CN111203115A - Oxidized polysaccharide anticoagulant coating hemodialysis membrane material and preparation method thereof - Google Patents
Oxidized polysaccharide anticoagulant coating hemodialysis membrane material and preparation method thereof Download PDFInfo
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- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
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Abstract
The invention relates to a preparation method of a hemodialysis membrane material, which comprises the following steps: (1) taking part of dialysis pipelines, and putting potassium permanganate concentrated sulfuric acid solution into the dialysis pipelines for acidification pretreatment; (2) putting the dialysis pipeline after acidification treatment into a polyethyleneimine solution for amination modification reaction to obtain a dialysis pipeline after surface modification; (3) adding sodium periodate into the polysaccharide solution, and reacting to obtain oxidized polysaccharide; (4) and pouring the oxidized polysaccharide solution into a dialysis pipeline with a modified surface, and reacting to obtain the oxidized polysaccharide coated dialysis pipeline membrane material. The hemodialysis membrane material can completely overcome the defect of abnormal bleeding caused by the existing heparin coating material, avoid potential safety hazards such as carrying animal allergens or viruses and the like, reduce the cost of production raw materials, and has good anticoagulation and biocompatibility.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to a hemodialysis membrane material.
Background
Hemodialysis (HD) is an effective replacement therapy for treating acute and chronic renal failure, and removes harmful substances in vivo through mechanisms such as dispersion, ultrafiltration, convection, adsorption and the like, so as to maintain water and electrolyte balance. However, the biological material contacting with blood in hemodialysis damages the blood stabilization mechanism to cause the cascade reaction of thrombus and embolism, and the blood directly contacts with the non-physiological surface of the hemodialysis tube, so that the non-physiological perfusion, endotoxemia, body temperature change and the like of the hemodialysis tube can trigger the complicated cascade inflammation reversal to cause the release of different bioactive products, therefore, the hemodialysis material also needs to inhibit the activation of the blood inflammatory system while meeting the anticoagulation condition, thereby improving the biocompatibility.
Conventional hemodialysis systems employ intravenous administration of heparin or low molecular heparin as an anticoagulant regimen, which, while reducing the risk of clotting, also increases the risk of bleeding, especially in patients with renal failure. Meanwhile, clinical practices of hemodialysis involve more and more high-risk bleeding people, such as patients with active bleeding of important organs, patients with high-risk bleeding of important organs, patients with severe blood coagulation abnormality, patients with thrombocytopenia, patients before and after major operations, heparins and other anticoagulant allergic patients, and clinically common solutions for high-risk bleeding patients include application of oral anticoagulants, local in vitro application of heparin, application of small-dose heparin, heparin-free dialysis and the like. The relative heparin-free dialysis method is characterized in that a dialyzer and a pipeline are pre-flushed by using heparin saline before hemodialysis, but the heparin falling rate is high in the method, and the continuous anticoagulation effect cannot be achieved, and the absolute heparin-free dialysis method is characterized in that the dialyzer and the pipeline are flushed by using 0.9% sodium chloride solution, and specifically comprises an intermittent saline flushing method and a continuous dilution method. The former is complicated to operate and increases the risk of coagulation while increasing the ultrafiltration volume, and the latter increases the volume load of the patient.
In recent years, coating technology is developed in the field of biomedical materials, and the aim of improving biocompatibility and anticoagulation activity of the surfaces of the biomedical materials is fulfilled by pre-modifying the surfaces of the materials. The biomedical material surface coating method can be summarized as a physical method and a chemical method. The physical method is to fix the heparin on the surface of the biological material by the ways of mechanical embedding, winding and permeation among molecular chains, adsorption by porous materials and the like, thereby achieving the purpose of immobilization. The chemical method is that abundant reactive functional groups such as sulfonic group, amino group, carboxyl group and the like on the molecular chain of the coating material react with corresponding reactive groups on the surface of the target material, and the coating material is fixed on the surface of the biological material in an ionic bond or covalent bond mode.
Currently, heparin is widely applied in the heparin coating technology, and belongs to acidic mucopolysaccharide, which can interact with various coagulation inhibiting factors in organisms to achieve the aim of anticoagulation by accelerating or improving the anticoagulation activity of the inhibiting factors. However, research shows that heparin has anticoagulant activity and antiplatelet activity, can cause side effects such as abnormal bleeding and the like, carries potential safety hazards such as animal allergens or viruses and the like, is high in heparin cost, and limits application and popularization of heparin coatings to a certain extent.
Therefore, it is a current problem to be solved to find a substance with better anticoagulant bioactivity as a heparin substitute to be applied to a coating technology so as to obtain a hemodialysis membrane material with better anticoagulant and biocompatibility.
Disclosure of Invention
The invention aims to provide a hemodialysis membrane material with good anticoagulation and biocompatibility and a preparation method thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of a hemodialysis membrane material comprises the following steps:
(1) taking part of dialysis pipelines, and putting potassium permanganate concentrated sulfuric acid solution into the dialysis pipelines for acidification pretreatment;
(2) washing the acidified dialysis pipeline with distilled water, then putting the acidified dialysis pipeline into a polyethyleneimine solution, adjusting the pH value to 8-10, carrying out amination modification reaction at normal temperature, taking out the acidified dialysis pipeline after reaction, washing the acidified dialysis pipeline with distilled water, and drying to obtain a dialysis pipeline with a modified surface;
(3) fully dissolving polysaccharide in deionized water, adding sodium periodate, reacting under photophobic magnetic stirring, adding ethylene glycol to terminate the reaction, adding NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture into deionized water again, dialyzing the mixture overnight in a dialysis bag, freezing, and performing low-temperature vacuum drying to obtain oxidized polysaccharide;
(4) and dissolving the oxidized polysaccharide in deionized water, pouring the solution into a dialysis pipeline with the surface modified, sealing two ends of the dialysis pipeline, and carrying out water bath to finally prepare the dialysis pipeline membrane material with the oxidized polysaccharide coating.
Preferably, the material of the dialysis pipeline is selected from one or more of polyvinyl chloride, polypropylene and polysulfone.
Preferably, the polysaccharide is selected from one or more of sodium alginate, hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate, bupleurum polysaccharide, ganoderma lucidum polysaccharide, ginseng polysaccharide, angelica polysaccharide, aloe polysaccharide, pleurotus citrinopileatus polysaccharide, spirulina polysaccharide, coriolus versicolor polysaccharide and agaric polysaccharide.
Preferably, the mass concentration of the concentrated sulfuric acid solution is 40-70%.
Preferably, the mass concentration of the polyethyleneimine solution is 0.05-0.1%.
Preferably, the amination modification reaction time is 20-30 min.
Preferably, the molar ratio of the polysaccharide to the sodium periodate is 1: 1-12.
More preferably, the molar ratio of the polysaccharide to the sodium periodate is 1: 10.
Preferably, the concentration of the oxidized polysaccharide poured into the dialysis pipeline after surface modification is 2-4g/L, and the pH is adjusted to 3-4.5.
Preferably, the temperature of the water bath is 30-50 ℃.
The second aspect of the invention is to provide a hemodialysis membrane material prepared by the preparation method of the hemodialysis membrane material.
The preparation method of the hemodialysis membrane material comprises the steps of firstly forming carboxyl on the surface of the material through acidification pretreatment of a dialysis pipeline, then combining the carboxyl with amino of strong positive polyethyleneimine on the surface of the material to construct a large number of 'space arms' mainly comprising amino, increasing binding sites, and then combining the space arms with aldehyde groups of oxidized polysaccharide to prepare the oxidized polysaccharide coating material with covalent bond combination.
The invention has the positive and beneficial effects that:
the hemodialysis membrane material prepared by the preparation method of the hemodialysis membrane material can completely overcome the defect of abnormal bleeding caused by the existing heparin coating material, avoid carrying potential safety hazards such as animal allergens or viruses and the like, reduce the cost of production raw materials, and has good anticoagulation and biocompatibility.
Detailed Description
The present invention will be further described with reference to the following examples, but the embodiments of the present invention are not limited thereto. The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Example 1: extraction and purification of coriolus versicolor polysaccharide
Pulverizing dried Coriolus versicolor fruiting body, sieving with 10-20 mesh sieve, soaking in 10 times of distilled water for 4 hr, heating to 90-100 deg.C, extracting for 10 hr, filtering, removing residue, concentrating the filtrate, cooling to room temperature, adding 10 times of 95% ethanol, precipitating white flocculent precipitate, standing for 24 hr, centrifuging, and drying at room temperature to obtain Coriolus versicolor polysaccharide.
Example 2
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; the coriolus versicolor polysaccharide prepared in the example 1 is fully dissolved in deionized water to prepare 100ml of coriolus versicolor polysaccharide aqueous solution with the mass fraction of 2%, sodium periodate is added according to the molar ratio of 1:10,and (3) reacting for 24 hours under magnetic stirring in a dark place, adding ethylene glycol to terminate the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and stirring according to a volume ratio of 1: and 5, pouring the obtained product into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the obtained product in deionized water again, dialyzing the obtained product in a dialysis bag overnight, freezing the obtained product, performing low-temperature vacuum drying to obtain coriolus versicolor oxide polysaccharide, dissolving the coriolus versicolor oxide polysaccharide in deionized water to prepare a coriolus versicolor oxide polysaccharide solution with the concentration of 2g/L, adjusting the pH value to 3.5, pouring the obtained product into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 50 ℃ for 2 hours to finally obtain the dialysis pipeline membrane material with the coriolus versicolor oxide polysaccharide coating.
Example 3
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-60% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.10% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving the coriolus versicolor polysaccharide prepared in the example 1 in deionized water to prepare 100ml of a coriolus versicolor polysaccharide aqueous solution with the mass fraction of 2%, adding sodium periodate in a molar ratio of 1:10, reacting for 24 hours under magnetic stirring in a dark place, adding ethylene glycol to stop the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to a volume ratio of 1: and 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture in deionized water again, dialyzing the dialysis bag overnight, freezing, performing low-temperature vacuum drying to obtain coriolus versicolor oxide polysaccharide, dissolving the coriolus versicolor oxide polysaccharide in deionized water to prepare a coriolus versicolor oxide polysaccharide solution with the concentration of 3g/L, adjusting the pH value to 4, pouring the solution into a dialysis pipeline with the modified surface, sealing two ends, and performing water bath at 40 ℃ for 2 hours to finally obtain the dialysis pipeline membrane material with the coriolus versicolor oxide polysaccharide coating.
Example 4
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-70% concentrated sulfuric acid solution, acidized and pretreated for 5min, the dialysis pipeline after acidized is firstly washed by distilled water and then put into 0.10% polyethyleneAdjusting the pH value to 9 in an ene imine solution, carrying out amination modification reaction for 20min at normal temperature, taking out, washing with distilled water, and drying to obtain a dialysis pipeline with a modified surface for later use; fully dissolving the coriolus versicolor polysaccharide prepared in the example 1 in deionized water to prepare 100ml of a coriolus versicolor polysaccharide aqueous solution with the mass fraction of 2%, adding sodium periodate in a molar ratio of 1:10, reacting for 24 hours under magnetic stirring in a dark place, adding ethylene glycol to stop the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to a volume ratio of 1: and 5, pouring the obtained product into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the obtained product in deionized water again, dialyzing the obtained product in a dialysis bag overnight, freezing the obtained product, performing low-temperature vacuum drying to obtain coriolus versicolor oxide polysaccharide, dissolving the coriolus versicolor oxide polysaccharide in deionized water to prepare a coriolus versicolor oxide polysaccharide solution with the concentration of 4g/L, adjusting the pH value to 4.5, pouring the obtained product into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 30 ℃ for 2 hours to finally obtain the dialysis pipeline membrane material with the coriolus versicolor oxide polysaccharide.
Example 5
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving the coriolus versicolor polysaccharide prepared in the example 1 in deionized water to prepare 100ml of a coriolus versicolor polysaccharide aqueous solution with the mass fraction of 2%, adding sodium periodate in a molar ratio of 1:6, reacting for 24 hours under magnetic stirring in a dark place, adding ethylene glycol to stop the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to a volume ratio of 1: 5 pouring into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving in deionized water again, dialyzing overnight in a dialysis bag, freezing, and vacuum drying at low temperature to obtain Coriolus versicolor polysaccharide oxide, dissolving the Coriolus versicolor polysaccharide oxide in deionized water to prepare Coriolus versicolor polysaccharide solution with concentration of 2g/L, adjusting pH to 3.5, pouring into a dialysis pipeline with modified surface, sealing two ends, and performing water bath at 50 deg.C for 2 hr to obtain oxygenA dialysis pipeline membrane material of a coriolus versicolor polysaccharide coating.
Example 6
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving the coriolus versicolor polysaccharide prepared in the example 1 in deionized water to prepare 100ml of a coriolus versicolor polysaccharide aqueous solution with the mass fraction of 2%, adding sodium periodate in a molar ratio of 1:12, reacting for 24 hours under magnetic stirring in a dark place, adding ethylene glycol to stop the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to a volume ratio of 1: and 5, pouring the obtained product into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the obtained product in deionized water again, dialyzing the obtained product in a dialysis bag overnight, freezing the obtained product, performing low-temperature vacuum drying to obtain coriolus versicolor oxide polysaccharide, dissolving the coriolus versicolor oxide polysaccharide in deionized water to prepare a coriolus versicolor oxide polysaccharide solution with the concentration of 2g/L, adjusting the pH value to 3.5, pouring the obtained product into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 50 ℃ for 2 hours to finally obtain the dialysis pipeline membrane material with the coriolus versicolor oxide polysaccharide coating.
Example 7
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving dermatan sulfate in deionized water to prepare 100ml of dermatan sulfate aqueous solution with the mass fraction of 2%, adding sodium periodate according to the molar ratio of 1:10, reacting for 24 hours under the magnetic stirring in the dark, adding ethylene glycol to terminate the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: 5 pouring into absolute ethyl alcohol, completely precipitating and separating out, filtering, dryingAnd dissolving the oxidized dermatan sulfate in deionized water, dialyzing in a dialysis bag overnight, freezing, performing low-temperature vacuum drying to obtain oxidized dermatan sulfate, dissolving the oxidized dermatan sulfate in deionized water to prepare an oxidized dermatan sulfate solution with the concentration of 2g/L, adjusting the pH value to 3.5, pouring the oxidized dermatan sulfate solution into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 50 ℃ for 2 hours to finally obtain the dialysis pipeline membrane material of the oxidized dermatan sulfate coating.
Example 8
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-60% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.10% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving dermatan sulfate in deionized water to prepare 100ml of dermatan sulfate aqueous solution with the mass fraction of 2%, adding sodium periodate according to the molar ratio of 1:10, reacting for 24 hours under the magnetic stirring in the dark, adding ethylene glycol to terminate the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: and 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture in deionized water again, dialyzing the dialysis bag overnight, freezing the mixture, performing low-temperature vacuum drying to obtain the dermatan oxide sulfate, dissolving the dermatan oxide sulfate in deionized water to prepare a dermatan oxide sulfate solution with the concentration of 3g/L, adjusting the pH value to 4, pouring the solution into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 40 ℃ for 2 hours to finally prepare the dialysis pipeline membrane material of the dermatan oxide coating.
Example 9
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-70% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.10% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; sulfur is added toFully dissolving the dermatan sulfate in deionized water to prepare 100ml of dermatan sulfate aqueous solution with the mass fraction of 2%, adding sodium periodate according to the molar ratio of 1:10, reacting for 24 hours under the magnetic stirring in the dark, adding ethylene glycol to terminate the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: and 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture in deionized water again, dialyzing the dialysis bag overnight, freezing the mixture, performing low-temperature vacuum drying to obtain the dermatan oxide sulfate, dissolving the dermatan oxide sulfate in deionized water to prepare a dermatan oxide sulfate solution with the concentration of 4g/L, adjusting the pH value to 4.5, pouring the solution into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 30 ℃ for 2 hours to finally prepare the dialysis pipeline membrane material of the dermatan oxide sulfate coating.
Example 10
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving dermatan sulfate in deionized water to prepare 100ml of dermatan sulfate aqueous solution with the mass fraction of 2%, adding sodium periodate according to the molar ratio of 1:6, reacting for 24 hours under the magnetic stirring in the dark, adding ethylene glycol to terminate the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: and 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture in deionized water again, dialyzing the dialysis bag overnight, freezing the mixture, performing low-temperature vacuum drying to obtain the dermatan oxide sulfate, dissolving the dermatan oxide sulfate in deionized water to prepare a dermatan oxide sulfate solution with the concentration of 2g/L, adjusting the pH value to 3.5, pouring the solution into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 50 ℃ for 2 hours to finally prepare the dialysis pipeline membrane material of the dermatan oxide sulfate coating.
Example 11
Taking the inner surface as 50cm2A polypropylene dialysis line ofPre-preparing a potassium permanganate-50% concentrated sulfuric acid solution, carrying out acidification pretreatment for 5min, washing the dialysis pipeline subjected to acidification treatment with distilled water, then putting the dialysis pipeline into a 0.05% polyethyleneimine solution, adjusting the pH value to 9, carrying out amination modification reaction for 20min at normal temperature, taking out, washing the dialysis pipeline with distilled water, and drying to obtain a dialysis pipeline subjected to surface modification for later use; fully dissolving dermatan sulfate in deionized water to prepare 100ml of dermatan sulfate aqueous solution with the mass fraction of 2%, adding sodium periodate according to the molar ratio of 1:12, reacting for 24 hours under the magnetic stirring in the dark, adding ethylene glycol to terminate the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: and 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture in deionized water again, dialyzing the dialysis bag overnight, freezing the mixture, performing low-temperature vacuum drying to obtain the dermatan oxide sulfate, dissolving the dermatan oxide sulfate in deionized water to prepare a dermatan oxide sulfate solution with the concentration of 2g/L, adjusting the pH value to 3.5, pouring the solution into a dialysis pipeline with the modified surface, sealing two ends of the dialysis pipeline, and performing water bath at 50 ℃ for 2 hours to finally prepare the dialysis pipeline membrane material of the dermatan oxide sulfate coating.
Example 12
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving sodium alginate in deionized water to prepare 100ml of sodium alginate aqueous solution with the mass fraction of 2%, adding sodium periodate in a molar ratio of 1:10, reacting for 24 hours under the condition of magnetic stirring in the dark, adding ethylene glycol to stop the reaction, adding 4g of NaCl into the reaction solution, uniformly mixing, and mixing according to a volume ratio of 1: 5 pouring into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving in deionized water again, dialyzing overnight in a dialysis bag, freezing, and vacuum drying at low temperature to obtain oxidized sodium alginate, dissolving the oxidized sodium alginate in deionized water to obtain oxidized sodium alginate with concentration of 2g/LAnd adjusting the pH value of the solution to 3.5, pouring the solution into a dialysis pipeline with the surface modified, sealing two ends of the dialysis pipeline, and carrying out water bath at 50 ℃ for 2 hours to finally obtain the sodium alginate oxide coating dialysis pipeline membrane material.
Comparative example 1
Taking the inner surface as 50cm2The polypropylene dialysis pipeline is put into a pre-prepared potassium permanganate-50% concentrated sulfuric acid solution, is subjected to acidification pretreatment for 5min, is washed by distilled water, is put into a 0.05% polyethyleneimine solution, is subjected to pH value adjustment to 9, is subjected to amination modification reaction for 20min at normal temperature, is taken out, is washed clean by distilled water, and is dried to obtain a dialysis pipeline with a modified surface for later use; fully dissolving 2g of heparin sodium powder in deionized water to prepare 100ml of heparin sodium aqueous solution with the mass fraction of 2%, adding 20mg of sodium nitrite, reacting for 2h at 0 ℃ in an acid environment, adjusting the pH value to 7.0, dialyzing overnight by a dialysis bag, freezing, performing low-temperature vacuum drying, dissolving in deionized water to prepare solution with the concentration of 2g/L, pouring the solution into a dialysis pipeline with the modified surface, sealing two ends, and performing water bath at 50 ℃ for 2h to finally prepare the heparin coated dialysis pipeline membrane material.
Test example 1 blood coagulation time on the surface of membrane material coating of dialysis line
Cut 10cm apart2Dialysis tubing membrane materials prepared according to inventive examples 2-12 and comparative example 1 and uncoated as samples for inventive groups (examples 2-12), comparative groups (comparative example 1) and blank control groups (uncoated dialysis tubing membrane material), were cut into pieces of about 0.5cm to 0.5cm, respectively, and placed in 24-well culture plates; taking 20mL of whole blood of a healthy volunteer, centrifuging for 10min under the condition of 3500r/min to obtain platelet poor plasma, adding 700 mu L of platelet poor plasma into each sample hole, incubating for 2h in a constant-temperature water bath box at 37 ℃, extracting the incubated plasma, and measuring thromboplastin time (APTT), Prothrombin Time (PT) and Thrombin Time (TT). The specific measurement results are shown in Table 1.
TABLE 1 blood coagulation time on the surface of each group of dialysis tubing membrane material coating
Test example 2 adsorption of proteins on the surface of Membrane Material coating for dialysis tubing
A standard curve for measuring protein adhesion by the BCA method is established according to a kit method. Taking samples of the invention group (examples 2-12), the comparative example group (comparative example 1) and the blank control group (uncoated dialysis tubing membrane material), respectively cutting into fragments of about 0.5cm by 0.5cm, adding a 24-hole culture plate, preparing 200 mu g/L of human serum albumin and human fibrinogen diluent, preparing BCA working solution, adding 1.5mL of human serum albumin and human fibrinogen diluent into each material hole, completely immersing the samples, placing the samples into a constant temperature water bath, incubating for 1h at 37 ℃, taking 100 mu L of protein solution to be tested, adding 1mL of BCA working solution, rapidly mixing, incubating at 60 ℃ for 30min, measuring the Abs value of the incubated mixed solution at 562nm by using an ultraviolet spectrophotometer, calculating the protein concentration difference between before and after reaction according to a standard curve, respectively obtaining human serum albumin adhesion (HAS) and human plasma fibrin adhesion (HPF), the specific results are shown in Table 2.
Test example 3 thrombosis on the surface of the Membrane Material coating of dialysis tubing
Samples of 10cm each of the inventive (examples 2-12), comparative (comparative example 1) and blank (uncoated dialysis tubing membrane material) groups were taken2Weighing after vacuum drying to obtain dry weight W1, placing the dry weight W1 on a 24-hole culture plate respectively, quickly adding 1.5mL of whole blood of a healthy volunteer into each material hole respectively, incubating for 1h in a 37 ℃ constant temperature water bath, taking out, washing 3 times with PBS, fixing with 3% glutaraldehyde, vacuum drying after gradient ethanol treatment, weighing again to obtain dry weight W2, and calculating the difference value before and after reaction, namely the thrombus adhesion amount, wherein the specific result is shown in Table 2.
TABLE 2 protein adsorption and thrombus adhesion on the surface of each group of dialysis tubing membrane material coating
The comparison experiment shows that the dialysis pipeline membrane material has good anticoagulation effect, and the protein adhesion amount and the thrombosis amount on the surface of the coating are obviously less than those of a blank control group and a comparison example group, which indicates that the dialysis pipeline membrane material has good biocompatibility.
Claims (10)
1. A preparation method of a hemodialysis membrane material is characterized by comprising the following steps:
(1) taking part of dialysis pipelines, and putting potassium permanganate concentrated sulfuric acid solution into the dialysis pipelines for acidification pretreatment;
(2) washing the acidified dialysis pipeline with distilled water, then putting the acidified dialysis pipeline into a polyethyleneimine solution, adjusting the pH value to 8-10, carrying out amination modification reaction at normal temperature, taking out the acidified dialysis pipeline after reaction, washing the acidified dialysis pipeline with distilled water, and drying to obtain a dialysis pipeline with a modified surface;
(3) fully dissolving polysaccharide in deionized water, adding sodium periodate, reacting under photophobic magnetic stirring, adding ethylene glycol to terminate the reaction, adding NaCl into the reaction solution, uniformly mixing, and mixing according to the volume ratio of 1: 5, pouring the mixture into absolute ethyl alcohol, completely precipitating and separating out, performing suction filtration and drying, dissolving the mixture into deionized water again, dialyzing the mixture overnight in a dialysis bag, freezing, and performing low-temperature vacuum drying to obtain oxidized polysaccharide;
(4) and dissolving the oxidized polysaccharide in deionized water, pouring the solution into a dialysis pipeline with the surface modified, sealing two ends of the dialysis pipeline, and carrying out water bath to finally prepare the dialysis pipeline membrane material with the oxidized polysaccharide coating.
2. The method for preparing a hemodialysis membrane material of claim 1, wherein the polysaccharide is one or more selected from sodium alginate, hyaluronic acid, heparan sulfate, chondroitin sulfate, dermatan sulfate, bupleurum polysaccharide, ganoderan, ginseng polysaccharide, angelicae sinensis polysaccharide, aloe polysaccharide, pleurotus citrinopileatus polysaccharide, spirulina polysaccharide, coriolus versicolor polysaccharide, and agaric polysaccharide.
3. The method for preparing a hemodialysis membrane material according to claim 2, wherein the dialysis tubing is made of one or more materials selected from the group consisting of polyvinyl chloride, polypropylene and polysulfone.
4. The method for preparing a hemodialysis membrane material according to claim 3, wherein the concentrated sulfuric acid solution has a mass concentration of 40-70%.
5. The method for preparing a hemodialysis membrane material according to claim 4, wherein the mass concentration of the polyethyleneimine solution is 0.05-0.1%.
6. The method for preparing a hemodialysis membrane material of claim 5, wherein the molar ratio of the polysaccharide to the sodium periodate is 1: 6-12.
7. The method for preparing a hemodialysis membrane material of claim 6, wherein the concentration of oxidized polysaccharide poured into the surface-modified dialysis tubing is 2-4 g/L.
8. The method for preparing a hemodialysis membrane material of claim 7, wherein the oxidized polysaccharide poured into the surface-modified dialysis tubing has a pH of 3 to 4.5.
9. The method for preparing a hemodialysis membrane material of claim 8, wherein the water bath temperature is 30-50 ℃.
10. A hemodialysis membrane material prepared by the method for preparing a hemodialysis membrane material according to any one of claims 1 to 9.
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