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 PDFInfo
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- resin sorbent
- bilirubin
- hemoperfusion
- preparation
- resin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/265—Synthetic macromolecular compounds modified or post-treated polymers
- B01J20/267—Cross-linked polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3679—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/02—General characteristics of the apparatus characterised by a particular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2207/00—Methods of manufacture, assembly or production
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- External Artificial Organs (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
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
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610821262.3A CN106238016B (en) | 2016-09-13 | 2016-09-13 | A kind of bilirubin removal preparation method of blood perfusion resin sorbent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610821262.3A CN106238016B (en) | 2016-09-13 | 2016-09-13 | A kind of bilirubin removal preparation method of blood perfusion resin sorbent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106238016A true CN106238016A (en) | 2016-12-21 |
| CN106238016B CN106238016B (en) | 2019-01-11 |
Family
ID=57598889
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610821262.3A Active CN106238016B (en) | 2016-09-13 | 2016-09-13 | A kind of bilirubin removal preparation method of blood perfusion resin sorbent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106238016B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557538A (en) * | 2004-01-30 | 2004-12-29 | 浙江科锐生物科技有限公司 | Method for preparing macromolecule resin type bilirubin sorbent |
| CN103055822A (en) * | 2011-10-21 | 2013-04-24 | 佛山市博新生物科技有限公司 | Blood-purifying adsorbent for clearing blood bilirubin and preparation method thereof |
| CN104001482A (en) * | 2014-05-12 | 2014-08-27 | 河南科技大学 | Selective perfusion adsorbent for medical bilirubin and preparation method thereof |
| CN104174385A (en) * | 2014-07-28 | 2014-12-03 | 南开大学 | Bilirubin adsorbent for blood perfusion |
| CN105478094A (en) * | 2015-12-25 | 2016-04-13 | 四川大学 | Aminated poly-glycidyl methacrylate crosslinked composite microsphere and preparation method as well as application thereof |
-
2016
- 2016-09-13 CN CN201610821262.3A patent/CN106238016B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557538A (en) * | 2004-01-30 | 2004-12-29 | 浙江科锐生物科技有限公司 | Method for preparing macromolecule resin type bilirubin sorbent |
| CN103055822A (en) * | 2011-10-21 | 2013-04-24 | 佛山市博新生物科技有限公司 | Blood-purifying adsorbent for clearing blood bilirubin and preparation method thereof |
| CN104001482A (en) * | 2014-05-12 | 2014-08-27 | 河南科技大学 | Selective perfusion adsorbent for medical bilirubin and preparation method thereof |
| CN104174385A (en) * | 2014-07-28 | 2014-12-03 | 南开大学 | Bilirubin adsorbent for blood perfusion |
| CN105478094A (en) * | 2015-12-25 | 2016-04-13 | 四川大学 | Aminated poly-glycidyl methacrylate crosslinked composite microsphere and preparation method as well as application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 张可喜 等: "《材料合成与制备研究》", 30 April 2014, 中国水利水电出版社 * |
| 陈志萍 等: "胺基化PGMA 交联微球对胆红素的吸附机理", 《物理化学学报》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN108031454A (en) * | 2017-12-19 | 2018-05-15 | 陈荣胜 | Possesses blood-purifying adsorbing agent of physics specific selectivity and preparation method thereof |
| CN108031454B (en) * | 2017-12-19 | 2021-08-13 | 陈荣胜 | Blood purification adsorbent with physical specificity selectivity and preparation method thereof |
| 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 |
| CN118384863B (en) * | 2024-04-25 | 2024-10-11 | 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106238016B (en) | 2019-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106238016A (en) | A kind of preparation method of bilirubin removal hemoperfusion resin sorbent | |
| Jiang et al. | Molecularly imprinted solid-phase extraction for the selective determination of 17β-estradiol in fishery samples with high performance liquid chromatography | |
| CN102532390B (en) | Triazine weedicide, and metabolite molecular engram polymer microspheres, preparation method and application thereof | |
| CA2603073C (en) | Absorbent and column for extracorporeal circulation | |
| CN104174385B (en) | A kind of adsorbent for bilirubin for blood perfusion | |
| Çorman | Poly-l-lysine modified cryogels for efficient bilirubin removal from human plasma | |
| Cai et al. | Preparation of monodisperse, restricted-access, media-molecularly imprinted polymers using bi-functional monomers for solid-phase extraction of sarafloxacin from complex samples | |
| CN103055822B (en) | Blood-purifying adsorbent for clearing blood bilirubin and preparation method thereof | |
| CN105218765B (en) | A kind of Preparation method and use of photoresponse intelligence trace mesoporous material | |
| Bagheri et al. | Chitosan-and/or cellulose-based materials in analytical extraction processes: A review | |
| Huang et al. | Evaluation of exosome loading characteristics in their purification via a glycerol‐assisted hydrophobic interaction chromatography method on a polyester, capillary‐channeled polymer fiber phase | |
| Díaz‐Álvarez et al. | Recent advances and future trends in molecularly imprinted polymers‐based sample preparation | |
| CN106103477A (en) | Sane antibody purification | |
| CN106432577A (en) | High selectivity tetracycline antibiotics molecularly imprinted polymer preparation method and application | |
| Ergün et al. | Ion imprinted beads embedded cryogels for in vitro removal of iron from β‐thalassemic human plasma | |
| CN104001486A (en) | Preparation method of hydrophilic sulfa drug molecularly imprinted solid-phase extraction column | |
| CN111151227A (en) | Semi-molecular imprinting material and preparation method and application thereof | |
| CN105153367A (en) | Preparation method of dicyandiamide mesoporous surface molecularly imprinted polymer microspheres | |
| CN103265666A (en) | Malathion molecularly imprinted polymer and synthetic method of malathion restricted access media-molecularly imprinted polymer | |
| CN110361462A (en) | Molecular engram tip micro-extracting head and preparation method thereof | |
| Yu et al. | Lysozyme-imprinted polymer synthesized using UV free-radical polymerization | |
| Gao et al. | Preparation and properties of cellulose acetate graft copolymer‐coated adsorbent resin for hemoperfusion device | |
| CN101864038A (en) | Surface grafting polar monomer modified polystyrene macroporous resin and preparation method thereof | |
| Wang et al. | Synthesis of ractopamine molecularly imprinted membrane and its application in the rapid determination of three β‐agonists in porcine urine samples | |
| Uzun et al. | Poly (hydroxyethyl methacrylate) based affinity membranes for in vitro removal of anti-dsDNA antibodies from SLE plasma |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201028 Address after: Room 128, building 9, No. 1800, Jiangchuan Road, Minhang District, Shanghai, 201100 Patentee after: Shanghai Hongcun New Material Technology Co., Ltd Address before: 215400 No. 6 West Beijing Road, Jiangsu Economic Development Zone Patentee before: Suzhou Yitong Filter Technology Co.,Ltd. |
|
| TR01 | Transfer of patent right |