A preparation method of macroporous adsorption resin and its application

Abstract

The invention discloses a preparation method and application of a macroporous adsorption resin, and relates to the technical field of anion exchange resins. The invention prepares a novel macroporous adsorption resin through suspension polymerization, chloromethylation and amination. The preparation method is simple and easy with good repeatability. In addition, the obtained macroporous adsorption resin has uniform particle size distribution, large specific surface area and high mechanical strength, and exhibits excellent selective adsorption and adsorption effect on bilirubin, thereby being suitable for efficient adsorption of bilirubin in solution or plasma.

Description

Technical field:

[0001] The invention relates to the technical field of anion exchange resins, and in particular to a preparation method and application of a macroporous adsorption resin. Background technology:

[0002] Bilirubin is a type of bile pigment and the main pigment in human bile. Bilirubin is the primary metabolite of iron porphyrin compounds in the body. It is toxic and can cause irreversible damage to the brain and nervous system, but it also has antioxidant properties, inhibiting the oxidation of linoleic acid and phospholipids. Bilirubin is an important clinical indicator of jaundice and a key indicator of liver function. Normal human plasma contains very little bilirubin. However, when excessive bilirubin is produced due to endogenous (blood cell defects or abnormalities) or exogenous factors (poisoning or acute illness, etc.), or when bilirubin metabolism is impaired due to impaired organ and tissue function, the plasma bilirubin concentration can increase abnormally, becoming an endogenous toxin and forming hyperbilirubinemia, which can lead to jaundice and even be life-threatening.

[0003] Hemoperfusion is an effective method for treating hyperbilirubinemia. Its principle is to use an extracorporeal circulation power device to introduce blood into a container filled with solid adsorption material to adsorb metabolites or toxins in the blood. Adsorption materials used for hemoperfusion mainly include activated carbon, synthetic resins, and other types of adsorbents. Although activated carbon can quickly adsorb bilirubin, it has low mechanical strength, is prone to shedding, and has poor adsorption selectivity. Synthetic resins are currently commonly used adsorption materials for hemoperfusion, including two major categories: adsorption resins and ion exchange resins. However, they have problems with poor adsorption selectivity and low adsorption rate for bilirubin. Therefore, it is necessary to develop a synthetic resin with good adsorption selectivity and high adsorption rate for bilirubin, so as to better treat hyperbilirubinemia. Summary of the invention:

[0004] The technical problem to be solved by the present invention is to provide a method for preparing a macroporous adsorption resin, and to apply the prepared macroporous adsorption resin to the adsorption of bilirubin in solution or plasma, with high mechanical strength and good adsorption selectivity.

[0005] The technical problem to be solved by the present invention is achieved by adopting the following technical solutions:

[0006] One of the objects of the present invention is to provide a method for preparing a macroporous adsorption resin, comprising the following steps:

[0007] (1) preparing white balls by suspension polymerization of monomers, crosslinking agents, porogens, dispersants, initiators and deionized water;

[0008] (2) preparing chlorine balls by chloromethylation reaction of white balls and chloromethylation reagent;

[0009] (3) Chlorine balls and an amination reagent are reacted to prepare a macroporous adsorption resin.

[0010] The monomers include styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane. While styrene is commonly used as a monomer in the art, the present invention uses styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane as comonomers. The introduction of 1,1,1-trimethyl-N-2-propylenepropylaminosilane molecules improves the surface properties and structure of the resin microspheres, increasing their specific surface area and enhancing adsorption selectivity.

[0011] A second object of the present invention is to provide a macroporous adsorption resin prepared according to the above-mentioned preparation method.

[0012] A third object of the present invention is to provide the use of the aforementioned macroporous adsorption resin in adsorbing bilirubin in solution or plasma.

[0013] The beneficial effects of the present invention are as follows: a novel macroporous adsorption resin is prepared by suspension polymerization, chloromethylation and amination, and the preparation method is simple and easy with good reproducibility, and the obtained macroporous adsorption resin has uniform particle size distribution, large specific surface area and high mechanical strength, and exhibits excellent selective adsorption and adsorption effect for bilirubin, thereby being suitable for efficient adsorption of bilirubin in solution or plasma. Specific implementation method:

[0014] In order to make the technical means, creative features, objectives and effects achieved by the present invention easier to understand, the present invention is further described below in conjunction with specific embodiments.

[0015] The present invention provides a method for preparing a macroporous adsorption resin, comprising the following steps:

[0016] (1) preparing white balls by suspension polymerization of monomers, crosslinking agents, porogens, dispersants, initiators and deionized water;

[0017] (2) preparing chlorine balls by chloromethylation reaction of white balls and chloromethylation reagent;

[0018] (3) Chlorine balls and an amination reagent are reacted to prepare a macroporous adsorption resin.

[0019] Preferably, the monomers include styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane, and the amount of styrene accounts for 75-85% of the weight of the monomers.

[0020] Preferably, the cross-linking agent is divinylbenzene, and the amount of divinylbenzene used is 5-20% by weight of the monomer.

[0021] Preferably, the porogen is at least one of toluene, xylene, 200# gasoline, n-hexane, n-heptane, liquid paraffin, and solid paraffin, and the amount of the porogen used is 0.5-2.5 times the weight of the monomer. Of course, other C7-C20 alkanes or alkanols not listed here can also be used as porogens.

[0022] Preferably, the dispersant is at least one of polyvinyl alcohol, gelatin, methyl cellulose, and sodium lignin sulfonate, and the amount of the dispersant is 0.5-2% of the mass of deionized water. Of course, sodium lauryl sulfate, hydroxyethyl cellulose, and other commonly used dispersants in the art can also be used.

[0023] Preferably, the initiator is at least one of benzoyl peroxide, azobisisobutyronitrile, ammonium persulfate, and potassium persulfate, and the amount of the initiator used is 0.5-2% of the monomer mass. Of course, commonly used initiators in the art, such as tert-butyl benzoyl peroxide, methyl ethyl ketone peroxide, and azobisisoheptylnitrile, can also be used.

[0024] Preferably, the volume ratio of the deionized water to the monomer is (1-3):1.

[0025] Preferably, the chloromethylating agent is chloromethyl ether, and the consumption of chloromethyl ether is 5-10 times of the mass of the white ball. Of course, other chloromethylating agents with lower toxicity relative to chloromethyl ether can also be adopted.

[0026] Preferably, the chloromethylation reaction uses a Lewis acid as a catalyst, which is selected from at least one of zinc chloride, ferric chloride, and aluminum chloride, and the amount of the catalyst is 10-50% of the mass of the white ball.

[0027] Preferably, the amination agent is trimethylamine, and the amount of trimethylamine used is 1-5 times the mass of the chlorine ball.

[0028] The present invention also provides a macroporous adsorption resin prepared according to the above preparation method.

[0029] The present invention further provides the use of the aforementioned macroporous adsorption resin in adsorbing bilirubin in solution or plasma.

[0030] The technical solution of the present invention is described in detail below through specific embodiments:

[0031] Example 1

[0032] (1) 50 g of monomer (styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane in a mass ratio of 75:25), 8 g of divinylbenzene, 35 g of n-heptane and 0.75 g of benzoyl peroxide were mixed and stirred to obtain an oil phase; polyvinyl alcohol was added to deionized water in a volume ratio of deionized water to monomer of 2:1, and the amount of polyvinyl alcohol was 1% of the mass of deionized water, and stirred to dissolve to obtain an aqueous phase; the oil phase was then added to the aqueous phase, the temperature was raised to 60°C for reaction for 2 h, and then the temperature was raised to 80°C for reaction for 8 h; after the reaction was completed, the mixture was washed with water, filtered, dried, the porogen was extracted with acetone, washed with water, and dried to obtain a white ball.

[0033] (2) Add 300 g of chloromethyl ether to 50 g of white balls, swell at 25 ° C for 2 h, then add 15 g of zinc chloride, heat to 35 ° C and react for 5 h, then heat to 50 ° C and react for 5 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain chlorine balls.

[0034] (3) Add 25 g of dimethylformamide to 50 g of chlorine balls, swell for 2 h at 25 ° C, then add trimethylamine aqueous solution (mass fraction 30%, trimethylamine dosage 150 g), heat to 30 ° C for reaction, and slowly add sodium hydroxide solution dropwise to control the pH above 10. After the addition is completed, continue the reaction for 1 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain a macroporous adsorption resin.

[0035] Example 2

[0036] (1) 50 g of monomer (styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane in a mass ratio of 80:20), 5 g of divinylbenzene, 35 g of liquid paraffin and 0.75 g of azobisisobutyronitrile were mixed and stirred to obtain an oil phase; polyvinyl alcohol was added to deionized water in a volume ratio of deionized water to monomer of 1:1, and the amount of polyvinyl alcohol was 1% of the mass of deionized water, and stirred to dissolve to obtain an aqueous phase; the oil phase was then added to the aqueous phase, the temperature was raised to 60°C for reaction for 2 h, and then the temperature was raised to 85°C for reaction for 5 h; after the reaction was completed, the mixture was washed with water, filtered, dried, the porogen was extracted with acetone, washed with water, and dried to obtain a white ball.

[0037] (2) Add 250 g of chloromethyl ether to 50 g of white balls, swell at 25 ° C for 2 h, then add 10 g of zinc chloride, heat to 35 ° C to react for 5 h, and then heat to 50 ° C to react for 5 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain chlorine balls.

[0038] (3) Add 25 g of dimethylformamide to 50 g of chlorine balls and allow to swell at 25 °C for 2 h. Then add trimethylamine aqueous solution (mass fraction 30%, trimethylamine dosage 100 g), heat to 30 °C for reaction, and slowly add sodium hydroxide solution dropwise to control the pH to be above 10. After the addition is complete, continue the reaction for 1 h. After the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain a macroporous adsorption resin.

[0039] Example 3

[0040] (1) 50 g of monomer (styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane in a mass ratio of 85:15), 5 g of divinylbenzene, 50 g of liquid paraffin and 0.5 g of benzoyl peroxide were mixed and stirred to obtain an oil phase; polyvinyl alcohol was added to deionized water in a volume ratio of deionized water to monomer of 2:1, and the amount of polyvinyl alcohol was 1.5% of the mass of deionized water, and stirred to dissolve to obtain an aqueous phase; the oil phase was then added to the aqueous phase, the temperature was raised to 60°C for reaction for 2 h, and then the temperature was raised to 80°C for reaction for 8 h; after the reaction was completed, the mixture was washed with water, filtered, dried, the porogen was extracted with acetone, washed with water, and dried to obtain a white ball.

[0041] (2) Add 350 g of chloromethyl ether to 50 g of white balls, swell at 25 ° C for 2 h, then add 20 g of aluminum chloride, heat to 35 ° C to react for 3 h, and then heat to 50 ° C to react for 5 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain chlorine balls.

[0042] (3) Add 25 g of dimethylformamide to 50 g of chlorine balls and allow to swell at 25 °C for 2 h. Then add trimethylamine aqueous solution (mass fraction 30%, trimethylamine dosage 100 g), heat to 30 °C for reaction, and slowly add sodium hydroxide solution dropwise to control the pH to be above 10. After the addition is complete, continue the reaction for 1 h. After the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain a macroporous adsorption resin.

[0043] Example 4

[0044] (1) 50 g of monomer (styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane in a mass ratio of 80:20), 8 g of divinylbenzene, 50 g of n-heptane and 0.5 g of azobisisobutyronitrile were mixed and stirred to obtain an oil phase; gelatin was added to deionized water in a volume ratio of deionized water to monomer of 1:1, and the amount of gelatin was 1.5% of the mass of deionized water, and stirred to dissolve to obtain an aqueous phase; the oil phase was then added to the aqueous phase, the temperature was raised to 60°C for reaction for 2 h, and then the temperature was raised to 80°C for reaction for 8 h; after the reaction was completed, the mixture was washed with water, filtered, dried, the porogen was extracted with acetone, washed with water, and dried to obtain a white ball.

[0045] (2) Add 250 g of chloromethyl ether to 50 g of white balls, swell at 25 ° C for 2 h, then add 10 g of aluminum chloride, heat to 35 ° C to react for 5 h, and then heat to 50 ° C to react for 5 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain chlorine balls.

[0046] (3) Add 25 g of dimethylformamide to 50 g of chlorine balls, swell for 2 h at 25 ° C, then add trimethylamine aqueous solution (mass fraction 30%, trimethylamine dosage 150 g), heat to 30 ° C for reaction, and slowly add sodium hydroxide solution dropwise to control the pH above 10. After the addition is completed, continue the reaction for 1 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain a macroporous adsorption resin.

[0047] Example 5

[0048] (1) 50 g of monomer (styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane in a mass ratio of 80:20), 8 g of divinylbenzene, 35 g of n-heptane and 0.75 g of benzoyl peroxide were mixed and stirred to obtain an oil phase; gelatin was added to deionized water in a volume ratio of deionized water to monomer of 2:1, and the amount of gelatin was 1% of the mass of deionized water, and stirred to dissolve to obtain an aqueous phase; the oil phase was then added to the aqueous phase, the temperature was raised to 60°C for reaction for 2 h, and then the temperature was raised to 80°C for reaction for 8 h; after the reaction was completed, the mixture was washed with water, filtered, dried, the porogen was extracted with acetone, washed with water, and dried to obtain a white ball.

[0049] (2) Add 300 g of chloromethyl ether to 50 g of white balls, swell at 25 ° C for 2 h, then add 15 g of ferric chloride, heat to 35 ° C and react for 5 h, then heat to 50 ° C and react for 5 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain chlorine balls.

[0050] (3) Add 25 g of dimethylformamide to 50 g of chlorine balls, swell for 2 h at 25 ° C, then add trimethylamine aqueous solution (mass fraction 30%, trimethylamine dosage 150 g), heat to 30 ° C for reaction, and slowly add sodium hydroxide solution dropwise to control the pH above 10. After the addition is completed, continue the reaction for 1 h; after the reaction is completed, filter, wash with water, wash with ethanol, and dry to obtain a macroporous adsorption resin.

[0051] Comparative Example 1

[0052] Comparative Example 1 is to replace the 1,1,1-trimethyl-N-2-propylenepropylaminosilane in Example 1 with methyl acrylate, and the remaining preparation steps are the same as Example 1.

[0053] Comparative Example 2

[0054] Comparative Example 2 is obtained by deleting 1,1,1-trimethyl-N-2-propylenepropylaminosilane in Example 1, that is, only using styrene as a monomer, and the remaining preparation steps are the same as in Example 1.

[0055] Example 6

[0056] According to the method of patent CN106238016A, the macroporous adsorption resin prepared in the above examples and comparative examples was subjected to a simulated plasma bilirubin adsorption performance evaluation test, and the adsorption rate and adsorption efficiency of the macroporous adsorption resin for bilirubin were calculated. The results are shown in Table 1.

[0057] Table 1

[0058]

[0059]

[0060] It can be seen from the data in Table 1 that the macroporous adsorption resin prepared by the present invention using styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane as polymerization monomers shows excellent adsorption selectivity and adsorption effect for bilirubin.

[0061] The macroporous adsorption resins prepared in the above examples and comparative examples were tested for sphericity after grinding according to the method of GB / T 12598-2001. The results are shown in Table 2. The higher the sphericity after grinding, the better the mechanical properties.

[0062] Table 2

[0063] Ball rate after grinding (%) Example 1 ＞95 Example 2 ＞95 Example 3 ＞95 Example 4 ＞95 Example 5 ＞95 Comparative Example 1 ＜92 Comparative Example 2 ＜92

[0064] It can be seen from the data in Table 2 that the macroporous adsorption resin prepared by using styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane as polymerization monomers in the present invention has excellent mechanical strength.

[0065] The basic principles, main features, and advantages of the present invention are shown and described above. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions are merely illustrative of the principles of the present invention. Various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention. Such changes and modifications are intended to fall within the scope of the present invention. The scope of protection claimed in the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a macroporous adsorption resin, characterized in that: The following steps are involved: (1) preparing white balls by suspension polymerization of monomers, crosslinking agent, porogen, dispersant, initiator and deionized water; (2) preparing chlorine balls by chloromethylation reaction of white balls and chloromethylation reagent; (3) preparing a macroporous adsorption resin by reacting chlorine balls with an amination reagent; The monomers include styrene and 1,1,1-trimethyl-N-2-propylenepropylaminosilane, and the amount of styrene accounts for 60-80% of the monomer mass.

2. The preparation method according to claim 1, wherein: The cross-linking agent is divinylbenzene, and the amount of divinylbenzene used is 5-20% by weight of the monomer.

3. The preparation method according to claim 1, wherein: The porogen is at least one of toluene, xylene, 200# gasoline, n-hexane, n-heptane, liquid paraffin, and solid paraffin. The amount of the porogen is 0.5-2.5 times the mass of the monomer.

4. The preparation method according to claim 1, wherein: The dispersant is at least one of polyvinyl alcohol, gelatin, methyl cellulose, and sodium lignin sulfonate, and the amount of the dispersant is 0.5-2% of the mass of deionized water; The volume ratio of the deionized water to the monomer is (1-3):

1.

5. The preparation method according to claim 1, wherein: The initiator is at least one of benzoyl peroxide, azobisisobutyronitrile, ammonium persulfate, and potassium persulfate, and the amount of the initiator is 0.5-2% of the monomer mass.

6. The preparation method according to claim 1, wherein: The chloromethylation agent is chloromethyl ether, and the amount of chloromethyl ether used is 5-10 times the mass of the white ball; The chloromethylation reaction uses Lewis acid as a catalyst, which is selected from at least one of zinc chloride, ferric chloride, and aluminum chloride, and the amount of the catalyst is 10-50% of the mass of the white ball.

7. The preparation method according to claim 1, wherein: The amination reagent is trimethylamine, and the amount of trimethylamine used is 1-5 times the mass of the chlorine ball.

8. The macroporous adsorption resin prepared according to the preparation method according to any one of claims 1 to 7.

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