Hemodialysis membrane preparation method, hemodialysis membrane and dialysis equipment

Abstract

The invention provides a hemodialysis membrane preparation method, a hemodialysis membrane and dialysis device.The hemodialysis membrane preparation method comprises the following steps that an acid neutralizer is added into an acrylic acid solution, then a sodium alginate solution is added, and a first solution is obtained through mixing; adding a cross-linking agent and an initiator into the first solution to obtain a copolymer solution; immersing the dialysis membrane into an initiator solution for pretreatment; immersing the pretreated dialysis membrane into a copolymer solution, and carrying out graft polymerization; and cleaning and drying the dialysis membrane after the reaction is completed so as to complete the anticoagulation modification treatment of the dialysis membrane. A polymer rich in carboxylic acid groups formed by polymerization of sodium alginate and acrylic acid is prepared, the polymer is combined to the surface of the dialysis membrane through free radicals of azodiisobutyronitrile, the blood compatibility of the dialysis membrane can be improved based on the hydrophilic performance of sodium alginate, meanwhile, carboxyl and hydroxyl can form electrostatic acting force with calcium ions, and therefore the dialysis membrane can be used for treating the blood stasis. Therefore, calcium ions are adsorbed on the surface, and the anticoagulation performance of the dialysis membrane can be improved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to a method for preparing a hemodialysis membrane, a hemodialysis membrane and a dialysis device. Background Art

[0002] Hemodialysis (HD) is one of the renal replacement therapies for patients with acute and chronic renal failure. It drains blood from the body to the outside of the body through a dialyzer composed of countless hollow fibers. The blood and the electrolyte solution (dialysate) containing similar concentrations to the body are exchanged inside and outside the hollow fibers through diffusion, ultrafiltration, adsorption and convection principles to remove metabolic waste from the body, maintain electrolyte and acid-base balance, remove excess water from the body, and return the purified blood. The whole process is called hemodialysis.

[0003] Coagulation refers to the process of blood changing from a flowing liquid state to a non-flowing gel state. The basic process of coagulation is a series of limited protein hydrolysis processes, which generally include the following three stages: prothrombin activator formation, thrombin formation and fibrin formation. In the process of thrombin formation, calcium ions Ca 2+ The role is indispensable.

[0004] In the prior art, the dialysis membrane, as a foreign substance, is different from human vascular endothelial cells and is prone to adsorb proteins, triggering the coagulation cascade, leading to blockage of membrane pores and reducing the dialyzer's toxin clearance rate in the human body. In clinical applications, heparin is usually injected to inhibit the formation of blood clots in the dialyzer. However, heparin is difficult to metabolize and is not suitable for some patients with symptoms of massive bleeding. Summary of the invention

[0005] In view of the deficiencies in the prior art, the object of the present invention is to provide a method for preparing a hemodialysis membrane, a hemodialysis membrane and a dialysis device, aiming to solve the technical problem in the prior art that the anticoagulant effect of the dialysis membrane is poor.

[0006] In order to achieve the above object, in a first aspect, the present invention is implemented by the following technical scheme: a method for preparing a hemodialysis membrane, comprising the following steps: Adding 14-18 parts of an acid neutralizer to 20-25 parts of an acrylic acid solution, and then adding 45-55 parts of a sodium alginate solution, and mixing to obtain a first solution; Adding 0.6 to 1 parts of a methylenebisacrylamide crosslinking agent and 0.8 to 1.2 parts of a potassium persulfate initiator to the first solution to obtain a copolymer solution; 4-6 parts of azobisisobutyronitrile initiator are added to a solvent to fully dissolve, mixed to obtain an initiator solution, and a dialysis membrane is immersed in the initiator solution for pretreatment, so that the azobisisobutyronitrile initiator is evenly distributed on the surface of the dialysis membrane ultrafiltration; Immersing the pretreated dialysis membrane in the copolymer solution to carry out copolymer graft polymerization so that the copolymer is bound to the surface of the dialysis membrane; The dialysis membrane after the reaction is cleaned and dried to complete the anticoagulant modification treatment of the dialysis membrane.

[0007] Compared with the prior art, the beneficial effects of the present invention are as follows: a carboxylic acid group-rich polymer is prepared by polymerizing sodium alginate and acrylic acid via a methylenebisacrylamide crosslinking agent, and the polymer is bonded to the surface of the dialysis membrane via free radicals of azobisisobutyronitrile; sodium alginate is a natural high molecular weight polysaccharide, which contains negatively charged carboxyl and hydroxyl groups, and can be combined with positively charged hydrogen ions in water molecules to form ionic bonds, and has excellent hydrophilic properties, and can improve the blood compatibility of the dialysis membrane; at the same time, the carboxyl and hydroxyl groups will form electrostatic forces with calcium ions, thereby adsorbing calcium ions on the surface, and can improve the anticoagulant performance of the dialysis membrane, thereby realizing the anticoagulant modification treatment of the dialysis membrane and improving the anticoagulant performance.

[0008] According to one aspect of the above technical solution, the acid neutralizer is potassium carbonate or potassium hydroxide.

[0009] According to one aspect of the above technical solution, in the step of uniformly distributing the initiator on the surface of the dialysis membrane ultrafiltration, the method further comprises: The treatment process was protected by inert gas to avoid deactivation of the azobisisobutyronitrile initiator.

[0010] According to one aspect of the above technical solution, during the process of graft polymerization of copolymers to bind the copolymers to the surface of the dialysis membrane: The reaction temperature is 75°C-85°C, and the reaction time is 5.5 hours-6.5 hours.

[0011] According to one aspect of the above technical solution, in the step of immersing the dialysis membrane in the initiator solution for pretreatment: The soaking time is 4 minutes to 6 minutes.

[0012] According to one aspect of the above technical solution, the solvent is ethanol, ethyl acetate or methanol.

[0013] According to one aspect of the above technical solution, the dialysis membrane is a polysulfone dialysis membrane, a polyethersulfone dialysis membrane or a cellulose acetate dialysis membrane.

[0014] In a second aspect, the present application also provides a hemodialysis membrane, which is prepared by the hemodialysis membrane preparation method in the above technical solution.

[0015] In a third aspect, the present application also provides a dialysis device, comprising the hemodialysis membrane in the above technical solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a flow chart of the hemodialysis preparation method in the first embodiment of the present invention; Figure 2 is the relevant polymerization reaction formula in step S200 of the hemodialysis preparation method in the first embodiment of the present invention; The following specific implementation manner will further illustrate the present invention in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0017] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. Several embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0018] It should be noted that when an element is referred to as being "fixed to" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which the present invention belongs. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0020] Embodiment 1 Please refer to the figure, which is a flow chart of a method for preparing a hemodialysis membrane according to a first embodiment of the present invention. Figure 1 The method shown comprises the following steps: Step S100, adding 14-18 parts of an acid neutralizer into 20-25 parts of an acrylic acid solution, and then adding 45-55 parts of a sodium alginate solution, and mixing to obtain a first solution.

[0021] Specifically, the acid neutralizer can be potassium hydroxide or potassium carbonate. The main purpose of potassium hydroxide and potassium carbonate is to adjust and neutralize the pH of the solution so as to improve the subsequent polymerization reaction rate and product characteristics. In this embodiment, the acid neutralizer is 16 parts of potassium hydroxide, the amount of acrylic acid is 22.5 parts, the mass fraction of the sodium alginate solution is 1.6 wt%, and the amount is 50 parts.

[0022] Step S200, adding 0.6-1 parts of methylenebisacrylamide crosslinking agent and 0.8-1.2 parts of potassium persulfate initiator to the first solution to obtain a copolymer solution. In this embodiment, the amount of the methylenebisacrylamide crosslinking agent is 0.8 parts, and the amount of the potassium persulfate initiator is 1 part. During the reaction, the carboxylic acid group carbon atom of the methylenebisacrylamide crosslinking agent is crosslinked with sodium alginate and acrylic acid monomers, thereby improving the strength and stability of the polymer. For ease of understanding, the relevant polymerization reaction formula is as follows: Figure 2 shown.

[0023] Step S300, adding 4-6 parts of azobisisobutyronitrile initiator to a solvent to fully dissolve, mixing to obtain an initiator solution, and immersing a dialysis membrane in the initiator solution for pretreatment so that the azobisisobutyronitrile initiator is evenly distributed on the surface of the dialysis membrane ultrafiltration.

[0024] Specifically, in this embodiment, during the process of immersing the dialysis membrane in the initiator solution for pretreatment, the immersion time is 4 minutes to 6 minutes, and the treatment process is protected by an inert gas to avoid inactivation of the azobisisobutyronitrile initiator.

[0025] In this embodiment, the amount of the azobisisobutyronitrile initiator is 5 parts. The solvent is ethanol, ethyl acetate or methanol. In this embodiment, a 50 wt% ethanol solution is selected as the solvent. Compared with polar solvents, ethanol as a semi-polar solvent will not affect the pore structure of the dialysis membrane.

[0026] During the reaction, azobisisobutyronitrile swells into the inner surface layer of the dialysis membrane material through the swelling effect of ethanol; in the subsequent reaction, due to the insolubility of azobisisobutyronitrile in water, the grafting polymerization can be limited to the vicinity of azobisisobutyronitrile, so the grafted chain can be firmly anchored below the membrane surface.

[0027] Step S400, immersing the pretreated dialysis membrane into the copolymer solution, performing copolymer graft polymerization, and making the copolymer bonded to the surface of the dialysis membrane. Specifically, in this step, the reaction temperature is 75°C-85°C, and the reaction time is 5.5 hours-6.5 hours. By heating the reaction environment, the azobisisobutyronitrile initiator is decomposed to form free radicals to graft polymerize the polymer. It should be noted that by adding an acid neutralizer to the acrylic acid solution and adjusting and neutralizing the pH of the solution, the activation energy of the reactant molecules can be increased, thereby accelerating the reaction rate. When the activity of the azobisisobutyronitrile initiator is better, the polymerization reaction can be initiated to improve the reaction rate and the characteristic quality of the product.

[0028] Step S500, cleaning and drying the dialysis membrane after the reaction to complete the anticoagulation modification of the dialysis membrane. The dialysis membrane is a commonly used dialysis membrane such as polysulfone dialysis membrane, polyethersulfone dialysis membrane or cellulose acetate dialysis membrane. In this embodiment, polysulfone dialysis membrane is used.

[0029] In summary, the method for preparing a hemodialysis membrane in the above-mentioned embodiment of the present invention is to configure a carboxylic acid-rich polymer formed by polymerization of sodium alginate and acrylic acid via a methylenebisacrylamide crosslinker, and to bind the polymer to the surface of the dialysis membrane via free radicals of azobisisobutyronitrile. Since sodium alginate is a natural high molecular weight polysaccharide, it contains negatively charged carboxyl and hydroxyl groups, which can combine with positively charged hydrogen ions in water molecules to form ionic bonds, and has excellent hydrophilic properties, which can improve the blood compatibility of the dialysis membrane. At the same time, the carboxyl and hydroxyl groups will form electrostatic forces with calcium ions, thereby adsorbing calcium ions on its surface, which can improve the anticoagulant properties of the dialysis membrane, thereby realizing the anticoagulant modification of the dialysis membrane and improving the anticoagulant properties.

[0030] Embodiment 2 A second embodiment of the present invention provides a hemodialysis membrane, which is prepared by the preparation method in the above embodiment.

[0031] Embodiment 3 The third embodiment of the present invention provides a dialysis device, comprising the hemodialysis membrane in the above embodiment.

[0032] Embodiment 4 In this embodiment, the steps and raw materials of the above preparation method are substantially the same as those of the first embodiment, except that: The acid neutralizer is 14 parts of potassium carbonate, the acrylic acid solution is 20 parts, the sodium alginate solution is 45 parts, the methylene bisacrylamide crosslinker is 0.6 parts, the potassium persulfate initiator is 0.8 parts, and the azobisisobutyronitrile initiator is 4 parts.

[0033] Embodiment 5 In this embodiment, the steps and raw materials of the above preparation method are substantially the same as those of the first embodiment, except that: The acid neutralizer is 18 parts of potassium hydroxide, the acrylic acid solution is 25 parts, the sodium alginate solution is 55 parts, the methylene bisacrylamide crosslinker is 1 part, the potassium persulfate initiator is 1.2 parts, and the azobisisobutyronitrile initiator is 6 parts.

[0034] Comparative Example 1 In this comparative example, the steps and raw materials of the above preparation method are substantially the same as those of Example 1, except that: The dosage of the above sodium alginate solution is 0.

[0035] Comparative Example 2 In this comparative example, the steps and raw materials of the above preparation method are substantially the same as those of Example 1, except that: The dosage of the sodium alginate solution, acrylic acid solution, methylenebisacrylamide crosslinking agent, azobisisobutyronitrile initiator and potassium persulfate initiator is 0.

[0036] Comparative Example 3 In this comparative example, the steps and raw materials of the above preparation method are substantially the same as those of Example 1, except that: The amount of the sodium alginate solution is 100 parts, and the amount of the acrylic acid solution is 10 parts.

[0037] Comparative Example 4 In this comparative example, the steps and raw materials of the above preparation method are substantially the same as those of Example 1, except that: The dosage of the acid neutralizer and the methylenebisacrylamide cross-linking agent is 0. The reaction time in step S400 is 10 hours.

[0038] The modified dialysis membranes prepared in Comparative Example 1, Comparative Example 2, Comparative Example 3, Comparative Example 4 and Example 1 were tested and analyzed.

[0039] Hydrophilicity analysis: The dialysis membrane was pasted on the glass, and then deionized water was dropped on the surface of the dialysis membrane to measure the instantaneous contact angle. The test results are as follows: ; From the above test results, it can be seen that compared with the non-modified membrane, that is, the dialysis membrane in Comparative Example 2, the contact angle of the modified dialysis membrane decreases rapidly, the hydrophilicity of the modified dialysis membrane is greatly improved, and the acrylic polymer without sodium alginate solution can also improve the hydrophilicity.

[0040] Calcium ion adsorption capacity test analysis: The dialysis membrane was immersed in a calcium chloride aqueous solution and incubated at 37 °C for 24 h to detect the unadsorbed Ca 2+ The calcium ion clearance rate was calculated based on the ratio of calcium ion concentration in the aqueous solution before and after incubation. The test results are as follows: ; From the above test results, it can be seen that the dialysis membrane in Comparative Example 2 has a much lower calcium ion clearance rate than that in Example 1 because it has not been modified. The dialysis membrane in Comparative Example 1 has a sodium alginate content of 0 and a low calcium ion clearance rate. The results show that the carboxyl and hydroxyl groups of the sodium alginate in this embodiment have the effect of adsorbing calcium ions; although the dialysis membrane in Comparative Example 3 has a higher sodium alginate content, the clearance rate is lower than that in Example 1. The results show that the proportion and dosage of sodium alginate in this embodiment have certain beneficial effects and a better polymerization effect; the calcium ion clearance rate corresponds to the adsorption effect of sodium alginate, that is, the characteristic quality of the copolymerization reaction. Although the reaction time of Comparative Example 4 is longer and the collision frequency between monomers is increased, the adsorption effect achieved is not as good as that in Example 1. The results show that the use of an acid neutralizer and a methylenebisacrylamide cross-linking agent improves the polymerization reaction rate and conversion rate, and also improves the characteristic quality of the polymer.

[0041] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner.

[0042] The above-described embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the present invention. It should be pointed out that, for a person of ordinary skill in the art, several modifications and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the attached claims.

Claims

1. A method for preparing a hemodialysis membrane, characterized in that: The following steps are involved: Adding 14-18 parts of an acid neutralizer to 20-25 parts of an acrylic acid solution, and then adding 45-55 parts of a sodium alginate solution, and mixing to obtain a first solution; Adding 0.6 to 1 parts of a methylenebisacrylamide crosslinking agent and 0.8 to 1.2 parts of a potassium persulfate initiator to the first solution to obtain a copolymer solution; 4-6 parts of azobisisobutyronitrile initiator are added to a solvent to fully dissolve, mixed to obtain an initiator solution, and a dialysis membrane is immersed in the initiator solution for pretreatment, so that the azobisisobutyronitrile initiator is evenly distributed on the surface of the dialysis membrane ultrafiltration; Immersing the pretreated dialysis membrane in the copolymer solution to carry out copolymer graft polymerization so that the copolymer is bound to the surface of the dialysis membrane; The dialysis membrane after the reaction is cleaned and dried to complete the anticoagulant modification treatment of the dialysis membrane.

2. The method for preparing a hemodialysis membrane according to claim 1, characterized in that: The acid neutralizer is potassium carbonate or potassium hydroxide.

3. The method for preparing a hemodialysis membrane according to claim 1, characterized in that: In the step of uniformly distributing the initiator on the surface of the dialysis membrane ultrafiltration, the method further comprises: The treatment process was protected by inert gas to avoid deactivation of the azobisisobutyronitrile initiator.

4. The method for preparing a hemodialysis membrane according to claim 1, characterized in that: In the process of graft polymerization of copolymers to bind the copolymers to the surface of the dialysis membrane: The reaction temperature is 75°C-85°C, and the reaction time is 5.5 hours-6.5 hours.

5. The method for preparing a hemodialysis membrane according to claim 1, characterized in that: The dialysis membrane is immersed in the initiator solution for pretreatment: The soaking time is 4 minutes to 6 minutes.

6. The method for preparing a hemodialysis membrane according to claim 1, characterized in that: The solvent is ethanol, ethyl acetate or methanol.

7. The method for preparing a hemodialysis membrane according to claim 1, characterized in that: The dialysis membrane is a polysulfone dialysis membrane, a polyethersulfone dialysis membrane or a cellulose acetate dialysis membrane.

8. A hemodialysis membrane, characterized in that: The hemodialysis membrane is prepared by the hemodialysis membrane preparation method according to any one of claims 1 to 7.

9. A dialysis device, characterized in that: Comprising the hemodialysis membrane according to claim 8.

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