Method for improving blood compatibility of pmp hollow fiber membrane for ECMO by zwitterionic-nanosilver antifouling antibacterial coating

Abstract

The application discloses a method for improving blood compatibility of PMP hollow fiber membranes for ECMO by using zwitterionic-nano silver antifouling and antibacterial coating, and the steps of the preparation method are as follows: (1) dissolving zwitterionic polymers and dopamine hydrochloride with different concentrations in PBS; (2) after cleaning the PMP membrane, the PMP membrane is soaked in the modified liquid obtained in step (1), so that the zwitterionic polymers are adhered to the membrane; (3) the above PMP hollow fiber membrane is sequentially immersed in AgNO3 solution, deionized water and NaBH4 solution, so that Ag + is fixed on the membrane surface, and silver nanoparticles are formed in situ on the membrane surface. Experiments prove that the method for improving blood compatibility of PMP hollow fiber membranes for ECMO by using zwitterionic-nano silver coating is simple and has strong universality, and the prepared PMP hollow fiber membrane has high hydrophilicity, excellent anti-platelet adsorption, anti-platelet adsorption and anti-protein adhesion performance, is beneficial to inhibiting thrombosis, and has good blood compatibility and biocompatibility.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of anticoagulant, antibiofouling materials and medical device surface modification, and relates to an anticoagulant and antibiofouling blood compatibility coating, a functional material coating with antithrombosis and antibioadhesion fouling and a preparation method thereof. BACKGROUND

[0002] Extracorporeal membrane oxygenation (ECMO) is a combination of artificial lung and artificial heart, which is a medical emergency technology and equipment. The most core part is the membrane lung and blood pump, which respectively plays the role of artificial lung and artificial heart. ECMO can provide short-term cardiopulmonary support for patients with severe heart and lung failure, and can win valuable time for the rescue of critically ill patients. ECMO support is an auxiliary treatment measure that cannot be replaced by other medical technologies at present, and to some extent, it represents the level of rescue of critically ill patients in a hospital. Gas-blood exchange membrane is the core component of membrane oxygenator, which is a blood-gas separation barrier and also provides a place for blood oxidation. The structure and distribution of the surface pores of the membrane skin have a very important influence on gas permeability and prevention of plasma leakage. The commonly used core materials of membrane oxygenator include polypropylene (PP) and poly-4-methyl-1-pentene (PMP). Compared with PP, PMP has higher oxygen permeability, and due to its better hydrophobicity, the blood flow resistance in the process is lower, and the blood permeation phenomenon is reduced.

[0003] Poly-4-methyl-1-pentene (PMP) is a thermoplastic polyolefin with good mechanical stability and thermal stability. PMP also has excellent gas permeability, which is 12 times higher than that of polypropylene (PP). Therefore, PMP is an excellent membrane material. However, ECMO has strict requirements on material performance, especially the requirement of high blood compatibility. Although PMP is a high-performance polymer material, there are still disadvantages such as thrombosis and protein adhesion in clinical application, so it is necessary to improve the blood compatibility of PMP hollow fiber membrane for ECMO. SUMMARY

[0004] The technical problem to be solved by the present application is to provide a method for improving the blood compatibility of PMP hollow fiber membrane by using a zwitterionic nano-silver antifouling antibacterial coating.

[0005] A PMP hollow fiber membrane has a porous PMP base membrane with a hollow fiber configuration, a modified layer formed by dopamine and a zwitterionic polymer is covered on the surface of the base membrane, and the surface of the modified layer further carries an Ag antibacterial layer.

[0006] The dopamine units in the antifouling coating are easily deposited on the hydrophobic surface, and the zwitterionic polymer layer is anchored on the surface of the dopamine coating at multiple points.

[0007] The zwitterionic polymer is sulfobetaine methacrylate (SBMA). Figure 9

[0008] The method for preparing the PMP hollow fiber membrane comprises the following steps:

[0009] Step 1: preparing a PBS buffer solution containing the zwitterionic polymer and dopamine hydrochloride;

[0010] Step 2: placing the PMP hollow fiber membrane into the solution obtained in step 1 for treatment;

[0011] Step 3: sequentially placing the hollow fiber membrane obtained in step 2 into a silver nitrate solution and a sodium borohydride solution, cleaning and drying to obtain the hollow fiber membrane. In this step, Ag is fixed on the membrane surface and silver nanoparticles are formed in situ on the membrane surface. In the silver nanoparticle antibacterial coating, Ag is fixed on the membrane surface through the terminal groups of the zwitterionic polymer, thereby further enhancing the antibacterial performance of the membrane.

[0012] In step 1, the concentration of the zwitterionic polymer is 2-10 mg / mL, and the weight ratio of the zwitterionic polymer to dopamine hydrochloride is 1:1-8:1.

[0013] The PBS buffer solution is prepared from potassium dihydrogen phosphate and sodium hydrogen phosphate, and has a total concentration of 1-30 mM and a pH of 8.0-9.0.

[0014] In step 2, the immersion temperature is 30-50°C, and the immersion time is 12-48 h.

[0015] In step 3, the silver nitrate solution is an aqueous silver nitrate solution with a concentration of 0.005 mol / L, the immersion temperature is 20-25°C, the immersion time is 10-15 min, the concentration of the sodium borohydride solution is 0.005 mol / L, and the immersion time is 5-10 min.

[0016] Advantages

[0017] Experiments prove that the zwitterionic silver nanoparticle antifouling antibacterial coating modified PMP hollow fiber membrane has high hydrophilicity, excellent antibacterial performance, and is beneficial to inhibiting thrombus formation. The modified PMP hollow fiber membrane has good blood compatibility and biocompatibility. The modification method is simple. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 Fig. 3 is an electron microscope analysis diagram of the PMP original membrane of the 3M company and the PMP membrane modified by the method.

[0019] Figures 2-4 ​Contact angle data for 3M PMP original film and PMP film modified by the present method.

[0020] Figures 5-7 Protein adsorption data for 3M PMP original film and PMP film modified by the present method.

[0021] Figure 8 Platelet adhesion graph for 3M PMP original film and PMP film modified by the present method.

[0022] Figure 9 Molecular structure of methacrylic acid sulfobetaine. DETAILED DESCRIPTION

[0023] Example 1

[0024] The method for modifying PMP hollow fiber membrane by zwitterionic-nanosilver antifouling antibacterial coating comprises the following steps:

[0025] (1) Dissolve dopamine and SBMA solution with a concentration of 2.0 mg / mL in PBS (10 mM, pH = 8.5) at a ratio of 1:1;

[0026] (2) Pre-wet the PMP membrane with ethanol, rinse with deionized water, and then soak in the solution obtained in step (1) at room temperature for 12 h, and then wash with water and dry.

[0027] (3) Place the PMP membrane obtained in step (2) in a silver nitrate solution with a concentration of 5 M and soak for 10 min, and then rinse with deionized water. Then place it in a NaBH4 solution with a concentration of 5 mM and soak for 5 min, and then rinse with deionized water and dry.

[0028] The results of electron microscopy analysis of the PMP hollow fiber membrane modified by the zwitterionic-nanosilver antifouling antibacterial coating are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0029] Example 2

[0030] The method for modifying PMP hollow fiber membrane by zwitterionic-nanosilver antifouling antibacterial coating comprises the following steps:

[0031] (1) Dissolve dopamine and SBMA solution with a concentration of 2.0 mg / mL in PBS (10 mM, pH = 8.5) at a ratio of 1:2;

[0032] (2) Pre-wet the PMP membrane with ethanol, rinse with deionized water, and then soak in the solution obtained in step (1) at room temperature for 12 h, and then wash with water and dry.

[0033] (3) The PMP membrane obtained in step (2) is immersed in a silver nitrate solution with a concentration of 5 mM for 10 min, and then washed with deionized water. Then it is immersed in a NaBH4 solution with a concentration of 5 mM for 5 min, and then washed with deionized water and dried.

[0034] The results of the electron microscope analysis of the zwitterion-nano silver antifouling antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0035] Example 3

[0036] A method for modifying a PMP hollow fiber membrane with a zwitterion-nano silver antifouling antibacterial coating, comprising the following steps:

[0037] (1) Dissolve dopamine and SBMA solutions with a concentration of 2.0 mg / mL in PBS (10 mM, pH = 8.5) at a ratio of 1:4;

[0038] (2) The PMP membrane is pre-wetted with ethanol, washed with deionized water, and then immersed in the solution obtained in step (1) at room temperature for 12 h, washed with water and dried.

[0039] (3) The PMP membrane obtained in step (2) is immersed in a silver nitrate solution with a concentration of 5 mM for 10 min, and then washed with deionized water. Then it is immersed in a NaBH4 solution with a concentration of 5 mM for 5 min, and then washed with deionized water and dried.

[0040] The results of the electron microscope analysis of the zwitterion-nano silver antifouling antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0041] Example 4

[0042] A method for modifying a PMP hollow fiber membrane with a zwitterion-nano silver antifouling antibacterial coating, comprising the following steps:

[0043] (1) Dissolve dopamine and SBMA solutions with a concentration of 2.0 mg / mL in PBS (10 mM, pH = 8.5) at a ratio of 1:8;

[0044] (2) The PMP membrane is pre-wetted with ethanol, washed with deionized water, and then immersed in the solution obtained in step (1) at room temperature for 12 h, washed with water and dried.

[0045] (2) The PMP membrane is pre-wetted with ethanol, rinsed with deionized water, and then soaked in the solution obtained in step (1) for 12 h at room temperature, washed with water and dried.

[0046] (3) The PMP membrane obtained in step (2) is soaked in a 5 M silver nitrate solution for 10 min, washed with deionized water, soaked in a 5 mM NaBH4 solution for 5 min, washed with deionized water and dried.

[0047] The results of the electron microscope analysis of the zwitterion-nano silver antifouling antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0048] Example 5

[0049] A method for modifying a PMP hollow fiber membrane with a zwitterion-nano silver antifouling antibacterial coating, comprising the following steps:

[0050] (1) Dopamine and SBMA solutions with a concentration of 2.0 mg / mL are dissolved in PBS (10 mM, pH = 8.5) at a ratio of 2:1;

[0051] (2) The PMP membrane is pre-wetted with ethanol, rinsed with deionized water, and then soaked in the solution obtained in step (1) for 12 h at room temperature, washed with water and dried.

[0052] (3) The PMP membrane obtained in step (2) is soaked in a 5 M silver nitrate solution for 10 min, washed with deionized water, soaked in a 5 mM NaBH4 solution for 5 min, washed with deionized water and dried.

[0053] The results of the electron microscope analysis of the zwitterion-nano silver antifouling antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0054] Example 6

[0055] A method for modifying a PMP hollow fiber membrane with a zwitterion-nano silver antifouling antibacterial coating, comprising the following steps:

[0056] (1) Dopamine and SBMA solutions with a concentration of 5.0 mg / mL are dissolved in PBS (10 mM, pH = 8.5) at a ratio of 1:2;

[0057] (2) The PMP membrane was pre-wetted with ethanol, rinsed with deionized water, and then soaked in the solution obtained in step (1) for 12 h at room temperature, washed with water and dried.

[0058] (3) The PMP membrane obtained in step (2) was soaked in a 5 M silver nitrate solution for 10 min, rinsed with deionized water, soaked in a 5 mM NaBH4 solution for 5 min, rinsed with deionized water and dried.

[0059] The results of the electron microscope analysis of the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0060] Example 7

[0061] A method for modifying a PMP hollow fiber membrane with a zwitterionic-nanosilver antifouling and antibacterial coating, comprising the following steps:

[0062] (1) Dopamine and SBMA solutions with a concentration of 5.0 mg / mL were dissolved in PBS (10 mM, pH = 8.5) at a ratio of 1:2;

[0063] (2) The PMP membrane was pre-wetted with ethanol, rinsed with deionized water, and then soaked in the solution obtained in step (1) for 24 h at room temperature, washed with water and dried.

[0064] (3) The PMP membrane obtained in step (2) was soaked in a 5 M silver nitrate solution for 10 min, rinsed with deionized water, soaked in a 5 mM NaBH4 solution for 5 min, rinsed with deionized water and dried.

[0065] The results of the electron microscope analysis of the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0066] Example 8

[0067] A method for modifying a PMP hollow fiber membrane with a zwitterionic-nanosilver antifouling and antibacterial coating, comprising the following steps:

[0068] (1) Dopamine and SBMA solutions with a concentration of 5.0 mg / mL were dissolved in PBS (10 mM, pH = 8.5) at a ratio of 1:2;

[0069] (2) PMP membrane was pre-wetted with ethanol, rinsed with deionized water, and then immersed in the solution obtained in step (1) for 48 h at room temperature, washed with water and dried.

[0070] (3) The PMP membrane obtained in step (2) was immersed in a 5 M silver nitrate solution for 10 min, and then rinsed with deionized water. It was then immersed in a 5 mM NaBH4 solution for 5 min, and then rinsed with deionized water and dried.

[0071] The results of the electron microscope analysis of the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0072] Example 9

[0073] A method for modifying a PMP hollow fiber membrane with a zwitterionic-nanosilver antifouling and antibacterial coating, comprising the following steps:

[0074] (1) Dopamine and SBMA solutions with a concentration of 10.0 mg / mL were dissolved in PBS (10 mM, pH = 8.5) at a ratio of 1:2; (2) PMP membrane was pre-wetted with ethanol, rinsed with deionized water, and then immersed in the solution obtained in step (1) for 12 h at room temperature, washed with water and dried.

[0075] (3) The PMP membrane obtained in step (2) was immersed in a 5 M silver nitrate solution for 10 min, and then rinsed with deionized water. It was then immersed in a 5 mM NaBH4 solution for 5 min, and then rinsed with deionized water and dried.

[0076] The results of the electron microscope analysis of the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0077] Example 10

[0078] A method for modifying a PMP hollow fiber membrane with a zwitterionic-nanosilver antifouling and antibacterial coating, comprising the following steps:

[0079] (1) Dopamine and SBMA solutions with a concentration of 10.0 mg / mL were dissolved in PBS (10 mM, pH = 8.5) at a ratio of 1:2;

[0080] (2) The PMP membrane is pre-wetted with ethanol, rinsed with deionized water, and then soaked in the solution obtained in step (1) at room temperature for 24 hours, washed with water and dried.

[0081] (3) The PMP membrane obtained in step (2) is soaked in a 5M silver nitrate solution for 10 minutes, rinsed with deionized water, soaked in a 5mM NaBH4 solution for 5 minutes, rinsed with deionized water and dried.

[0082] The electron microscope analysis results of the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 .

[0083] Example 11

[0084] The method for modifying the PMP hollow fiber membrane with the zwitterionic-nanosilver antifouling and antibacterial coating comprises the following steps:

[0085] (1) Dopamine and SBMA solutions with a concentration of 10.0mg / mL are dissolved in PBS (10mM, pH=8.5) at a ratio of 1:2;

[0086] (2) The PMP membrane is pre-wetted with ethanol, rinsed with deionized water, and then soaked in the solution obtained in step (1) at room temperature for 48 hours, washed with water and dried.

[0087] (3) The PMP membrane obtained in step (2) is soaked in a 5M silver nitrate solution for 10 minutes, rinsed with deionized water, soaked in a 5mM NaBH4 solution for 5 minutes, rinsed with deionized water and dried.

[0088] The electron microscope analysis results of the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane are shown in Figure 1 , the water contact angle analysis is shown in Figures 2-4 , the protein adsorption test results are shown in Figures 5-7 , and the platelet adhesion test results are shown in Figure 8 Figure 1 Figures 2-4 Figures 5-7 Figure 8 Figure 1 Figures 2-4 Figures 5-7 Figure 8 Figure 1 Figures 2-4 Figures 5-7 Figure 8 Figure 1 Figures 2-4 Figures 5-7 Figure 8 Figure 1 Figures 2-4 Figures 5-7 Figure 8 Figure 1 Figures 2-4 Figures 5- .

[0089] The experiment proves that the zwitterionic-nanosilver antifouling and antibacterial coating modified PMP hollow fiber membrane has high hydrophilic performance, excellent anti-platelet adsorption and anti-protein adhesion performance, which is conducive to inhibiting thrombus formation. It has good blood compatibility and biocompatibility. The modification method of the present application is simple.

Claims

1. An extracorporeal membrane oxygenator, characterized by, The gas-blood exchange membrane is a PMP hollow fiber membrane; The preparation method of the PMP hollow fiber membrane comprises the following steps: (1) dissolving dopamine and SBMA solutions with a concentration of 2.0 mg / mL in 10 mM PBS with pH=8.5 at a ratio of 1:4; (2) pre-wetting the PMP membrane with ethanol, washing with deionized water, and then soaking in the solution obtained in step (1) at room temperature for 12 h, washing with water and drying; (3) placing the PMP membrane obtained in step (2) in a 5 mM silver nitrate solution for 10 min, washing with deionized water, and then placing in a 5 mM NaBH4 solution for 5 min, washing with deionized water and drying.

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