CN113350589B - Anti-fouling modification method of hemodialyzer and application thereof - Google Patents
Anti-fouling modification method of hemodialyzer and application thereof Download PDFInfo
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- CN113350589B CN113350589B CN202010146538.9A CN202010146538A CN113350589B CN 113350589 B CN113350589 B CN 113350589B CN 202010146538 A CN202010146538 A CN 202010146538A CN 113350589 B CN113350589 B CN 113350589B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1621—Constructional aspects thereof
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
- B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
Abstract
The invention discloses an anti-fouling modification method of a hemodialyzer and application thereof. The anti-fouling modification method of the hemodialyzer comprises the following steps: reacting a uniformly mixed reaction system containing a zwitterion monomer, an imine monomer and water at 50-60 ℃ for 2-4 h to obtain a zwitterion polymer aqueous solution with an end group containing amino; contacting the inner surface of the membrane wire of the hemodialyzer with a phenol substance aqueous solution for 12-24 h, and then separating; and contacting the inner surface of the membrane wire of the hemodialyzer with the zwitterionic polymer aqueous solution, reacting for 2-5 h at 55-65 ℃, and obtaining the high-stain-resistant hemodialyzer through Schiff base reaction polymerization. The high-pollution-resistance hemodialyzer prepared by the invention has excellent pollution resistance, can prevent protein in blood plasma from adsorbing so as to inhibit thrombus from being generated on the surface of hemodialysis, and meanwhile, the preparation method has the advantages of green and pollution-free process, mild reaction conditions, easiness in operation and realization and easiness in industrialization.
Description
Technical Field
The invention belongs to the field of blood purification, and particularly relates to a high anti-pollution modification method of a hemodialyzer and application of the high anti-pollution modification method in blood purification.
Background
End-stage renal disease (ESRD) refers to the irreversible loss of the function of the kidney to remove excess water, metabolic wastes and endotoxins from the human body, and all patients with chronic kidney disease eventually progress to end-stage renal disease. Hemodialysis is a main means for treating end-stage renal diseases, and a hemodialyzer is commonly called as an artificial kidney and has the functions of replacing the kidney of a human body to remove metabolic wastes and redundant water accumulated in the body, simultaneously supplementing substances required in the body and maintaining the balance of electrolytes and acid and alkali. In the hemodialysis process, venous blood is drained from a human body to the outside of the body and passes through the inner side of a membrane of a hemodialyzer, dialysate is arranged on the outer side of the membrane, and driving force is generated by the difference of the flow speed and the concentration of solutes of liquid on the two sides, so that redundant moisture and toxins in the blood are diffused into the dialysate on the outer side of the membrane, and clean blood returns to an arterial blood vessel.
The polymer membrane has the advantages of multiple types, convenient processing and easy modification to obtain the required performance, so the polymer membrane as a second generation membrane replaces a cellulose membrane and quickly occupies the market, and comprises a polysulfone membrane PS, a polyether sulfone membrane PES, a polyacrylonitrile membrane PAN and polymethyl methacrylate PMMA. However, the inherent hydrophobic property of the polymeric membrane is easy to adhere to various proteins in blood plasma through hydrophobic-hydrophobic adsorption, which not only can block the membrane pores of the hemodialyzer to cause rapid reduction of dialysis efficiency, but also can trigger two coagulation paths of coagulation waterfall, which causes thrombus to form on the inner surface of the membrane filaments of the hemodialyzer to cause interruption of the dialysis process. Therefore, in order to prevent proteins in plasma from adhering to the surface of the hydrophobic material, improvement of hemocompatibility on the inner surface of the membrane filaments of the dialyzer can effectively solve this problem.
In recent years, many documents and patents have been reported in terms of improving the hemocompatibility of hemodialysis materials. Patent publication No. CN109675134A discloses a hemodialyzer with self-anticoagulation properties prepared by a slightly swelling crosslinking method. CN106310970A grafts acryloyl morpholine and argatroban on PVDF by alkali treatment method, then blends and modifies the copolymer and PVDF, and prepares modified hollow fiber hemodialysis membrane with good biocompatibility and anticoagulation characteristic by dry-wet spinning technology. CN104208766A prepares membrane material with hydrophilic property by blending zwitterionic polymer to spin hollow membrane, and reduces pollution of protein. However, these modification methods have the characteristics of difficult processing, complex preparation means and difficulty in realizing large-scale production. In addition, the modified polymer and the modification process are all participated in by the organic solvent, the subsequent removal is very difficult, and the residue of the organic solvent has great potential safety hazard to patients in the dialysis process.
Disclosure of Invention
The invention mainly aims to provide a method for modifying the pollution resistance of a hemodialyzer, thereby overcoming the defects of the prior art.
It is another object of the present invention to provide a highly fouling resistant hemodialyzer obtained by the aforementioned fouling resistant modification process.
Another object of the present invention is to provide the use of said hemodialyzer of the highly dirt-resistant type in the field of blood purification.
In order to achieve the purpose, the technical scheme adopted by the invention comprises the following steps:
the embodiment of the invention provides an anti-fouling modification method of a hemodialyzer, which comprises the following steps:
reacting a uniformly mixed reaction system containing a zwitterion monomer, an imine monomer and water at 50-60 ℃ for 2-4 h to obtain a zwitterion polymer aqueous solution with an end group containing amino;
the inner surface of the membrane wire of the hemodialyzer is contacted with a phenol substance water solution for 12 to 24 hours and then separated; and
the inner surface of the membrane wire of the hemodialyzer is contacted with the zwitterionic polymer aqueous solution and reacts for 2 to 5 hours at the temperature of between 55 and 65 ℃, and the high-pollution-resistant hemodialyzer is obtained through Schiff base reaction polymerization.
In some embodiments, the anti-fouling modification process specifically comprises: and injecting the zwitterionic polymer aqueous solution into a hemodialyzer, heating to 55-65 ℃, and reacting amino in the zwitterionic polymer with the phenol substances on the inner surface of the membrane filaments of the hemodialyzer for 3-5 hours through Schiff base, so that the zwitterionic polymer is stably loaded on the inner surface of the membrane filaments of the hemodialyzer to which the phenol substances are adhered.
The embodiment of the invention also provides a high anti-fouling hemodialyzer obtained by the method.
The embodiment of the invention also provides the application of the high anti-pollution hemodialyzer in the field of blood purification.
Compared with the prior art, the invention has the beneficial effects that:
1) The anti-fouling modification method of the hemodialyzer provided by the invention has the advantages that the zwitterionic polymer with amino groups at the end groups is synthesized, and then the amino groups in the zwitterionic polymer are reacted with the phenol substances on the inner surface of the membrane filaments of the hemodialyzer through Schiff base so as to realize the stable load of zwitterions on the inner surface of the membrane filaments, so that a hydrophilic functional layer is formed on the inner surface of the membrane filaments of the hemodialyzer, and the hemodialyzer prepared by effectively inhibiting the adsorption of proteins in blood plasma has excellent anti-fouling performance and blood compatibility;
2) The anti-fouling modification method of the hemodialyzer provided by the invention is based on a water system in the whole process, and does not generate the influence of swelling on membrane filaments of the hemodialyzer and damage the porous structure of the membrane, so that the ultrafiltration coefficient and the toxin clearance rate of the hemodialyzer are not reduced. Furthermore, the method does not involve an organic solvent, so that the subsequent cleaning treatment is very simple;
3) The anti-fouling modification method provided by the invention has the advantages of mild reaction conditions, easiness in operation and realization and easiness in realization of industrialization.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments described in the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
Fig. 1 is a view showing the inner surface micro-topography of membrane filaments of the hemodialyzer of comparative example 1.
FIG. 2 is a structural view of the inner surface micro-topography of membrane filaments of a high anti-fouling hemodialyzer obtained in example 1 of the present invention.
FIG. 3 is a graph showing the results of membrane filament ultrafiltration coefficient tests of the hemodialyzer of comparative example 1 and the hemodialyzer with high fouling resistance obtained in example 1.
FIG. 4 is a schematic view showing the adsorption test of plasma proteins by the hemodialyzer membrane filaments of comparative example 1, and the observation of the proteins adhered to the inner surface of the membrane filaments under a scanning electron microscope.
FIG. 5 is a schematic diagram of the adsorption test of plasma proteins by the membrane filaments of the high anti-fouling hemodialyzer obtained in example 1 of the present invention, and the proteins adhered to the inner surfaces of the membrane filaments are observed under a scanning electron microscope.
Detailed Description
As described above, in view of the deficiencies of the prior art, the inventors of the present invention have made extensive studies and extensive practices, and propose a technical solution of the present invention, which provides a method for improving the anti-fouling performance of a hemodialyzer, wherein a zwitterionic polymer having an amino group at the end group is synthesized, and then the amino group in the zwitterionic polymer is linked with a phenol substance on the inner surface of a membrane filament of the hemodialyzer through a schiff base reaction, so that a stable loading of the zwitterion on the inner surface of the membrane filament is realized, thereby imparting excellent anti-fouling performance and hemocompatibility to the hemodialyzer.
The invention fixes the zwitterion hydrophilic functional layer on the inner surface of the hollow fiber membrane wire of the hemodialyzer in a layer-by-layer assembly mode. The hemodialyzer with excellent stain resistance can be prepared by simple soaking and then under mild reaction conditions, and the preparation method is simple. In addition, the whole synthesis process and the modification process of the modified polymer are water-based systems, so that the participation of organic solvents is eliminated, and the modified polymer has great application prospect in the field of subsequent clinical hemodialysis.
The technical solution, its implementation and principles, etc. will be further explained as follows.
One aspect of an embodiment of the present invention provides a method for modifying an anti-fouling of a hemodialyzer, comprising:
reacting a uniformly mixed reaction system containing a zwitterion monomer, an imine monomer and water at 50-60 ℃ for 2-4 h to obtain a zwitterion polymer aqueous solution with an end group containing amino;
the inner surface of the membrane wire of the hemodialyzer is contacted with a phenol substance water solution for 12 to 24 hours and then separated; and
the inner surface of the membrane wire of the hemodialyzer is contacted with the zwitterionic polymer aqueous solution, reacts for 2-5 h at 55-65 ℃, and is polymerized by Schiff base reaction to obtain the high anti-fouling hemodialyzer.
In some embodiments, the anti-fouling modification process specifically comprises: dissolving the phenol substances in an alkaline aqueous solution or a Tris-HCl aqueous solution, and standing in the air for 12-24 h to obtain a uniform phenol substance aqueous solution.
In some preferred embodiments, the phenolic substances include any one or a combination of two or more of tannic acid, dopamine, epinephrine, norepinephrine, and the like, but are not limited thereto.
In some preferred embodiments, the pH of the aqueous alkaline solution or aqueous Tris-HCl solution is between 8 and 8.5.
In some preferred embodiments, the mass ratio of the phenol substance to the alkaline aqueous solution or the Tris-HCl aqueous solution is 0.2-0.25: 1.
in some embodiments, the zwitterionic monomer includes any one or a combination of two or more of phosphorylcholine, carboxybetaine, sulfobetaine, trimethoxy derivative, and the like, but is not limited thereto.
In some embodiments, the imine-based monomer includes any one or a combination of two or more of polyethyleneimine, p-phenylenediamine, polypropyleneimine, and the like, but is not limited thereto.
Further, the mass ratio of the combination of the zwitterionic monomer and the imine monomer to water (preferably deionized water) is 20-60: 100, more specifically, the mass ratio of the deionized water to the combination of the zwitterionic monomer and the imine monomer is 100:20 to 60, namely, the total amount of the zwitterion monomer and the imine monomer added is 20 to 60 parts by mass per 100 parts by mass of the deionized water.
In some embodiments, the anti-fouling modification process specifically comprises: and injecting the phenol substance aqueous solution into a hemodialyzer, fully wetting the inner surface of the membrane wire of the hemodialyzer by the phenol substance aqueous solution, keeping the inner surface for 12-24 hours, adsorbing the phenol substance on the inner surface of the membrane wire of the hemodialyzer, and then discharging the phenol substance aqueous solution out of the hemodialyzer.
In some embodiments, the anti-fouling modification process specifically comprises: and injecting the zwitterionic polymer aqueous solution into a hemodialyzer, heating to 55-65 ℃, and reacting amino in the zwitterionic polymer with the phenol substances on the inner surface of the membrane filaments of the hemodialyzer for 3-5 hours through Schiff base, so that the zwitterionic polymer is stably loaded on the inner surface of the membrane filaments of the hemodialyzer to which the phenol substances are adhered.
Further, the anti-fouling modification method further comprises the following steps: and discharging the zwitterionic polymer aqueous solution out of the hemodialyzer, finally cleaning, and drying at the temperature of 80-90 ℃ for 24-28 h to obtain the high-pollution-resistance hemodialyzer.
In some more preferred embodiments, the method of anti-fouling modification of a hemodialyzer comprises:
dissolving a phenol substance in an aqueous solution to obtain a uniform phenol substance aqueous solution;
contacting the inner surface of the membrane wire of the hemodialyzer with the phenol substance aqueous solution for 12-24 h, and then separating;
reacting a uniformly mixed reaction system of a zwitterionic monomer, an imine monomer and water at 50-60 ℃ for 2-4 h to obtain a zwitterionic polymer aqueous solution with an amino-containing end group;
and (3) placing the inner surface of the membrane wire of the hemodialyzer in the zwitterion polymer aqueous solution, reacting for 3-5 h at the temperature of 55-65 ℃, and carrying out Schiff base reaction polymerization to obtain the hemodialyzer with high anti-pollution property.
Further, the anti-fouling modification method comprises the following steps: firstly, introducing a phenol substance water solution into a polysulfone hemodialyzer to ensure that the phenol substance can be uniformly adhered to the inner surface of a membrane wire of the dialyzer; and then contacting the hemodialyzer with a zwitterionic polymer aqueous solution, reacting for 2-4 h at 55-65 ℃, further performing polymerization reaction to fix the zwitterionic polymer on the phenol coating, and then cleaning and drying the hemodialyzer to obtain the hemodialyzer with stable and excellent antifouling performance.
As a more specific embodiment, the method for modifying the anti-fouling of the hemodialyzer comprises the following steps:
s1: preparing a phenol substance aqueous solution;
s2: injecting the prepared phenol substance water solution into a hemodialyzer to enable the hemodialyzer to completely infiltrate the inner surface of the membrane yarn, and then staying for 12-24 hours;
s3: synthesizing a zwitterionic polymer aqueous solution with amino at the end group;
s4: and (2) discharging the phenol substance water solution from the hemodialyzer, then injecting the zwitterionic polymer water solution, reacting for 2-5 h at 55-65 ℃, then discharging the zwitterionic polymer water solution, and cleaning and drying by using a large amount of deionized water to finally obtain the hemodialyzer with high anti-pollution performance.
In some embodiments, in step S1, in order to better prepare the aqueous solution of phenols so that it can exert better self-adhesion properties, the prepared aqueous solution of phenols should be left standing in the air for not less than 24 hours so as to be sufficiently oxidized into quinone group. The pH of the solution is preferably 8.0 to 8.5, and too high or too low a pH may affect the conversion of quinone groups of the phenolic substances and thus the adhesion properties of the phenolic substances.
In some embodiments, the membrane silk material of the hemodialyzer includes any one or a combination of two or more of polysulfone membrane, polyethersulfone membrane, polyacrylonitrile, polymethylmethacrylate, and the like, but is not limited thereto.
Another aspect of embodiments of the invention also provides a highly fouling resistant hemodialyzer obtained by the aforementioned method.
Further, high anti-soil type hemodialyzer includes the hemodialyzer body, and is formed in the anti-soil coating of hemodialyzer body membrane silk internal surface, anti-soil coating includes hydrophilic functional layer, hydrophilic functional layer is by zwitterionic polymer and phenol class material through the free bridging effect of imine class, and the mode through layer upon layer equipment is solid-carried hemodialyzer body membrane silk internal surface.
Another aspect of the embodiments of the present invention also provides the use of the high anti-fouling hemodialyzer obtained by the aforementioned method in the field of blood purification.
In conclusion, the zwitterionic polymer and the phenol substances are connected through the bridging effect of the imine monomers in a layer-by-layer assembly mode, so that the zwitterionic polymer is stably immobilized on the inner surface of the membrane wire of the hemodialyzer, a hydrophilic functional layer is formed on the inner surface of the membrane wire, protein adsorption in blood plasma can be effectively blocked, and the hemodialyzer is endowed with extremely strong anti-fouling property and blood compatibility. Meanwhile, the whole modification process is based on a water system, so that the membrane filaments of the hemodialyzer are not affected by swelling, and the porous structure of the membrane is not damaged, so that the ultrafiltration coefficient and the toxin clearance of the hemodialyzer are not reduced. Furthermore, the method does not involve organic solvent, so that the subsequent cleaning treatment is very simple. Moreover, the reaction condition is mild, the operation and the realization are easy, and the industrialization is easy to realize.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be further explained with reference to the following detailed description and accompanying drawings. It should be understood that the specific embodiments described herein are merely illustrative of the invention, and that experimental conditions and set parameters therein are not to be considered as limitations of the basic embodiments of the invention. And the scope of the present invention is not limited to the following examples. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
To better illustrate the anti-fouling modification method of hemodialyzer and the high anti-fouling property of hemodialyzer prepared by modification, a commercially available hemodialyzer product (encapsulating polysulfone membrane) was first selected as comparative example 1.
Example 1
Dissolving 20g of dopamine powder in 100g of Tris-HCl aqueous solution with the pH value of 8.5, and then standing in the air for 24 hours;
step (2) cleaning a polysulfone dialyzer (packaged polysulfone membrane, namely the product in the comparative example 1) purchased from a market with deionized water for 15min, then injecting the dopamine solution prepared in the step (1) into the hemodialyzer, and staying for 12h to completely wet the inner surface of membrane filaments of the dialyzer;
dissolving 40g of zwitterionic trimethoxy derivative and 20g of polyethyleneimine into 100g of deionized water, and reacting at 60 ℃ for 2h to obtain a zwitterionic polymer aqueous solution rich in amino;
and (4) discharging the dopamine solution out of the hemodialyzer, then injecting the zwitterionic polymer aqueous solution synthesized in the step (3), reacting for 4 hours at 55 ℃, then discharging the solution, washing with deionized water, and drying for 28 hours at 80 ℃ to finally obtain the hemodialyzer with high anti-pollution performance.
And respectively taking out the membrane filaments of the hemodialyzer in the comparative example 1 and the high anti-fouling hemodialyzer obtained in the embodiment, and observing the inner surface micro-topography structure of the membrane filaments by a scanning electron microscope. As can be seen from fig. 1 and fig. 2, the pore structure and distribution of the inner surface of the membrane filament of the hemodialyzer with high anti-fouling performance prepared in this example are almost the same as those of the inner surface of the membrane filament of the hemodialyzer in comparative example 1, which indicates that the anti-fouling modification technology of the present invention does not damage the membrane filament structure of the hemodialyzer and does not reduce the ultrafiltration coefficient and toxin clearance of the hemodialyzer.
The membrane filaments of the hemodialyzer with high fouling resistance obtained in comparative example 1 and the hemodialyzer with high fouling resistance obtained in this example were taken out and subjected to ultrafiltration coefficient tests, respectively. As shown in FIG. 3, the ultrafiltration coefficient of the high anti-fouling hemodialyzer membrane filament obtained in the present example is significantly improved compared to that of the hemodialyzer membrane filament described in comparative example 1, and is increased from 27mL/mmHg h of comparative example 1 to 35mL/mmHg h, which indicates that the modification of the anti-fouling modification technology described in the present invention has no influence on the pore structure of the membrane filament encapsulated by the hemodialyzer, and the hydrophilicity is effectively improved, so that the water flux of the dialyzer is significantly improved.
Respectively take out the pairsThe membrane filaments of the hemodialyzer and the highly anti-fouling hemodialyzer obtained in example 1 were subjected to a plasma protein adsorption test, and the adhesion of proteins to the inner surface of the membrane filaments was observed under a scanning electron microscope. As shown in FIG. 5, the inner surface of the membrane filament of the high anti-fouling dialyzer obtained in the present example has almost no adhesion of plasma proteins, and the adsorption mass of the plasma proteins on the surface of the membrane is roughly estimated to be about 2.5 mug/cm 2 . While the membrane filaments of the hemodialyzer in comparative example 1 shown in FIG. 4 were observed under a microscopic electron microscope, and severe plasma protein adhesion occurred on the inner surface thereof, which was more than 5. Mu.g/cm 2 . The result shows that the blood compatibility of the hemodialyzer is obviously improved after the anti-pollution modification technology is used for modification, and the adsorption of plasma protein can be effectively inhibited.
Example 2
Dissolving 25g of norepinephrine in 100g of water solution, adjusting the pH value to 8.0 by using NaOH, and then standing in the air for 24 hours;
step (2) cleaning a polymethyl methacrylate (PMMA) dialyser purchased from a market by using deionized water for 10min, then injecting the norepinephrine solution prepared in the step (1) into a hemodialyzer, and staying for 14h to ensure that the norepinephrine solution completely wets the inner surface of a membrane wire of the hemodialyzer;
dissolving 25g of zwitterionic carboxyl betaine and 25g of polypropyleneimine in 100g of deionized water, and reacting at 50 ℃ for 3 hours to obtain a zwitterionic polymer aqueous solution rich in amino;
and (4) discharging the noradrenaline solution out of the hemodialyzer, then injecting the zwitterionic polymer aqueous solution synthesized in the step (3), reacting for 4 hours at 55 ℃, then discharging the solution, washing with deionized water, and drying for 26 hours at 85 ℃, thus finally obtaining the hemodialyzer with high antifouling performance.
The ultrafiltration coefficient of the high anti-fouling dialyzer prepared by the embodiment is increased from 25mL/mmHg h to 33mL/mmHg h compared with that of the unmodified dialyzer through ultrafiltration coefficient detection and plasma protein adsorption detection. The adhesion amount of plasma protein of the hemodialyzer prepared in this example was 3. Mu.g/cm 2 。
Example 3
Putting 20g of tannic acid substance into 100g of deionized water solution, adjusting the pH value to 8.0 by using NaOH, and then standing in the air for 20 hours;
step (2) cleaning a polyacrylonitrile dialyzer purchased from a market by using deionized water for 5min, then injecting the tannic acid solution prepared in the step (1) into a hemodialyzer, and staying for 12h to completely wet the inner surface of a membrane wire of the dialyzer;
dissolving 30g of zwitterionic sulfobetaine and 25g of polyethyleneimine into 100g of deionized water, and reacting at 60 ℃ for 2h to obtain a zwitterionic polymer aqueous solution rich in amino;
and (4) discharging the mononetinic acid solution out of the hemodialyzer, then injecting the zwitterionic polymer aqueous solution synthesized in the step (3), reacting for 2 hours at 60 ℃, then discharging the solution, washing with deionized water, and drying for 24 hours at 90 ℃ to finally obtain the hemodialyzer with high anti-pollution performance.
According to the ultrafiltration coefficient detection and the plasma protein adsorption detection, the ultrafiltration coefficient of the high-pollution-resistance dialyzer prepared in the embodiment is increased to 28mL/mmHg h from 20mL/mmHg h compared with that of an unmodified dialyzer. The adhesion amount of plasma protein of the hemodialyzer prepared in this example was 3.5. Mu.g/cm 2 。
Example 4
Putting 20g of epinephrine substance into 100g of deionized water solution, adjusting the pH value to 8.0 by using NaOH, and then standing in the air for 24 hours;
step (2) cleaning a polyacrylonitrile dialyzer purchased from a market by using deionized water for 5min, then injecting the epinephrine solution prepared in the step (1) into a hemodialyzer, and staying for 20h to completely wet the inner surface of a membrane wire of the dialyzer;
dissolving 10g of zwitterionic sulfobetaine and 10g of p-phenylenediamine in 100g of deionized water, and reacting at 55 ℃ for 4h to obtain a zwitterionic polymer aqueous solution rich in amino;
and (4) discharging the epinephrine solution out of the hemodialyzer, then injecting the zwitterionic polymer aqueous solution synthesized in the step (3), reacting for 3h at 60 ℃, then discharging the solution, washing with deionized water, and drying for 28h at 88 ℃, thus finally obtaining the hemodialyzer with high anti-pollution performance.
The ultrafiltration coefficient of the high anti-fouling dialyzer prepared in the embodiment is increased from 17mL/mmHg h to 23mL/mmHg h compared with that of the unmodified dialyzer through ultrafiltration coefficient detection and plasma protein adsorption detection. The adhesion amount of plasma protein of the hemodialyzer prepared in this example was 4. Mu.g/cm 2 。
Example 5
Dissolving 10g of dopamine and 10g of norepinephrine in 100g of Tris-HCl aqueous solution with the pH value of 8.5, and standing in the air for 12 hours;
step (2) cleaning a polyether sulfone dialyzer purchased from a market with deionized water for 10min, then injecting the phenol substance solution prepared in the step (1) into a hemodialyzer, and staying for 20h to completely wet the inner surface of a membrane wire of the dialyzer;
dissolving 10g of zwitterionic sulfobetaine, 25g of carboxybetaine and 20g of polyethyleneimine into 100g of deionized water, and reacting at 60 ℃ for 2 hours to obtain a zwitterionic polymer aqueous solution rich in amino;
and (4) discharging the phenol substance solution out of the hemodialyzer, then injecting the zwitterionic polymer aqueous solution synthesized in the step (3), reacting for 5h at 55 ℃, then discharging the solution, cleaning with deionized water, and drying for 25h at 85 ℃, thus finally obtaining the hemodialyzer with high anti-pollution performance.
The ultrafiltration coefficient of the high anti-fouling dialyzer prepared in the embodiment is increased from 22mL/mmHg h to 27mL/mmHg h compared with that of the unmodified dialyzer through ultrafiltration coefficient detection and plasma protein adsorption detection. The adhesion amount of plasma protein of the hemodialyzer prepared in this example was 3.5. Mu.g/cm 2 。
Example 6
Dissolving 15g of tannic acid and 5g of norepinephrine in 100g of water solution, adjusting the pH value to 8.0 by using NaOH, and standing in the air for 24 hours;
step (2) cleaning a polysulfone dialyzer purchased from a market with deionized water for 15min, then injecting the phenol substance solution prepared in the step (1) into a hemodialyzer, and staying for 24h to completely wet the inner surface of a membrane wire of the dialyzer;
dissolving 25g of phosphorylcholine, 10g of polyethylene imine and 15g of polypropylene imine in 100g of deionized water, and reacting at 60 ℃ for 2 hours to obtain a zwitterionic polymer aqueous solution rich in amino;
and (4) discharging the phenol substance solution out of the hemodialyzer, then injecting the zwitterionic polymer aqueous solution synthesized in the step (3), reacting for 2h at 65 ℃, then discharging the solution, cleaning with deionized water, and drying for 28h at 90 ℃, thus finally obtaining the hemodialyzer with high anti-pollution performance.
According to the ultrafiltration coefficient detection and the plasma protein adsorption detection, the ultrafiltration coefficient of the high-pollution-resistance dialyzer prepared in the embodiment is increased to 30mL/mmHg h from 20mL/mmHg h compared with that of an unmodified dialyzer. The adhesion amount of plasma protein of the hemodialyzer prepared in this example was 3. Mu.g/cm 2 。
The aspects, embodiments, features and examples of the present invention should be considered as illustrative in all respects and not intended to be limiting of the invention, the scope of which is defined only by the claims. Other embodiments, modifications, and uses will be apparent to those skilled in the art without departing from the spirit and scope of the claimed invention.
The use of headings and chapters in this disclosure is not meant to limit the disclosure; each section may apply to any aspect, embodiment, or feature of the disclosure.
Throughout this specification, where a composition is described as having, containing, or comprising specific components or where a process is described as having, containing, or comprising specific process steps, it is contemplated that the composition of the present teachings also consist essentially of, or consist of, the recited components, and the process of the present teachings also consist essentially of, or consist of, the recited process steps.
Unless specifically stated otherwise, use of the terms "include," have, has "and the like are generally to be understood as open-ended and not limiting.
It should be understood that the order of steps or order in which certain actions are performed is not critical, so long as the present teachings remain operable. Further, two or more steps or actions may be performed simultaneously.
In addition, the inventor also carries out corresponding tests by using other raw materials listed above and other process conditions to replace various raw materials and corresponding process conditions in examples 1-6, and the obtained modified hemodialyzer has antifouling performance and excellent hemocompatibility, and is basically similar to the products of examples 1-6.
Although the present invention has been described with reference to illustrative embodiments, it will be understood by those skilled in the art that various other changes, omissions and/or additions may be made and substantial equivalents may be substituted for elements thereof without departing from the spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from its scope. Therefore, it is intended that the invention not be limited to the particular embodiment disclosed for carrying out this invention, but that the invention will include all embodiments falling within the scope of the appended claims. Moreover, unless specifically stated any use of the terms first, second, etc. do not denote any order or importance, but rather the terms first, second, etc. are used to distinguish one element from another.
Claims (4)
1. A method for modifying the fouling resistance of a hemodialyzer, comprising:
dissolving a phenol substance in an alkaline aqueous solution or a Tris-HCl aqueous solution, and standing in the air for 12-24 hours to obtain a uniform phenol substance aqueous solution, wherein the phenol substance is any one or a combination of more than two of tannic acid, dopamine, epinephrine and norepinephrine, the pH value of the alkaline aqueous solution or the Tris-HCl aqueous solution is 8-8.5, and the mass ratio of the phenol substance to the alkaline aqueous solution or the Tris-HCl aqueous solution is 0.2-0.25: 1;
reacting a uniformly mixed reaction system containing a zwitterionic monomer, an imine monomer and water at 50-60 ℃ for 2-4 h to obtain a zwitterionic polymer aqueous solution with an amino group at an end group, wherein the zwitterionic monomer is any one or combination of more than two of phosphorylcholine, carboxyl betaine, sulfo betaine and trimethoxy derivative, the imine monomer is any one or combination of more than two of polyethylene imine, p-phenylenediamine and polypropylene imine, and the mass ratio of the combination of the zwitterionic monomer and the imine monomer to the water is 20-60: 100, respectively;
injecting the phenol substance water solution into a hemodialyzer, fully wetting the inner surface of membrane filaments of the hemodialyzer by the phenol substance water solution, keeping the inner surface for 12-24 hours, adsorbing the phenol substance on the inner surface of the membrane filaments of the hemodialyzer, and then discharging the phenol substance water solution out of the hemodialyzer;
injecting the zwitterionic polymer aqueous solution into a hemodialyzer, and then heating to 55-65 ℃, so that amino in the zwitterionic polymer reacts with phenol substances on the inner surface of membrane filaments of the hemodialyzer for 3-5 h through Schiff base, thereby stably loading the zwitterionic polymer on the inner surface of the membrane filaments of the hemodialyzer to which the phenol substances are adhered;
and discharging the zwitterionic polymer aqueous solution out of the hemodialyzer, cleaning, and drying at the temperature of 80-90 ℃ for 24-28 h to obtain the high-pollution-resistance hemodialyzer.
2. The anti-soil modification process of claim 1, wherein: the membrane silk material of the hemodialyzer is any one or the combination of more than two of polysulfone membrane, polyethersulfone membrane, polyacrylonitrile and polymethyl methacrylate.
3. A highly fouling resistant hemodialyzer obtainable by the process of any one of claims 1 to 2.
4. A hemodialyzer with high stain resistance as claimed in claim 3, characterized in that: high anti-soil type hemodialyzer includes the hemodialyzer body, and form in the anti-soil coating of hemodialyzer body membrane silk internal surface, the anti-soil coating includes hydrophilic functional layer, hydrophilic functional layer is by zwitterionic polymer and phenol class material through the free bridging effect of imine class, and the mode through layer-by-layer assembly is carried admittedly hemodialyzer body membrane silk internal surface.
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