CN106238016A - A kind of preparation method of bilirubin removal hemoperfusion resin sorbent - Google Patents

A kind of preparation method of bilirubin removal hemoperfusion resin sorbent Download PDF

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CN106238016A
CN106238016A CN201610821262.3A CN201610821262A CN106238016A CN 106238016 A CN106238016 A CN 106238016A CN 201610821262 A CN201610821262 A CN 201610821262A CN 106238016 A CN106238016 A CN 106238016A
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resin sorbent
bilirubin
hemoperfusion
preparation
resin
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CN106238016B (en
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孙康
王解兵
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Shanghai Hongcun New Material Technology Co., Ltd
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SUZHOU YITONG FILTER TECHNOLOGY Co Ltd
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26Synthetic macromolecular compounds
    • B01J20/265Synthetic macromolecular compounds modified or post-treated polymers
    • B01J20/267Cross-linked polymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3679Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2205/00General characteristics of the apparatus
    • A61M2205/02General characteristics of the apparatus characterised by a particular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M2207/00Methods of manufacture, assembly or production

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Abstract

The present invention relates to the preparation method of the bilirubin removal hemoperfusion resin sorbent of a kind of biomedical materials field, select the degree of cross linking 4~20%, grand mean aperture 10~100nm, particle diameter 30~80 mesh crosslinked acrylate polymers microsphere as carrier, first pass through amination grafting and there is the spacerarm of certain length, then quaternized to spacerarm end, finally to this adsorbent peplos Hydroxyethyl methacrylate.The preparation method difficulty that the present invention provides is low, easily controllable, clear mechanism;The hemoperfusion resin sorbent that bilirubin prepared by the present invention is removed has good biocompatibility, has higher selection adsorption rate to bilirubin, can be applicable to hemoperfusion treatment field.

Description

A kind of preparation method of bilirubin removal hemoperfusion resin sorbent
Technical field
The present invention relates to the preparation method of the hemoperfusion adsorbing material of a kind of biomedical materials field, particularly relate to A kind of preparation method of bilirubin removal hemoperfusion resin sorbent.
Background technology
Bilirubin (Bilirubin, BR) is the one of bile pigments, in orange-yellow, is that the main metabolic of internal haemachrome is produced Thing.Bilirubin is nonpolar liposoluble substance, is insoluble in water, but has the highest affinity to plasma albumin.Normal person Bilirubin in serum, one is conjugated bilirubin (or claiming bilirubin direct), through hepatocyte endoplasmic reticulum effect, with glucose aldehyde Acid or other materials combine;Another kind is unconjugated bilirubin (or claiming unconjugated bilirubin), and the gallbladder produced from hematoclasis is red Element, in blood plasma mainly with albumin bound and transport.Bilirubin in human normal plasma is little, when internal because of endogenous (blood Cell defect or abnormal) or extrinsic factor (such as poisoning, acute disease etc.) to cause bilirubin to generate too much, or because of organ-tissue merit Impaired can cause bilirubinic dysbolismus, plasma bilirubin concentration abnormality can be made to raise, become endogenous toxin and form height Hyperbilirubinemia.It is characterized in that bilirubin can diffuse into through biomembrane and be deposited on tissue when plasma concentration is too high In (including brain), cause jaundice, serious caused tissue cell necrosis threat to life.
Hemoperfusion be at present can effective one of method treating hyperbilirubinemia, its core is for removing blood Metabolite in liquid or the adsorbing material of toxin.The main active charcoal of adsorbing material of hemoperfusion and synthetic resin (include All kinds of anion exchange resin and macroporous adsorbent resin) and (Novel adsorption microsphere, the function filtration of other kinds of adsorbent Film, doughnut etc.).
Acticarbon wide material sources, with low cost, self there is bigger specific surface area and abundant duct, permissible Quick adsorption removes ectogenic toxin, but it is poor to there is blood compatibility, and mechanical strength is low, easily falls off, the choosing of absorption The shortcomings such as selecting property difference.
Synthetic resin is a currently used more more ripe class hemoperfusion adsorbent.One type is macropore tree Lipid adsorbent, polystyrene based on crosslinking, polyvinyl alcohol etc., make use of big specific surface area and bigger aperture and good Good mechanical performance, by hydrophobic interaction or coordinate the group of modified grafting to carry out bilirubinic absorption, has adsorbance big Advantage, as domestic Zhuhai be good for sail produce HA type blood perfusion device series of products.The subject matter of macroporous resin adsorption agent is The strongest to bilirubinic selectivity, although can to introduce functional group by modification, such as cyano group, (Li Naihong etc., Chinese biological is cured Engineering journal, 1982,1 (1): 40-43) etc., but correlational study (Chinese patent, publication number CN 102049242B) points out it Have that protein adsorption quantity is too high or the problem such as group vulnerable to pollution.Another kind of is ion exchange resin adsorbent, and cardinal principle is The electrostatic attraction effect that resin sorbent institute band ion positive charge is electronegative with bilirubin, with crosslinked polystyrene divinyl Base benzene resin is main carriers.At present in bilirubin perfusion is treated more ripe product have Kuraray BL-300 type and The BRS-350 type adsorber of Asahi Chemical Industry, domestic realize list marketing have the HB-L-6 of Tianjin purple ripple, Langfang in Hebei Province Ai Er AR-350 adsorption column etc..The subject matter of this kind of adsorbent is: (1) existing product, particularly imported product is expensive, and portion Divide product treatment time longer;(2) adsorption rate of domestic bilirubin resin anion (R.A.) adsorbent product is still less than external product Level, as a example by AR-350, to bilirubin adsorption rate (Dong Ming is clear, Jilin University's journal (medicine), 2010,36 (01): 19) about 30%, and the BL-300 adsorption column of Kuraray to the adsorption rate of plasma bilirubin up to 58.1% (Gao Lei Deng. China's blood purification, 2008,11 (7): 615-617.).
Other kinds of adsorbent for bilirubin rarely has the report of commercial goods at present, is more at development in laboratory In, still there is more technical problem to need to solve.
Summary of the invention
For complicated process of preparation present in existing bilirubin perfusion adsorber technologies, cost intensive, product absorption effect Rate is relatively low waits deficiency, it is an object of the invention to provide the preparation side of the hemoperfusion resin sorbent that a kind of bilirubin is removed Method.
The present invention is directed to the feature requirement of bilirubin adsorption, choose and there is the polymer microballoon of certain structural parameters as load Body, first passes through amination to selected resin carrier, and grafting has the spacerarm of certain length, then spacerarm end is carried out quaternary ammonium Change, finally to this adsorbent peplos polymethylacrylic acid-beta-hydroxy ethyl ester.It is low, easily controllable that this preparation method has difficulty Advantage, it is thus achieved that bilirubin remove hemoperfusion resin sorbent there is good biocompatibility, to the gallbladder in blood plasma Red pigment has preferable Selective adsorption, can be applicable to hemoperfusion treatment field.
The invention discloses the preparation method of a kind of bilirubin removal hemoperfusion resin sorbent, specifically include following Step:
(1) selecting the degree of cross linking 4~20%, grand mean aperture 10~100nm, the crosslink propylene acid esters of particle diameter 30~80 mesh gathers Compound microsphere is as the bilirubin removal carrier of hemoperfusion resin sorbent;
Described acrylate polymer microspheres is selected from: acrylic acid methyl ester., methyl methacrylate, ethyl acrylate, first Base ethyl acrylate or glycidyl methacrylate;
(2) the carrier surface grafting spacerarm to selected resin sorbent:
The carrier of above-mentioned resin sorbent is cleaned and dried with a large amount of ethanol and deionized water, adds in solvent swelling 1-2 hour, it is subsequently added aminating agent and carries out amination, be warming up to 80~120 DEG C, 300 revs/min of lower isothermal reaction 12-18 of stirring Discharging after hour, is washed with deionized filtration, obtains being grafted the resin sorbent of spacerarm;
Described solvent is selected from: dimethylformamide, 1-Phenylethanone., dichloroethanes or n-butyl alcohol, and it carries with resin sorbent The mass ratio of body is 2:1~5:1.
Described aminating agent is selected from: hexamethylene diamine, triethylene tetramine or TEPA, itself and the matter of resin absorption agent carrier Amount ratio is 1:1~3:1.
(3) quaternized to the spacerarm end being grafted on above-mentioned resin sorbent.
(4) resin sorbent obtaining step (3) carries out surface-coating process:
Will clean after resin sorbent with containing methacrylic acid-beta-hydroxy ethyl ester monomer (HEMA), cross-linking agent, porogen And the oil-phase solution of initiator is sufficiently mixed, be then transferred to be incubated 50-55 DEG C containing 3% sodium chloride and 1% gelatin In aqueous phase solution, under the stirring condition of 300 revs/min, react 10-20 minute, then heat to 65-70 DEG C of reaction 4-6 little Time, then it is warming up to 75-80 DEG C of solidification 4-6 hour.Finally product is filtered dry, with the ethanol relative to described 3-5 times of volume of product Alternately clean 3 times with the deionized water of 8-10 times of volume, filter;
Described cross-linking agent is selected from: ethyleneglycol dimethyacrylate, ethylene glycol bisthioglycolate ethyl diallyl ester, two propylene Acid-BDO ester or butyl acrylate.
Described initiator is selected from: azo-bis-isobutyl cyanide, 2,2'-Azobis(2,4-dimethylvaleronitrile), benzoyl peroxide or peroxidating Laurel Acyl.
Described porogen is selected from: ethyl acetate, n-butyl alcohol, lauryl alcohol or multiple in them.
Described initiator is 1:2000~1:4000 with the mass ratio of resin sorbent.
Described HEMA monomer is 1:0.01~0.02:0.5:2 with cross-linking agent, porogen, the volume ratio of resin sorbent ~8.
Advantages of the present invention and beneficial effect:
Compared with prior art, to belong to esters of acrylic acid cross linked polymer micro-for the carrier of the resin sorbent that the present invention chooses Ball, they have the advantages that surface hydrophilic, inner skeleton are hydrophobic, coordinate preferred carrier hole structural parameters and particle diameter distribution, Be conducive to attracting fat-soluble bilirubin to enter absorbent interior;When being grafted spacerarm, the carrier selected by the present invention avoids General crosslinked polystyrene-divinylbenzene resin usually needs first to use strong carcinogen chloromethyl methyl ether or dichlormethyl ether to carry out The problem of chloromethylation, therefore preparation technology division operation difficulty low easily controllable outside, also green safety, environment amenable excellent Point;The present invention is quaternized to spacerarm end after introducing spacerarm, compares existing simple grafting or quaternized technical side Formula, can effectively utilize the strong electrostatic attraction adsorbing bilirubin molecule of steric effect and group, improves bilirubin adsorption efficiency; Utilize the good HEMA of biocompatibility for adsorbent peplos, effectively improve the blood compatibility of adsorbent.
Accompanying drawing explanation
Fig. 1 is bilirubin standard adsorption curve.
Fig. 2 is that 6 resin sorbent samples of the present invention are during adsorption test in different time points simulating blood plasma Bilirubin concentration.
Detailed description of the invention
Below by embodiment, the present invention is described in further detail:
Embodiment one:
(1) degree of cross linking 4~20%, grand mean aperture 10~100nm, the cross-linked poly methyl propylene of particle diameter 30~80 mesh are selected Acid methyl ester is as the bilirubin removal carrier of macromolecule resin type adsorbent;
(2) to selected resin sorbent carrier surface grafting spacerarm:
Weigh above-mentioned resin absorption agent carrier 100g, clean be placed on thermometer, agitator there-necked flask in, add Enter 200g dimethylformamide swelling 1 hour, be subsequently added 200g hexamethylene diamine and carry out amination, be warming up to 120 DEG C, at 300 revs/min Discharging after the lower isothermal reaction of clock stirring 12 hours, is washed with deionized filtration, obtains being grafted the resin sorbent of spacerarm;
(3) quaternized to the spacerarm end being grafted on above-mentioned resin sorbent:
The resin sorbent being grafted spacerarm obtained in step (2) is put into three mouthfuls with agitator and thermometer In flask, NaOH solution 60mL of addition 10%, addition 8.16g iodomethane, discharging after reacting 10 hours at water-bath holding 20 DEG C, Hydrochloric acid solution with 5% cleans after making the transition;
(4) resin sorbent to above-mentioned acquisition carries out surface-coating process:
Will clean after resin sorbent with containing 50ml methacrylic acid-beta-hydroxy ethyl ester monomer, 1ml ethylene glycol bisthioglycolate ethyl The oil-phase solution of diallyl ester, 25ml n-butyl alcohol and 0.05g azodiisobutyronitrile is sufficiently mixed, be then transferred to containing 300ml is incubated in the there-necked flask containing 3% sodium chloride and the aqueous phase solution of 1% gelatin of 50 DEG C, at 300 revs/min Under stirring condition, react 20 minutes, then heat to 70 DEG C and react 6 hours, then be warming up to 80 DEG C of solidifications 6 hours.Finally will produce Thing is filtered dry, and alternately cleans 3 times with 8-10 times of deionized water with the ethanol of 3-5 times, filters.
Embodiment two
The method of the present embodiment is essentially identical with embodiment one with step, and difference is in step (1): select crosslinking Degree 4~20%, grand mean aperture 10~100nm, the cross-linked poly-methyl methacrylate ethylene oxidic ester of particle diameter 30~80 mesh is as gallbladder Red pigment is removed with the carrier of macromolecule resin type adsorbent.
Embodiment three
The method of the present embodiment is essentially identical with embodiment one with step, and difference is in step (2): add 200g Swelling 1 hour of dimethylformamide, is subsequently added 300g TEPA and carries out amination.
Embodiment four
The method of the present embodiment is essentially identical with embodiment one with step, and difference is in step (2): be warming up to 80 DEG C, discharging after isothermal reaction 18 hours under 300 revs/min of stirrings.
Embodiment five
The method of the present embodiment is essentially identical with embodiment one with step, and difference is in step (4): after cleaning Resin sorbent with containing 25ml methacrylic acid-beta-hydroxy ethyl ester monomer, 0.5ml butyl acrylate, 25ml lauryl alcohol and The oil-phase solution of 0.05g 2,2'-Azobis(2,4-dimethylvaleronitrile) is sufficiently mixed.
Embodiment six
The method of the present embodiment is essentially identical with embodiment one with step, and difference is in step (4): after cleaning Resin sorbent with containing 100ml methacrylic acid-beta-hydroxy ethyl ester monomer, 1ml ethyleneglycol dimethyacrylate, 25ml second Acetoacetic ester is sufficiently mixed with the oil-phase solution of lauryl alcohol equal-volume mixture and 0.1g benzoyl peroxide.
Embodiment seven: bilirubin removal hemoperfusion resin sorbent of the present invention is to bilirubin adsorption evaluation.
The hemoperfusion resin sorbent removing the bilirubin of embodiment one to six preparation is simulated in blood plasma high The bilirubinic adsorption assessment of concentration:
(1) resin pretreatment: the resin sorbent number consecutively prepared by above-described embodiment one to six is SP1-SP6, disappears After poison, and it is filtered dry to neutrality with normal saline flushing, stand-by.
(2) test preparation reagent:
A) diazo reagent preparation (needing Fresh, now with the current): reagent A: 1.25g p-aminobenzene sulfonic acid and the dense salt of 15ml Acid mixing, with distilled water diluting to 250ml;Reagent B:2g sodium nitrite is dissolved in 100ml distilled water, is placed in cold preservation in refrigerator;Will 12ml reagent A mixes with 0.4ml reagent B and i.e. obtains diazo reagent;
B) ultraviolet detection buffer (UV detection buffer) is prepared: 12ml methanol mixes with 0.4ml distilled water Molten;
C) preparation of simulating blood plasma: 2g human serum albumin be dissolved in PBS, is configured to containing 3.5% albumin Simulating blood plasma;
D) preparation of bilirubin reagent (Bil.Reagent): 0.02g bilirubin is dissolved in 3ml dimethyl sulfoxide (DMSO) and 2ml concentration is in the mixed solution of the Na2CO3 of 0.1M, is diluted to 100ml with the simulating blood plasma of above-mentioned preparation, cold with brown bottle It is hidden in refrigerator (avoiding strong illumination during preparation, storage bottle applies black paper bag to wrap up in).
(3) test method:
A) standard specimen of 6 kinds of variable concentrations is prepared for Specification Curve of Increasing according to table 1.
1 six kinds of variable concentrations standard specimens of table
Sequence number A B C D E F
Simulating blood plasma (μ l) 400 360 300 200 100 0
Bil.Reagent(μl) 0 40 100 200 300 400
Bilirubin concentration (mg/ml) 0 0.02 0.05 0.10 0.15 0.20
B) Specification Curve of Increasing: according to table 2 by (or the test of UV detection buffer and diazo reagent and standard specimen Sample) mixed preparing as detection solution.Keep 30 minutes in the dark, read standard specimen sequence with ultraviolet-visible spectrophotometer Number B-F absorption value (using above-mentioned A standard specimen as blank comparison, calibrate optical density zero point) at 560nm wavelength, with corresponding Bilirubin concentration draws standard curve, as shown in Figure 1.
Table 2 bilirubin adsorption mensuration solution is prepared
Solution composition Volume (ml)
UV detection buffer 4.2
Diazo reagent 0.4
Standard specimen (or sample) 0.2
C) the resin sorbent sample mensuration to bilirubin adsorption rate: weigh the pretreated resin sorbent to be measured of 1g and put In conical flask, adding the bilirubin reagent of 30ml, 37 DEG C of water-baths are vibrated 4 hours;Solution sample is extracted according to different time points Product, measure bilirubin concentration.
D) resin sorbent is to bilirubin adsorption rate and the calculating of adsorption efficiency:
Adsorption rate (%)=(0.20-C)/0.20 × 100%,
Adsorption efficiency (mg/g)=(0.20-C) (mg/ml) × 30ml/1g,
Wherein, C=(A-0.0048)/4.6831,
Bilirubin concentration in simulating blood plasma after C representative absorption certain time,
The ultraviolet absorption value that in the simulating blood plasma that A records after representing absorption certain time, bilirubin concentration is corresponding.
(4) test result: resin sorbent sample SP1-SP6 is to bilirubinic adsorption rate and adsorption efficiency test result As shown in table 3, under different condition, the high concentration bilirubin in simulating blood plasma is all had very by 6 resin sorbent samples of preparation High adsorption rate and adsorption efficiency, wherein the sample adsorption effect prepared by embodiment one is optimum.Above-mentioned 6 resin sorbent samples Remaining bilirubin concentration in the simulating blood plasma that product different time points during adsorption test is corresponding is as in figure 2 it is shown, adsorbing Start latter 0.5 hour to make bilirubin concentration decline more than 75%, within 1-2 hour, i.e. can reach adsorption equilibrium.
3 six kinds of different resins sample of sorbent of table are to bilirubinic adsorption rate and adsorption efficiency (adsorption time: 4 hours)
Sample number into spectrum SP1 SP2 SP3 SP4 SP5 SP6
Adsorption rate % 93.87 87.46 90.02 83.59 91.65 86.13
Adsorption efficiency mg/g 5.632 5.247 5.401 5.015 5.499 5.168
According to the above results, choose the resin sorbent sample SP1 of embodiment one preparation, for the suction of hyperbilirubinemia slurry Attached effect assessment.
After above-mentioned SP1 resin sorbent sample strict sterilization, moisten with normal saline and fill in 30ml adsorption column, About 300ml hyperbilirubinemia slurry is circulated at 37 DEG C perfusion 4 hours (flow velocity about 3ml/ minute) of absorption.Perfusion absorption examination The total bilirubin concentration tested in rear blood plasma drops to 149.92 ± 19.26 μm ol/L, adsorption rate from 389.61 ± 53.65 μm ol/L Being 62.2%, bilirubin direct concentration drops to 56.57 ± 30.98 μm ol/L from 142.85 ± 64.20 μm ol/L, and adsorption rate is 60.4%, unconjugated bilirubin concentration drops to 81.92 ± 88.30 μm ol/L from 246.76 ± 89.45 μm ol/L, and adsorption rate is 67.1%.Before and after test, in blood plasma, total protein, albumin and globulin levels rate of change are all below 5%, are inhaled by resin The impact of attached dose is little.
Embodiment described above only have expressed embodiments of the present invention, and it describes more concrete and detailed, but can not Therefore the restriction to the scope of the claims of the present invention it is interpreted as.It should be pointed out that, for the person of ordinary skill of the art, Without departing from the inventive concept of the premise, it is also possible to make some deformation and improvement, these broadly fall into the protection model of the present invention Enclose.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.

Claims (7)

1. a bilirubin is removed by the preparation method of hemoperfusion resin sorbent, it is characterised in that comprise the following steps:
(1) select the degree of cross linking be 4~20%, grand mean aperture be 10~100nm, particle diameter be the crosslink propylene acid esters of 30~80 mesh Polymer microballoon is as the bilirubin removal carrier of hemoperfusion resin sorbent;
(2) the carrier surface grafting spacerarm to described resin sorbent:
The carrier ethanol of described resin sorbent and deionized water are cleaned and dried, add in solvent swelling 1-2 hour, Being subsequently added aminating agent and carry out amination, be warming up to 80~120 DEG C, under 300 revs/min of stirrings, isothermal reaction went out after 12-18 hour Material, is washed with deionized filtration, obtains being grafted the resin sorbent of spacerarm;
(3) quaternized to the spacerarm end being grafted on described resin sorbent;
(4) resin sorbent obtaining step (3) carries out surface-coating process:
Resin sorbent after cleaning with containing methacrylic acid-beta-hydroxy ethyl ester monomer HEMA, cross-linking agent, porogen and draw The oil-phase solution sending out agent is sufficiently mixed, and is then transferred to insulation molten at the aqueous phase containing 3% sodium chloride and 1% gelatin of 50-55 DEG C In liquid, under the stirring condition of 300 revs/min, react 10-20 minute, then heat to 65-70 DEG C and react 4-6 hour, then rise Temperature to 75-80 DEG C solidify 4-6 hour, finally product is filtered dry, with relative to described 3-5 times of volume of product ethanol with 8-10 times The deionized water of volume alternately cleans 3 times, filters.
The preparation method of bilirubin removal hemoperfusion resin sorbent the most according to claim 1, it is characterised in that Crosslinked acrylate polymers microsphere described in step (1) is selected from: acrylic acid methyl ester., methyl methacrylate, acrylic acid second One in ester, ethyl methacrylate and glycidyl methacrylate.
The preparation method of bilirubin removal hemoperfusion resin sorbent the most according to claim 1, it is characterised in that Solvent described in step (2) is selected from: the one in dimethylformamide, 1-Phenylethanone., dichloroethanes and n-butyl alcohol, described solvent It is 2:1~5:1 with the mass ratio of the carrier of described resin sorbent.
The preparation method of bilirubin removal hemoperfusion resin sorbent the most according to claim 1, it is characterised in that Aminating agent described in step (2) is selected from: the one in hexamethylene diamine, triethylene tetramine and TEPA, described aminating agent with The mass ratio of the carrier of resin sorbent is 1:1~3:1.
The preparation method of bilirubin removal hemoperfusion resin sorbent the most according to claim 1, it is characterised in that Cross-linking agent described in step (4) is selected from: ethyleneglycol dimethyacrylate, ethylene glycol bisthioglycolate ethyl diallyl ester, two propylene One in acid-BDO ester and butyl acrylate;Initiator described in step (4) is selected from: azo-bis-isobutyl cyanide, idol One in the different heptonitrile of nitrogen two, benzoyl peroxide and lauroyl peroxide;Porogen described in step (4) is selected from: acetic acid One or more in ethyl ester, n-butyl alcohol and lauryl alcohol.
6. according to the preparation method of described bilirubin removal hemoperfusion resin sorbent arbitrary in claim 1-5, its Being characterised by, the initiator described in step (4) is 1:2000~1:4000 with the mass ratio of described resin sorbent.
7. according to the preparation method of described bilirubin removal hemoperfusion resin sorbent arbitrary in claim 1-5, its It is characterised by, the HEMA monomer described in step (4) and described cross-linking agent, described porogen, the volume of described resin sorbent Ratio is 1:0.01~0.03:0.5:2~8.
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Cited By (6)

* Cited by examiner, † Cited by third party
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CN108031454A (en) * 2017-12-19 2018-05-15 陈荣胜 Possesses blood-purifying adsorbing agent of physics specific selectivity and preparation method thereof
CN109513429A (en) * 2017-09-18 2019-03-26 重庆希尔康血液净化器材研发有限公司 A kind of preparation method of modified adsorbent for bilirubin
CN110237831A (en) * 2019-06-28 2019-09-17 淄博康贝医疗器械有限公司 Anionic polymer microballoon and preparation method thereof for adsorbing bilirubin
CN115634673A (en) * 2022-12-07 2023-01-24 盱眙凹土能源环保材料研发中心 Preparation method of ultrahigh cross-linked resin for bilirubin adsorption and blood perfusion
CN115920861A (en) * 2022-12-23 2023-04-07 中美华世通生物医药科技(武汉)股份有限公司 Adsorbent, preparation method and application thereof
CN118384863A (en) * 2024-04-25 2024-07-26 重庆希尔康血液净化器材研发有限公司 Adsorption material for removing bilirubin and bile acid and preparation method thereof

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