WO2023184852A1 - 一种形状记忆聚氨酯及其制成的自增强规则孔隙聚合物薄膜 - Google Patents

一种形状记忆聚氨酯及其制成的自增强规则孔隙聚合物薄膜 Download PDF

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WO2023184852A1
WO2023184852A1 PCT/CN2022/116391 CN2022116391W WO2023184852A1 WO 2023184852 A1 WO2023184852 A1 WO 2023184852A1 CN 2022116391 W CN2022116391 W CN 2022116391W WO 2023184852 A1 WO2023184852 A1 WO 2023184852A1
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porous
shape memory
iso
diisocyanate
film
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PCT/CN2022/116391
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French (fr)
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罗彦凤
王远亮
杨伟
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重庆大学
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Priority claimed from CN202210335238.4A external-priority patent/CN114634608B/zh
Priority claimed from CN202210335221.9A external-priority patent/CN114634641B/zh
Priority claimed from CN202210333364.6A external-priority patent/CN114656678B/zh
Application filed by 重庆大学 filed Critical 重庆大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/40—High-molecular-weight compounds
    • C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
    • C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
    • C08G18/72—Polyisocyanates or polyisothiocyanates
    • C08G18/80—Masked polyisocyanates
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J5/00—Manufacture of articles or shaped materials containing macromolecular substances
    • C08J5/18—Manufacture of films or sheets
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L75/00—Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
    • C08L75/04—Polyurethanes
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L75/00—Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
    • C08L75/04—Polyurethanes
    • C08L75/06—Polyurethanes from polyesters

Definitions

  • the invention belongs to the technical field of polymer materials, and specifically relates to a shape memory polyurethane material and a self-reinforced regular pore polymer film made of it.
  • Shape Memory Polymer also known as shape memory polymer, refers to a product with an initial shape that changes its initial condition under certain conditions and is fixed through external conditions (such as heat, electricity, A polymer material that can restore its original shape when stimulated by light, chemical induction, etc.). Shape memory polymers are widely used in biomedicine, aerospace, optics, textiles and other fields due to their shape recovery properties.
  • Shape memory polymers include thermal type, electrotype, phototype, chemical induction type, etc. according to their recovery principles.
  • thermotropic shape memory polymers can be used in medicine by controlling their glass transition temperature and adjusting their recovery temperature to be consistent with body temperature.
  • a film or device of a specific shape made of thermotropic shape memory polymer material can be miniaturized and deformed, and then implanted into the body through a microcatheter. After reaching the correct position, it can restore its original set shape.
  • Thermotropic shape memory polymers include polyurethanes, ethylene/vinyl acetate copolymers, and cross-linked polyethylene. When these materials are used to prepare membranes or devices for implantation in the human body, they need to meet a series of performance requirements such as permeability, biocompatibility, and mechanical properties according to the location and purpose of implantation. However, ordinary dense membranes made from these existing thermotropic shape memory polymer materials cannot meet these permeability and biocompatibility requirements. In order to improve this problem, porous polymer films with regular pores have the potential to be used as membranes implanted in the human body due to their unique performance characteristics (such as permeability to molecules/ions, biocompatibility, ductility, etc.) potential.
  • thermotropic shape memory polymer materials may suffer from insufficient mechanical properties during the process of introducing a large number of pores to form porous membranes.
  • "CN201110224930.1 A method for forming a polyurethane porous membrane” provides a method for preparing a polyurethane porous membrane using a water droplet template method.
  • porous polymer films made of these polyurethane materials are still difficult to be used in fields such as bionics and tissue engineering that have higher requirements for material mechanical properties. This has placed great restrictions on the development and application of porous polymer films. Designing and preparing polymer films with both good mechanical properties and regular porous structures will help expand the applications of this type of material. The ordered arrangement of polymer molecules, crystals or micro-phase separation can all help to enhance the mechanical properties of materials.
  • the type and structure of ideal shape memory polymer materials cannot be deduced based on existing theories, which is an urgent problem to be solved. .
  • the present invention provides a shape memory polyurethane material and a self-reinforced regular pore polymer film made of the same.
  • the purpose is to provide a porous polymer film with regular pores that has both mechanical properties.
  • a shape memory polyurethane which is an amorphous polymer with a glass transition temperature of 37-45°C or a semi-crystalline polymer with a melting point of 37-45°C. It is composed of diisocyanate, soft segment polymer and
  • the linear polymer polymerized according to the molar ratio of 1.2-8:1:0.2-7 has a molecular weight of 30000-150000;
  • the soft segment polymer is polylactic acid, polyglycolic acid, polycaprolactone, polypolyol or a copolymer of two or more thereof.
  • diisocyanates Preferably, diisocyanates, soft segment polymers and The molar ratio is 2.78:1:1.80.
  • x is selected from 1-10, and y is selected from 1-10;
  • diisocyanate is a repeating unit of diisocyanate, or diisocyanate and
  • the soft segment polymer is a polymer of lactic acid and polyol.
  • the structural formula of the soft segment polymer is as shown in Formula II:
  • n and n are independently selected from 4-50, and r is selected from 1-20.
  • the diisocyanate is selected from aliphatic diisocyanate or aromatic diisocyanate, and the aliphatic diisocyanate is selected from hexamethylene diisocyanate, lysine diisocyanate, isophorone diisocyanate, and dicyclohexyl diisocyanate.
  • Methane diisocyanate or a mixture of two or more thereof the aromatic diisocyanate is selected from toluene diisocyanate, diphenylmethane diisocyanate or a mixture of two or more thereof.
  • the invention also provides a porous polymer film with regular pores and high mechanical properties, which is prepared by using the above-mentioned shape memory polyurethane as a raw material and using a water drop template method.
  • the parameters of the water droplet template method are selected as follows: ambient temperature 4-50°C, humidity 25-80%, so that the evaporation rate of the solvent is 5-50 ⁇ L/min.
  • the present invention also provides a preparation method for the above-mentioned porous polymer film, which includes the following steps:
  • Step 1 Dissolve the above shape memory polyurethane in a volatile solvent to obtain a polyurethane solution
  • Step 2 Coat the polyurethane solution on the surface of the substrate and evaporate it to dryness in humid air.
  • the volatile solvent is selected from chloroform, dichloromethane, tetrahydrofuran, carbon disulfide or a mixture of two or more thereof;
  • the concentration of the polyurethane solution is 5-200mg/mL
  • step 2 the substrate coated with the polyurethane solution is dried at an ambient temperature of 4-50°C and a humidity of 25-80%, and the evaporation rate of the solvent is 5-50 ⁇ L/min.
  • the present invention also provides the use of the above-mentioned shape memory polyurethane for preparing a porous polymer film with regular pores with high mechanical properties.
  • the method for preparing the porous polymer film from the shape memory polyurethane is a water drop template method.
  • the present invention also provides the use of the above-mentioned porous polymer film with regular pores for preparing artificial periosteum.
  • the present invention also provides an artificial periosteum, which is made of the above-mentioned porous polymer film with regular pores.
  • the present invention also provides the use of the above-mentioned porous polymer film with regular pores for preparing an anti-adhesion film.
  • the present invention also provides an anti-adhesion film, which is made of the above-mentioned porous polymer film with regular pores.
  • the present invention designs a new shape memory polyurethane material. After this shape memory polyurethane material is made into a porous polymer film with regular pores using the water droplet template method, the microstructure of the film material reflects certain crystal characteristics. This shows that the arrangement of molecular chains in the porous polymer film is more orderly and the hard segments are better assembled, which makes the porous polymer film have good mechanical properties. Compared with similar porous polymer films, the porous polymer film with high mechanical properties provided by the present invention has good application prospects in fields such as artificial periosteum and anti-adhesion membranes that have higher requirements on the mechanical properties of the film.
  • Figure 1 is the 1 H NMR spectra of the two coupling agents in Example 1;
  • Figure 2 is the FT-IR spectra of the two coupling agents in Example 1;
  • Figure 3 is the FT-IR spectrum of PDLLA-PEG400-PDLLA macrodiol and ISO-PUs in Example 1 (the spectrum on the right is an enlargement of the rectangular marked part of the spectrum on the left);
  • Figure 4 is the 1 H NMR spectra of PDLLA-PEG400-PDLLA and ISO-PUs in Example 1;
  • Figure 5 is the GPC curve of ISO-PUs in Example 1.
  • Figure 7 is an optical microscope image of water droplets condensing on the surface of the ISO-PUs solution during the formation of the porous film
  • Figure 8 is the SEM image of the ISO-PUs porous film after drying.
  • (b) is an enlargement of the red area in the middle phase of (a);
  • Figure 9 shows the optical microscope image (a) of the ISO-PUs porous film and the optical microscope image (b-d) under crossed polarizers.
  • (c) and (d) are magnifications of the red area in (b);
  • Figure 10 shows optical microscope images and microscope images under crossed polarizers of ISO-PUs porous films prepared at rates of 10 ⁇ l/min ((a) and (b)) and 40 ⁇ l/min ((d) and (e)) ( (c) and (f) are enlarged views of the red areas in (b) and (e) respectively);
  • Figure 11 shows the microscopic morphology of PPZ-PU (a and b), Upy-PU (c and d) and PDLLA (e and f) porous films under optical microscope and crossed polarizer;
  • Figure 12 shows the DSC curves of ISO-PUs nonporous control film and ISO-PUs porous film ((a) is the first heating cycle curve, (b) is the cooling and second heating curve);
  • Figure 13 shows the 2D-WAXD diffraction patterns of ISO-PUs nonporous control film (a) and ISO-PUs porous film (b), as well as the ISO-PUs nonporous control film (c) and ISO-PUs porous film (d). 1D-WAXD curve;
  • Figure 14 shows the FT-IR spectrum (a) of ISO-PUs control film and porous film and the fitted peak split curve (b) in the 3260-3460cm -1 region;
  • Figure 15 shows the tensile stress-strain curve (a) and mechanical properties (b) of ISO-PUs porous film and non-porous transparent control film at 25°C;
  • Figure 16 shows the cell morphology of rMSCs cultured on ISO-PUs non-porous control film (a and c) and porous film (b and d) for 24 hours;
  • Figure 17 shows the spreading area and aspect ratio distribution of rMSCs after culturing for 24 hours on ISO-PUs non-porous control film and porous film;
  • Figure 18 shows the alkaline phosphatase (ALP) staining experimental results of rMSCs cultured on ISO-PUs non-porous control film and porous film for 14 days;
  • ALP alkaline phosphatase
  • Figure 19 shows the morphological observation results of the cytocompatibility experiment of ISO-PUs porous anti-adhesion film and non-porous control film;
  • Figure 20 shows the absorbance values of NIH 3T3 cells measured by CCK-8 method for different culture times in the cytocompatibility experiment of ISO-PUs porous anti-adhesion film and non-porous control film (* means p ⁇ 0.05, ** means p ⁇ 0.01).
  • This embodiment provides a shape memory polyurethane material. Its preparation method is as follows:
  • OCN-DI ⁇ -NCO is a new diisocyanate synthesized in step 2 above.
  • Figure 1(a) and (b) are respectively the hydrogen nuclear magnetic spectrum ( 1 H NMR) spectrum of the new diisocyanate diisocyanate sample HDI-capped ISO obtained by reacting HDI and ISO at 4:1 and 2:1, with two spectral lines. The positions of the proton absorption peaks are the same, but their intensities are quite different.
  • HDI/ISO is close to 2 (7.74/(1.00 ⁇ 4) ⁇ 2), indicating that HDI and ISO react at 4:1 to obtain HDI-ISO-HDI.
  • HDI/ISO is close to 1.5 (6.37/(1.00 ⁇ 4) ⁇ 1.5), indicating that HDI and ISO react at a ratio of 2:1 to obtain HDI-ISO-HDI-ISO-HDI.
  • the sample synthesized with HDI as the coupling agent was named ISO1-PU, while the samples synthesized with HDI-ISO-HDI and HDI-ISO-HDI-ISO-HDI as the coupling agent were named ISO2-PU and ISO3-PU respectively.
  • the -CH 3 proton absorption peak in the lactic acid residue at the end of the molecular alcohol comes from the -CH 2 proton absorption peak in PEG400;
  • the proton characteristic peaks on the ISO ring (H-1 ⁇ H-6) are obvious in the spectra of ISO2-PU and ISO3-PU, but cannot be observed in the spectrum of ISO1-PU due to the low ISO content. arrive.
  • the integrated area (I H-4 ) represents the content of ISO, and the integrated value of H-a' peak (I H-a' ) represents the content of HDI.
  • the actual concentration of PDLLA-PEG400-PDLLA/ISO/HDI in ISO-PUs can be calculated. Ratio, the calculation results are shown in Table 1.
  • the M w and PDI of ISO-PUs obtained from the GPC test ( Figure 5) are also listed in Table 1.
  • the difference between the actual ratio of PDLLA-PEG400-PDLLA/ISO/HDI and the theoretical ratio becomes larger, and the molecular weight of PU becomes lower. This is caused by the difference in reactivity of the coupling agent.
  • Example 2 Porous polymer film with regular pores and high mechanical properties
  • the shape memory polyurethane material of Example 1 is prepared into a porous polymer film with regular pores and high mechanical properties through the following method:
  • porous film with a regular hexagonal pore structure can be obtained.
  • the pore size of the porous film can be adjusted by controlling the evaporation rate. The faster the evaporation rate of the solution, the smaller the pore size, and vice versa. Using this principle, porous films with different pore sizes were prepared at 10 ⁇ L/min and 40 ⁇ L/min respectively.
  • the R group of PPZ-PU is:
  • the R group of Upy-PU is:
  • PPZ-PU or Upy-PU was purified twice using a methylene chloride/absolute ethanol co-precipitation system, and then dried for later use.
  • the reaction was continued for 14 hours; after the reaction, the product was purified three times using a dichloromethane/normal temperature anhydrous ethanol co-precipitation system, and vacuum dried at room temperature for 72 hours to obtain the target product PDLLA for later use.
  • This comparative example uses a method similar to Example 2 to prepare ISO-PUs non-porous control film.
  • the difference between this comparative example and Example 2 is that the humidity is set to 30%, and the air flow rate is adjusted to make the evaporation rate 20 ⁇ L/min.
  • the samples used in this experimental example are the ISO-PUs porous polymer film prepared in Example 2, the PPZ-PU, Upy-PU and PDLLA honeycomb porous films prepared in Comparative Example 1, and the ISO-PUs non-porous control prepared in Comparative Example 2. film.
  • SEM test Remove the completely dry porous film sample from the cover glass, and conduct SEM test on the film surface using a JSM-7800F scanning electron microscope (JEOL Corporation). Before testing, the sample needs to be sprayed with gold, the thickness is about 0.5nm, and the test voltage is 8KV. At the same time, X-ray electron spectroscopy (EDS) was used to image the C, O, and N elements of the sample.
  • EDS X-ray electron spectroscopy
  • Two-dimensional wide-angle X-ray diffraction (2D-WAXD) test Two-dimensional wide-angle X-ray diffraction (2D-WAXD) analysis was performed on the film at the BL16B1 beamline station of the Shanghai Synchrotron Radiation Facility (SSRF). The distance between the sample and the detector is 30mm, the diffraction pattern is collected by a Pilatus300K detector with a resolution of 487 ⁇ 619 pixels, and the test time is 45s.
  • SSRF Synchrotron Radiation Facility
  • FT-IR test The Fourier transform infrared (FT-IR) spectrum of the film sample was collected using an IRTracer-100 attenuated reflection FT-IR spectrometer (Shimadzu, Japan). Each sample was scanned 16 times with a resolution of 4cm -1 , and the spectrum of the sample was recorded in the range of 4000 to 700cm -1 . After the test is completed, OriginPro 9.0 software is used to perform peak splitting and integration on the spectrum.
  • Figure 1 shows the macroscopic morphology comparison photos of ISO-PUs porous film and non-porous control film.
  • the porous film ( Figure 6(a)) is visually translucent except for the edge area where the solution evaporates too quickly and does not form a complete porous structure. Most areas are white and opaque. All subsequent testing of porous membranes was performed on visually white opaque areas.
  • the ISO-PUs nonporous film ( Figure 6(b)) is colorless and transparent, which indicates that there is no phase separation structure in the nonporous control film or that the phase separation structure does not exceed the nanometer scale.
  • Figure 7 is a photo of condensed water droplets gathering on the surface of the solution during the preparation of various ISO-PUs films (the solvent evaporation rate is about 20 ⁇ L/min). It can be observed that condensed water droplets (similar to white particles) are regularly arranged in most areas. The water droplets are regular hexagons and have clear boundaries between individual water droplets. This part of the area appears as a single-layer regular hexagonal hole area in the SEM test ( Figure 8(a)) after the solvent and water are completely evaporated. In a small area, the droplets are connected and overlap with each other, and finally the solvent and water are completely evaporated to form a multi-layered hole area (Figure 8(a)).
  • Figure 3 is a morphology picture obtained by SEM test after the honeycomb porous film is completely dried. The size of the holes is very uniform, and the diameter of each regular hexagonal hole is about 4.0 ⁇ m ( Figure 8 (b)).
  • Example 2 by adjusting the air flow rate so that the solvent evaporation rate was 10 ⁇ l/min and 40 ⁇ l/min respectively, ISO-PUs porous films with pore diameters of ⁇ 1.5 ⁇ m and ⁇ 7.0 ⁇ m were obtained.
  • the optical microscope morphology of these two films And the microscopic morphology under crossed polarizers is shown in Figure 10.
  • the optical microscope morphology in Figure 10(a) and (d) is compared with the morphology of the porous film with a pore diameter of approximately 4.0 ⁇ m in Figure 9(a), it can be seen that the pore diameter is related to the size of the multilayer pore formation area. Directly proportional, that is, films with larger pore sizes exhibit larger multilayer pore area.
  • PPZ-PU, Upy-PU and PDLLA porous membranes were respectively prepared by the BF method, in which PPZ-PU and Upy-PU have the same PDLLA-PEG400-PDLLA soft segment molecular chain as ISO-PUs.
  • Figure 11 shows the microscopic morphology of these porous films under an optical microscope and crossed polarizers.
  • the PPZ-PU ( Figure 11(a)) and UPy-PU ( Figure 11(c)) porous films are also honeycomb-shaped, that is, the surface The pores are all regular hexagons, and the diameter of the pores is similar to that of the ISO-PUs porous membrane in Figure 9(a).
  • the pores on the surface of the PDLLA porous membrane are irregular, and the pore size is significantly smaller than PPZ-PU and Upy-PU.
  • the porous films of these three materials showed no crystalline features when viewed under a polarizer ( Figure 11(b), (d) and (f)), i.e., complete darkness in the field of view. Since the only difference between ISO-PUs and PPZ-PU (and Upy-PU) is the presence of repeating units of bicyclic ISO small molecules, it can be speculated that bicyclic ISO small molecules play a crucial role in the formation of similar crystal structures in Figures 9 and 10 important role.
  • the porous film with a pore size of ⁇ 4.0 ⁇ m was tested by two-dimensional wide-angle X-ray diffraction (2D-WAXD) and one-dimensional wide-angle X-ray diffraction (1D-WAXD).
  • 2D-WAXD two-dimensional wide-angle X-ray diffraction
  • 1D-WAXD one-dimensional wide-angle X-ray diffraction
  • the total reflection FT-IR spectra of the ISO-PUs non-porous transparent control film and the honeycomb porous film with a pore size of ⁇ 4.0 ⁇ m are shown in Figure 14(a).
  • the fitting peak splitting results of the FT-IR spectrum in the 3260-3460cm -1 region are shown in Figure 14(b).
  • the free -NH groups in the two films appear at 3408cm -1 , but they form an ordered and disordered hydrogen bonding - the position of the NH group is different.
  • the absorption peak of the disordered hydrogen bond-NH group appears at 3357 cm -1
  • the absorption peak of the ordered hydrogen bond-NH group appears at 3323 cm -1 .
  • the absorption peaks of disordered and ordered hydrogen bonds formed in the porous film -NH groups appear at lower wavenumbers than the corresponding -NH groups in the control film, and they shift to 3350 cm -1 and 3315 cm -1 respectively.
  • the peak integrated areas corresponding to different states of -NH groups in the two sample curves obtained by peak split fitting are shown in Table 2.
  • the peak integrated areas corresponding to the ordered and disordered hydrogen bonded -NH groups in the porous membrane are much larger.
  • the peak area corresponding to the free -NH group is much smaller than that of the control film. This shows that the orientation of the molecular chains in the ISO-PUs porous film is significantly stronger than that of the control film.
  • the characterization results of this experimental example show that the combination of the shape memory polyurethane material provided by the present invention and the water drop template method can prepare a porous polymer film containing an ordered crystal structure.
  • the samples used in this experimental example are the ISO-PUs porous polymer film prepared in Example 2 and the ISO-PUs non-porous control film prepared in Comparative Example 2.
  • the mechanical properties of the samples were tested on an ElectroPuls TM E1000 testing instrument (Instron, USA) equipped with an optical extensometer at a loading speed of 5.0mm/min.
  • the sample is a strip film (approximately 32 ⁇ m thick, 10 mm wide, 50 mm total length, 25 mm gauge length).
  • the final result is the average of 5 repetitions.
  • the tensile strength of the film is 21.5 ⁇ 4.1MPa and 16.3 ⁇ 1.8MPa respectively; the Young's modulus is 942.9 ⁇ 111.7MPa and 759.9 ⁇ 99.7MPa respectively; the elongation at break is 31.6 ⁇ 3.2% and 11.4 ⁇ 2.7% respectively.
  • the porous polymer film prepared by the present invention has significantly improved mechanical properties.
  • the porous polymer film of the present invention has reached the level of artificial periosteum (tensile strength 3-4MPa, elongation at break 19.6-34.8%, from Biomech., 2003, 18: 760-764 ) and anti-adhesion film (Young's modulus 131.4MPa, tensile strength 9.5MPa, elongation at break 630%, Materials Science and Engineering: C, 2020, 117: 111283) mechanical property requirements.
  • the samples used in this experimental example are the ISO-PUs porous polymer film prepared in Example 2 and the ISO-PUs non-porous control film prepared in Comparative Example 2.
  • ISO-PUs porous films and nonporous control films were vacuum dried at 40°C for 7 days to completely remove chloroform. Both sides of the sample were irradiated with ultraviolet light for 30 minutes and then placed in a 24-well plate (with the material membrane side facing up). Rat bone marrow mesenchymal stem cells (rMSCs) were inoculated at a cell density of 0.6 ⁇ 104 cells/cm2. After co-culture for 24 h in high-glucose medium supplemented with 10% fetal calf serum and 1% penicillin-streptomycin, the medium was aspirated from the 24-well plate and washed three times with PBS. Then, they were fixed with immunostaining fixative for 2 hours at room temperature.
  • rMSCs Rat bone marrow mesenchymal stem cells
  • the nuclei and skeleton were stained with H33258 and phalloidin respectively, and then the morphology of rMSCs was observed using a TCS SP8 laser confocal microscope.
  • the aspect ratio and spreading area of rMSCs were statistically analyzed using ImageJ software.
  • the culture medium was aspirated from the 24-well plate and washed three times with PBS; then fixed with immunostaining fixative for 2 hours at room temperature; then stained with an alkaline phosphatase (ALP) staining kit for 2 hours at room temperature; finally, An optical microscope (MP41, Minmei Optoelectronics) with a camera attached was used to observe and record the staining of the samples.
  • ALP alkaline phosphatase
  • FIG. 16 The cell morphology of rMSCs cultured on ISO-PUs nonporous control film and honeycomb porous film with a pore size of ⁇ 4.0 ⁇ m for 24 h is shown in Figure 16. There are obvious differences in the cell morphology on the surface of the two films. Most of the rMSCs on the surface of the ISO-PUs non-porous control film are triangular or quadrilateral, and a few are round ( Figure 16(a) and (c)), while ISO-PUs is porous. The rMSCs on the surface of the film are almost all elongated quadrilaterals ( Figure 16(b) and (d)), and the cell pseudopods can be clearly seen adhering to the edges of the hexagonal holes.
  • the aspect ratio distribution of rMSCs on the surface of the control film is more concentrated, while the aspect ratio distribution of rMSCs on the surface of the porous film is more dispersed, and the aspect ratio is generally larger than that of rMSCs on the surface of the control film.
  • ALP is an early marker of osteogenesis, which can directly reflect the activity or functional status of osteoblasts. It can be seen from Figure 18 that the cells on the control film and the honeycomb porous film are dark blue after staining, and the cells on the honeycomb porous film are darker in color, that is, the ALP content is higher. Such results showed that rMSCs underwent osteogenic differentiation on both films, but the osteogenic differentiation of rMSCs on the honeycomb porous film was more obvious, and the osteogenic activity was higher after differentiation into osteoblasts.
  • the above results show that compared with the non-porous control film, the ISO-PUs porous film has a better promotion effect on the osteogenic differentiation of rMSCs.
  • the porous polymer film provided by the present invention has application potential as artificial periosteum.
  • the samples used in this experimental example are the ISO-PUs porous polymer film prepared in Example 2 and the ISO-PUs non-porous control film prepared in Comparative Example 2.
  • Mouse embryonic fibroblasts (NIH 3T3) were used as model cells to evaluate the cytocompatibility of ISO-PUs porous anti-adhesion films and non-porous control films.
  • the porous film and the non-porous control film were placed in a vacuum oven to evaporate and remove the organic solvent.
  • the oven temperature was set to 45°C, and the drying time was 72 hours until the organic solvent weight content was less than 0.01%.
  • Figure 19 shows the morphological observation of NIH 3T3 cells 1 and 3 days after inoculation with two films. There was no major difference in cell morphology and number on the two films after 1 day of culture. After 3 days, the number of cells on the porous film was significantly higher than that on the control film. In terms of cell morphology, more cells on the porous film extend pseudopodia to form contact points with the polymer surface, and spread to form a long spindle or triangular shape.
  • Figure 20 shows the absorbance values of NIH 3T3 cells measured by the CCK-8 method on the surface of porous films and control films at different culture times. The size of the absorbance value represents the level of proliferation activity.
  • NIH 3T3 cells proliferated significantly on both groups of materials. During this period, there were significant differences in the cell proliferation activity of the two groups of materials at different time points, including 1 day, 5 days, 7 There is a very significant difference between days (p ⁇ 0.01).
  • the present invention designs a new shape memory polyurethane material, and combines this shape memory polyurethane material with the water drop template method to form a porous polymer film containing a crystal structure.
  • This porous film material has excellent mechanical properties and can meet the performance requirements of application scenarios such as artificial periosteum and anti-adhesive membranes, and has good application prospects.

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Abstract

本发明属于聚合物材料技术领域，具体涉及一种形状记忆聚氨酯材料及其制成的自增强规则孔隙聚合物薄膜。本发明的形状记忆聚氨酯是由二异氰酸酯、软段聚合物和（aa）聚合而成的；所述软段聚合物是聚乳酸、聚乙醇酸、聚己内酯、聚多元醇或它们当中至少两种的共聚物。将这种形状记忆聚氨酯材料与水滴模板法结合，能够形成包含晶体结构的多孔聚合物薄膜。这种多孔薄膜材料具有优异的力学性能，能够满足人工骨膜和防粘连膜等应用场景的性能需求，具有很好的应用前景。

Description

一种形状记忆聚氨酯及其制成的自增强规则孔隙聚合物薄膜 技术领域
本发明属于聚合物材料技术领域，具体涉及一种形状记忆聚氨酯材料及其制成的自增强规则孔隙聚合物薄膜。
背景技术
形状记忆聚合物(Shape Memory Polymer，简称SMP)，又称为形状记忆高分子，是指具有初始形状的制品在一定的条件下改变其初始条件并固定后，通过外界条件(如热、电、光、化学感应等)的刺激又可恢复其初始形状的高分子材料。形状记忆聚合物由于其形状回复的特性，在生物医学、航空航天、光学和纺织物等领域有着广泛的应用。
形状记忆聚合物根据其回复原理包括热致型、电致型、光致型、化学感应型等。其中热致型形状记忆聚合物可通过控制其玻璃化温度，将其回复温度调整到与体温一致，从而实现在医学中的应用。例如：可以将热致型形状记忆聚合物材料制成的膜或特定形状的器件小型化和变形后，通过微导管植入体内，到达正确位置后，恢复其原始设定形状。
热致型形状记忆聚合物包括聚氨酯、乙烯/醋酸乙烯共聚物和交联聚乙烯等多种类别。而将这些材料用于制备植入人体的膜或器件时，需要根据其植入的部位和目的需要满足透过性、生物相容性和力学性能等一系列的性能要求。而这些现有的热致型形状记忆聚合物材料制成普通的致密的膜并不能够满足这些透过性能和生物相容性的要求。为了改善该问题，具有规则孔隙的多孔聚合物薄膜由于其独特的性能特点(如：对分子/离子的透过性能、生物相容性和延展性能等等)，而具有作为植入人体的膜的潜力。
然而，现有的热致型形状记忆聚合物材料在引入大量孔隙制成多孔膜的过程中，会导致力学性能不足的问题。例如，“CN201110224930.1一种聚氨酯多孔膜的成形方法”提供了一种利用水滴模板法制备聚氨酯多孔膜的方法。然而，由于力学性能的限制，这些聚氨酯类材料制成的多孔聚合物薄膜仍然难以应用于仿生、组织工程等对材料力学性能有较高要求的领域。这对多孔聚合物薄膜的开发和应用造成了较大的限制，而设计制备兼具良好力学性能和规则多孔结构的聚合物薄膜则有助于拓展这类材料的应用。聚合物分子的有序排列、晶体或微相分离都有助于增强材料力学性能，然而，根据现有理 论并不能推导出理想的形状记忆聚合物材料的种类和结构，是目前亟待解决的问题。
发明内容
针对现有技术的缺陷，本发明提供一种形状记忆聚氨酯材料及其制成的自增强规则孔隙聚合物薄膜，目的在于提供一种兼具力学性能的具有规则孔隙的多孔聚合物薄膜。
一种形状记忆聚氨酯，它是玻璃化转变温度37～45℃的无定型聚合物或熔点为37～45℃的半结晶型聚合物，它由二异氰酸酯、软段聚合物和
Figure PCTCN2022116391-appb-000001
按照摩尔比1.2-8：1：0.2-7聚合而成的线性聚合物，其分子量为30000-150000；
所述软段聚合物是聚乳酸、聚乙醇酸、聚己内酯、聚多元醇或其中两种及以上的共聚物。
优选的，二异氰酸酯、软段聚合物和
Figure PCTCN2022116391-appb-000002
的摩尔比为2.78:1:1.80。
优选的，它的结构式如式Ⅰ所示：
Figure PCTCN2022116391-appb-000003
其中，x选自1-10，y选自1-10；
Figure PCTCN2022116391-appb-000004
为所述软段聚合物的重复单元；
Figure PCTCN2022116391-appb-000005
为二异氰酸酯的重复单元，或二异氰酸酯与
Figure PCTCN2022116391-appb-000006
的共聚物的重复单元。
优选的，所述软段聚合物为乳酸和多元醇的聚合物。
优选的，所述软段聚合物的结构式如式Ⅱ所示：
Figure PCTCN2022116391-appb-000007
其中，m、n分别独立选自4-50，r选自1-20。
优选的，所述二异氰酸酯选自脂肪族二异氰酸酯或芳香族二异氰酸酯，所述脂肪族二异氰酸酯选自六亚甲基二异氰酸酯、赖氨酸二异氰酸酯、异佛尔酮二异氰酸酯、二环己基甲烷二异氰酸酯或其中两种及以上的混合物，所述芳香族二异氰酸酯选自甲苯二异氰酸酯、二苯基甲烷二异氰酸酯或其中两种及以上的混合物。
本发明还提供一种具有规则孔隙的高力学性能多孔聚合物薄膜，它是以上述形状记忆聚氨酯为原料，采用水滴模板法制备而成的。
优选的，所述水滴模板法的参数选择为：环境温度4-50℃，湿度25-80％，使溶剂的挥发速率为5-50μL/min。
本发明还提供上述多孔聚合物薄膜的制备方法，包括如下步骤：
步骤1，将上述形状记忆聚氨酯溶解在挥发性溶剂中，得到聚氨酯溶液；
步骤2，将所述聚氨酯溶液涂覆在基底表面，于潮湿空气中挥干，即得。
优选的，步骤1中，所述挥发性溶剂选自三氯甲烷、二氯甲烷、四氢呋喃、二硫化碳或其中两种及以上的混合物；
和/或，所述聚氨酯溶液的浓度为5-200mg/mL；
和/或，步骤2中，涂覆有聚氨酯溶液的基底在环境温度4-50℃，湿度25-80％的条件下干燥，溶剂的挥发速率为5-50μL/min。
本发明还提供上述形状记忆聚氨酯用于制备高力学性能的具有规则孔隙的多孔聚合物薄膜的用途，所述形状记忆聚氨酯制备成所述多孔聚合物薄膜的方法为水滴模板法。
本发明还提供上述具有规则孔隙的多孔聚合物薄膜用于制备人工骨膜的用途。
本发明还提供一种人工骨膜，它是用上述具有规则孔隙的多孔聚合物薄膜制成的。
本发明还提供上述具有规则孔隙的多孔聚合物薄膜用于制备防粘连膜的用途。
本发明还提供一种防粘连膜，它是用上述具有规则孔隙的多孔聚合物薄膜制成的。
本发明设计了一种新的形状记忆聚氨酯材料，将这种形状记忆聚氨酯材料利用水滴模板法制成具有规则孔隙的多孔聚合物薄膜后，薄膜材料的微观结构体现出一定的晶体特征。这表明该多孔聚合物薄膜中分子链的排列更加有序，硬段组装更好，这使得制成的多孔聚合物薄膜具有良好的力学性能。相比于同类多孔聚合物薄膜，本发明提供的高力学性能多孔聚合物薄膜在人工骨膜和防粘连膜等对薄膜力学性能有较高要求的领域具有很好的应用前景。
显然，根据本发明的上述内容，按照本领域的普通技术知识和惯用手段，在不脱离本发明上述基本技术思想前提下，还可以做出其它多种形式的修改、替换或变更。
以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。凡基于本发明上述内容所实现的技术均属于本发明的范围。
附图说明
图1为实施例1中两种偶联剂的 1H NMR谱图；
图2为实施例1中两种偶联剂的FT-IR谱图；
图3为实施例1中PDLLA-PEG400-PDLLA大分子二醇和ISO-PUs的FT-IR谱图(右边谱图是左边谱图矩形标记部分的放大)；
图4为实施例1中PDLLA-PEG400-PDLLA和ISO-PUs的 1H NMR谱图；
图5为实施例1中ISO-PUs的GPC曲线；
图6为ISO-PUs多孔薄膜(a)和无孔对照膜(b)的宏观形貌(厚度＝0.032±0.011mm)；
图7为多孔薄膜形成过程中水滴凝聚在ISO-PUs溶液表面的光学显微镜图像；
图8为ISO-PUs多孔膜干燥后的SEM图像，(b)是(a)中相红色区域的放大；
图9为ISO-PUs多孔膜的光学显微镜图像(a)和交叉偏振器下的光学显微 镜图像(b-d)，(c)和(d)是(b)中红色区域的放大；
图10为以速率10μl/min((a)和(b))和40μl/min((d)和(e))制备的ISO-PUs多孔膜的光学显微镜图像和交叉偏振镜下的显微镜图像((c)和(f)分别为(b)和(e)中红色区域的放大图)；
图11为PPZ-PU(a和b)、Upy-PU(c和d)和PDLLA(e和f)多孔膜光学显微镜和交叉偏振镜下的显微形貌；
图12为ISO-PUs无孔对照薄膜和ISO-PUs多孔膜的DSC曲线((a)为第一次加热循环曲线，(b)为降温和第二次加热曲线)；
图13为ISO-PUs无孔对照薄膜(a)和ISO-PUs多孔薄膜(b)的2D-WAXD衍射图案，以及ISO-PUs无孔对照薄膜(c)和ISO-PUs多孔薄膜(d)的1D-WAXD曲线；
图14为ISO-PUs对照薄膜和多孔膜的FT-IR谱图(a)和3260-3460cm -1区域的拟合分峰曲线(b)；
图15为ISO-PUs多孔膜和无孔透明的对照膜在25℃下的拉伸应力-应变曲线(a)和力学性能(b)；
图16为rMSCs在ISO-PUs无孔对照薄膜(a和c)和多孔薄膜(b和d)上培养24h后的细胞形态；
图17为rMSCs在ISO-PUs无孔对照薄膜和多孔薄膜上培养24h后细胞的铺展面积和长径比分布；
图18为rMSCs在ISO-PUs无孔对照薄膜和多孔薄膜上培养14天后的碱性磷酸酶(ALP)染色实验结果；
图19为ISO-PUs多孔防粘连薄膜和无孔对照薄膜进行细胞相容性实验形态观察结果；
图20为ISO-PUs多孔防粘连薄膜和无孔对照薄膜进行细胞相容性实验中，不同培养时间的NIH 3T3细胞经过CCK-8法测定的吸光值(*表示p<0.05，**表示p<0.01)。
具体实施方式
以下实施例和实验例中未特别说明的试剂和材料均为市售品。
实施例1形状记忆聚氨酯
本实施例提供一种形状记忆聚氨酯材料。其制备方法如下：
1、PDLLA-PEG400-PDLLA大分子二醇的合成与纯化
Figure PCTCN2022116391-appb-000008
将D,L-丙交酯(D,L-Lactide，熔点:118℃，纯度：99.9％)、PEG400(阿拉丁、CAS号：25322-68-3、货号：P103723)、Sn(Oct) 2(Sigma-Aldrich、CAS号：301-10-0、货号：S3252)按摩尔比5000:100:1的比例加入放有磁力搅拌子的圆底烧瓶，抽真空30min后密封；将单口瓶放入140℃油浴锅中，待混合物完全融化后开启磁力搅拌将反应体系搅拌均匀，持续反应24h；反应结束后采用二氯甲烷/冰无水乙醇(-15℃)共沉淀体系重复纯化产物三次，再以二氯甲烷/冰正己烷(-15℃)共沉淀体系纯化一次；室温下真空干燥72h，即得到目标产物PDLLA-PEG400-PDLLA大分子二醇(结构式中m＝46、n＝46和r＝10)，备用。
2、HDI封端ISO的新型二异氰酸酯的合成与纯化
Figure PCTCN2022116391-appb-000009
将HDI(阿拉丁、CAS号：822-06-0、货号：H106723)和ISO
(
Figure PCTCN2022116391-appb-000010
Sigma-Aldrich、CAS号：652-67-5、货号：I157515)分别以摩尔比4:1的比例加入不同的圆底单口烧瓶，同时放入磁力搅拌子，以m(ISO，g)：V(DMF,mL)＝1:6的比例加在两个单口瓶中入无水级DMF， 磁力搅拌使ISO完全溶解；再以ISO与Sn(Oct) 2摩尔比500:1的比例加入Sn(Oct) 2，氮气置换三次后在氮气保护下75℃反应1h；待反应结束后冷却至室温，用分子筛干燥过的正己烷置出未反应的HDI，得到白色粉末干燥至恒重即为HDI封端ISO的新型二异氰酸酯偶联剂(本实施例中结构式中z的值为z＝0)，备用。
3、ISO-PUs的合成与纯化
Figure PCTCN2022116391-appb-000011
其中，OCN-DI`-NCO为上述步骤2合成的新型二异氰酸酯。其中，y的取值为y＝5。
将OCN-DI`-NCO和PDLLA-PEG400-PDLLA(大分子二醇)以摩尔比1.5:1.0的比例加入配有机械搅拌和温度计的圆底四口烧瓶，同时以m(大分子二醇，g)：V(DMF,mL)＝1.0:0.8的比例加加入无水级DMF，机械搅拌使大分子二醇完全溶解；接着以大分子二醇与Sn(Oct) 2摩尔比500:1的比例加入Sn(Oct) 2，在氮气保护下75℃反应6h(每2h向反应体系中加入初始体积20vol％的无水级DMF，以降低体系粘度)；再以ISO与大分子二醇摩尔比0.5:1.0的比例加入ISO，继续在氮气保护下75℃反应12h(每4h向反应体系中加入初始体积20vol％的无水级DMF，以降低体系粘度)。待反应结束后冷却至室温，将反应体系倒入常温无水乙醇中沉淀，析出白色固体即为ISO-PUs。最后，以二氯甲烷/无水乙醇共沉淀体系将ISO-PUs纯化两次，烘干备用。经测定ISO-Pus的玻璃化温度为42℃。
4、结构表征
4.1偶联剂结构表征
图1(a)和(b)分别是HDI和ISO以4:1和2:1反应所获得的样品HDI封端ISO的新型二异氰酸酯核磁氢谱( 1H NMR)谱图，两条谱线上的质子吸收峰 位置一致，但强度有较大差异。其中，σ＝3.98～4.29(H-1、H-6)、σ＝4.78(H-3)、σ＝5.12(H-4)和σ＝5.28～5.32(H-2,H-5)处的峰是ISO中的质子吸收峰；σ＝1.30～1.48(H-c',H-c),σ＝1.58～1.72(H-b',H-b)和σ＝3.14～3.29(H-a',H-a)处的峰属于HDI中的亚甲基质子吸收峰；两种产物的 1H NMR谱图中都未出现未反应的ISO环上的质子吸收峰，表明ISO被HDI完全封端。根据理论分子式(HDI-ISO(-HDI-ISO) z-HDI)可以看出，两种偶联剂中HDI与ISO的摩尔比可由H-a',a和峰H-3的积分面积计算得出，计算式如式(4-1)所示：
HDI/ISO＝I H-a′+a/(I H-3×4)    (4-1)
对于图1(a)，HDI/ISO接近于2(7.74/(1.00×4)≈2)，表明HDI和ISO以4:1反应得到的是HDI-ISO-HDI。而图1(b)中HDI/ISO接近1.5(6.37/(1.00×4)≈1.5)，表明HDI和ISO以2:1反应得到的是HDI-ISO-HDI-ISO-HDI。
此外，在两种偶联剂的FT-IR谱图中(图2)可以清楚地观察到在2273cm -1出现了-NCO基团的吸收峰，以及在1698cm -1出现了氨基甲酸酯键中-C＝O基团的吸收峰。并且HDI-ISO-HDI-ISO-HDI谱图中的1698cm -1与2273cm -1处的峰面积明显大于HDI-ISO-HDI谱图中的两处峰面积比。这些都进一步证明了新型二异氰酸酯HDI-ISO-HDI和HDI-ISO-HDI-ISO-HDI的成功合成。
4.2ISO-PUs结构表征
将由HDI作为偶联剂合成的样品命名为ISO1-PU，而由HDI-ISO-HDI和HDI-ISO-HDI-ISO-HDI作为偶联剂合成的样品分别命名为ISO2-PU和ISO3-PU。PDLLA-PEG400-PDLLA和ISO-PUs的FT-IR谱图如图3所示。PDLLA-PEG400-PDLLA曲线中，1751cm -1处的吸收峰为PDLLA-PEG400-PDLLA中酯-C＝O吸收峰。在所有ISO-PUs谱图中都没有观察到在2273cm -1处出现的-NCO吸收峰，并且与PDLLA-PEG400-PDLLA的谱图相比出现了一些新的峰。即3300-3400cm -1、～1621cm -1和～1529cm -1处分别属于氨基甲酸酯键中-NH、酰胺I带(-C＝O)和酰胺II带(-NH)的伸缩振动吸收峰。总之，这些吸收峰的出现都证明ISO-PUs已成功合成。
为了进一步探索ISO-PUs的分子结构，也对PDLLA-PEG400-PDLLA和ISO-PUs进行了 1H NMR测试，获得的谱图如图4所示。在PDLLA-PEG400-PDLLA的 1H NMR中谱，σ＝1.57ppm(H-B)和σ＝1.48ppm(H-B')处的峰分别属于大分子二醇内乳酰单元的-CH 3和大分子醇末端乳酸残基中-CH 3质子吸收峰；σ＝3.64ppm(H-D)处的峰来自PEG400内的-CH 2质子吸收峰；峰σ＝5.16ppm(H-A)为大分子二醇内乳酰单元上的-CH质子吸收峰；σ＝4.23～4.46ppm(H-A',H-C)处的峰是大分子醇末端乳酸残基上与-OH相连的-CH和PEG400中与PDLLA嵌段相邻的-CH 2的质子吸收峰。利用峰σ＝5.16 ppm(I H-A＝17.08)和σ＝4.23～4.36ppm(I H-A'+C＝1.00)的积分值和式(4-2)，计算出所用的PDLLA-PEG400-PDLLA的分子量(M n)为7700。
Figure PCTCN2022116391-appb-000012
三种ISO-Pus它们的 1H NMR中谱σ＝4.36～4.46ppm和σ＝1.48ppm处PDLLA-PEG400-PDLLA末端乳酸残基上与-OH相连的-CH和-CH3(H-A',H-B')质子吸收峰几乎完全消失，并且在σ＝3.14ppm、σ＝1.38ppm和σ＝1.28ppm出现了属于HDI的H-a'、H-b'和H-c'的质子吸收峰。此外，ISO环上(H-1～H-6)的质子特征峰在ISO2-PU和ISO3-PU的谱图中很明显，而在ISO1-PU的谱图中由于ISO含量低而不能被观察到。以σ＝3.64ppm处归属于PDLLA-PEG400-PDLLA中H-D的质子吸收峰作为内标(I H-D＝1.00)，同时以H-3峰的积分面积(I H-3)或H-4峰的积分面积(I H-4)代表ISO的含量，以H-a'峰的积分值(I H-a')代表HDI的含量，可以计算出ISO-PUs中PDLLA-PEG400-PDLLA/ISO/HDI的实际比率，计算结果如表1所示。同时由GPC测试(图5)得出的ISO-PUs的M w和PDI也在表1列出。随着偶联剂分子长度增加，PDLLA-PEG400-PDLLA/ISO/HDI的实际比例与理论比例差异越大，同时PU的分子量越低，这是由偶联剂的反应活性差异造成的。
表1三种ISO-PUs的组成比例和分子量数据
Figure PCTCN2022116391-appb-000013
以上测试结果表明ISO-PUs已被成功合成，且它们的分子结构与理论结构一直。
实施例2具有规则孔隙的高力学性能多孔聚合物薄膜
本实施例通过如下方法将实施例1的形状记忆聚氨酯材料制备成具有规则孔隙的高力学性能多孔聚合物薄膜：
称取实施例1制备的ISO-PUs(ISO2-PU,M w＝61kDa,PDI＝1.57)，在烧杯中用三氯甲烷完全溶解后用容量瓶定容，配置成50mg/mL的溶液。盖玻片经过三次二蒸水洗，两次无水乙醇洗后晾干。将盖玻片置于环境温度28℃，湿度70％的通风橱内水平实验台上，用移液枪取约200μL的ISO-PUs 溶液均匀的涂在盖玻片表面，同时调节空气流速使挥发速率约为20μL/min。待溶剂完全挥发后即可获得具有规整六边形孔结构的多孔薄膜。通过控制挥发速率可调节多孔薄膜的孔径，溶液的挥发速率越快孔径越小，反之越大。利用该原理分别以10μL/min和40μL/min制备出不同孔径的多孔薄膜。
对比例1PPZ-PU、Upy-PU和PDLLA蜂窝状多孔薄膜
本对比例按照实施例2的方法，将PPZ-PU(M w＝80kDa,PDI＝1.66)、Upy-PU(M w＝25kDa,PDI＝2.12)和PDLLA(M w＝75kDa,PDI＝1.35)制成蜂窝状多孔薄膜。其中，PPZ-PU和Upy-PU的合成过程如下：
Figure PCTCN2022116391-appb-000014
其中，PPZ-PU的R基团为：
Figure PCTCN2022116391-appb-000015
Upy-PU的R基团为：
Figure PCTCN2022116391-appb-000016
将HDI和PDLLA-PEG400-PDLLA(大分子二醇)以摩尔比1.5:1.0的比例加入配有机械搅拌和温度计的圆底四口烧瓶，同时以m(大分子二醇，g)：V(DMF,mL)＝1.0:4.0的比例加加入无水级甲苯(Tol)，机械搅拌使大分子二醇完全溶解；接着以大分子二醇与Sn(Oct) 2摩尔比500:1的比例加入Sn(Oct) 2，在氮气保护下75℃反应3h；再以PPZ或Upy与大分子二醇摩尔比0.5:1.0的比例加入PPZ或Upy，继续在氮气保护下75℃反应6h。待反应结束后冷却至室温，将反应体系倒入常温无水乙醇中沉淀，析出白色固体即为PPZ-PU或Upy-PU。最后，以二氯甲烷/无水乙醇共沉淀体系将PPZ-PU或Upy-PU纯化两次，烘干备用。
PDLLA的合成过程如下：
Figure PCTCN2022116391-appb-000017
将D,L-丙交酯(D,L-Lactide，熔点:118℃，纯度：99.9％)，Sn(Oct) 2(Sigma-Aldrich、CAS号：301-10-0、货号：S3252)按摩尔比5000:1的比例加入放有磁力搅拌子的圆底烧瓶，抽真空30min后密封；将单口瓶放入140℃油浴锅中，待混合物完全融化后开启磁力搅拌将反应体系搅拌均匀，持续反应14h；反应结束后采用二氯甲烷/常温无水乙醇共沉淀体系重复纯化产 物三次，室温下真空干燥72h，即得到目标产物PDLLA，备用。
对比例2ISO-PUs无孔对照薄膜
本对比例采用与实施例2相似的方法制备ISO-PUs无孔对照薄膜，本对比例与实施例2的区别在于：湿度设置为30％，调整空气流速使挥发速率为20μL/min。
下面通过实验对本发明的有益效果作进一步说明。
实验例1结构表征
本实验例所用的样品为实施例2制备的ISO-PUs多孔聚合物薄膜、对比例1制备的PPZ-PU、Upy-PU和PDLLA蜂窝状多孔薄膜和对比例2制备的ISO-PUs无孔对照薄膜。
一、实验方法
①偏光显微镜测试：待盖玻片上的多孔薄膜完全干燥后，将玻片置于MP41型偏光显微镜(明美光电)载物台上，用高倍镜头(20-50倍)透射模式下分别观察多孔薄膜在普通透射光和相应位置正交偏光下的形貌，并用数码相机记录。
②扫描电镜测试(SEM)测试：将完全干燥的多孔薄膜样品从盖玻片上取下，利用JSM-7800F型扫描电子显微镜(日本电子株式会社)对薄膜表面进行SEM测试。测试前需对样品喷金，厚度约0.5nm，测试电压8KV。同时利用x射线电子能谱(EDS)对样品的C、O和N元素成像。
③一维广角X射线衍射(1D-WAXD)测试：利用Panalytic-Empyrean高分辨X射线衍射仪(马尔文帕纳科，荷兰)对薄膜样品进行1D-WAXD测试，Cu靶，扫描速率2θ＝1°/min，扫描范围5°-35°。
④二维广角X射线衍射(2D-WAXD)测试：在上海同步辐射装置(SSRF)的BL16B1光束线站上对薄膜进行了二维广角x射线衍射(2D-WAXD)分析。样品与检测器的距离为30mm，衍射图案由分辨率为487×619像素的Pilatus300K探测器采集，测试时间为45s。
⑤FT-IR测试：利用IRTracer-100型衰减反射FT-IR光谱仪(岛津，日本)采集了薄膜样品的傅里叶变换红外(FT-IR)光谱。每个样品扫描16次，分辨率为4cm -1，记录样品在4000～700cm -1范围内光谱。测试完成后使用OriginPro 9.0软件对光谱进行分峰和积分。
⑥DSC测试：采用DSC 200F3型(Netzsch，德国)差示扫描量热仪(DSC)在N 2气氛下，以升温(降温)速率为10℃/min进行测试。样品先从-10℃加热到150℃，然后冷却到-10℃，最后再次加热到150℃。第一次升温、降 温和第二次升温循环数据都被记录。
二、实验结果
1、ISO-PUs多孔薄膜宏观形貌
图1为ISO-PUs多孔薄膜和无孔对照薄膜的宏观形貌对比照片。多孔膜(图6(a))在视觉上除了边缘区域因溶液挥发过快，未形成完整的多孔结构而呈半透明，绝大部分区域是白色且不透明的。所有后续多孔膜的测试均针对视觉白色不透明区域进行。而作为对照的ISO-PUs无孔薄膜(图6(b))呈现无色透明，这表明该无孔对照薄膜中不存在相分离结构或相分离结构不超过纳米尺度。
2、ISO-PUs多孔薄膜微观形貌
图7是ISO-PUs多种薄膜制备过程中冷凝的水滴聚集在溶液表面的照片(溶剂挥发率约为20μL/min)。可以观察到凝聚的水滴(类似白色颗粒)规整的排列在大部分区域，水滴呈正六边形且单个水滴之间具有明显的边界。这部分区域在溶剂和水完全蒸发后的SEM测试(图8(a))中呈现为单层正六边形孔区域。而在少部分区域，液滴之间相互连接并重叠，最后溶剂和水完全蒸发呈现为多层孔区域(图8(a))。图3是蜂窝状多孔薄膜完整干燥后的SEM测试获得的形貌图片，孔的尺寸非常均匀，每个正六边形孔直径约为4.0μm(图8(b))。
当使用显微镜在透射模式下观察多孔膜时，由于透光率的差异，单层孔视觉上为白色，而多层孔在视觉上为红色(图9(a))。当在交叉偏振器下进一步观察时(图9(b))，在单层区域可以观察到一种奇特的图像，四条对称分布在六边形两侧的棱边显示出类似晶体的特征，而位于这四条棱边之间的其余两条棱边则没有显示出晶体特征，即视觉上完全黑暗。同时，这些具有晶体特征的棱边具有区域取向性，而这些不同取向区域的边界正是多层孔区域。将这些区域进一步放大观察可以看出每条具有晶体特征的棱边都呈“Z”字形，且同一取向区域中相邻的两条结晶棱边没有紧密相连，它们之间存在约0.3-0.5μm的间隔(图9(c)和(d))。
此外，实施例2通过调节空气流速使溶剂挥发速率分别为10μl/min和40μl/min，获得了孔径为～1.5μm和～7.0μm的ISO-PUs多孔薄膜，这两种薄膜的光学显微镜形貌和交叉偏振器下的显微镜形貌如图10所示。当图10(a)和(d)中的光学显微镜形貌与图9(a)中的孔径约为4.0μm的多孔薄膜形貌进行比较时，可以看出孔径与多层孔形成区域的大小成正比，即孔径较大的薄膜呈现出更大的多层孔区域面积。交叉偏振器下的这两种直径为～1.5μm和～7.0μm(图10(b)和(e))的六边形孔显示出与图9(b)中的六边形孔相近的类似晶体形态。但由于光学显微镜的分辨率原因，直径为～1.5μm六边形孔棱 边上的“Z”字形晶体形态变得不明显(图10(c))，而直径为～7.0μm的六边形孔棱边上的“Z”字形晶体形态变得更明显(图10(f))。
对比例1还以BF法分别制备了PPZ-PU、Upy-PU和PDLLA多孔膜，其中PPZ-PU和Upy-PU具有与ISO-PUs相同的PDLLA-PEG400-PDLLA软段分子链。图11为这些多孔薄膜在光学显微镜和交叉偏振器下的显微镜形貌，PPZ-PU(图11(a))和UPy-PU(图11(c))多孔膜同样呈蜂窝状，即表面的孔均为正六边形，孔的直径与图9(a)中的ISO-PUs多孔膜相近。而PDLLA多孔膜表面的孔洞呈不规则状，且孔径明显小于PPZ-PU和Upy-PU。重要的是，这三种材料的多孔膜在偏振器下观察时没有显示出晶体特征(图11(b),(d)和(f))，即视野中完全黑暗。由于ISO-PUs与PPZ-PU(以及Upy-PU)的区别仅在于存在双环ISO小分子的重复单元，由此可推测双环ISO小分子对图9和10中类似晶体结构的形成起着至关重要的作用。
3、ISO-PUs多孔薄膜的热性能
为了进一步证实ISO-PUs多孔膜棱边上晶体的存在，对直径为～4.0μm的ISO-PUs多孔膜和ISO-PUs无孔对照薄膜进行了DSC测试。第一次热扫描曲线如图12(a)所示，多孔薄膜的DSC曲线上存在一个典型的晶体熔融峰，熔程为46.5-55.7℃，熔点为51.7℃，熔融焓为9.97J/g，而在对照薄膜的DSC曲线上没有类似的熔融峰。此外，多孔薄膜的玻璃化转变温度为43.1℃，远高于对照膜的31.4℃，这可能是由于晶体对非晶态区域分子链的限制作用，表明两种薄膜中的软段和硬段相分离程度和结构存在差异。
两种薄膜的冷却曲线和二次加热曲线没有明显差异(图12(b))，它们的降温曲线上都没有出现结晶峰，二次加热曲线上也都没有出现晶体熔融峰。此外，降温曲线和二次加热曲线上两种薄膜的玻璃化转变温度基本相同。说明ISO-PUs确实是一种无定形聚合物，多孔膜中的晶体是通过BF法形成的。
4、ISO-PUs多孔薄膜的WAXD分析
为了进一步探测ISO-PUs多孔薄膜中的晶体结构，将孔径为～4.0μm的多孔膜进行了二维广角X射线衍射(2D-WAXD)和一维广角X射线衍射(1D-WAXD)测试。测试时同样用ISO-PUs无孔透明的薄膜作为对照样品，获得的2D-WAXD衍射图案和1D-WAXD曲线如图13所示。ISO-PUs对照薄膜的2D-WAXD衍射图案(图13(a))中只在赤道上出现强烈的衍射斑，相应的1D-WAXD衍射曲线中(图13(c))，除了非晶相的宽衍射峰外在2θ＝9.8°处有一个明显的尖锐衍射峰。这些结果表明，ISO-PUs对照薄膜中的分子链自发组装形成了纳米级且具有超高取向度的结构。然而这种有序纳米结构的含量太少，无法在其DSC曲线中观察到明显的熔融峰(图12(a))。ISO-PUs多孔薄膜的2D-WAXD衍射图案(图13(b))与对照薄膜明显不同，图案中 有5个典型的椭圆衍射环，与1D-WAXD衍射曲线中的5个晶体衍射峰完全对应(图13(d))。这些现象进一步验证了多孔膜中存在典型的晶体结构，并且晶体结构具有一定的取向。
5、ISO-PUs多孔薄膜的FT-IR分析
ISO-PUs无孔透明的对照薄膜和孔径为～4.0μm的蜂窝状多孔薄膜的全反射FT-IR谱图如图14(a)所示。在1528cm -1处可以看到酰胺键中的酰胺II带(-NH基团)、在1590～1870cm -1区域可以观察到大分子二醇中的酯-C＝O基团和酰胺键中的-C＝O基团吸收峰。由于两类-C＝O基团部分重叠，3260-3460cm -1处的-NH基团更适合表征氢键的形成。3260-3460cm -1区域的FT-IR谱图的拟合分峰结果如图14(b)所示，两种薄膜中的游离-NH基团出现在3408cm -1处、但它们形成了有序和无序氢键-NH基团的位置不同。对照薄膜的谱图中，形成了无序氢键-NH基团的吸收峰出现在3357cm -1处，形成了有序氢键-NH基团的吸收峰出现在3323cm -1处。然而，多孔薄膜中形成了无序和有序氢键-NH基团吸收峰出现在比对照薄膜中相应的-NH基团更低波数，它们分别移动到了3350cm -1和3315cm -1处。由分峰拟合得出的两种样品曲线中不同状态-NH基团对应的峰积分面积如表2所示，多孔膜中有序和无序氢键-NH基团对应的峰积分面积远大于对照薄膜，而自由-NH基团对应的峰面积远小于对照薄膜。这表明ISO-PUs多孔薄膜中分子链的取向性明显强于对照薄膜。
表2ISO-PUs对照膜和多孔膜中-NH基团的拟合分峰和积分计算结果
Figure PCTCN2022116391-appb-000018
综上所述，本实验例的各项表征结果表明，本发明提供的形状记忆聚氨酯材料与水滴模板法结合，可制备出一种包含有序晶体结构的多孔聚合物薄膜。
实验例2力学性能表征
本实验例所用的样品为实施例2制备的ISO-PUs多孔聚合物薄膜和对比例2制备的ISO-PUs无孔对照薄膜。
一、实验方法
样品的力学性能测试在配备光学引伸计的ElectroPuls TME1000测试仪器(Instron,美国)上，以5.0mm/min的加载速度进行拉伸力学测试。样品为条状薄膜(厚约32μm，宽10mm，全长50mm，标距25mm)。最终的结果是5次重复的平均值。
二、实验结果
聚合物的相结构对其力学性能有重要影响。因此，本章评估了孔径为～4.0μm的ISO-PUs蜂窝状多孔膜的拉伸力学性能，并同样使用无孔透明的ISO-PUs薄膜作为对照，两种膜的厚度非常接近。得到的应力-应变曲线以及根据应力-应变曲线计算出的力学性能如图15(a)和(b)所示，多孔薄膜显然具有比对照薄膜更好的力学性能，计算得出多孔薄膜与对照薄膜的拉伸强度分别为21.5±4.1MPa和16.3±1.8MPa；杨氏模量分别为942.9±111.7MPa和759.9±99.7MPa；断裂伸长率分别为31.6±3.2％和11.4±2.7％。
可见，相比于厚度接近聚合物原料相同的对照薄膜，本发明制备的多孔聚合物薄膜具有显著提升的力学性能。且根据上述力学性能的表征结果，本发明的多孔聚合物薄膜已经达到了满足人工骨膜(拉伸强度3–4MPa，断裂伸长率19.6-34.8％，出自Biomech.,2003,18:760-764)和防粘连膜(杨氏模量131.4MPa，拉伸强度9.5MPa，断裂伸长率630％，Materials Science and Engineering:C,2020,117:111283)的力学性能要求。
实验例3多孔结构对rMSCs形态和成骨分化的影响
本实验例所用的样品为实施例2制备的ISO-PUs多孔聚合物薄膜和对比例2制备的ISO-PUs无孔对照薄膜。
一、实验方法
ISO-PUs多孔薄膜和无孔对照薄膜在40℃下真空干燥7天以彻底除去三氯甲烷。样品两面分别紫外线照射30min后置于24孔板中(材料膜面朝上)，以0.6×104个/cm2的细胞密度接种大鼠骨髓间充质干细胞(rMSCs)。在补充有10％胎牛血清和1％青霉素-链霉素的高糖培养基中共培养24h后，从24孔板中吸出培养基，用PBS洗涤3次。然后用免疫染色固定液室温下固定2h，经H33258和鬼笔环肽分别对细胞核和骨架染色后用TCS SP8型激光共聚焦显微镜观察rMSCs的形态。rMSCs的长径比和铺展面积利用ImageJ 软件进行统计分析。共培养14天后，从24孔板中吸出培养基，用PBS洗涤3次；然后用免疫染色固定液室温下固定2h；接着利用碱性磷酸酶(ALP)染色试剂盒室温下染色2h；最后用附摄像机的光学显微镜(MP41，明美光电)观察并记录样品的染色情况。
二、实验结果
rMSCs在ISO-PUs无孔对照薄膜和孔径为～4.0μm的蜂窝状多孔薄膜上培养24h后的细胞形态如图16所示。两种薄膜表面的细胞形态存在明显差异，ISO-PUs无孔对照薄膜表面的rMSCs大部分呈三角形或四边形，少部分呈圆形(图16(a)和(c))，而ISO-PUs多孔薄膜表面的rMSCs几乎都是呈细长的四边形(图16(b)和(d))，可以清晰的看到细胞伪足粘附在六边形孔的棱边上。本研究还统计了两种薄膜上rMSCs的铺展面积和长径比分布，获得的分布图如图17所示。图中分别统计了116个ISO-PUs多孔薄膜和105个ISO-PUs无孔对照薄膜表面的rMSCs，总体上两种薄膜上rMSCs的铺展面积相近，只有少数多孔薄膜表面的rMSCs具有远大于对照薄膜表面rMSCs的铺展面积。同时对照薄膜表面的rMSCs长径比分布较为集中，而多孔薄膜表面的rMSCs长径比分布较为分散，且长径比普遍比对照薄膜表面的rMSCs长径比更大。ALP是成骨早期标志物，它可直接反映成骨细胞的活性或功能状况。从图18可以看出经过染色后对照薄膜和蜂窝状多孔薄膜上的细胞都呈深蓝色，且蜂窝状多孔薄膜上的细胞的颜色更深，即ALP含量更高。这样的结果表明，rMSCs在两种薄膜上都进行了成骨分化，但是在蜂窝状多孔薄膜上的rMSCs成骨分化更明显，分化成为成骨细胞后成骨活性更高。
以上结果表明，相比于无孔的对照薄膜，ISO-PUs多孔薄膜对rMSCs的成骨分化具有更好的促进作用。本发明提供的多孔聚合物薄膜具有作为人工骨膜的应用潜力。
实验例4防粘连膜细胞相容性表征
本实验例所用的样品为实施例2制备的ISO-PUs多孔聚合物薄膜和对比例2制备的ISO-PUs无孔对照薄膜。以小鼠胚胎成纤维细胞(NIH 3T3)为模型细胞，对ISO-PUs多孔防粘连薄膜和无孔对照薄膜进行细胞相容性评价。
一、实验方法
细胞实验前将多孔薄膜和无孔对照薄膜置于真空烘箱中蒸发脱除有机溶剂，烘箱温度设置为45℃，干燥时间为72小时，直到有机溶剂重量含量小于0.01％。
将干燥好的多孔防粘连薄膜和无孔对照薄膜紫外灭菌后放入24孔细胞培养板中，然后把NIH 3T3细胞悬液加入24孔板中，密度约为1板中， 4个/孔。最后把24孔板放入孵箱中进行细胞培养，期间每两天更换一次培养液。培养1天和3天后取出样品，经过清洗、固定、染色和封片等步骤后，在倒置荧光显微镜下观察细胞并拍照记录其形态。于接种后4个时间点(1天、3天、5天、7天)取出样品，采用CCK-8法测定各组吸光值，以评价细胞的 增殖活性。
二、实验结果
图19为两种薄膜接种NIH 3T3细胞1天和3天后的形态观察。培养1天后两种薄膜上的细胞形态和数量没有较大差别。3天后，多孔薄膜上的细胞数量明显多于对照薄膜。在细胞形态方面，多孔薄膜上有更多细胞伸出伪足形成与聚合物表面的接触点，发生铺展，形成长梭形或三角形的形态。图20为不同培养时间多孔薄膜和对照薄膜表面的NIH 3T3细胞经过CCK-8法测定的吸光值，吸光值的大小代表了增殖活性的高低。从接种的第1天到第7天，NIH 3T3细胞在两组材料上均增殖明显，这期间在不同时间点两组材料的细胞增殖活性都存在显著性差异，其中1天后、5天后、7天后存在非常显著性差异(p<0.01)。
NIH 3T3细胞的形态和增殖实验结果表明，多孔薄膜表面更有利于细胞粘附、铺展，从而促进细胞增殖。这初步证明了ISO-PUs多孔薄膜具有良好的细胞相容性，适合用于防粘连膜植入后支持组织修复。
通过上述实施例和实验例可以看到，本发明设计了一种新的形状记忆聚氨酯材料，并且将这种形状记忆聚氨酯材料与水滴模板法结合，能够包含晶体结构的多孔聚合物薄膜。这种多孔薄膜材料具有优异的力学性能，能够满足人工骨膜和防粘连膜等应用场景的性能需求，具有很好的应用前景。

Claims (14)

  1. 一种形状记忆聚氨酯，其特征在于：它是玻璃化转变温度37～45℃的无定型聚合物或熔点为37～45℃的半结晶型聚合物，它由二异氰酸酯、软段聚合物和
    Figure PCTCN2022116391-appb-100001
    按照摩尔比1.2-8：1：0.2-7聚合而成的线性聚合物，其分子量为30000-150000；
    所述软段聚合物是聚乳酸、聚乙醇酸、聚己内酯、聚多元醇或其中两种及以上的共聚物。
  2. 按照权利要求1所述的形状记忆聚氨酯，其特征在于：它的结构式如式Ⅰ所示：
    Figure PCTCN2022116391-appb-100002
    其中，x选自1-10，y选自1-10；
    Figure PCTCN2022116391-appb-100003
    为所述软段聚合物的重复单元；
    Figure PCTCN2022116391-appb-100004
    为二异氰酸酯的重复单元，或二异氰酸酯与
    Figure PCTCN2022116391-appb-100005
    的共聚物的重复单元。
  3. 按照权利要求1或2所述的形状记忆聚氨酯，其特征在于：所述软段聚合物为乳酸和多元醇的聚合物。
  4. 按照权利要求3所述的形状记忆聚氨酯，其特征在于：所述软段聚合物的结构式如式Ⅱ所示：
    Figure PCTCN2022116391-appb-100006
    Figure PCTCN2022116391-appb-100007
    其中，m、n分别独立选自4-50，r选自1-20。
  5. 按照权利要求1或2所述的形状记忆聚氨酯，其特征在于：所述二异氰酸酯选自脂肪族二异氰酸酯或芳香族二异氰酸酯，所述脂肪族二异氰酸酯选自六亚甲基二异氰酸酯、赖氨酸二异氰酸酯、异佛尔酮二异氰酸酯、二环己基甲烷二异氰酸酯或其中两种及以上的混合物，所述芳香族二异氰酸酯选自甲苯二异氰酸酯、二苯基甲烷二异氰酸酯或其中两种及以上的混合物。
  6. 权利要求1-5任一项所述的形状记忆聚氨酯用于制备高力学性能的具有规则孔隙的多孔聚合物薄膜的用途，其特征在于：所述形状记忆聚氨酯制备成所述多孔聚合物薄膜的方法为水滴模板法。
  7. 一种具有规则孔隙的高力学性能多孔聚合物薄膜，其特征在于：它是以权利要求1-5任一项所述的形状记忆聚氨酯为原料，采用水滴模板法制备而成的。
  8. 按照权利要求7所述的多孔聚合物薄膜，其特征在于：所述水滴模板法的参数选择为：环境温度4-50℃，湿度25-80％，使溶剂的挥发速率为5-50μL/min。
  9. 权利要求7或8所述的多孔聚合物薄膜的制备方法，其特征在于，包括如下步骤：
    步骤1，将权利要求1-5任一项所述的形状记忆聚氨酯溶解在挥发性溶剂中，得到聚氨酯溶液；
    步骤2，将所述聚氨酯溶液涂覆在基底表面，于潮湿空气中挥干，即得。
  10. 按照权利要求9所述的制备方法，其特征在于：步骤1中，所述挥发性溶剂选自三氯甲烷、二氯甲烷、四氢呋喃、二硫化碳或其中两种及以上的混合物；
    和/或，所述聚氨酯溶液的浓度为5-200 mg/mL；
    和/或，步骤2中，涂覆有聚氨酯溶液的基底在环境温度4-50℃，湿度25-80％的条件下干燥，溶剂的挥发速率为5-50μL/min。
  11. 权利要求7-10任一项所述具有规则孔隙的多孔聚合物薄膜用于制备人工骨膜的用途。
  12. 一种人工骨膜，其特征在于：它是用权利要求7-10任一项所述具有规则孔隙的多孔聚合物薄膜制成的。
  13. 权利要求7-10任一项所述具有规则孔隙的多孔聚合物薄膜用于制备 防粘连膜的用途。
  14. 一种防粘连膜，其特征在于：它是用权利要求7-10任一项所述具有规则孔隙的多孔聚合物薄膜制成的。
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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1338950A (zh) * 1999-02-02 2002-03-06 阿提姆普兰特公司 一种由线型聚氨酯嵌段共聚物组成的医用薄膜及其生产方法
WO2015144435A1 (de) * 2014-03-27 2015-10-01 Basf Se Thermoplastisches formgedächtnismaterial
CN105670015A (zh) * 2016-01-27 2016-06-15 江苏巨贤合成材料有限公司 聚酰亚胺立体多孔膜的气态非良溶剂诱导成形制备方法
WO2019115678A1 (en) * 2017-12-14 2019-06-20 Basf Se Method for preparing a thermoplastic polyurethane having a low glass transition temperature
CN111205429A (zh) * 2020-02-06 2020-05-29 重庆大学 一种聚氨酯材料及其制备方法
CN114634641A (zh) * 2022-03-31 2022-06-17 重庆大学 具有规则孔隙的多孔聚合物薄膜用于制备防粘连膜的用途
CN114634608A (zh) * 2022-03-31 2022-06-17 重庆大学 一种形状记忆聚氨酯及其制成的自增强规则孔隙聚合物薄膜
CN114656678A (zh) * 2022-03-31 2022-06-24 重庆大学 具有规则孔隙的多孔聚合物薄膜用于制备人工骨膜的用途
CN114790329A (zh) * 2022-05-31 2022-07-26 重庆大学 高力学性能线性形状记忆聚氨酯/纤维素纳米晶复合材料及其制备方法和应用

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1338950A (zh) * 1999-02-02 2002-03-06 阿提姆普兰特公司 一种由线型聚氨酯嵌段共聚物组成的医用薄膜及其生产方法
WO2015144435A1 (de) * 2014-03-27 2015-10-01 Basf Se Thermoplastisches formgedächtnismaterial
CN105670015A (zh) * 2016-01-27 2016-06-15 江苏巨贤合成材料有限公司 聚酰亚胺立体多孔膜的气态非良溶剂诱导成形制备方法
WO2019115678A1 (en) * 2017-12-14 2019-06-20 Basf Se Method for preparing a thermoplastic polyurethane having a low glass transition temperature
CN111448234A (zh) * 2017-12-14 2020-07-24 巴斯夫欧洲公司 制备具有低玻璃化转变温度的热塑性聚氨酯的方法
CN111205429A (zh) * 2020-02-06 2020-05-29 重庆大学 一种聚氨酯材料及其制备方法
CN114634641A (zh) * 2022-03-31 2022-06-17 重庆大学 具有规则孔隙的多孔聚合物薄膜用于制备防粘连膜的用途
CN114634608A (zh) * 2022-03-31 2022-06-17 重庆大学 一种形状记忆聚氨酯及其制成的自增强规则孔隙聚合物薄膜
CN114656678A (zh) * 2022-03-31 2022-06-24 重庆大学 具有规则孔隙的多孔聚合物薄膜用于制备人工骨膜的用途
CN114790329A (zh) * 2022-05-31 2022-07-26 重庆大学 高力学性能线性形状记忆聚氨酯/纤维素纳米晶复合材料及其制备方法和应用
CN114891342A (zh) * 2022-05-31 2022-08-12 重庆大学 一种形状记忆聚氨酯复合材料在制备骨组织工程生物材料中的用途

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YANG WEI, GUAN DI, LIU JUAN, LUO YANFENG, WANG YUANLIANG: "Synthesis and characterization of biodegradable linear shape memory polyurethanes with high mechanical performance by incorporating novel long chain diisocyanates", NEW JOURNAL OF CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 44, no. 8, 24 February 2020 (2020-02-24), GB , pages 3493 - 3503, XP093096345, ISSN: 1144-0546, DOI: 10.1039/C9NJ06017K *

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