a mold and shaped into a cylinder. The cylinder was frozen at -35°C and then transferred to a freeze-drying equipment. The mixture was freeze-dried at -30±1°C. After molding, the mixture was demolded to obtain a porous polyurethane structure with an inner diameter of 4 mm, an outer diameter of 5 mm, and a length of 5 cm.
[0047] Example 7 Polyurethane and chloroform were mixed at a weight ratio of 1:2 and dissolved evenly at room temperature. The mixture was then added to a mold and shaped into a cylinder. The cylinder was frozen at -70°C and then transferred to a freeze-vacuum drying equipment. The mixture was freeze-dried at -68 to -67°C. After molding, the mixture was demolded to obtain a porous polyurethane structure with an inner diameter of 4 mm, an outer diameter of 5 mm, and a length of 5 cm.
[0048] Example 8 Polyurethane and DMF were mixed at a weight ratio of 1:1.8 and dissolved evenly at room temperature. The mixture was then added to a mold and shaped into sheets. The sheets were frozen at -65°C and then transferred to a freeze-drying equipment. The sheets were freeze-dried at -64 to -63°C. After molding, the sheets were demolded to obtain a porous polyurethane structure with dimensions of 10cm × 5cm × 4mm.
[0049] Comparative Example 1 According to existing technology, 10 wt% sodium chloride particles (average particle size 0.7 μm) are added to polyurethane material, mixed evenly, and melt-extruded into tubular polyurethane tubes with an inner diameter of 6 mm and a wall thickness of 0.5 mm. These tubes are then cut to 5 cm lengths and immersed in clean water for sodium chloride replacement for 72 hours, with the water changed every 12 hours. The tubes are then removed, cleaned, and vacuum-dried overnight at 60°C to obtain the polyurethane tubing.
[0050] Appendix Figure 2 SEM images of polyurethane pipes manufactured using existing technology, attached. Figure 1 A comparison shows that polyurethane pipes prepared by existing technologies have fewer openings and contain a significant amount of sodium chloride residue.
[0051] Comparative Example 2 The difference between Comparative Example 2 and Example 6: In Example 6, the freezing temperature was adjusted to 0°C, and the freeze-drying temperature was adjusted to 2-3°C. The remaining steps remained unchanged.
[0052] Comparative Example 3 The difference between Comparative Example 3 and Example 7 is that in Example 7, the freezing temperature was adjusted to -50°C, and the freeze-drying temperature was adjusted to -48 to -47°C. The remaining steps remained unchanged.
[0053] The density of the porous polyurethane structures in the examples and comparative examples was tested using the water displacement method, and the results are shown in Table 1 below.
[0054] Table 1 Density / g / cm³ 3 polyurethane Example 1 Example 2 Example 3 Example 4 Example 5 1.159 0.648 0.623 0.601 0.584 0.627 Example 6 Example 7 Example 8 Comparative Example 1 Comparative Example 2 Comparative Example 3 0.618 0.603 0.610 0.804 1.017 1.134 The results in Table 1 show that the porous polyurethane structure of this application has a low density, indicating the formation of more micropores. Comparing the data from Examples 1-4, the density of the polyurethane decreases with increasing undesirable solvent content in the organic solvent. Comparative Example 1 shows that using sodium chloride as a pore-forming agent results in poor pore formation and a high density. Comparative Example 2 shows that if the organic solvent has a high melting point, even with freeze-drying below the melting point, the pore-forming effect is poor if the temperature is not low enough. This may be because the polyurethane polymer chains are still relatively mobile at this temperature, and the polymer chain movement compensates for the micropores formed by solvent evaporation. Comparative Example 3 shows that if the freeze-drying temperature is not lower than the melting point of the organic solvent, the polyurethane solution is in a liquid state, and even at lower temperatures, fewer micropores are formed.
[0055] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.
Claims
1. A porous polymer material, characterized in that, The raw material components include: polyurethane and organic solvents; The organic solvent has a melting point of -70℃ to 20℃; The organic solvent is compatible with the polyurethane at 20°C; The polyurethane and the organic solvent are mixed and dissolved, and then freeze-dried under vacuum to produce the porous polymer material.
2. The porous polymer material according to claim 1, characterized in that, The organic solvent has a melting point of -40℃ to 15℃.
3. The porous polymer material according to claim 1, characterized in that, The organic solvent is selected from good solvents for the polyurethane.
4. The porous polymer material according to claim 1, characterized in that, The organic solvent is selected from a combination of good and bad solvents of the polyurethane in a weight ratio of 8-20:
1.
5. The porous polymer material according to claim 1, characterized in that, The weight ratio of the polyurethane to the organic solvent is 1:0.1-10.
6. The porous polymer material according to claim 1, characterized in that, The molecular structure of the polyurethane includes at least one first block and at least one second block, the first block and the second block are arranged alternately, and adjacent first blocks and second blocks are connected by urethane bonds; The first block is formed from an aliphatic polyester diol or an alicyclic polyester diol; The second block is formed from polyether diol.
7. A method for preparing a porous polymer material according to any one of claims 1-6, characterized in that, include: The polyurethane and the organic solvent are mixed and dissolved, shaped into a certain form, frozen, and then freeze-dried under freeze-drying conditions to obtain the porous polymer material.
8. The method for preparing the porous polymer material according to claim 7, characterized in that, The freezing temperature is 2°C or more lower than the melting point of the organic solvent.
9. The method for preparing the porous polymer material according to claim 7, characterized in that, The temperature of the freeze-drying is not lower than the freezing temperature and is lower than the melting point of the organic solvent.
10. The method for preparing the porous polymer material according to claim 7, characterized in that, After the freeze-drying and shaping process, the method further includes: heating to above 0°C for drying or placing in an environment of 20-60°C for drying for 1-24 hours.