CN115400600B

CN115400600B - Hollow fiber composite membrane and preparation method and application thereof

Info

Publication number: CN115400600B
Application number: CN202211021897.7A
Authority: CN
Inventors: 董凡; 阮万民; 祁腾腾; 黄臣勇; 曾凯; 范斌
Original assignee: Zhuhai Jianhang Medical Technology Co ltd; Jafron Biomedical Co Ltd
Current assignee: Zhuhai Jianfan Blood Purification Technology Co ltd; Jafron Biomedical Co Ltd
Priority date: 2022-08-24
Filing date: 2022-08-24
Publication date: 2023-08-04
Anticipated expiration: 2042-08-24
Also published as: CN115400600A

Abstract

The invention provides a hollow fiber composite membrane, a preparation method and application thereof, wherein the preparation method of the hollow fiber composite membrane comprises the following steps: uniformly mixing the modified polyethersulfone mixture, the hydrophilic additive and the organic solvent to prepare a separation layer spinning solution; uniformly mixing the modified polyethersulfone mixture, the plasticizer, the pore-forming agent and the organic solvent to prepare a supporting layer spinning solution; forming an initial membrane by a coextrusion process of the separation layer spinning solution, the support layer spinning solution and the core solution, and solidifying and cleaning the initial membrane to obtain a hollow fiber composite membrane; the modified polyethersulfone mixture comprises polyethersulfone and/or end hydroxylated polyethersulfone. The invention solves the problems that the existing hollow fiber membrane is not easy to realize large-scale production, and the performance consistency is poor, so that the production cost of the hollow fiber membrane is increased.

Description

Hollow fiber composite membrane and preparation method and application thereof

Technical Field

The invention relates to the technical field of blood purification materials, in particular to a hollow fiber composite membrane and a preparation method and application thereof.

Background

Hemodialysis is a blood purification technology for removing harmful substances and excessive water in blood by using dispersion, ultrafiltration and convection principles, is one of the most commonly used kidney substitution treatment methods, and can also be used for treating excessive drugs or poison poisoning. Hemofiltration is a medical technique that removes excess water and uremic toxins in the body in a convective manner. Hemodiafiltration is a combination of hemodialysis and hemofiltration, and has the advantage of two modes of treatment, with the solute being removed by both diffusion and convection mechanisms.

Ultrafiltration membranes are the most important component for achieving the above-mentioned medical techniques. The surface chemical composition and hydrophilic properties of ultrafiltration membranes have a great influence on the blood compatibility of the membranes. Currently, hemodialysis, hemofiltration and hemodiafiltration membranes are commonly used, and Polysulfone (PSF) and Polyethersulfone (PES) are poor in hydrophilicity, so that blood compatibility is not satisfactory. The common improvement method is to add hydrophilic substances such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) for blending modification or coat modification on the surface of the membrane to prepare modified hemodialysis, hemofiltration and hemodiafiltration membranes, so as to improve the hydrophilicity of the membrane material and the blood compatibility of the membrane material.

However, hydrophilic substances such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) are added to carry out blending modification to prepare the membrane, and although the membrane is convenient and easy to realize mass production, the separation layer and the support layer of the membrane belong to the same formula system, and the formulas of the separation layer and the support layer are difficult to regulate and control respectively according to actual needs in membrane structure control, namely, the differential control of the separation layer and the support layer in structure and performance cannot be realized through formula regulation and control. The coating modification on the surface of the base film is a step-by-step film making process, namely, the base film is firstly prepared, and then the second step of coating film making is carried out on the surface of the base film.

In view of the above, it is necessary to provide a method for producing a hollow fiber composite membrane which is easy to realize mass production, has good uniformity of performance, and can reduce production cost.

Disclosure of Invention

The invention aims to solve the problems that the existing hollow fiber membrane is not easy to realize large-scale production, and the performance consistency is poor, so that the production cost of the hollow fiber membrane is increased.

In order to solve the above problems, the first aspect of the present invention provides a method for preparing a hollow fiber composite membrane, comprising the steps of:

uniformly mixing the modified polyethersulfone mixture, the hydrophilic additive and the organic solvent to prepare a separation layer spinning solution;

uniformly mixing the modified polyethersulfone mixture, the plasticizer, the pore-forming agent and the organic solvent to prepare a supporting layer spinning solution;

the separation layer spinning solution, the support layer spinning solution and the core solution form an initial membrane through a coextrusion process, and the initial membrane is solidified and cleaned to obtain a hollow fiber composite membrane;

wherein the modified polyethersulfone mixture comprises polyethersulfone and/or end hydroxylated polyethersulfone.

Further, the spinning solution for the separation layer is prepared by the following method:

mixing 15-35% of modified polyethersulfone mixture, 25-40% of hydrophilic additive and 45-60% of organic solvent at 30-80 ℃ for 12-24 hours, filtering and vacuum defoaming to obtain the spinning solution.

Further, the hydrophilic additive is one or a combination of two of polyethylene glycol, cellulose acetate, polyvinyl alcohol and polymethyl methacrylate;

the organic solvent is one or the combination of two of triethyl phosphate, N-methyl formamide, N-dimethyl acetamide and N-methyl pyrrolidone.

Further, the supporting layer spinning solution is prepared by the following method:

10 to 25 mass percent of modified polyethersulfone mixture, 5 to 30 mass percent of plasticizer, 15 to 40 mass percent of pore-forming agent and 30 to 65 mass percent of organic solvent are mixed for 12 to 24 hours at 30 to 80 ℃, and the spinning solution of the support layer is prepared after filtration and vacuum deaeration.

Further, the plasticizer is one or a combination of two of polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxyethyl cellulose and polymethyl methacrylate;

the pore-forming agent is one or the combination of two of ethanol, glycol, isopropanol, glycol monomethyl ether, diethylene glycol and glycerol;

Further, the modified polyethersulfone mixture in the spinning solution of the separation layer comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture is hydroxyl-terminated polyethersulfone;

the modified polyethersulfone mixture in the supporting layer spinning solution comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture is polyethersulfone.

Further, the initial film is prepared by the following method:

and extruding the separation layer spinning solution, the support layer spinning solution and the core solution from a three-hole annular spinneret simultaneously to prepare an initial membrane, wherein the three-hole annular spinneret comprises a core solution channel, a separation layer solution channel and a support layer solution channel which are sequentially arranged from inside to outside, the core solution is extruded from the core solution channel, the separation layer spinning solution is extruded from the separation layer solution channel, and the support layer spinning solution is extruded from the support layer solution channel.

Further, the initial film was solidified by the following method:

the initial film is sequentially solidified through an air section and a coagulating bath, wherein the relative humidity of the air section is 30-90%, the temperature is 30-50 ℃, and the residence time of the initial film in the air section is 0.5-1.5 s; the coagulating bath is prepared by mixing water and a pore-forming agent, or the coagulating bath is prepared by mixing water and an organic solvent, and the liquid level of the coagulating bath is kept constant.

In a second aspect, the present invention provides a hollow fiber composite membrane produced by the method for producing a hollow fiber composite membrane according to any one of the first aspects.

In a third aspect the present invention provides the use of a hollow fibre composite membrane as described in the second aspect in hemodialysis.

According to the preparation method of the hollow fiber composite membrane, the separation layer spinning solution and the support layer spinning solution are prepared from the modified polyethersulfone mixture, the modified polyethersulfone mixture comprises polyethersulfone and/or hydroxyl-terminated polyethersulfone, the hydroxyl-terminated polyethersulfone is water-insoluble hydrophilic modified polyethersulfone, and the hydrophilic modified polyethersulfone is formed by blending the modified polyethersulfone and the polyethersulfone, so that the hydrophilic performance of the hollow fiber composite membrane can be improved, and the blood compatibility of the hollow fiber composite membrane can be improved; in the film forming process, hydroxyl end groups in hydroxyl end polyether sulfone can form hydrogen bonds with hydrophilic substances (such as water-soluble PVP or PEG molecules and the like), so that the hydrophilic substances are anchored on the surface of the hollow fiber composite film, the blood compatibility of the hollow fiber composite film can be further improved, and the hydroxyl end groups in the hydroxyl end polyether sulfone are connected with the hydrophilic substances through the hydrogen bonds, so that the hydrophilic substances can be more firmly combined on the film forming substances, and the phenomena of falling off or dissolution of the hydrophilic substances are avoided; the polyethersulfone has excellent mechanical properties, and the polyethersulfone is used as a supporting layer spinning solution, so that the structural strength of the hollow fiber composite membrane is improved; in addition, through separately regulating and controlling the membrane preparation formulas of the spinning solution of the separation layer and the spinning solution of the support layer, the hydrophilic separation layer can be prepared, so that the hydration layer is formed on the surface and the pores of the separation layer to improve the hydrophilicity, the blood compatibility of the hollow fiber composite membrane is improved, meanwhile, the wall thickness of the separation layer can be regulated and controlled, the filtration resistance of the hollow fiber composite membrane is reduced, the porous layer can be prepared by regulating the membrane preparation formulas of the spinning solution of the support layer, so that the filtration resistance of the hollow fiber composite membrane is further reduced, and the spinning solution of the separation layer and the spinning solution of the support layer use main materials with similar structures.

In addition, the separation layer spinning solution, the support layer spinning solution and the core solution are prepared into the hollow fiber composite membrane through the coextrusion process by the coextrusion process, one-step membrane formation can be realized, the large-scale production is convenient, and the membrane is prepared through the coextrusion process, so that the hydrophilic separation layer in direct contact with blood can be combined on the support layer, the blood compatibility of the hollow fiber composite membrane is improved, the membrane preparation formulas of the separation layer and the support layer can be regulated and controlled separately, the structure of the hollow fiber composite membrane is optimized, and the performance of the hollow fiber composite membrane is improved.

Drawings

FIG. 1 is a flow chart of a method for preparing a hollow fiber composite membrane according to an embodiment of the present invention;

FIG. 2 is a schematic view of a three-hole annular spinneret according to an embodiment of the present invention;

FIG. 3 is a cross-sectional electron microscope of the hollow fiber composite membrane prepared in example 1 of the present invention;

FIG. 4 is a sectional electron microscopic view of a separation layer of a hollow fiber membrane produced in example 1 of the present invention.

Reference numerals illustrate:

200-core liquid channels; 210-separation layer solution channel; 220-support layer solution channels.

Detailed Description

In order that the above objects, features and advantages of the invention will be readily understood, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.

It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other.

In addition, the terms "comprising," "including," "containing," "having" and their derivatives are not limiting, as other steps and other ingredients not affecting the result may be added. Materials, equipment, reagents are commercially available unless otherwise specified.

In addition, although the steps in the preparation are described in the form of step S100, step S200, step S300, etc., the description is only for convenience of understanding, and the form of step S100, step S200, step S300, etc. does not represent a limitation of the sequence of the steps.

Referring to fig. 1, the embodiment of the invention provides a preparation method of a hollow fiber composite membrane, which comprises the following steps:

step S100, uniformly mixing the modified polyethersulfone mixture, the hydrophilic additive and the organic solvent to prepare a separation layer spinning solution;

step 200, uniformly mixing the modified polyethersulfone mixture, the plasticizer, the pore-forming agent and the organic solvent to prepare a supporting layer spinning solution;

step S300, forming an initial membrane by using a separation layer spinning solution, a support layer spinning solution and core liquid through a coextrusion process, and obtaining a hollow fiber composite membrane after solidifying and cleaning the initial membrane;

According to the preparation method of the hollow fiber composite membrane provided by the embodiment, the separation layer spinning solution and the support layer spinning solution are prepared from the modified polyethersulfone mixture, the modified polyethersulfone mixture comprises polyethersulfone and/or hydroxyl-terminated polyethersulfone, the hydroxyl-terminated polyethersulfone is water-insoluble hydrophilic modified polyethersulfone, and the hydrophilic modified polyethersulfone is formed by blending the hydrophilic modified polyethersulfone and the polyethersulfone, so that the hydrophilic performance of the hollow fiber composite membrane can be improved, and the blood compatibility of the hollow fiber composite membrane can be improved; in the film forming process, hydroxyl end groups in hydroxyl end polyether sulfone can form hydrogen bonds with hydrophilic substances (such as water-soluble PVP or PEG molecules and the like), so that the hydrophilic substances are anchored on the surface of the hollow fiber composite film, the blood compatibility of the hollow fiber composite film can be further improved, and the hydroxyl end groups in the hydroxyl end polyether sulfone are connected with the hydrophilic substances through the hydrogen bonds, so that the hydrophilic substances can be more firmly combined on the film forming substances, and the phenomena of falling off or dissolution of the hydrophilic substances are avoided; the polyethersulfone has excellent mechanical properties, and the polyethersulfone is used as a supporting layer spinning solution, so that the structural strength of the hollow fiber composite membrane is improved; in addition, in this embodiment, the hydrophilic separation layer can be prepared by separately controlling the membrane preparation formulation of the separation layer spinning solution and the support layer spinning solution, so that the surface and the pores of the separation layer form a hydration layer to improve the hydrophilicity, thereby improving the blood compatibility of the hollow fiber composite membrane, and simultaneously, the wall thickness of the separation layer can be controlled, and the filtration resistance of the hollow fiber composite membrane is reduced.

Specifically, in step S100, a separation layer spinning solution may be prepared as follows:

and stirring 15 to 35 mass percent of modified polyethersulfone mixture, 25 to 40 mass percent of hydrophilic additive and 45 to 60 mass percent of organic solvent at 30 to 80 ℃ for 12 to 24 hours until the mixture is uniformly mixed, and filtering and vacuum defoaming for 10 to 12 hours to prepare a clear and transparent spinning solution of the separation layer.

The proportion of the components in the spinning solution of the separation layer is limited in a certain range, so that the quality of the hollow fiber composite membrane is improved, the blood compatibility of the hollow fiber composite membrane is further improved, the wall thickness of the separation layer is regulated and controlled, the filtration resistance of the hollow fiber composite membrane is further reduced, and the efficiency of blood purification is improved.

Wherein the modified polyethersulfone mixture comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture is hydroxyl-terminated polyethersulfone.

If the modified polyethersulfone mixture comprises polyethersulfone and hydroxyl terminated polyethersulfone, the polyethersulfone and hydroxyl terminated polyethersulfone may be combined in any ratio, without further limitation in this example. For example: the polyethersulfone and the end-hydroxylated polyethersulfone may be mixed according to 25% polyethersulfone and 75% end-hydroxylated polyethersulfone.

The hydroxyl-terminated polyethersulfone in this example is commercially available, and the molecular structure of the hydroxyl-terminated polyethersulfone is as follows:

in this embodiment, the hydrophilic additive is one or a combination of two of polyethylene glycol, cellulose acetate, polyvinyl alcohol and polymethyl methacrylate, wherein the polyethylene glycol may be one or a combination of two of PEG200, PEG400, PEG600, PEG800 and PEG 1000. The organic solvent is one or two of triethyl phosphate, N-methyl formamide, N-dimethyl acetamide and N-methyl pyrrolidone. The use of the above-described types of hydrophilic additives and organic solvents can further improve the hydrophilicity and biocompatibility of the resulting hollow fiber composite membrane relative to other types of hydrophilic additives and organic solvents in the prior art.

When the spinning solution is prepared, the polyether sulfone, the hydroxyl-terminated polyether sulfone and the hydrophilic additive are dissolved in the organic solvent together, so that blending is realized, and the hollow fiber composite membrane with good blood compatibility is favorably prepared through the advantages of blending and hydrogen bonding, and hydrophilic substances are favorably and firmly combined on the modified polyether sulfone mixture.

Specifically, the support layer spinning solution may be prepared in step S200 as follows:

10 to 25 mass percent of modified polyethersulfone mixture, 5 to 30 mass percent of plasticizer, 15 to 40 mass percent of pore-forming agent and 30 to 65 mass percent of organic solvent are stirred at 30 to 80 ℃ for 12 to 24 hours until the mixture is uniform, and clear and transparent supporting layer spinning solution is prepared after filtration and vacuum defoamation for 10 to 12 hours.

The proportion of the usage amount of each component in the spinning solution of the support layer is limited in a certain range, the aperture of the support layer is favorably regulated and controlled, and the support layer with a porous structure is prepared, so that the filtration resistance of the hollow fiber composite membrane is further reduced, and the efficiency of blood purification is favorably improved.

Wherein the modified polyethersulfone mixture comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture is polyethersulfone.

If the separation layer spinning solution contains polyethersulfone and hydroxyl-terminated polyethersulfone, the support layer spinning solution may contain both polyethersulfone and hydroxyl-terminated polyethersulfone, or may contain only polyethersulfone; if the separation layer spinning solution contains hydroxyl-terminated polyethersulfone, the support layer spinning solution can contain polyethersulfone and hydroxyl-terminated polyethersulfone at the same time, or can only contain polyethersulfone, so long as the mixture of modified polyethersulfone in the separation layer spinning solution and the mixture of modified polyethersulfone in the support layer spinning solution can contain polyethersulfone and hydroxyl-terminated polyethersulfone at the same time, and the blending membrane preparation of polyethersulfone and hydroxyl-terminated polyethersulfone is ensured, thereby being beneficial to improving the hydrophilic performance of the hollow fiber composite membrane and improving the blood compatibility of the hollow fiber composite membrane.

If the modified polyethersulfone mixture comprises polyethersulfone and hydroxyl terminated polyethersulfone, the polyethersulfone and hydroxyl terminated polyethersulfone may be combined in any ratio, without further limitation in this example. For example: the polyethersulfone and the end-hydroxylated polyethersulfone may be mixed as 50% polyethersulfone and 50% end-hydroxylated polyethersulfone.

In this embodiment, the plasticizer is one or two of polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxyethyl cellulose and polymethyl methacrylate, wherein the polyvinylpyrrolidone may be one or two of PVPK15, PVPK17, PVPK30 and PVPK60, and the polyethylene glycol may be one or two of PEG8000, PEG10000 and PEG 20000. The pore-forming agent is one or two of ethanol, glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol and glycerol. The organic solvent is one or two of triethyl phosphate, N-methyl formamide, N-dimethyl acetamide and N-methyl pyrrolidone. Compared with other types of plasticizers, pore-forming agents and organic solvents in the prior art, when the plasticizers, pore-forming agents and organic solvents are adopted, the filtration resistance of the obtained hollow fiber composite membrane can be further improved, and the bonding strength of the separation layer and the support layer can be further improved.

Specifically, the initial film may be prepared in step S300 as follows:

The structure of the three-hole annular spinneret is shown in fig. 2, and the three-hole annular spinneret comprises a core liquid channel 200, a separation layer solution channel 210 and a support layer solution channel 220 which are sequentially arranged from inside to outside, wherein the core liquid channel 200 is a circular channel, the separation layer solution channel 210 and the support layer solution channel 220 are annular channels, and core liquid, separation layer spinning solution and support layer spinning solution are sequentially arranged from inside to outside, so that an initial membrane with good blood compatibility and mechanical property is formed.

After the initial film is prepared, the initial film firstly passes through an air section, the relative humidity of the air section is 30-90%, the temperature is 30-50 ℃, and the residence time of the initial film in the air section is 0.5-1.5 s; after passing through the air section, the initial film enters a coagulating bath for coagulation, the liquid level of the coagulating bath is kept constant, and the hollow fiber composite film is prepared by fully coagulating and forming in the coagulating bath.

In the embodiment, the initial membrane passes through the air section and then passes through the coagulating bath, so that the aperture from the inner wall of the hollow fiber composite membrane to the aperture from the outer wall of the hollow fiber composite membrane is increased gradually, the thickness of the inner wall of the hollow fiber composite membrane is reduced, the resistance in the dialysis process of the hollow fiber composite membrane is reduced, and the efficiency of blood purification is improved.

In this embodiment, the core liquid may be prepared by mixing the porogen and the organic solvent, or the core liquid may be prepared by mixing water and the organic solvent.

In order to be able to further improve the hydrophilicity and biocompatibility of the resulting hollow fiber composite membrane, the porogen comprises one or a combination of two of ethanol, ethylene glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol and glycerol; the organic solvent comprises one or two of triethyl phosphate, N-methyl formamide, N-dimethyl acetamide and N-methyl pyrrolidone.

In this example, the coagulation bath was prepared by mixing water and an organic solvent, specifically, 40 to 90% by mass of water and 10 to 60% by mass of an organic solvent were uniformly mixed to prepare the coagulation bath.

Alternatively, in this embodiment, the coagulation bath is prepared by mixing water and a pore-forming agent, specifically, water with a mass percentage of 30% to 80% and a pore-forming agent with a mass percentage of 20% to 70% are uniformly mixed, and the coagulation bath is prepared.

In order to be able to further improve the hydrophilicity and biocompatibility of the resulting hollow fiber composite membrane, the organic solvent includes one or a combination of two of triethyl phosphate, N-methyl formamide, N-dimethylacetamide, N-methylpyrrolidone.

And after the hollow fiber composite membrane is fully solidified in the coagulating bath, the method further comprises the steps of washing the initial membrane after shaping by water, and drying after the water washing is finished to obtain the hollow fiber composite membrane, wherein the water temperature is 80-100 ℃ during the water washing, and the drying temperature is 30-60 ℃.

The water washing can remove chemical substances such as additives and solvents in the hollow fiber composite membrane, the residual quantity of the chemical substances has great influence on blood compatibility, and the drying can remove the water in the hollow fiber composite membrane, so that the internal stress can be eliminated, and the dimensional stability of the hollow fiber composite membrane can be improved.

The water used in this example was purified water or hemodialysis water.

In order to further explain the present invention in detail, the present invention will be further described with reference to specific examples. The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified; materials, reagents, and the like used in the examples of the present invention were commercially available, and the model was Hydroxyl terminatedPES, as described in no particular way, and were obtained by commercially purchasing a hydroxyl-terminated polyethersulfone from SUMITOMO CHEMICAL.

Example 1

The embodiment provides a preparation method of a hollow fiber composite membrane, which comprises the following steps:

(1) Stirring and mixing 70wt% of polyethersulfone and 30wt% of hydroxyl-terminated polyethersulfone uniformly to prepare a modified polyethersulfone mixture; stirring 18wt% of modified polyethersulfone mixture, 40wt% of hydrophilic additive PEG600 and 52wt% of organic solvent N, N-dimethylacetamide at 50 ℃ for 24 hours until the mixture is uniformly mixed, and filtering and vacuum defoaming for 12 hours to prepare a clear and transparent spinning solution of a separation layer;

16% of polyethersulfone, 8% of plasticizer polyvinylpyrrolidone, 25% of pore-forming agent ethylene glycol monomethyl ether and 51% of organic solvent N, N-dimethylacetamide by mass percentage are stirred at 50 ℃ for 24 hours until the mixture is uniform, and clear and transparent spinning solution of the support layer is prepared after filtration and vacuum defoamation for 12 hours;

uniformly stirring and mixing 5wt% of organic solvent N, N-dimethylacetamide and 95wt% of water to prepare core liquid;

70 weight percent of water and 30 weight percent of organic solvent N, N-dimethylacetamide are stirred and mixed uniformly to prepare the coagulation bath.

(2) Extruding the spinning solution of the separation layer, the spinning solution of the support layer and the core solution from a three-hole annular spinneret simultaneously, wherein the three-hole annular spinneret comprises a core solution channel, a separation layer solution channel and a support layer solution channel which are sequentially arranged from inside to outside, the core solution is extruded from the core solution channel, the spinning solution of the separation layer is extruded from the separation layer solution channel, and the spinning solution of the support layer is extruded from the support layer solution channel to prepare the initial membrane.

(3) The method comprises the steps of enabling an initial film to pass through an air section, keeping the temperature and the humidity of the air section constant, keeping the relative humidity of the air section at 60%, keeping the temperature at 40 ℃, keeping the residence time of the initial film in the air section at 1s, enabling the pre-phase initial film to enter a coagulating bath for coagulating after the initial film passes through the air section, keeping the liquid level of the coagulating bath constant, enabling the pre-phase initial film to enter a cleaning water tank after being fully coagulated in the coagulating bath, keeping the temperature of the cleaning water tank at 90 ℃, enabling the initial film after cleaning to enter a circulating hot air drying box after cleaning, and drying at 45 ℃ to obtain the hollow fiber composite film.

The cross-sectional electron microscope of the hollow fiber composite membrane prepared in this example is shown in fig. 3, and the cross-sectional electron microscope of the separation layer of the hollow fiber composite membrane prepared in this example is shown in fig. 4. As can be seen from fig. 3 to fig. 4, the interface between the separation layer and the support layer of the hollow fiber composite membrane prepared in this embodiment is relatively firm, which is favorable for improving the mechanical strength of the hollow fiber composite membrane, and the support layer is of a porous structure, so that the wall thickness of the separation layer is smaller, which is favorable for reducing the filtration resistance of the hollow fiber composite membrane and improving the efficiency of blood purification.

Example 2

The present embodiment provides a method for preparing a hollow fiber composite membrane, which is substantially the same as the method for preparing the hollow fiber composite membrane in embodiment 1, except that the proportions of the components in the spinning solution for the separation layer and the spinning solution for the support layer are different, specifically:

stirring and mixing 20wt% of polyethersulfone and 80wt% of hydroxyl-terminated polyethersulfone uniformly to prepare a modified polyethersulfone mixture; stirring 18wt% of modified polyethersulfone mixture, 35wt% of hydrophilic additive PEG600 and 57wt% of organic solvent N, N-dimethylacetamide at 50 ℃ for 24 hours until the mixture is uniformly mixed, and filtering and vacuum defoaming for 12 hours to prepare a clear and transparent spinning solution of a separation layer;

16 mass percent of polyethersulfone, 8 mass percent of plasticizer polyvinylpyrrolidone, 28 mass percent of Kong Jibing triol and 48 mass percent of organic solvent N, N-dimethylacetamide are stirred at 50 ℃ for 24 hours until the mixture is uniform, and the clear and transparent spinning solution of the support layer is prepared after filtration and vacuum defoamation for 12 hours.

Example 3

the modified polyethersulfone mixture is only hydroxyl-terminated polyethersulfone; stirring 18wt% of modified polyethersulfone mixture, 35wt% of hydrophilic additive PEG600 and 57wt% of organic solvent N, N-dimethylacetamide at 50 ℃ for 24 hours until the mixture is uniformly mixed, and filtering and vacuum defoaming for 12 hours to prepare a clear and transparent spinning solution of a separation layer;

the preparation method comprises the steps of stirring polyether sulfone with the mass percentage of 15%, polyvinylpyrrolidone with the mass percentage of 10%, kong Jibing triol with the mass percentage of 27% and organic solvent N, N-dimethylacetamide with the mass percentage of 48% at 50 ℃ for 24 hours until the mixture is uniform, and obtaining clear and transparent spinning solution of the support layer after filtration and vacuum defoamation for 12 hours.

Example 4

stirring and mixing 20wt% of polyethersulfone and 80wt% of hydroxyl-terminated polyethersulfone uniformly to prepare a modified polyethersulfone mixture; stirring 18wt% of modified polyethersulfone mixture, 35wt% of hydrophilic additive PEG400 and 57wt% of organic solvent N, N-dimethylacetamide at 50 ℃ for 24 hours until the mixture is uniformly mixed, and filtering and vacuum defoaming for 12 hours to prepare a clear and transparent spinning solution of a separation layer;

8% of polyether sulfone, 8% of hydroxyl-terminated polyether sulfone, 9% of plasticizer polyvinylpyrrolidone, 25% of pore-forming agent ethylene glycol monomethyl ether and 50% of organic solvent N, N-dimethylacetamide are stirred for 24 hours at 50 ℃ until the components are uniformly mixed, and the clear and transparent spinning solution of the support layer is prepared after filtration and vacuum defoaming for 12 hours.

The performance of the hollow fiber composite membranes of examples 1 to 4 was tested, and the blood compatibility of the hollow fiber composite membranes was mainly characterized by adopting an inner surface contact angle, a calcium recovery time and a hemolysis rate, wherein the smaller the inner surface contact angle is, the better the surface hydrophilicity of the hollow fiber composite membranes is; the longer the recalcification time, the lower the hemolysis rate, indicating better blood compatibility. The specific test method is as follows:

1. contact angle test of inner surface

The hollow fiber composite membrane sample is flatly paved on a carrying platform, a baseline is leveled, then about 5 mu L of deionized water is dripped on the surface of the membrane, a rotation tester is regulated, and a contact angle is read. Three parallel samples were measured for each hollow fiber composite membrane, 7 test points were taken on each sample, and the average of the test results was taken.

2. Multiple calcium time (PRT) test

(1) Taking 5mL of bovine whole blood, centrifuging (2000 g, about 4411r/min,10 min), and taking supernatant to obtain Platelet Poor Plasma (PPP);

(2) Placing the hollow fiber composite membrane into a 24-hole cell culture plate, marking, dripping 0.1mL of PPP onto the surface of the membrane in a constant-temperature water bath at 37 ℃ and keeping for one minute;

(3) 0.1mL of CaCl 2 solution, preheated to 37℃at 0.025mol/L, was added dropwise to the surface of the above film, the timing was stopped when the first fibrin thread was observed to appear, and the recalcification time was recorded.

3. Hemolysis Rate (HR) test

(1) Washing the hollow fiber composite membrane with deionized water for 10min, and then washing the membrane with NaCl solution with mass fraction of 0.9% for 10min;

(2) Soaking the membrane in NaCl solution with the mass fraction of 0.9% at 37 ℃ for 30min;

(3) Adding 200 mu L of whole bovine blood into the NaCl solution with the membrane, the NaCl solution without the membrane and pure water respectively, and keeping the temperature at 37 ℃ for 1h;

(4) The above sample was centrifuged (800 g, about 2790r/min,10 min), the supernatant was taken and the absorbance was measured at 545nm with an ultraviolet spectrophotometer. 0.9wt% NaCl aqueous solution was used as a negative control, deionized water was used as a positive control, and the hemolysis ratio was calculated by the following formula (1):

HR= (AS-AN)/(AP-AN). Times.100% equation (1)

Wherein: AS-absorbance of the sample; absorbance of AN-negative control; absorbance of the AP-positive control.

The hollow fiber composite membrane prepared by the method is applied to the separation of plasma components, and pathogenic substances in blood are removed (the pathogenic substances depend on the types of diseases), so that an application occasion of the invention, such as severe autoimmune diseases (SAID), is realized, immune complex, immunoglobulin, complement and other pathogenic factors in plasma are directly removed by double plasma replacement treatment, and the cellular immune function and reticuloendothelial phagocytic function of a patient are recovered, and links of SAID generation and development are blocked in time, so that the purpose of relieving the illness state can be achieved.

The hollow fiber composite membranes prepared in examples 1 to 4 were processed to obtain a hollow fiber plasma component separator having an effective membrane area of 1.0m ² . The blood plasma is fresh anticoagulated bovine blood, and bovine blood plasma at 37deg.C

Controlling the flow rate of the plasma inlet at 100ml/min, the flow rate of the filtered solution at 25ml/min, the flow rate of the waste plasma at 5-10ml/min, and the treatment time at 3h. Membrane performance was assessed by determining the concentration of each protein in the solution and in the plasma prior to filtration.

Clearance (%) = (1-concentration in filtrate/concentration in stock solution) ×100%

The hollow fiber composite membrane was subjected to a hemolysis test, and the plasma component separator made of the hollow fiber composite membrane was subjected to an immunoglobulin removal performance test, the test results being shown in table 1.

TABLE 1

As can be seen from table 1, compared with example 1, the contact angle of the inner surface of the hollow fiber composite membranes in examples 2 to 4 is greatly reduced, which indicates that the content of hydroxyl-terminated polyethersulfone in the separation layer of the hollow fiber composite membrane is increased, which is beneficial to improving the hydrophilic performance of the inner surface of the membrane; and the calcium recovery time of the hollow fiber composite membranes in examples 2 to 4 is longer than that of the hollow fiber composite membrane in example 1, and the hemolysis rate of the hollow fiber composite membranes in examples 2 to 4 is lower than that of the hollow fiber composite membrane in example 1, which means that as the content of hydroxyl-terminated polyethersulfone in the separation layer of the hollow fiber composite membrane increases, the hemolysis rate decreases, and the calcium recovery time increases, which is advantageous for improving the blood compatibility of the hollow fiber composite membrane. The separation layer and the support layer of the hollow fiber composite membrane of example 4 both contain hydroxyl-terminated polyethersulfone and polyethersulfone, which is advantageous for further improving the blood compatibility of the whole membrane section as compared with the hollow fiber composite membranes of examples 2 and 3 in which only the separation layer contains both hydroxyl-terminated polyethersulfone and polyethersulfone.

The hollow fiber composite membranes in examples 1 to 4 can be used in a plasma component separator to remove various pathogenic factors such as immunoglobulin, complement, immune complex, macromolecular lipoprotein in blood, and the like, and albumin with smaller molecular mass can permeate back to a patient through a membrane hole, so that the purposes of removing harmful components in blood and treating diseases are achieved. The hollow fiber composite membranes of examples 1 to 4 were used for the immunoglobulin clearance test, and the test results showed that the hollow fiber composite membranes prepared in examples 1 to 4 all showed good clearance performance for immunoglobulins, and the hollow fiber composite membrane prepared in example 2 showed the most prominent clearance performance for three immunoglobulins, igG, igM, and IgA.

In order to further explain the present invention in detail, the present invention will be further described with reference to specific examples. The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified; materials, reagents, and the like used in the examples of the present invention were commercially available unless otherwise specified.

Claims

1. The preparation method of the hollow fiber composite membrane is characterized by comprising the following steps:

uniformly mixing a modified polyethersulfone mixture, a hydrophilic additive and an organic solvent to prepare a separation layer spinning solution, wherein the hydrophilic additive is one or a combination of two of polyethylene glycol, cellulose acetate, polyvinyl alcohol and polymethyl methacrylate;

uniformly mixing a modified polyethersulfone mixture, a plasticizer, a pore-forming agent and an organic solvent to prepare a supporting layer spinning solution, wherein the plasticizer is one or two of polyvinylpyrrolidone, polyethylene glycol, carboxymethyl cellulose, hydroxyethyl cellulose and polymethyl methacrylate, and the pore-forming agent is one or two of ethanol, ethylene glycol, isopropanol, ethylene glycol monomethyl ether, diethylene glycol and glycerol;

wherein the modified polyethersulfone mixture in the spinning solution of the separation layer comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture in the spinning solution of the separation layer is hydroxyl-terminated polyethersulfone;

the modified polyethersulfone mixture in the supporting layer spinning solution comprises polyethersulfone and hydroxyl-terminated polyethersulfone, or the modified polyethersulfone mixture in the supporting layer spinning solution is polyethersulfone.

2. The method for preparing a hollow fiber composite membrane according to claim 1, wherein the spinning solution for the separation layer is prepared by the following method:

3. The method for preparing a hollow fiber composite membrane according to claim 1, wherein the support layer spinning solution is prepared by the following method:

4. The method for producing a hollow fiber composite membrane according to claim 1, wherein,

5. The method for preparing a hollow fiber composite membrane according to claim 1, wherein the initial membrane is prepared by the following method:

6. The method for producing a hollow fiber composite membrane according to claim 1, wherein the initial membrane is coagulated by:

7. A hollow fiber composite membrane produced by the method for producing a hollow fiber composite membrane according to any one of claims 1 to 6.