CN106334540A - Adsorbent used for blood or plasma perfusion to remove endotoxin and preparation method thereof - Google Patents

Adsorbent used for blood or plasma perfusion to remove endotoxin and preparation method thereof Download PDF

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CN106334540A
CN106334540A CN201610879594.7A CN201610879594A CN106334540A CN 106334540 A CN106334540 A CN 106334540A CN 201610879594 A CN201610879594 A CN 201610879594A CN 106334540 A CN106334540 A CN 106334540A
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carrier
adsorbent
aglucon
blood
ammonium
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CN106334540B (en
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欧来良
宗文辉
俞耀庭
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Nankai University
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Nankai University
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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
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/74Synthetic polymeric materials
    • A61K31/765Polymers containing oxygen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/44Elemental carbon, e.g. charcoal, carbon black
    • 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
    • B01J20/02Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B01J20/20Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising free carbon; comprising carbon obtained by carbonising processes

Abstract

The invention relates to an adsorbent used for blood or plasma perfusion to remove endotoxin (lipopolysaccharide) and a preparation method thereof. The adsorbent is a nano-composite structure adsorbent. Large-aperture polyvinyl alcohol serves as a carrier, amino (ammonio) carbon nanotubes (single-walled or multi-walled) serve as a ligand, epichlorohydrin or glutaraldehyde, etc. serves as a crosslinking agent, and the ligand and the carrier microspheres undergo covalent coupling to obtain the adsorbent. The adsorbent is simple to prepare, and an endotoxin adsorption property is good. The adsorbent is suitable for blood or plasma perfusion to remove excessive endotoxin in the body of a patient.

Description

One kind removes endotoxic adsorbent and preparation method thereof for blood or plasma perfusion
Technical field:
The invention belongs to biomedicine technical field.Relate to blood perfusion remove blood in endotoxic adsorbent and Its preparation method.
Technical background:
Endotoxin (et) is a kind of extremely strong pyrogenic substances of toxicity, usually by cell membrane institute after gram-negative bacteria death The lipopolysaccharides (lps) of release, lipopolysaccharides forms endotoxemia after entering blood.Endotoxemia is that a kind of clinic is common One of fatal disease, the death rate is up to 40%-90%.The U.S., Europe and Japan have nearly 4,000,000 people to suffer from endotoxin blood every year Disease, because the excessive use of antibiotic, annual endotoxemia patient is also up to millions of people, and there is no at present effectively for China Treatment means.
Blood perfusion technique can effectively remove the total toxin of blood and morbid substance, and has been widely used in multiple diseases Treatment.In Europe, the United States, Deng state, the cellulose spherical adsorbent wherein with polymyxins b as aglucon is successfully applied to face Bed, in order to remove the endotoxin of too high levels in blood, Chinese scholars also have more research report to this product, but because gluing more Rhzomorph b aglucon comes off and toxicity problem, and Countries food and medicine Surveillance Authority fda has alerted and used this product with caution. And China does not also have the clinical practice of such product so far.
Domestic scholars or industrial circle have also been made many effort, applied for a lot of patents such as 200810028948.2, Zl03144383.4,200510046452.4 etc. respectively with cellulose, shitosan, Ago-Gel as carrier, with endotoxin parent Make adsorbent with molecule for aglucon, though achieving good vitro Adsorption effect, because support strength is poor, ligand cou amount is little The problems such as bring obstacle to practical application.In order to improve the intensity of adsorbent, patent 200180040297.9, With styrene-divinylbenzene as skeleton, covalent modification small molecule aglucon prepares endotoxin absorbent to 201310161110.1 grades, but Because of such adsorbent average aperture less (5-10nm about), and lps molecular weight is typically more than 100,000 dalton, molecule Size larger it is impossible to fully be efficiently entering adsorbent endoporus, simultaneously because the hydrophobic effect of such carrier is stronger, lack to blood The adsorptive selectivity of middle beneficial proteins.201110113987.4 patent adopts grafting molecules cluster on agarose carrier, then connect again Branch lysine or glycine betaine make endotoxin absorbent, molecular cluster as a macromolecular due to space steric effect, in carrier On supported quantity limited, and complex manufacturing process, expensive.With polymyxins b for the adsorbent of endotoxin affinity ligand There is more research, but the potential kidney of polymyxins b and neurotoxicity so as to increased all multi-risk Systems, the U.S. in clinical practice The application to this product have issued warning to fda.Therefore, develop a kind of biocompatibility good, can selective absorption endogenous toxic material Element, and beneficial proteins in less absorption blood, and the endotoxin absorbent product of process is simple, are that Present clinical is badly in need of, have Important Economic and the product of social value.
Content of the invention:
It is an object of the invention to overcoming deficiencies of the prior art, providing and a kind of new can be used for blood perfusion Remove endotoxic adsorbent and preparation method thereof in blood or blood plasma.
Removing endotoxic adsorbent provided by the present invention for blood or plasma perfusion is a kind of nano composite structure Adsorbent, is with porous large aperture polyvinyl alcohol as carrier, with single wall or many walls amine (ammonium) base carbon nano tube as aglucon, with Epoxychloropropane or glutaraldehyde as cross linker, the new selective Endotoxin adsorption making aglucon and carrier covalent coupling and making Agent, on carrier, the load capacity of aglucon is in 10-50mg/ml.
Described PVA Carrier is spherical, and, between 100-500um, on carrier bracket, hydroxy radical content is in 100- for granularity Between 900umol/ml;Carrier material be loose structure, pore-size distribution between 50-500nm, between preferably 50-100nm.
Described adsorbent aglucon is amine (ammonium) base carbon nano tube (single wall or many walls), amine (ammonium) base content on nanotube Between 0.1%-1%, length of carbon nanotube between 0.5-5 micron, between carbon nanotube diameter 0.5-100nm.Carbon nanometer On pipe, amine (ammonium) base can be by crosslinked arm and the covalent binding of carrier.
The preparation method removing endotoxic adsorbent provided by the present invention for blood or plasma perfusion includes following step Rapid:
1st, macromolecule carrier (polyvinyl alcohol-triallyl isocyanate copolymer) microballoon synthesis;
1.1 polymerizations: monomer vinyl acetate, crosslinking agent Triallyl isocyanurate, pore-foaming agent ethyl acetate and positive heptan The mixture of alkane mixes in proportion, and adds appropriate (typically taking 0.5%-2%) initiator azodiisobutyronitrile, adds after dissolving Enter in the aqueous solution containing polyvinyl alcohol and sodium chloride, adjustment mixing speed is dispersed to drop, heat up and cause polymerization, solidification. After completion of the reaction, go out ball, ethanol dries after fully washing, secure satisfactory grades subcarrier microballoon.
1.2 alcoholysis: above-mentioned polymer microballoon is added in sodium hydrate methanol solution and carries out ester exchange reaction, reaction finishes Fully washed with methyl alcohol afterwards, dry, the subcarrier that secures satisfactory grades (polyvinyl alcohol-triallyl isocyanate copolymer) microballoon.
2nd, support-activated
With known reagent and method, carrier is activated, such as epoxychloropropane and glutaraldehyde etc., but is not limited to these, Washes clean after activation.
3rd, aglucon is fixed
Carrier microballoons after activation and 0.1-2 times amount (weight ratio) amine (ammonium) base carbon nano tube (single wall or many walls) are super React at lower 20-50 DEG C of sound effect, after completion of the reaction abundant washes clean.
The concrete operations of first step macromolecule carrier microballoon synthesis of the present invention are:
Monomer vinyl acetate and crosslinking agent Triallyl isocyanurate with weight the mixed system than 0.5-5:1 In, add 0.5-5 times of mixed system (volume ratio) pore-foaming agent (mass ratio of pore-foaming agent ethyl acetate and normal heptane be 0.5-2: 1), add the initiator azodiisobutyronitrile accounting for mixed system weight 0.1%-2% in mass ratio, be warming up to after stirring and dissolving 30-50 DEG C, it is then added to the polyvinyl alcohol containing 0.5%-2% of 1-10 times of volume and the sodium-chloride water solution of 0.5%-10% In, stirring is allowed to be uniformly dispersed, and is warming up to 60-85 DEG C of polymerization 2-6 hour, then is warming up to 85-95 DEG C, is polymerized 1-5 hour, reaction After finishing, filter, fully washed with water, ethanol successively, be added in NaOH-methanol solution after being dried and carry out alcoholysis, instead Fully washed, be dried with methyl alcohol after should finishing, obtain final product macromolecule carrier polymer microballoon.
The coupling of macromolecule carrier microballoon of the present invention and aglucon is to carry out idol by method knowable to document and reaction condition Connection, can be by first activated carrier microballoon, then immobilized ligands;Also can directly and be joined come coupling carrier with bifunctional coupling agents Base.
The present invention relates to during the preparation of macromolecule carrier microballoon, the weight of reaction monomers and crosslinking agent is than preferably 0.5-5:1, excellent Select 1-4:1.
Aglucon [amine (ammonium) base carbon nano tube (single wall or many walls)] fixed amount according to the present invention is 20-120mg/ml, Preferably 40-100mg/ml.
The adsorbent of present invention design has higher mechanical strength and physical and chemical stability, can using conventional method such as Damp and hot and ray sterilizing etc..
The adsorbent that the present invention provides can be used for blood plasma or whole blood perfusion for the endotoxin removing in blood samples of patients, is used for The related disease for the treatment of endotoxemia.
Advantages of the present invention and beneficial effect
According to reference to endotoxic molecular size and surface chemical property, design has synthesized large aperture polyvinyl alcohol to the present invention Microballoon, then inside or outside microballoon aperture, grafting carries amine (ammonium) the base carbon nano tube with endotoxin surface opposite charges (single wall or many walls), prepares the adsorbent with nano composite structure, and this nano composite structure adsorbent has larger aperture, Endotoxin molecule can be freely accessible to absorbent interior, simultaneously CNT hydrophobic effect and nano effect (small-size effect etc.) Work in coordination with the electrostatic force of amine/ammonium on CNT, greatly improve the adsorption capacity of adsorbent induced by endotoxin.Absorption is real Test and show, the endotoxin absorbent of the present invention has excellent adsorption capacity to the endotoxin in blood, can be used for treating endogenous toxic material Plain mass formed by blood stasis.
Specific embodiment
Embodiment 1
(1) carrier microballoons preparation
Respectively by 15g vinyl acetate, 30g triallyl second cyanurate, 15ml ethyl acetate and 30ml normal heptane add Enter to tri- mouthfuls of 2000ml flat in, be warming up to 30 DEG C, be stirring evenly and then adding into 0.9g azo-bis-isobutyl cyanide, after dissolving, add 1500ml The aqueous solution (polyvinyl alcohol containing 0.5% and 10% sodium chloride), adjustment mixing speed makes drop to suitable size and disperse Uniformly, it is warming up to 65 DEG C, insulation polymerization 2 hours, then heat to 85 DEG C in insulation 2 hours, filter to obtain white sphere polymers. White sphere polymers water, ethanol fully clean successively, dry.The above-mentioned white sphere polymers drying are added to 2% Naoh methanol solution in, in 40 DEG C of alcoholysis reactions 12 hours, after completion of the reaction, suction filtration, methyl alcohol fully washs, and dries, and obtains final product Required carrier microballoons.Carrier microballoons particle diameter 150-450um, average pore size 100nm, hydroxy radical content is that 120umol/ml carrier is micro- Ball.
(2) carrier microballoons activation
Take the carrier microballoons that 15g is dried, add 150ml dimethyl sulfoxide (DMSO), 100ml epoxychloropropane, with the hydrogen of 3mol/l Sodium oxide molybdena adjusts ph10-11, and 40 DEG C are reacted 3 hours, distillation water wash to neutrality, and survey epoxide number is 80umol/ml carrier microballoons.
(3) amido CNT aglucon is fixed
Weigh carrier microballoons 10ml after activation, be added to 50ml in advance ultrasonic disperse containing 1% aminated multi-wall carbon nano-tube In the pipe aqueous solution, under ultrasonication, 45 DEG C of concussion reactions 3 hours, fully rinsed with distilled water after completion of the reaction, that is, be fixed There is the nano composite structure adsorbent (adsorbent 1) of amido multi-walled carbon nano-tube, content of carbon nanotubes is adsorbed for 40mg/ml Agent.
Embodiment 2
(1) carrier microballoons preparation
Respectively by 20g vinyl acetate, 5g triallyl second cyanurate, 20ml ethyl acetate and the addition of 20ml normal heptane To tri- mouthfuls of 1500ml flat in, be warming up to 45 DEG C, be stirring evenly and then adding into 0.5g azo-bis-isobutyl cyanide, after dissolving, add 1000ml water Solution (polyvinyl alcohol containing 1.0% and 5% sodium chloride), adjustment mixing speed makes drop to suitable size and disperses all Even, it is warming up to 75 DEG C, insulation polymerization 4 hours, then heat to 90 DEG C in insulation 3 hours, the white sphere polymers of filtration.In vain Chromosphere shaped polymer water, ethanol fully clean successively, dry.By spherical for the above-mentioned white dried be added to 2% naoh first In alcoholic solution, in 45 DEG C of alcoholysis reactions 24 hours, after completion of the reaction, suction filtration, methyl alcohol fully washs, and dries, and obtains final product required carrier Microballoon.Carrier microballoons particle diameter 200-400um, average pore size 120nm, hydroxy radical content is 200umol/ml carrier microballoons.
(2) carrier microballoons activation
Take the carrier microballoons that 15g is dried, add 150ml dimethyl sulfoxide (DMSO), 100ml epoxychloropropane, with the hydrogen of 3mol/l Sodium oxide molybdena adjusts ph10-11, and 45 DEG C are reacted 5 hours, distillation water wash to neutrality, and survey epoxide number is 62umol/ml carrier microballoons.
(3) amido CNT aglucon
Weigh carrier microballoons 10ml after activation, be added to 1% aminated SWCN of 50ml ultrasonic disperse in advance In the aqueous solution, under ultrasonication, 37 DEG C of concussion reactions 5 hours, fully rinsed with distilled water after completion of the reaction, that is, be fixed with The nano composite structure adsorbent (adsorbent 2) of aminated SWCN, content of carbon nanotubes is 50mg/ml adsorbent.
Embodiment 3
(1) carrier microballoons preparation
Respectively by 15g vinyl acetate, 15g triallyl second cyanurate, 25ml ethyl acetate and 10ml normal heptane add Enter to tri- mouthfuls of 1500ml flat in, be warming up to 40 DEG C, be stirring evenly and then adding into 0.3g azo-bis-isobutyl cyanide, after dissolving, add 1000ml The aqueous solution (polyvinyl alcohol containing 1.5% and 3% sodium chloride), adjustment mixing speed makes drop to suitable size and disperses all Even, it is warming up to 65 DEG C, insulation polymerization 6 hours, then heat to 95 DEG C in insulation 4 hours, the white sphere polymers of filtration.In vain Chromosphere shaped polymer water, ethanol fully clean successively, dry.By spherical for the above-mentioned white dried be added to 2% naoh first In alcoholic solution, in 40 DEG C of alcoholysis reactions 6 hours, after completion of the reaction, suction filtration, methyl alcohol fully washs, and dries, and obtains final product required carrier micro- Ball.Carrier microballoons particle diameter 250-350um, average pore size 80nm, hydroxy radical content is 150umol/ml carrier microballoons.
(2) carrier microballoons activation
Take the carrier microballoons that 10g is dried, add 80ml dimethyl sulfoxide (DMSO), 80ml epoxychloropropane, with the hydrogen-oxygen of 3mol/l Change sodium and adjust ph10-11,40 DEG C are reacted 6 hours, distillation water wash is extremely neutral, survey epoxide number is 51umol/ml carrier microballoons.
(3) ammonium CNT aglucon
Weigh carrier microballoons 10ml after activation, be added to 0.5% ammonium multi-wall carbon nano-tube of 50ml ultrasonic disperse in advance In the pipe aqueous solution, under ultrasonication, 30 DEG C of concussion reactions 5 hours, fully rinsed with distilled water after completion of the reaction, that is, be fixed There is the nano composite structure adsorbent (adsorbent 3) of ammonium multi-walled carbon nano-tubes, content of carbon nanotubes is 30mg/ml adsorbent.
Embodiment 4
(1) carrier microballoons preparation
Respectively by 10g vinyl acetate, 15g triallyl second cyanurate, 20ml ethyl acetate and 10ml normal heptane add Enter to tri- mouthfuls of 1500ml flat in, be warming up to 40 DEG C, be stirring evenly and then adding into 0.25g azo-bis-isobutyl cyanide, add after dissolving The 1000ml aqueous solution (polyvinyl alcohol containing 2.0% and 0.5% sodium chloride), adjustment mixing speed makes drop to suitable size And be uniformly dispersed, it is warming up to 65 DEG C, is incubated polyase 13 hour, then heat to 90 DEG C in insulation 4 hours, the white of filtration is spherical Polymer.White sphere polymers water, ethanol fully clean successively, dry.It is added to 2% by spherical for the above-mentioned white dried Naoh methanol solution in, in 45 DEG C of alcoholysis reactions 4 hours, after completion of the reaction, suction filtration, methyl alcohol fully washs, and dries, and obtains final product institute Need carrier microballoons.Carrier microballoons particle diameter 200-500um, average pore size 50nm, hydroxy radical content is 120umol/ml carrier microballoons.
(2) carrier microballoons activation
Take the carrier microballoons that 10g is dried, add 10% glutaraldehyde water solution 50ml, the hcl solution of 0.15mol/l 10ml, 40 DEG C are reacted 6 hours, distillation water wash to neutrality, and survey aldehyde group content value is 105umol/ml carrier microballoons.
(3) amido CNT aglucon
Weigh carrier microballoons 10ml after activation, be added to 1.5% aminated multi-wall carbon nano-tube of 50ml ultrasonic disperse in advance In the pipe aqueous solution, under ultrasonication, 45 DEG C of concussion reactions 5 hours, fully rinsed with distilled water after completion of the reaction, that is, be fixed There is the nano composite structure adsorbent (adsorbent 4) of amido multi-walled carbon nano-tubes, content of carbon nanotubes is 75mg/ml adsorbent.
Embodiment 5: contrast test
It is comparison with external commercialization endotoxin absorbent (polymyxins b is as aglucon), respectively take above-mentioned 4 kinds of adsorbents and right Appropriate according to adsorbent, clean with the abundant drip washing of sodium chloride injection after moist heat sterilization, accurately weigh 1ml and remove depyrogenation in 25ml In conical flask, 10ml is added to contain endotoxic blood or blood plasma (endotoxin concns are 15eu/ml), after sealing, 37 DEG C in shaking table In 120 beats/min of concussion absorption 3 hours, then use endogenous toxic material in blood or blood plasma before and after the detection absorption of chromogenic substrate limulus reagent test The concentration of element, calculates adsorption rate, as shown in Table 1, result shows result, with amine (ammonium) base (single wall or many walls) CNT For the nano composite structure adsorbent of aglucon, compare with external identical product, endotoxin in blood or blood plasma is all had higher Adsorption efficiency.
Table one adsorbent is to endotoxic absorption property in blood plasma and blood

Claims (8)

1. a kind of remove endotoxic adsorbent for blood or plasma perfusion it is characterised in that this adsorbent to be a kind of nanometer multiple Close structure adsorbent, this adsorbent with large aperture polyvinyl alcohol as carrier, with single wall or many walls amine (ammonium) base carbon nano tube For aglucon, with epoxychloropropane or glutaraldehyde as cross linker, make aglucon and carrier covalent coupling, obtained nano composite structure Adsorbent preparation is simple, and induced by endotoxin has good absorption property.
2., it is characterised in that described PVA Carrier is spherical, granularity is in 100- for adsorbent according to claim 1 Between 500um, on carrier bracket, hydroxy radical content is between 100-900umol/ml;Carrier material is loose structure, pore-size distribution Between 50-500nm.
3. adsorbent according to claim 1 it is characterised in that on described aglucon CNT amine (ammonium) base content exist Between 0.1%-1%, length of carbon nanotube between 0.5-5 micron, between carbon nanotube diameter 0.5-100nm, described carrier The load capacity of upper aglucon is in 10-50mg/ml;On CNT, amine (ammonium) base can be by crosslinked arm and the covalent binding of carrier.
4. the adsorbent described in claim 1, cannot be only used for plasma perfusion and removes endotoxin it can also be used to whole blood perfusion.
5. it is used for blood described in claim 1 or plasma perfusion removes the preparation method of endotoxic adsorbent, walk including following Rapid:
1st step, high-molecular polyivnyl alcohol-triallyl isocyanate copolymerization carrier microballoon synthesis;
1.1st step, polymerization: monomer vinyl acetate, crosslinking agent Triallyl isocyanurate, pore-foaming agent ethyl acetate and positive heptan The mixture of alkane mixes, and adds 0.5%-2% initiator azodiisobutyronitrile, adds and contain polyvinyl alcohol and chlorination after dissolving In the aqueous solution of sodium, adjustment mixing speed is dispersed to wild country, heats up and causes polymerization, solidification;After completion of the reaction, ball, second are gone out Alcohol dries after fully washing, and obtains polymer microballoon;
1.2nd step, alcoholysis: above-mentioned polymer microballoon is added in sodium hydrate methanol solution and carries out ester exchange reaction, reacted Fully washed with methyl alcohol after finishing, dry, the sub- polyvinyl alcohol that secures satisfactory grades-triallyl isocyanate copolymerization carrier microballoon;
2nd step, support-activated
With known reagent and method, carrier is activated, washes clean after activation;
3rd step, aglucon are fixed
Carrier microballoons after activation and the single wall by weight 0.1-2 times amount or many walls amine (ammonium) base carbon nano tube are in ultrasonic work With reacting at lower 20-50 DEG C, abundant washes clean after completion of the reaction.
6. the preparation method of adsorbent according to claim 5 is it is characterised in that macromolecule carrier microballoon described in the 1st step closes The concrete operations becoming are as follows:
In the mixed system of 0.5-5:1, pressed with weight ratio in monomer vinyl acetate and crosslinking agent Triallyl isocyanurate Volume ratio adds 0.5-5 times of pore-foaming agent, and in pore-foaming agent, the mass ratio of ethyl acetate and normal heptane is 0.5-2:1, in mass ratio Add the initiator azodiisobutyronitrile of 0.1%-2%, be warming up to 30-50 DEG C after stirring and dissolving, be then added to 1-10 times of body In the sodium-chloride water solution of the long-pending polyvinyl alcohol of 0.5%-2% containing mass percent and 0.5%-10%, stirring is allowed to dispersion all Even, it is warming up to 60-85 DEG C of polymerization 2-6 hour, then is warming up to 85-95 DEG C, be polymerized 1-5 hour, after completion of the reaction, filter, successively Fully washed with water, ethanol, be added in NaOH-methanol solution after being dried and carry out alcoholysis, filled with methyl alcohol after completion of the reaction Divide washing, be dried, obtain final product macromolecule carrier polymer microballoon.
7. the preparation method of the adsorbent according to claim 5 or 6 is it is characterised in that described aglucon single wall or many walls amine The fixed amount of (ammonium) base carbon nano tube is 20-120mg/ml.
8. the preparation method of adsorbent according to claim 7 is it is characterised in that described aglucon single wall or many walls amine (ammonium) The preferred 40-100mg/ml of fixed amount of base carbon nano tube.
CN201610879594.7A 2016-10-09 2016-10-09 One kind removing endotoxic adsorbent and preparation method thereof for blood or plasma perfusion Active CN106334540B (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108855003A (en) * 2018-06-28 2018-11-23 南开大学 It is a kind of for removing the immunosorbent and preparation method thereof of inflammatory factor in blood
CN111632202A (en) * 2020-06-29 2020-09-08 南开大学 Tumor cell adhesion material and preparation method and application thereof
CN111686704A (en) * 2020-07-02 2020-09-22 苏州仝康医疗科技有限公司 Blood purification adsorbent and preparation method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130011824A1 (en) * 2011-01-06 2013-01-10 Cytosorbents Corporation Polymeric Sorbent for Removal of Impurities From Whole Blood and Blood Products
CN104828804A (en) * 2015-03-25 2015-08-12 清华大学 A preparing method of a porous carbon nanotube-charcoal spherical composite material

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130011824A1 (en) * 2011-01-06 2013-01-10 Cytosorbents Corporation Polymeric Sorbent for Removal of Impurities From Whole Blood and Blood Products
CN104828804A (en) * 2015-03-25 2015-08-12 清华大学 A preparing method of a porous carbon nanotube-charcoal spherical composite material

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
E. SALEHI等: "Novel chitosan/poly(vinyl) alcohol thin adsorptive membranes modified with amino functionalized multi-walled carbon nanotubes for Cu(II) removal from water: Preparation, characterization, adsorption kinetics and thermodynamics", 《SEPARATION AND PURIFICATION TECHNOLOGY》 *
李桂芬等: "多壁碳纳米管与活性炭吸附中分子毒素的比较", 《生物医学工程学杂志》 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108855003A (en) * 2018-06-28 2018-11-23 南开大学 It is a kind of for removing the immunosorbent and preparation method thereof of inflammatory factor in blood
CN108855003B (en) * 2018-06-28 2021-01-05 南开大学 Immunoadsorbent for removing inflammatory factors in blood and preparation method thereof
CN111632202A (en) * 2020-06-29 2020-09-08 南开大学 Tumor cell adhesion material and preparation method and application thereof
CN111686704A (en) * 2020-07-02 2020-09-22 苏州仝康医疗科技有限公司 Blood purification adsorbent and preparation method and application thereof
CN111686704B (en) * 2020-07-02 2023-08-08 苏州仝康医疗科技有限公司 Blood purification adsorbent and preparation method and application thereof

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