COF-doped mixed matrix membrane, preparation method and application in ECCO2R system

Abstract

The invention discloses a COF-doped mixed matrix membrane, a preparation method and application in an ECCO2R system, the mixed matrix membrane comprises a PMP hollow fiber membrane, and the PMP hollow fiber membrane is doped with a COF material and a polymer; wherein the polymer is Pebax and / or PDMS (Polydimethylsiloxane). The mixed matrix membrane can effectively improve the CO2 / O2 selective adsorption performance and enhance the CO2 removal capacity in an ECCO2R system, has good biocompatibility and blood compatibility, and has great application potential in the field of biomedicine.

Description

Technical Field

[0001] The invention relates to a COF-doped mixed matrix membrane, a preparation method and application in an ECCO2R system, and belongs to the technical field of membranes for ECCO2R systems. Background Art

[0002] Extracorporeal CO2 removal (ECCO2R) is another extracorporeal life support technology after extracorporeal membrane oxygenation (ECMO). Its purpose is to remove carbon dioxide from small-flow blood and improve problems such as extrapulmonary organ dysfunction caused by hypercapnia and related acidosis. With the promotion of extracorporeal life support technology and the accumulation of clinical experience, ECCO2R has important potential application value in a variety of critical conditions such as acute exacerbation of chronic obstructive pulmonary disease (AECOPD), acute respiratory distress syndrome (ARDS), perioperative lung transplantation, and persistent asthma. ECCO2R technology was first used in clinical practice in the 1980s. Due to the backwardness of extracorporeal life support technology and insufficient clinical understanding at that time, early clinical studies failed to confirm the role of this technology and many complications occurred. In recent years, with the innovation of extracorporeal life support equipment and technology, the accumulation of clinical experience, and the recent publication of relevant clinical evidence, the clinical application value of ECCO2R has once again attracted widespread attention from international scholars.

[0003] The ECCO2R system is similar to the ECMO system. The blood in the human body is drawn out of the body and enters the lung dialyzer. The carbon dioxide is discharged through the gas concentration difference on both sides of the membrane, and finally the blood is injected into the human body. The treatment mechanism of ECCO2R is based on the "solution-saturation-dissolution" of CO2 transport behavior in the body. CO2 has a very high solubility, a very fast saturation rate, and a diffusion rate in the blood that is 20 times that of O2. During the transport of CO2, 80% to 90% is converted into bicarbonate and hydrogen ions, 5% to 10% is bound to hemoglobin, and 5% to 10% is dissolved in plasma. A slight change in PaCO2 will release a large amount of CO2, and the total amount of CO2 in 1L of blood can be as high as 500ml. Therefore, when a patient has CO2 retention, ECCO2R can use the partial pressure difference on both sides of the gas-blood exchange membrane to remove the retained CO2 from the patient's body. Existing ECCO2R applications usually increase the emission rate of carbon dioxide by increasing the gas flow rate, but at the same time oxygen will also be extracted, and the blood oxygen concentration will decrease accordingly. Therefore, improving the CO2 / O2 selectivity helps to promote the emission of CO2 and retain more O2 in the blood.

[0004] High-performance mixed matrix membranes (MMMs) are an effective way to improve gas separation. In recent years, MOFs and HOFs have been studied in ECMO systems. Studies have shown that doping MOFs and HOFs in copolymers can effectively improve CO2 / O2 selectivity. In addition to MOFs and HOFs, covalent organic frameworks (COFs) are also a class of crystalline porous materials composed of organic molecules connected by covalent bonds. These frameworks are constructed by self-assembly of organic monomers to form two-dimensional (2D) or three-dimensional (3D) networks with highly ordered pore structures. COFs have the characteristics of adjustable pore size and high crystallinity, which are their unique physical and chemical properties. COFs are widely used in gas separation and storage, catalyst carriers, sensors, drug delivery and other fields due to their advantages such as large specific surface area, chemical controllability and chemical / thermal stability. At the same time, compared with framework structures such as MOFs, COFs have good biocompatibility and low toxicity due to their non-metallic properties, and have great application potential in the biomedical field. Summary of the invention

[0005] The purpose of the present invention is to provide a COF-doped mixed matrix membrane, a preparation method and an application in an ECCO2R system. The mixed matrix membrane has good CO2 / O2 selectivity, exhibits excellent CO2 removal ability in the ECCO2R system, and has good blood compatibility and biocompatibility.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] A COF-doped mixed matrix membrane, the mixed matrix membrane comprising a PMP hollow fiber membrane, the PMP hollow fiber membrane is doped with COF material and polymer; wherein the polymer is Pebax and / or PDMS.

[0008] The method for preparing the COF-doped mixed matrix membrane is as follows: the prepared COF powder is added to a polymer solution to prepare a casting solution; a PMP hollow fiber membrane is then immersed in the casting solution, taken out and dried to obtain a COF-doped mixed matrix membrane.

[0009] Preferably, the preparation method of COF powder is: adding 1,4-phenyldiboronic acid and 2,3,6,7,10,11-hexahydroxytriphenyl to a mixture of trimethylol and 1,4-dioxane, freezing after ultrasonication, heating after degassing, centrifuging and washing to obtain COF powder.

[0010] Preferably, the usage ratio of 1,4-phenyldiboronic acid, 2,3,6,7,10,11-hexahydroxytriphenyl, trimethylol and 1,4-dioxane is (20-45) mg:(10-30) mg:(0.1-2) mL:(0.1-2) mL.

[0011] Preferably, the freezing conditions are: 50-100K, N2; the heating conditions are: 100-150°C, 50-90h.

[0012] Preferably, in the polymer solution, the polymer concentration is 1-5%; in the casting solution, the mass of the COF powder is 5-60% of the mass of the polymer.

[0013] Preferably, the dipping time is 5-60 seconds.

[0014] Preferably, the drying conditions are: air drying at 15-25°C for 5-15h, and then heat drying at 50-70°C for 10-15h.

[0015] The above-mentioned COF-doped mixed matrix membrane is used in the ECCO2R system, and the mixed matrix membrane is used for the selective adsorption of CO2 / O2.

[0016] A method for improving the blood compatibility and biocompatibility of a membrane used in an ECCO2R system is to dope a COF material and a polymer on the membrane used in the ECMO system; wherein the polymer is Pebax and / or PDMS;

[0017] The preparation method of COF material is as follows: 1,4-phenyldiboronic acid and 2,3,6,7,10,11-hexahydroxytriphenyl are added to a mixture of trimethylol and 1,4-dioxane, and then the mixture is frozen after ultrasonication, and then heated, centrifuged and washed after degassing.

[0018] The membrane used in the ECCO2R system is a PMP hollow fiber membrane.

[0019] The beneficial effects of the present invention are:

[0020] The prepared COF powder has a large specific surface area, adjustable pore size and good modifiability, which can effectively improve the transmission rate of CO2 and enhance the CO2 / O2 selectivity. It also has non-metallic properties and can enhance the blood compatibility, biocompatibility and low toxicity of the mixed matrix membrane. Polyether block polyamide (Pebax) and polydimethylsiloxane (PDMS) have good mechanical properties and economic benefits, and have good solubility in CO2, which can further enhance the selectivity of the mixed matrix membrane for CO2 / O2.

[0021] The COF-doped mixed matrix membrane prepared by the present invention effectively improves the CO2 / O2 selective adsorption performance, enhances the ability to remove CO2 in the ECCO2R system and has excellent anti-protein adhesion performance, while having good biocompatibility and blood compatibility, and has great application potential in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 XRD pattern of COF prepared by liquid nitrogen freezing method;

[0023] Figure 2 This is the infrared spectrum of COF prepared by liquid nitrogen freezing method;

[0024] Figure 3 This is an electron microscope image of COF prepared by liquid nitrogen freezing method;

[0025] Figure 4 is the infrared spectrum of the modified PMP membrane;

[0026] Figure 5 The electron microscope images of the original PMP membrane and the modified PMP membrane;

[0027] Figure 6-7 The gas permeability of the original PMP membrane and the modified PMP membrane and the CO2 / O2 selectivity of the modified PMP membrane are shown respectively;

[0028] Figure 8 The protein adsorption data of the original PMP membrane, the membrane obtained in Comparative Example 1, and the modified PMP membrane;

[0029] Fig. 9 The hemolysis time data of the original PMP membrane, the membrane obtained in Comparative Example 1, and the modified PMP membrane;

[0030] Fig.10 The coagulation time data of the original PMP membrane, the membrane obtained in Comparative Example 1, and the modified PMP membrane;

[0031] Figure 11-12 These are the CO2 removal effects of the original PMP membrane and the modified PMP membrane. DETAILED DESCRIPTION

[0032] Example 1

[0033] The preparation method of COF-5 powder comprises the following steps:

[0034] (1) 25 mg of 1,4-phenyldiboronic acid (BDBA) and 16 mg of 2,3,6,7,10,11-hexahydroxytriphenyl (HHTP) were placed in a Pyrex tube containing 0.5 mL of trimethylol and 0.5 mL of 1,4-dioxane, respectively.

[0035] (2) The mixture was ultrasonically treated at room temperature for 30 min to form a uniformly dispersed solution. The mixed solution was then rapidly frozen in a 77K N2 liquid bath and thawed three times by a refrigeration pump for degassing.

[0036] (3) The mixture was heated at 120°C for 72 h and centrifuged and washed to obtain COF-5 powder.

[0037] The XRD results of COF are shown in Figure 1 , infrared spectrum results are shown in Figure 2 The electron microscopy results are shown in Figure 3 .

[0038] Example 2

[0039] The preparation method of COF mixed matrix membrane comprises the following steps:

[0040] (1) 25 mg of 1,4-phenyldiboronic acid (BDBA) and 16 mg of 2,3,6,7,10,11-hexahydroxytriphenyl (HHTP) were placed in a Pyrex tube containing 0.5 mL of trimethylol and 0.5 mL of 1,4-dioxane, respectively, and ultrasonically treated at room temperature for 30 min. The mixed solution was then quickly frozen in N2 at 77 K and thawed three times for degassing. It was then heated at 120°C for 72 h and centrifuged and washed to obtain COF-5 powder.

[0041] (2) A certain amount of Pebax was added to a 70% ethanol-water mixture, and then heated at 80°C to obtain a 3% Pebax / ethanol / water mixed solution. Then, 0.09 g of COF-5 powder was added to 6 g of the 3% Pebax / ethanol / water mixed solution, and after vigorous stirring and ultrasonic treatment, a COF / Pebax uniform solution with a loading of 50% was obtained.

[0042] (3) The cut PMP hollow fiber membrane was immersed in a uniform casting solution for 10 s, 20 s, 30 s, 40 s and 50 s respectively.

[0043] (4) The membrane was air-dried at 25 °C and heat-dried at 60 °C for 12 h to remove the residual solution.

[0044] Example 3

[0045] The preparation method of COF mixed matrix membrane comprises the following steps:

[0046] (1) 25 mg of 1,4-phenyldiboronic acid (BDBA) and 16 mg of 2,3,6,7,10,11-hexahydroxytriphenyl (HHTP) were placed in a Pyrex tube containing 0.5 mL of trimethylol and 0.5 mL of 1,4-dioxane, respectively, and ultrasonically treated at room temperature for 30 min. The mixed solution was then quickly frozen in N2 at 77 K and thawed three times for degassing. It was then heated at 120°C for 72 h and centrifuged and washed to obtain COF-5 powder.

[0047] (2) A certain amount of Pebax was added to a 70% ethanol-water mixture, and then heated at 80°C to obtain a Pebax / ethanol / water mixed solution with a concentration of 3%. Then, 0.09 g of COF-5 powder was added to 7.5 g of the 3% Pebax / ethanol / water mixed solution, and after vigorous stirring and ultrasonic treatment, a COF / Pebax uniform solution with a loading of 40% was obtained.

[0048] (3) The cut PMP hollow fiber membrane was immersed in a uniform casting solution for 10 s, 20 s, 30 s, 40 s and 50 s respectively.

[0049] (4) The membrane was air-dried at 25 °C and heat-dried at 60 °C for 12 h to remove the residual solution.

[0050] Example 4

[0051] The preparation method of COF mixed matrix membrane comprises the following steps:

[0052] (1) 25 mg of 1,4-phenyldiboronic acid (BDBA) and 16 mg of 2,3,6,7,10,11-hexahydroxytriphenyl (HHTP) were placed in a Pyrex tube containing 0.5 mL of trimethylol and 0.5 mL of 1,4-dioxane, respectively, and ultrasonically treated at room temperature for 30 min. The mixed solution was then quickly frozen in N2 at 77 K and thawed three times for degassing. It was then heated at 120°C for 72 h and centrifuged and washed to obtain COF-5 powder.

[0053] (2) A certain amount of Pebax was added to a 70% ethanol-water mixture, and then heated at 80°C to obtain a Pebax / ethanol / water mixed solution with a concentration of 3%. Then, 0.09 g of COF-5 powder was added to 10.0 g of the 3% Pebax / ethanol / water mixed solution, and after vigorous stirring and ultrasonic treatment, a COF / Pebax uniform solution with a loading of 30% was obtained.

[0054] (3) The cut PMP hollow fiber membrane was immersed in a uniform casting solution for 10 s, 20 s, 30 s, 40 s and 50 s respectively.

[0055] (4) The membrane was air-dried at 25 °C and heat-dried at 60 °C for 12 h to remove the residual solution.

[0056] Example 5

[0057] The preparation method of COF mixed matrix membrane comprises the following steps:

[0058] (1) 25 mg of 1,4-phenyldiboronic acid (BDBA) and 16 mg of 2,3,6,7,10,11-hexahydroxytriphenyl (HHTP) were placed in a Pyrex tube containing 0.5 mL of trimethylol and 0.5 mL of 1,4-dioxane, respectively, and ultrasonically treated at room temperature for 30 min. The mixed solution was then quickly frozen in N2 at 77 K and thawed three times for degassing. It was then heated at 120°C for 72 h and centrifuged and washed to obtain COF-5 powder.

[0059] (2) A certain amount of Pebax was added to a 70% ethanol-water mixture, and then heated at 80°C to obtain a Pebax / ethanol / water mixed solution with a concentration of 3%. Then, 0.036 g of COF-5 powder was added to 6.0 g of the 3% Pebax / ethanol / water mixed solution, and after vigorous stirring and ultrasonic treatment, a COF / Pebax uniform solution with a loading of 20% was obtained.

[0060] (3) The cut PMP hollow fiber membrane was immersed in a uniform casting solution for 10 s, 20 s, 30 s, 40 s and 50 s respectively.

[0061] (4) The membrane was air-dried at 25 °C and heat-dried at 60 °C for 12 h to remove the residual solution.

[0062] Example 6

[0063] The preparation method of COF mixed matrix membrane comprises the following steps:

[0064] (1) 25 mg of 1,4-phenyldiboronic acid (BDBA) and 16 mg of 2,3,6,7,10,11-hexahydroxytriphenyl (HHTP) were placed in a Pyrex tube containing 0.5 mL of trimethylol and 0.5 mL of 1,4-dioxane, respectively, and ultrasonically treated at room temperature for 30 min. The mixed solution was then quickly frozen in N2 at 77 K and thawed three times for degassing. It was then heated at 120°C for 72 h and centrifuged and washed to obtain COF-5 powder.

[0065] (2) A certain amount of Pebax was added to a 70% ethanol-water mixture, and then heated at 80°C to obtain a Pebax / ethanol / water mixed solution with a concentration of 3%. Then, 0.036 g of COF-5 powder was added to 12.0 g of the 3% Pebax / ethanol / water mixed solution, and after vigorous stirring and ultrasonic treatment, a COF / Pebax uniform solution with a loading of 10% was obtained.

[0066] (3) The cut PMP hollow fiber membrane was immersed in a uniform casting solution for 10 s, 20 s, 30 s, 40 s and 50 s respectively.

[0067] (4) The membrane was air-dried at 25 °C and heat-dried at 60 °C for 12 h to remove the residual solution.

[0068] Comparative Example 1

[0069] A method for preparing a single Pebax mixed matrix membrane comprises the following steps:

[0070] (1) A certain amount of Pebax was added to a 70% ethanol-water mixture, and then heated at 80° C. to obtain a Pebax / ethanol / water mixed solution with a concentration of 3%.

[0071] (2) Immerse the cut PMP hollow fiber membrane in a uniform casting solution for 40 seconds.

[0072] (3) The membrane was air-dried at 25 °C and heat-dried at 60 °C for 12 h to remove the residual solution.

[0073] The infrared analysis results of the original PMP hollow fiber membrane and the modified mixed matrix membrane (10-50wt%, referring to the COF loading in the COF / Pebax uniform solution) with an immersion time of 40s are shown in Figure 4 The electron microscopic analysis results of the modified mixed matrix membrane with an immersion time of 40 s in Example 3 are shown in Figure 5 The gas permeability and CO2 / O2 selectivity of the original PMP hollow fiber membrane and the modified mixed matrix membrane (10-50wt%, referring to the COF loading in the COF / Pebax homogeneous solution) with an immersion time of 40s are shown in Figure 6 The gas permeability and CO2 / O2 selectivity of the modified mixed matrix membrane at different immersion times in Example 3 are shown in Figure 7 The protein adsorption test results of the original PMP hollow fiber membrane, the single Pebax mixed matrix membrane obtained in Comparative Example 1, and the modified mixed matrix membrane with an immersion time of 40 s in Example 3 are shown in Figure 8 , hemolysis test results are shown in Fig. 9 , the clotting time test results are shown in Fig.10The CO2 removal effects of the original PMP hollow fiber membrane and the modified mixed matrix membrane (40 wt%) with an immersion time of 40 s are shown in Figure 2. Figure 11-12 .

[0074] Depend on Figure 6 and Figure 7 It can be seen that the modified mixed matrix membrane with a COF loading of 40% and an immersion time of 40s has the highest CO2 / O2 selectivity, which is about 75% higher than that of the original PMP hollow fiber membrane. Figure 8 It can be seen that the protein adsorption of the modified mixed matrix membrane decreased by about 45% compared with the original PMP hollow fiber membrane, and was lower than the protein adsorption of the single Pebax-doped mixed matrix membrane; Fig. 9 It can be seen that the hemolysis rate of the modified mixed matrix membrane decreased by about 36% compared with the original PMP hollow fiber membrane and was lower than 5%, and was lower than the hemolysis rate of the single Pebax-doped mixed matrix membrane; Fig.10 It can be seen that the clotting time of the modified mixed matrix membrane increased by 12.6% compared with the original PMP hollow fiber membrane, and was higher than the clotting time of the single Pebax-doped mixed matrix membrane; Fig.11 and Fig.12 It can be seen that the CO2 removal rate of the modified mixed matrix membrane is increased by 10.9% compared with the original PMP hollow fiber membrane.

[0075] The above results prove that the prepared COF-doped mixed matrix membrane effectively improves the CO2 / O2 selective adsorption performance and enhances the ability to remove CO2 in the ECCO2R system. It also has good biocompatibility and blood compatibility and has great application potential in the biomedical field.

[0076] The above is only a preferred implementation of the patent of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the patent of the present invention. These improvements and modifications should also be regarded as the scope of protection of the patent of the present invention.

Claims

1. A COF-doped mixed matrix membrane, characterized in that: The mixed matrix membrane comprises a PMP hollow fiber membrane, on which COF material and polymer are doped; wherein the polymer is Pebax and / or PDMS.

2. The method for preparing a COF-doped mixed matrix membrane according to claim 1, characterized in that: The prepared COF The powder is added to a polymer solution to prepare a casting solution; then the PMP hollow fiber membrane is immersed in the casting solution, taken out and dried to obtain a COF-doped mixed matrix membrane.

3. The method for preparing a COF-doped mixed matrix membrane according to claim 2, characterized in that: The preparation method of COF powder is as follows: 1,4-phenyldiboronic acid and 2,3,6,7,10,11-hexahydroxytriphenylene are added to trimethylol and 1,4- The mixture was added to a dioxane solution, and then was frozen after ultrasonication. After degassing, it was heated, centrifuged, and washed to obtain COF powder.

4. The method for preparing a COF-doped mixed matrix membrane according to claim 3, characterized in that: The usage ratio of 1,4-phenyldiboronic acid, 2,3,6,7,10,11-hexahydroxytriphenyl, trimethylol and 1,4-dioxane is (20-45) mg:(10-30) mg:(0.1-2) mL:(0.1-2) mL.

5. The method for preparing a COF-doped mixed matrix membrane according to claim 3, characterized in that: The freezing conditions are: 50-100K, N2; the heating conditions are: 100-150℃, 50-90h.

6. The method for preparing a COF-doped mixed matrix membrane according to claim 2, characterized in that: In the polymer solution, the polymer concentration is 1-5%; in the casting solution, the mass of the COF powder is 5-60% of the mass of the polymer.

7. The method for preparing a COF-doped mixed matrix membrane according to claim 2, characterized in that: The dipping time is 5-60s.

8. The method for preparing a COF-doped mixed matrix membrane according to claim 2, characterized in that: The drying conditions are: air drying at 15-25℃ for 5-15h, and then heat drying at 50-70℃ for 10-15h.

9. The use of the COF-doped mixed matrix membrane according to claim 1 in an ECCO2R system, characterized in that: The mixed matrix membrane is used for the selective adsorption of CO2 / O2.

10. A method for improving the blood compatibility and biocompatibility of a membrane used in an ECCO2R system, characterized in that COF material and polymer are doped on the membrane used in the ECCO2R system; wherein the polymer is Pebax and / or PDMS; the preparation method of the COF material is: adding 1,4-phenyldiboronic acid and 2,3,6,7,10,11-hexahydroxytriphenyl to a mixed solution of trimethylol and 1,4-dioxane, freezing after ultrasonication, heating after degassing, centrifuging and washing; The membrane used in the ECCO2R system is a PMP hollow fiber membrane.

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