Filter membrane for removing red blood cells and preparation method thereof

Abstract

The present invention belongs to the field of filter membrane preparation, and specifically discloses a filter membrane for removing red blood cells and a preparation method thereof, comprising the following steps: step S1, mixing PTFE resin, polyetherimide and lubricant, stirring evenly, and drying at a constant temperature to obtain a mixture; step S2, calendering and extruding the mixture obtained in step S1 to obtain a preliminary material; step S3, deoiling and longitudinally pulling and stretching the preliminary material obtained in step S2 to obtain a PTFE composite membrane; step S4, immersing the PTFE composite membrane obtained in step S3 in a newly prepared functional solution, shaking at a constant temperature, washing and drying after taking out, to obtain a filter membrane for removing red blood cells. The present invention loads dopamine and polyvinyl pyrrolidone onto the PTFE composite membrane, successfully modifies the PTFE composite membrane, and obtains a filter membrane for removing red blood cells with high red blood cell removal rate, good antibacterial properties and biocompatibility, which has good application prospects in the medical field.

Description

Technical Field

[0001] The invention relates to a filter membrane for removing red blood cells and a preparation method thereof, belonging to the field of preparation of medical filter membranes. Background Art

[0002] Blood transfusion is one of the important clinical treatment methods. It is the infusion of blood components through the patient's intravenous channel. It is an indispensable treatment technology for critically ill patients and has saved the lives of countless patients. Adverse reactions to blood transfusion are inevitable during the blood transfusion process. Mild adverse reactions can often be treated with symptomatic treatment, but in severe cases, they can also threaten the patient's life safety. At present, most studies have pointed out that reducing white blood cell components during blood transfusion therapy is beneficial to reducing the incidence of adverse reactions to blood transfusion. However, for some special populations, such as those with ineffective platelet transfusions and patients with severe trauma, allogeneic blood transfusions are very likely to cause a series of adverse reactions and may also be infected with certain cell-associated viruses. At this time, the blood needs to be de-reduce, which may reduce the incidence of ineffective platelet transfusions caused by alloimmunization related to human leukocyte antigens and human platelet-specific antigens.

[0003] In addition, with the improvement of medical level and the application of pathological technology, clarifying the pathological results based on the specimens sent for examination of pleural and abdominal effusion has become the main work of the pathology department. However, the pleural and abdominal effusion specimens sent for clinical examination often contain a large number of red blood cells and proteins. After staining, multiple cells overlap and accumulate, and the background is blurred, making it difficult to distinguish tumor cells, affecting the diagnosis results. Therefore, red blood cell removal is required during the preparation of bloody body fluid specimens to reduce the interference of irrelevant cells, make the diagnostic cell outline and background clearer, and make the cell structure easier to observe, thereby improving the accuracy of pathological diagnosis.

[0004] Polytetrafluoroethylene (PTFE) has become an attractive membrane material due to its excellent chemical resistance, good thermal stability and high mechanical strength, and is widely used in many fields. Due to the low surface energy, strong non-polarity and strong hydrophobic and oleophobic properties of PTFE, PTFE filter membranes can filter almost all organic solvents, have high mechanical strength, can withstand high temperature liquids, and can filter air and particulate impurities. However, if it is necessary to filter an aqueous solution with a PTFE filter membrane, it must be pre-soaked with ethanol or isopropanol before filtering the aqueous solution, otherwise the filtered aqueous solution will be difficult to advance the filtered sample due to tension hindrance. In addition, due to its special structure, PTFE is difficult to process and modify. Chinese patent CN113921877A discloses a composite proton exchange membrane based on a modified PTFE membrane matrix, in which the PTFE membrane is first modified with inorganic nanoparticles to make it hydrophilic, thereby achieving better compatibility with the perfluorosulfonic acid membrane and improving the performance of the proton exchange membrane. Patent CN113318615A uses dopamine and polyethylene maleic anhydride copolymer as raw materials and provides a method for preparing a hydrophilic PTFE filter membrane through a series of chemical reactions. The filter membrane is suitable for treating oily wastewater and has the advantages of high hydrophilicity and strong oil-water separation ability. The above modified PTFE membranes are all used in the field of water treatment and are rarely used in the medical field. It is very challenging to apply PTFE to red blood cell filters for blood transfusion.

[0005] In view of the above practical problems, it is of practical significance to find a simple way to prepare PTFE material into red blood cell removal filter membrane and apply it in the medical field according to actual needs. Summary of the invention

[0006] In view of the above problems, the present invention provides a filter membrane for removing red blood cells and a preparation method thereof. Dopamine and polyvinyl pyrrolidone are loaded onto the prepared PTFE composite membrane by a co-deposition method to obtain a filter membrane with high removal rate of white blood cells and red blood cells in the blood and good biocompatibility, which has good application prospects in the medical and biological fields.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0008] The first aspect of the present invention provides a method for preparing a filter membrane for removing red blood cells, which specifically comprises the following steps:

[0009] Step S1, mixing PTFE resin, polyetherimide and lubricant, stirring evenly, and drying at a constant temperature to obtain a mixture;

[0010] Step S2, calendering and extruding the mixture obtained in step S1 to obtain a primary material;

[0011] Step S3, removing oil from the initial material obtained in step S2, and longitudinally drawing and stretching to obtain a PTFE composite membrane;

[0012] Step S4, immersing the PTFE composite membrane obtained in step S3 into the newly prepared functional solution, shaking at a constant temperature, taking it out, washing and drying it, and obtaining a filter membrane for removing red blood cells.

[0013] The PTFE resin and polyetherimide used in the present invention are both in powder form.

[0014] Preferably, in step S1, the mass ratio of PTFE resin, polyetherimide and lubricant is 100:(50-60):(10-20).

[0015] Further preferably, in step S1, the mass ratio of PTFE resin, polyetherimide and lubricant is 100:55:15.

[0016] The applicant found that strictly controlling the raw material ratio can improve the comprehensive performance of the PTFE composite membrane. On the one hand, the prepared PTFE composite membrane can have uniform texture, good mechanical properties, high temperature resistance and ozone resistance. On the other hand, the addition of polyetherimide is conducive to the adhesion of dopamine and polyvinyl pyrrolidone to the surface of the PTFE composite membrane. Both dopamine and polyvinyl pyrrolidone have good hydrophilicity and biocompatibility, thereby improving the comprehensive performance of the composite membrane.

[0017] Preferably, the lubricant in step S1 is methyl silicone oil.

[0018] The applicant has found that after methyl silicone oil is mixed with PTFE resin and polyetherimide, the PTFE composite film obtained by extrusion molding has good lubrication performance and friction and wear resistance.

[0019] Preferably, in step S1, the drying temperature is 65-70° C., and the drying time is 12-24 hours.

[0020] The applicant has found that strictly controlling the drying temperature and drying time can improve the comprehensive performance of the filter membrane. Controlling the drying temperature and time can improve the peel strength and friction coefficient of the filter membrane. The main reason is that on the one hand, it is conducive to accelerating the reaction speed of PTFE resin and polyetherimide, so that the peel strength is increased. On the other hand, the lubricant is absorbed by PTFE resin and polyetherimide, and as the temperature rises, the absorption speed is accelerated, which significantly improves the friction coefficient.

[0021] Preferably, in step S2, the calendering extrusion pressure is 30-50 MPa, and the extrusion speed is 10-20 m / min.

[0022] Further preferably, in the step S2, the calendering extrusion pressure is 48 MPa and the extrusion speed is 18 m / min.

[0023] Preferably, in step S3, the longitudinal stretching ratio is controlled to be 5-12 times, and the transverse stretching ratio is controlled to be 10-15 times.

[0024] Strictly controlling the longitudinal stretching ratio and transverse stretching can make the prepared filter membrane more uniform and thin. After longitudinal stretching, the polymer molecular chain has a higher degree of orientation along the longitudinal direction, and a certain degree of crystallinity is produced. When the longitudinally stretched film enters the transverse stretching zone and transverse stretching stress is applied to the edge of the film, the deformation stress concentrates in the thin area, and one or more stretching point areas appear along the transverse stretching direction, and the thin neck stretching develops to both sides, producing an "automatic leveling" effect, making the prepared PTFE composite film material more uniform.

[0025] Preferably, the functional solution in step S4 is obtained by dissolving dopamine and polyvinyl pyrrolidone in a buffer solution.

[0026] Preferably, the mass ratio of dopamine, polyvinyl pyrrolidone and buffer solution is (1-1.5):(2-3):500.

[0027] Further preferably, the mass ratio of dopamine, polyvinyl pyrrolidone and buffer solution is 1:2.5:500.

[0028] Preferably, the degree of polymerization of the polyvinyl pyrrolidone is 8000-10000.

[0029] The applicant found that dopamine and polyvinyl pyrrolidone would polymerize, and controlling the amount of both added could make them adhere to the PTFE composite membrane uniformly and stably. This may be because, on the one hand, dopamine contains a large number of phenolic hydroxyl groups and amino groups, and while polymerizing itself, it can also polymerize with the lactam group of polyvinyl pyrrolidone through covalent forces and adhere to the surface of the PTFE composite membrane together; on the other hand, the phenolic hydroxyl groups in dopamine react chemically with the aromatic amine functional groups in the PTFE composite membrane, and are tightly bonded to the PTFE composite membrane.

[0030] In addition, dopamine and polyvinyl pyrrolidone both have good hydrophilicity, biological inertness and good biocompatibility. Loading them together on the surface of the PTFE composite membrane not only improves the hydrophilicity of the membrane, but also makes the prepared red blood cell removal filter membrane have good viscosity and biocompatibility, which can significantly improve the removal rate of red blood cells in the blood by the filter membrane.

[0031] Preferably, the buffer is a Tris-HCl buffer solution with a pH of 8-9 and a concentration of 10-15 mM.

[0032] The use of the Tris-HCl buffer system has less interference with the chemical process and is conducive to the occurrence and progress of the reaction.

[0033] The second aspect of the present invention provides an application of the red blood cell removal filter membrane obtained according to the above preparation method in the medical field.

[0034] The present invention has the following beneficial effects:

[0035] 1. The present invention loads dopamine and polyvinyl pyrrolidone onto a PTFE composite membrane, successfully modifies the PTFE composite membrane, and obtains a red blood cell removal filter membrane with high red blood cell removal rate, good antibacterial property and biocompatibility.

[0036] 2. The present invention processes PTFE and polyetherimide into a PTFE composite membrane, the internal structure of the membrane is stable and the pores are uniform; and the addition of polyetherimide introduces functional groups (aromatic amines, ether bonds), which is beneficial to the modification of the PTFE composite membrane.

[0037] 3. The present invention loads dopamine and polyvinyl pyrrolidone onto the PTFE composite membrane by co-deposition, which greatly improves the comprehensive performance of the PTFE composite filter membrane and has good application prospects in the medical and biological fields. DETAILED DESCRIPTION

[0038] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0039] In order to better illustrate the specific implementation mode of the present invention, further examples are given below.

[0040] The lubricant used in the examples and comparative examples is methyl silicone oil, the PTFE resin used is purchased from Daikin Fluorochemical Co., Ltd., the polyetherimide used is purchased from Shangfu New Materials, and the degree of polymerization of polyvinyl pyrrolidone used is 8000, which is purchased from Sinopharm Chemical Reagent Network.

[0041] Example 1

[0042] A method for preparing a filter membrane for removing red blood cells comprises the following steps:

[0043] Step S1, 50 g of PTFE resin, 25 g of polyetherimide and 5 g of lubricant are mixed in a stirrer, stirred evenly, and dried at a constant temperature of 65° C. for 12 h to obtain a mixture;

[0044] Step S2, calendering the mixture obtained in step S1 at 30 MPa and an extrusion speed of 15 m / min to obtain a primary material;

[0045] Step S3, removing oil from the initial material obtained in step S2, and longitudinally stretching and stretching the initial material, wherein the longitudinal stretching ratio is 8 times and the transverse stretching ratio is 12 times, to obtain a PTFE composite membrane;

[0046] Step S4, immersing the PTFE composite membrane obtained in step S3 into the newly prepared functional solution, shaking at a constant temperature, taking it out, washing and drying it, and obtaining a filter membrane for removing red blood cells.

[0047] The functional solution used in step S4 is prepared by fully dissolving 1.5 g dopamine and 2.5 g polyvinyl pyrrolidone in 500 g Tris-HCl buffer solution (pH=8, 10 mM) to obtain a functional solution.

[0048] Example 2

[0049] A method for preparing a filter membrane for removing red blood cells comprises the following steps:

[0050] Step S1, 50 g of PTFE resin, 28 g of polyetherimide and 8 g of lubricant are mixed in a stirrer, stirred evenly, and dried at a constant temperature of 70° C. for 12 h to obtain a mixture;

[0051] Step S2, calendering the mixture obtained in step S1 at 50 MPa and an extrusion speed of 20 m / min to obtain a primary material;

[0052] Step S3, removing oil from the initial material obtained in step S2, and longitudinally stretching and stretching the initial material, wherein the longitudinal stretching ratio is 8 times and the transverse stretching ratio is 12 times, to obtain a PTFE composite membrane;

[0053] Step S4, immersing the PTFE composite membrane obtained in step S3 into the newly prepared functional solution, shaking at a constant temperature, taking it out, washing and drying it, and obtaining a filter membrane for removing red blood cells.

[0054] The functional solution used in step S4 is prepared by fully dissolving 1.5 g dopamine and 3 g polyvinyl pyrrolidone in 500 g Tris-HCl buffer solution (pH=9, 12 mM) to obtain a functional solution.

[0055] Example 3

[0056] A method for preparing a filter membrane for removing red blood cells comprises the following steps:

[0057] Step S1, 50 g of PTFE resin, 30 g of polyetherimide and 10 g of lubricant are mixed in a stirrer, stirred evenly, and dried at a constant temperature of 65° C. for 24 h to obtain a mixture;

[0058] Step S2, calendering the mixture obtained in step S1 at 48 MPa and an extrusion speed of 18 m / min to obtain a primary material;

[0059] Step S3, removing oil from the initial material obtained in step S2, and stretching it longitudinally, with the longitudinal stretching ratio being 12 times and the transverse stretching ratio being 15 times, to obtain a PTFE composite membrane;

[0060] Step S4, immersing the PTFE composite membrane obtained in step S3 into the newly prepared functional solution, shaking at a constant temperature, taking it out, washing and drying it, and obtaining a filter membrane for removing red blood cells.

[0061] The functional solution used in step S4 is prepared by fully dissolving 1 g of dopamine and 2.5 g of polyvinyl pyrrolidone in 500 g of Tris-HCl buffer solution (pH=9, 15 mM) to obtain a functional solution.

[0062] Example 4

[0063] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that the PTFE resin used in step S1 is 60 g.

[0064] Example 5

[0065] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that the drying temperature in step S1 is 50°C.

[0066] Example 6

[0067] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that the amount of polyvinyl pyrrolidone in the functional solution in step S4 is 5 g.

[0068] Example 7

[0069] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that the amount of polyvinyl pyrrolidone in the functional solution in step S4 is 1 g.

[0070] Example 8

[0071] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that the dopamine in the functional solution in step S4 is 0.5 g.

[0072] Example 9

[0073] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that the dopamine in the functional solution in step S4 is 4 g.

[0074] Example 10

[0075] The preparation process of the filter membrane in this embodiment is consistent with the preparation steps in Example 3, except that deionized water is used instead of the buffer solution in the functional solution in step S4.

[0076] Performance test of filter membrane for red blood cell removal

[0077] The performance of the filter membranes prepared in the examples and comparative examples was determined by the following method:

[0078] The filter membrane prepared in the example was used in the red blood cell filtration transfusion equipment to carry out the following experiments.

[0079] 1. Red blood cell removal rate: One unit of red blood cell suspension is filtered using the filter membrane prepared in the above embodiment or comparative example. After sterilization, the red blood cell filtering transfusion device is inserted into the red blood cell suspension blood bag by needle puncture. The blood is filtered into the transfer blood bag by gravity flow. Samples before and after filtration are obtained from each bag of red blood cell suspension for platelet counting.

[0080] The calculation formula of platelet removal rate is as follows: Platelet removal rate = (platelet count before filtration × volume of red blood cell suspension before filtration - platelet count after filtration × volume of red blood cell suspension after filtration) ÷ (platelet count before filtration × volume of red blood cell suspension before filtration) × 100%.

[0081] 2. Leukocyte removal rate: Fresh blood provided by volunteers is filtered through a red blood cell filter, and the residual white blood cells are counted using the Adam-rWBC system.

[0082] The calculation formula of leukocyte removal rate is as follows: leukocyte removal rate = (leukocyte count of blood before filtration × volume of blood before filtration - leukocyte count of blood after filtration × volume of blood after filtration) ÷ (leukocyte count before filtration × volume of blood before filtration) × 100%.

[0083] The tested performance is shown in Table 1 below.

[0084] Table 1

[0085] serial number Thickness(mm) Leukocyte removal rate (%) Red blood cell removal rate (%) Example 1 0.6 99.0 86.3 Example 2 0.2 99.2 88.7 Example 3 0.2 99.9 93.9 Example 4 0.3 98.3 85.6 Example 5 0.3 97.4 83.5 Example 6 0.2 96.7 78.4 Example 7 0.2 90.2 75.8 Example 8 0.2 92.3 78.9 Example 9 0.2 93.5 80.7 Example 10 0.2 89.6 78.5

[0086] From the results in Table 1, it can be seen that the filter membranes prepared in Examples 1-3 have moderate thickness and good removal rates for white blood cells and red blood cells.

[0087] The amount of PTFE resin used in Example 4 is relatively large, resulting in a high PTFE content in the prepared composite membrane, which is not conducive to the surface modification of the functional solution, thereby reducing the removal rate of white blood cells and red blood cells by the red blood cell removal filter membrane.

[0088] The drying temperature used in Example 5 is relatively low, resulting in a decrease in the comprehensive performance, peel strength and friction coefficient of the prepared PTFE composite membrane, thereby affecting the reduction in the removal rate of white blood cells and red blood cells by the red blood cell removal filter membrane.

[0089] The amount of polyvinyl pyrrolidone added in the functional solution in Examples 6 and 7 is not within the preferred range, and the amount of dopamine added in the functional solution in Examples 8 and 9 is not within the preferred range, resulting in the surface coating formed by dopamine and polyvinyl pyrrolidone being not uniform and the internal structure of the coating being changed, thereby reducing the removal rate of white blood cells and red blood cells by the red blood cell removal filter membrane.

[0090] In Example 10, deionized water was used instead of the buffer solution, which failed to stabilize the pH of the solution and affected the loading of dopamine and polyvinyl pyrrolidone on the surface of the PTFE composite membrane, thereby reducing the removal rate of white blood cells and red blood cells by the red blood cell removal filter membrane.

[0091] The above is only a preferred embodiment of the present invention and does not constitute any form of limitation to the present application. Although the present application is disclosed as above in the preferred embodiment, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution.

Claims

1. A method for preparing a filter membrane for removing red blood cells, characterized in that: The following steps are involved: Step S1, mixing PTFE resin, polyetherimide and lubricant, stirring evenly, and drying at a constant temperature to obtain a mixture; Step S2, calendering and extruding the mixture obtained in step S1 to obtain a primary material; Step S3, removing oil from the initial material obtained in step S2, and longitudinally drawing and stretching to obtain a PTFE composite membrane; Step S4, immersing the PTFE composite membrane obtained in step S3 into the newly prepared functional solution, shaking at a constant temperature, taking it out, washing, and drying it to obtain a filter membrane for removing red blood cells; The functional solution in step S4 is obtained by dissolving dopamine and polyvinyl pyrrolidone in a buffer solution; The mass ratio of dopamine, polyvinyl pyrrolidone and buffer solution is 1-1.5:2.5-3:500; The buffer solution is a Tris-HCl buffer solution with a pH of 8-9 and a concentration of 10-15 mM.

2. The method for preparing a filter membrane for removing red blood cells according to claim 1, characterized in that: In the step S1, the mass ratio of PTFE resin, polyetherimide and lubricant is 100:50-60:10-20.

3. The method for preparing a filter membrane for removing red blood cells according to claim 1, characterized in that: In step S1, the lubricant is methyl silicone oil.

4. The method for preparing a filter membrane for removing red blood cells according to claim 1, characterized in that: In step S1, the drying temperature is 65-70° C. and the drying time is 12-24 h.

5. The method for preparing a filter membrane for removing red blood cells according to claim 1, characterized in that: In the step S2, the calendering extrusion pressure is 30-50 MPa, and the extrusion speed is 10-20 m / min.

6. The method for preparing a filter membrane for removing red blood cells according to claim 1, characterized in that: The degree of polymerization of the polyvinyl pyrrolidone is 8000-10000.

7. A filter membrane for removing red blood cells obtained by the preparation method according to any one of claims 1 to 6, characterized in that: The thickness of the filter membrane is 0.2-0.6 mm, and the red blood cell removal rate is greater than 86%.