CN109012630A - Magnetic composite adsorbent for blood perfusion and preparation method thereof and perfusion device - Google Patents
Magnetic composite adsorbent for blood perfusion and preparation method thereof and perfusion device Download PDFInfo
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- CN109012630A CN109012630A CN201811005346.5A CN201811005346A CN109012630A CN 109012630 A CN109012630 A CN 109012630A CN 201811005346 A CN201811005346 A CN 201811005346A CN 109012630 A CN109012630 A CN 109012630A
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
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Abstract
The present invention relates to magnetic composite adsorbent for blood perfusion and preparation method thereof and perfusion devices.The adsorbent includes magnetic carrier, adhesion layer and with base；Adhesion layer includes the poly-dopamine being adhered on magnetic carrier；Adhesion layer is coated with base, includes the polyanion aglucon being connected on adhesion layer with base.The preparation method includes coupling reaction, dopamine polymerization reaction and aglucon polymerization reaction.Adsorbent of the invention removes the absorption of LDL and radionuclide suitable for blood perfusion.
Description
Technical field
The present invention relates to field of blood purification, and in particular to one kind suitable for blood perfusion remove low-density lipoprotein with
Magnetic composite adsorbent of radionuclide and its preparation method and application.
Background technique
Blood perfusion is a kind of mode of blood purification, compared to sides such as haemodialysis, blood plasma filtration and plasma exchanges
Formula has obvious advantage in terms of the especially middle macromolecular removal of the selective removal to morbid substance.And blood fills
The key of stream is the design and synthesis of blood-purifying adsorbing agent, many applied to the adsorbent type of blood perfusion at present, from
There are physical absorption class, ion exchange class, biological affine class and physical chemistry parent from the point of view of the interaction of ligand and target toxin
And class, therefore select suitable effect ligand most important for the performance for improving adsorbent.Anionic adsorbent material is blood
Common one kind adsorbent in liquid perfusion, usually by the carrier institute group of the anion aglucon of performance adsorption function and carrying aglucon
At electrostatic force occurs for positively charged toxin in the negative electrical charge and blood using anion institute band, to realize to object
The selective removal of matter.
Low-density lipoprotein is a kind of typical positively charged substance, low concentration lipoprotein (LDL-C) and extremely low in blood
Horizontal abnormal increase of density lipoprotein (VLDL-C) causes the excess generation of the low-density lipoprotein of oxidation state to be to cause artery
The principal element of atherosis, and cardiovascular and cerebrovascular disease caused by atherosclerosis be major causes of death in recent years it
One.At present for patients with mild, the level of the LDL-C in blood samples of patients can be reduced by modes such as diet, drugs, reaches alleviation
The effect of with the disease is cured.But for serious hyperlipemia and familial hyperlipemia, traditional mode therapeutic effect is simultaneously
It is undesirable, it needs by blood purification therapy, many scholars have carried out many research work in terms of LDL removes adsorbent,
It mainly include immunosorbent and affinity adsorbent.The former is mainly by loading to base for biomolecule such as LDL antibody, polypeptides
On body material, using aglucon to the specific recognition of LDL, the reduction to LDL level in blood, such as Germany Baxter public affairs are realized
LDL antibody is grafted on Ago-Gel by department, prepares LDL immunosorbent, but this method preparation cost valuableness and aglucon
It is easy to fall off, and then triggers an immune response, be unfavorable for practical application.Affinity adsorbent is a research emphasis of LDL adsorbent,
Be mainly based upon that low-density lipoprotein is positively charged, in conjunction with the electrostatic interaction between anion aglucon, as sulfonic acid, carboxylic acid,
Phosphoric acid etc. realizes the removal to LDL.Nankai University Wang Shenqi et al. (Wang Shenqi, Li Changming, Guo
Xinji et al, Reactive and Functional Polymers, 2008,68:261-267) with phosphoric acid, sulfonic acid, carboxylic acid
Deng for aglucon, using cellulose as carrier, a variety of LDL adsorbents of preparation, and absorption property is investigated and compared.
Radionuclide is another typical positively charged substance, and accumulation in vivo can cause long-term interior photograph
It penetrates, and then induces the generation of a variety of diseases, and is larger from difficulty fully erased in vivo.EDTA, calcium trisodium pentetate are mainly used at present
(Ca-DTPA) etc. the decorporation medicines of spectrum removes intracorporal radionuclide, although this method can be to a certain extent
The radiation new isotope accumulated in removal blood, but can also cause some adverse reactions simultaneously, for example Toxicity of Kidney, microelement lack
It is weary etc., very big side effect is caused to the body of patient.Therefore, it is badly in need of finding a kind of alternative that people is intracorporal to put for removing
Penetrating property nucleic, and blood perfusion shows certain application prospect in this respect, by designing suitable adsorbent, selectively
The radionuclide in blood is removed, is impacted without other organs to human body, the appearance of adverse reaction is avoided, accelerates to suffer from
The rehabilitation of person.Radionuclide in solution is mostly positively charged, therefore can pass through the adsorbent of design anionic, realization pair
The removal of nucleic.University Of Suzhou Zhang Shuang et al. (Zhang Shuang, Shu Xiaowen, Zhou Yuan et al,
Chemical Engineering Journal, 2014,253:55-62) polymer microsphere of polyacrylic acid functionalization has been synthesized,
For removing the uranium in solution (VI) ion, 990mg/g is reached to the adsorption capacity of uranium (VI), shows good adsorptivity
Energy.
The basis material of anionic adsorbent is all much bioabsorbable polymer material at present, although biocompatibility compared with
It is good, but mechanical strength is insufficient, while absorption property is easy to be influenced by steric hindrance, especially for the absorption of LDL, due to it
Molecular dimension is larger, and diameter is about 7.5nm to 10nm, as LDL is in the covering of adsorbent surface, adsorption site is caused to be covered
It covers, and then influences the further absorption of LDL molecule.Although the influence of steric hindrance can be reduced by introducing linking arm,
The grafting amount of aglucon can be reduced, again such that the adsorption capacity to LDL is lower.
Summary of the invention
In order to overcome the shortcomings and deficiencies of the prior art described above, the main purpose of the present invention is to provide one kind in blood
The magnetic composite adsorbent of LDL and radionuclide are removed in liquid perfusion.
Another object of the present invention is to provide a kind of for removing the magnetism of LDL and radionuclide in blood perfusion
The preparation method of compound adsorbent.
Another object of the present invention is to provide a kind of for removing the magnetism of LDL and radionuclide in blood perfusion
Application of the compound adsorbent in perfusion device.
Main purpose to realize the present invention, the present invention provides the magnetic composite adsorbent for blood perfusion, packets
Include magnetic carrier, adhesion layer and with base；Adhesion layer includes the poly-dopamine being adhered on magnetic carrier；It coats and adheres to base
Layer, includes the polyanion aglucon being connected on adhesion layer with base.
By above scheme as it can be seen that the present invention provides a kind of novel for removing LDL and radioactivity in blood perfusion
The magnetic composite adsorbent of nucleic, the adsorbent be magnetic composite, including magnetic carrier, adhesion layer and match three, base
Part.Magnetic carrier refers to the magnetic carrier of tool, the preferably oxide of iron, cobalt and nickel, more preferably ferroso-ferric oxide.This
Invention forms adhesion layer by the adherency of poly-dopamine and autohemagglutination effect, in surfaces of magnetic carriers；By adhesion layer and poly- yin from
Sub- aglucon connection coats a strata anion aglucon in the outer surface of the carrier with adhesion layer.Polyanion aglucon to LDL and
Radionuclide shows higher absorption property, and aglucon is present in the outer surface of carrier, reduces steric hindrance to absorption
The influence of process, while being also beneficial to adsorbate in adsorption process and arriving more quickly at adsorption site, promote the quick of adsorption equilibrium
It establishes, improves the adsorption efficiency of adsorbent.Adhesion layer poly-dopamine and aglucon polyanion all have good blood phase
Capacitive ensure that the safety of adsorbent in use.Magnetic composite adsorbent of the invention uses magnetic carrier, makes
The intermediate product and final product for obtaining adsorbent preparation process can be easily separated, and make in use in high-throughput feelings
Under condition, it is able to maintain low pressure drop, can be effectively prevented from de- by the way that Magnetic Isolation equipment is added in cylinder treated pipeline
The particle fallen enters in blood, improves the safety of blood perfusion.
Further technical solution is that polyanion aglucon is polyacrylate or polyacrylic acid.
By above scheme as it can be seen that polyanion aglucon can use polyacrylate or polyacrylic acid, due to polyacrylic acid
Ester or polyacrylic acid contain anionic group, can generate very strong electrostatic force to positively charged LDL and radionuclide,
To realize the selective removal to the two.
Further technical solution is that being covalently attached in poly-dopamine has initiator, and initiator has terminal bromine atoms；It is poly-
Anion aglucon causes atom transfer radical polymerization by surface and is formed.
Therefore initiator of the invention and poly-dopamine are covalently attached, and are fixed initiator by dopamine autohemagglutination
On magnetic carrier, initiator is firmly combined with dopamine, and it is not easily to fall off to cause the aglucon that polymerization is formed by initiator.Initiator
It is preferred that having terminal bromine atoms, initiator causes monomer and carries out surface initiation atom transferred free radical in the outer surface of carrier material
Polymerization reaction, in-situ polymerization obtain polyanion with base.Atom transition free radical polymerization reaction has reaction condition mild, anti-
Should be easy to control, molecular weight of product narrowly distributing the advantages that.Ligand content number can by regulate and control polymerization reaction condition come
It realizes.Preferably, initiator is 2- bromo isobutyl acylbromide.2- bromo isobutyl acylbromide both ends have bromine atom, and one of bromine is former
Son is reacted with dopamine, another bromine atom is for causing atom transfer radical polymerization.2- bromo isobutyl acylbromide has reaction
The advantages that active high, reaction effect is good.
Further technical solution is, magnetic carrier is ferriferrous oxide particles, the partial size of magnetic carrier be 0.1 μm extremely
200μm。
By above scheme as it can be seen that magnetic carrier is ferriferrous oxide particles in the present invention.Ferriferous oxide magnetic carrier draws
Enter the disadvantage for overcoming existing bioabsorbable polymer material mechanical strength deficiency, and magnetic ferroferric oxide also has as carrier
Good blood compatibility.The partial size of magnetic carrier is in above range, and it is too small and be easily accessible in blood to can be avoided particle, together
When prevent particle is excessive from surface area being caused to reduce, reduce ligand content.Wherein, magnetic ferroferric oxide particle can pass through Fe2+
And Fe3+Mixed solution, in alkaline system occur coprecipitation reaction and be prepared；It can also be by by ferric chloride hexahydrate
It is dispersed in the system that ethylene glycol and surfactant coexist, is heated at high temperature certain time in a kettle and is prepared.
Another object to realize the present invention, the present invention provides the preparations of the magnetic composite adsorbent for blood perfusion
Method, comprising the following steps:
Step 1: dopamine hydrochloride and initiator carry out coupling reaction；
Step 2: the resulting dopamine for being fixed with initiator of step 1 is polymerize on magnetic carrier, forms adherency
Layer；
Step 3: step 2 products therefrom causes monomer polymerization and obtains polyanion aglucon, is formed and matches base.
By above scheme as it can be seen that initiator is first introduced into dopamine by the present invention, then by dopamine in magnetic carrier table
Initiator is fixed on surfaces of magnetic carriers, finally causes monomer polymerization by initiator, in poly-dopamine adhesion layer by face auto polymerization
Outside forms a strata anion aglucon.Preparation method of the invention is successfully prepared for a kind of for removing in blood perfusion
The magnetic composite adsorbent of LDL and radionuclide, which has easily separated, good biocompatibility, mass transfer rate fast, right
The advantages that LDL and radionuclide show higher absorption property.
Further technical solution is, in step 1: initiator is 2- bromo isobutyl acylbromide；Coupling reaction includes will be more
Bar amine hydrochlorate and 2- bromo isobutyl acylbromide are dispersed in organic solvent, basic catalyst are added, in protective gas and at room temperature
React 1h to 12h；Organic solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran；Alkalinity is urged
Agent is triethylamine；Protective gas is nitrogen or argon gas；Dopamine hydrochloride, 2- bromo isobutyl acylbromide, organic solvent and alkalinity
The molar ratio of catalyst is 1:(0.2 to 0.8): (4 to 250): (0.2 to 0.8).
By above scheme as it can be seen that the present invention utilizes the coupling reaction of dopamine hydrochloride and 2- bromo isobutyl acylbromide, by 2-
Bromo isobutyl acylbromide is covalently attached on dopamine molecule, while the bromine atom for remaining 2- bromo isobutyl acylbromide end participates in certainly
It is polymerize by base.
Further technical solution is that in step 2, magnetic carrier is ferriferrous oxide particles, and magnetic carrier partial size is
0.1 μm to 200 μm；Polymerization reaction include ferriferrous oxide particles are added in alkaline buffer solution to carry out ultrasonic disperse, then
The resulting dopamine for being fixed with initiator of step 1 is added, mechanic whirl-nett reaction 2h is to for 24 hours at normal temperature, after reaction,
Obtained solid water and ethanol washing is multiple, it is dry；Alkaline buffer solution is trishydroxymethylaminomethane buffer solution, and pH is
8.5；The mass ratio of ferriferrous oxide particles, alkaline buffer solution and dopamine hydrochloride is (1.5 to 10): (100 to 1200):
1。
By above scheme as it can be seen that the present invention utilizes the adhesiveness and autohemagglutination of dopamine, formed in surfaces of magnetic carriers poly-
Dopamine adhesion layer.Wherein, magnetic carrier is capable of providing higher mechanical strength, and poly-dopamine has good bio-compatible
Property, initiator is fixed on the surface of magnetic carrier.
Further technical solution is, in step 3, monomer is acrylic acid or acrylate；Polymerization procedure includes that will walk
In organic solvent, under a shielding gas, ligand solution is added, in room temperature in rapid two products therefrom, catalyst and monomer dispersion
Or 2h is reacted under conditions of heating to for 24 hours；After reaction, obtained solid washed, dried；Catalyst be copper, iron,
Ruthenium, rhodium, palladium or nickel compound at least one；Organic solvent is N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran
At least one of；Ligand solution be solution of the ligand in the organic solvent, ligand be three (2- dimethylaminoethyl) amine,
2-2'- bipyridyl, N, N, N', N ", at least one of N "-pentamethyl-diethylenetriamine；Step 2 products therefrom, catalyst,
Monomer, organic solvent, organic ligand solution mass ratio be 1:(0.01 to 0.05): (5 to 200): (10-200): (1 to 15)；
The volume ratio of ligand and organic solvent is 1:(20 to 150) in organic ligand solution.
By above scheme as it can be seen that the present invention, which causes atom transition free radical polymerization reaction by surface, makes acrylic acid or propylene
Acid esters polymerize in magnetic carrier outer surface, forms polyanion aglucon.Reaction condition is mild, can be obtained by controlling reaction condition
To the polyanion aglucon of required grafting amount.
Further technical solution is in step 2 and step 3, to be separated by solid-liquid separation after reaction by magnet.
By above scheme as it can be seen that the present invention can use during the preparation process magnetic carrier Magnetic Isolation intermediate product and
Final product, it is easy to operate.
Another object to realize the present invention, the present invention provides for removing low-density lipoprotein and radioactivity in blood
The perfusion device of nucleic, it is characterised in that: the perfusion device include above-mentioned blood perfusion magnetic composite adsorbent or above-mentioned system
The magnetic composite adsorbent of blood perfusion made from Preparation Method.
By above scheme as it can be seen that blood perfusion magnetic composite adsorbent of the invention or by preparation method system of the invention
The blood perfusion magnetic composite adsorbent obtained can be used for adsorbing LDL and radionuclide, specifically, Ke Yiyong in blood perfusion
In perfusion device, as adsorbent.
Specific embodiment
Combined with specific embodiments below, product of the invention, method and its technical effect are described further.
Embodiment 1
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide of 40mL, and logical nitrogen
It is protected, the triethylamine of 2- bromo isobutyl acylbromide (BiBB, about 3mmol) and 0.28mL that 0.25mL is then added is (about
3mmol), 1h is reacted at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 0.1 μm) of 4g are added to the trishydroxymethylaminomethane of 500mL
In buffer solution (pH=8.5), then ultrasonic disperse is slowly added dropwise above-mentioned dopamine-BiBB conjugate solution, reacts at normal temperature
2h, after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-Br.
3) surface aggregate
By the two of the acrylate monomer of CuCl, 40mL of the magnetic-particle of 2g/poly-dopamine-Br, 40mg and 40mL
Methyl sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 5mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.08mL), reacts 12h under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylate aglucon composite adsorption
Agent.
Embodiment 2
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the dimethyl sulfoxide of 60mL, and logical nitrogen is protected
Shield, the triethylamine of 2- bromo isobutyl acylbromide (BiBB, about 1.2mmol) and 0.11mL that 0.1mL is then added is (about
1.2mmol), 6h is reacted at normal temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 0.8 μm) of 2g are added to the trishydroxymethylaminomethane of 200mL
In buffer solution (pH=8.5), then ultrasonic disperse is slowly added dropwise above-mentioned dopamine-BiBB conjugate solution, reacts at normal temperature
6h, after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-Br.
3) surface aggregate
By the acrylate monomer of CuCl, 100mL of the magnetic-particle of 1g/poly-dopamine-Br, 40mg and 100mL
N,N-Dimethylformamide (DMF) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- diformazans of 10mL are then added
Amino-ethyl) amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.08mL), at room temperature instead
12h is answered, is separated by solid-liquid separation with strong magnet, is purified, it is dry, it obtains magnetic-particle/poly-dopamine/polyacrylate aglucon and answers
Close adsorbent.
Embodiment 3
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the tetrahydrofuran solution of 100mL, and logical nitrogen into
Row protection, the triethylamine of 2- bromo isobutyl acylbromide (BiBB, about 4.8mmol) and 0.43mL that 0.38mL is then added is (about
2mmol), 12h is reacted at normal temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 0.8 μm) of 10g are added to the trishydroxymethylaminomethane of 1000mL
Buffer solution in (pH=8.5), then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise, at normal temperature instead in ultrasonic disperse
Should for 24 hours, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-Br.
3) surface aggregate
By the acrylate monomer of CuCl, 20mL of the magnetic-particle of 1g/poly-dopamine-Br, 10mg and the N of 20mL,
Dinethylformamide (DMF) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminos of 2mL are then added
Ethyl) amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.02mL), reacts under the conditions of 60 DEG C
2h is separated by solid-liquid separation with strong magnet, is purified, dry, and it is compound to obtain magnetic-particle/poly-dopamine/polyacrylate aglucon
Adsorbent.
Embodiment 4
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 0.3 μm) of 4g are added to the trishydroxymethylaminomethane of 500mL
In buffer solution (pH=8.5), then ultrasonic disperse is slowly added dropwise above-mentioned dopamine-BiBB conjugate solution, reacts at normal temperature
4h, after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-Br.
3) surface aggregate
By the acrylate monomer of CuCl, 100mL of the magnetic-particle of 2g/poly-dopamine-Br, 20mg and 100mL
Dimethyl sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylamino second of 3mL are then added
Base) amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.06mL), it is reacted for 24 hours under the conditions of 60 DEG C,
It is separated by solid-liquid separation, is purified with strong magnet, it is dry, obtain magnetic-particle/poly-dopamine/polyacrylate aglucon composite adsorption
Agent.
Embodiment 5
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 200 μm) of 4g are added to the trishydroxymethylaminomethane of 200mL
In buffer solution then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise in (pH=8.5, solvent are water), ultrasonic disperse,
6h is reacted under room temperature, after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly- DOPA
Amine-Br.
3) surface aggregate
By the two of the acrylate monomer of CuCl, 20mL of the magnetic-particle of 2g/poly-dopamine-Br, 20mg and 20mL
Methyl sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 2mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.06mL), reacts 12h under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylate aglucon composite adsorption
Agent.
Embodiment 6
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 20 μm) of 4g are added to the slow of the trishydroxymethylaminomethane of 500mL
(pH=8.5, solvent are water) is rushed in solution, then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise, normal in ultrasonic disperse
Temperature is lower to react 6h, and after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-
Br。
3) surface aggregate
By the two of the acrylate monomer of CuCl, 50mL of the magnetic-particle of 2g/poly-dopamine-Br, 20mg and 100mL
Methyl sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 2mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.08mL), reacts for 24 hours under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylate aglucon composite adsorption
Agent.
Embodiment 7
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 20 μm) of 4g are added to the slow of the trishydroxymethylaminomethane of 500mL
(pH=8.5, solvent are water) is rushed in solution, then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise, normal in ultrasonic disperse
Temperature is lower to react 6h, and after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-
Br。
3) surface aggregate
By the two of the acrylate monomer of CuCl, 60mL of the magnetic-particle of 2g/poly-dopamine-Br, 80mg and 100mL
Methyl sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 6mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.08mL), reacts for 24 hours under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylate aglucon composite adsorption
Agent.
Embodiment 8
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 20 μm) of 4g are added to the slow of the trishydroxymethylaminomethane of 500mL
(pH=8.5, solvent are water) is rushed in solution, then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise, normal in ultrasonic disperse
Temperature is lower to react 6h, and after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-
Br。
3) surface aggregate
By the acrylic monomers of CuCl, 20mL of the magnetic-particle of 2g/poly-dopamine-Br, 20mg and the diformazan of 40mL
Base sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 3mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.06mL), reacts 12h under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylic acid aglucon compound adsorbent.
Embodiment 9
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 20 μm) of 4g are added to the slow of the trishydroxymethylaminomethane of 500mL
(pH=8.5, solvent are water) is rushed in solution, then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise, normal in ultrasonic disperse
Temperature is lower to react 6h, and after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-
Br。
3) surface aggregate
By the acrylic monomers of CuCl, 40mL of the magnetic-particle of 2g/poly-dopamine-Br, 20mg and the diformazan of 40mL
Base sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 3mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.06mL), reacts 12h under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylic acid aglucon compound adsorbent.
Embodiment 10
1) coupling reaction
The dopamine hydrochloride (about 6mmol) of 1.14g is dissolved in the n,N-Dimethylformamide solution of 40mL, and is led to
Nitrogen is protected, and the 2- bromo isobutyl acylbromide (BiBB, about 3mmol) of 0.25mL and the triethylamine of 0.28mL is then added
(about 3mmol), reacts 3h at room temperature, obtains the conjugate solution of dopamine-BiBB.
2) the adherency polymerization of dopamine
The ferriferrous oxide particles (partial size is about 20 μm) of 4g are added to the slow of the trishydroxymethylaminomethane of 500mL
(pH=8.5, solvent are water) is rushed in solution, then above-mentioned dopamine-BiBB conjugate solution is slowly added dropwise, normal in ultrasonic disperse
Temperature is lower to react 6h, and after reaction, three times with water and ethanol washing, vacuum drying obtains sample magnetic-particle/poly-dopamine-
Br。
3) surface aggregate
By the acrylic monomers of CuCl, 60mL of the magnetic-particle of 2g/poly-dopamine-Br, 20mg and the diformazan of 40mL
Base sulfoxide (DMSO) is added in three-necked flask, and logical nitrogen is protected, and three (the 2- dimethylaminoethyls) of 3mL are then added
Amine/DMSO solution (wherein the additional amount of three (2- dimethylaminoethyl) amine is 0.06mL), reacts 12h under the conditions of 60 DEG C, uses
Strong magnet is separated by solid-liquid separation, and is purified, dry, obtains magnetic-particle/poly-dopamine/polyacrylic acid aglucon compound adsorbent.
Adsorbent evaluates LDL absorption property
Then three times with brine first suitable physiology salt is added in adsorbent 1mL made from Example 1 to 7
Water balance 2h removes free physiological saline with suction pipe, and 10mL hyperlipemia disease human plasma, 37 DEG C of oscillation 2h is added, and revolving speed is
140rpm.After absorption, supernatant is taken, is become using low-density lipoprotein (LDL) concentration in ELISA method measurement supernatant
Change.Removal rate R is calculate by the following formula:
R=(C0-C1)/C0* 100%；
C in formula0And C1Respectively indicate the concentration (mg/dL) of absorption front and back LDL.
Adsorbent made from embodiment 1 to 7 is as shown in table 1 below to the absorption property of LDL.
Absorption property of 1 adsorbent of table to LDL
Therefore adsorbent made from embodiment 1 to 7 has good absorption property to LDL, to LDL in blood plasma
Removal rate is up to 50% or more, even up to 70% or more.
Adsorbent evaluates the absorption property of uranyl ion
Adsorbent 0.1g in Example 8 to 10 is added the 1 × 10 of 25mL in 50mL conical flask-5Mol/L's
UO2 2+Solution, 37 DEG C of oscillations 2h, revolving speed 140rpm.After absorption, supernatant is taken, takes arsenazo III development process, with purple
Outside-visible spectrophotometer at wavelength 652nm to absorption before and after the concentration of solution be measured, and according to above-mentioned removal rate meter
Formula R=(C0-C1)/C0* 100%, calculate its removal rate R.
2 adsorbent of table is to UO2 2+Absorption property
Therefore the adsorbent that is prepared of embodiment 8 to 10 has a good adsorptivity to uranyl ion, uranyl from
The removal rate of son is up to 90% or more.
It is excellent that adsorbent provided by the invention has that mechanical strength is higher, easily separated, good biocompatibility, mass transfer rate are fast etc.
Point shows higher absorption property to LDL and radionuclide, LDL and radionuclide suitable for blood perfusion
Absorption is removed.Has the advantages that fluidized bed and fixed bed in traditional post separation, including low pressure drop, high throughput, high mass transfer speed simultaneously
Rate and high-adsorption-capacity.
It finally it is emphasized that the above is only a preferred embodiment of the present invention, is not intended to restrict the invention, for this
For the technical staff in field, the present invention can have various change and change.All within the spirits and principles of the present invention, it is done
Any modification, equivalent substitution, improvement and etc., should all be included in the protection scope of the present invention.
Claims (10)
1. being used for the magnetic composite adsorbent of blood perfusion, it is characterised in that including magnetic carrier, adhesion layer and match base；It is described
Adhesion layer includes the poly-dopamine being adhered on the magnetic carrier；It is described to coat the adhesion layer with base, it is described to match base
Including the polyanion aglucon being connected on the adhesion layer.
2. the magnetic composite adsorbent according to claim 1 for blood perfusion, it is characterised in that:
The polyanion aglucon is polyacrylate or polyacrylic acid.
3. the magnetic composite adsorbent according to claim 1 for blood perfusion, it is characterised in that:
Being covalently attached in the poly-dopamine has initiator, and the initiator has terminal bromine atoms；The polyanion aglucon
Cause atom transfer radical polymerization by surface to be formed.
4. the magnetic composite adsorbent according to any one of claims 1 to 3 for blood perfusion, it is characterised in that:
The magnetic carrier is ferriferrous oxide particles, and the partial size of the magnetic carrier is 0.1 μm to 200 μm.
5. the preparation method of the magnetic composite adsorbent for blood perfusion, it is characterised in that the following steps are included:
Step 1: dopamine hydrochloride and initiator carry out coupling reaction；
Step 2: the resulting dopamine for being fixed with initiator of step 1 carries out polymerization reaction on magnetic carrier, forms adherency
Layer；
Step 3: step 2 products therefrom causes monomer polymerization and obtains polyanion aglucon, is formed and matches base.
6. the preparation method of the magnetic composite adsorbent according to claim 5 for blood perfusion, it is characterised in that
In step 1:
The initiator is 2- bromo isobutyl acylbromide；
The coupling reaction includes that dopamine hydrochloride and 2- bromo isobutyl acylbromide are dispersed in organic solvent, and alkalinity is added and urges
Agent reacts 1h to 12h in protective gas and at room temperature；
The organic solvent is at least one of N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran；The alkalinity is urged
Agent is triethylamine；The protective gas is nitrogen or argon gas；
The molar ratio of dopamine hydrochloride, 2- bromo isobutyl acylbromide and basic catalyst is 1:(0.2 to 0.8): (0.2 to 0.8).
7. the preparation method of the magnetic composite adsorbent according to claim 5 for blood perfusion, it is characterised in that
In step 2:
The magnetic carrier is ferriferrous oxide particles, and the magnetic carrier partial size is 0.1 μm to 200 μm；
The polymerization reaction includes being added to ferriferrous oxide particles in alkaline buffer solution to carry out ultrasonic disperse, adds step
The rapid one resulting dopamine for being fixed with initiator is stirred to react 2h to for 24 hours, after reaction, by obtained solid at normal temperature
It is multiple with water and ethanol washing, it is dry；
The alkaline buffer solution is trishydroxymethylaminomethane buffer solution, pH 8.5；
The mass ratio of ferriferrous oxide particles, alkaline buffer solution and dopamine hydrochloride is (1.5 to 10): (100 to 1200):
1。
8. the preparation method of the magnetic composite adsorbent according to claim 5 for blood perfusion, it is characterised in that
In step 3:
The monomer is acrylic acid or acrylate；
The polymerization includes dispersing step 2 products therefrom, catalyst and monomer in organic solvent, under a shielding gas,
Ligand solution is added, 2h is reacted under conditions of room temperature or heating to for 24 hours；After reaction, obtained solid washed, done
It is dry；
The catalyst is at least one of the compound of copper, iron, ruthenium, rhodium, palladium or nickel；The organic solvent is N, N- dimethyl
At least one of formamide, dimethyl sulfoxide, tetrahydrofuran；The ligand solution is that ligand is molten in the organic solvent
Liquid, the ligand are three (2- dimethylaminoethyl) amine, 2-2'- bipyridyl, N, N, N', N ", in N "-pentamethyl-diethylenetriamine
At least one；
Step 2 products therefrom, catalyst, monomer, organic ligand solution mass ratio be 1:(0.01 to 0.05): (5 to 200):
(1 to 15)；
The volume ratio of ligand and organic solvent is 1:(20 to 150) in the organic ligand solution.
9. special according to the preparation method of the described in any item magnetic composite adsorbents for blood perfusion of claim 5 to 8
Sign is:
In step 2 and step 3, it is separated by solid-liquid separation after reaction by magnet.
10. the perfusion device for removing low-density lipoprotein and radionuclide in blood, it is characterised in that: the perfusion device packet
It includes described in magnetic composite adsorbent or any one of claim 5 to 9 of the described in any item blood perfusions of Claims 1-4
Blood perfusion magnetic composite adsorbent preparation method made from blood perfusion magnetic composite adsorbent.
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| CN106552603A (en) * | 2016-11-11 | 2017-04-05 | 四川大学 | PH response type magnetic metal organic frame composite nano materials and preparation method and application |
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| CN101341203A (en) * | 2005-12-09 | 2009-01-07 | 恰根有限公司 | Magnetic polymer particles |
| CN103736156A (en) * | 2013-10-10 | 2014-04-23 | 西北大学 | Method for constructing functionalized surface and interface by polydopamine coating layer |
| CN104927010A (en) * | 2015-05-18 | 2015-09-23 | 复旦大学 | Polyelectrolyte-rich core-shell type magnetic composite microspheres and preparation method therefor and application thereof |
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| CN111282064A (en) * | 2020-02-21 | 2020-06-16 | 中国人民解放军陆军军医大学第一附属医院 | ZnNa3-DTPA chelating resin and its use in removing radionuclides |
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