CN109046282A - Blood perfusion and aqueous solution remove the adsorbent and preparation method thereof of endotoxin - Google Patents
Blood perfusion and aqueous solution remove the adsorbent and preparation method thereof of endotoxin Download PDFInfo
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- CN109046282A CN109046282A CN201811014894.4A CN201811014894A CN109046282A CN 109046282 A CN109046282 A CN 109046282A CN 201811014894 A CN201811014894 A CN 201811014894A CN 109046282 A CN109046282 A CN 109046282A
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- woven fabrics
- adsorbent
- endotoxin
- aqueous solution
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- 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
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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
Abstract
The present invention relates to the adsorbent and preparation method thereof that blood perfusion and aqueous solution remove endotoxin, which is mainly connected in a manner of covalent bond or covalent groups grafted chain and polyethyleneimine by non-woven fabrics and is formed；The preparation method mainly includes the steps that the activation of nonwoven surface fibre grafting and immobilized polyethyleneimine amine ligand.Preparation method of the present invention is simple, low in the pollution of the environment, and gained adsorbent has good Endotoxin adsorption performance, blood compatibility and safety.
Description
Technical field
The present invention relates to blood purifications and water treatment field, and in particular to blood perfusion and aqueous solution remove endotoxin
Adsorbent and preparation method thereof.
Background technique
A variety of situations can all cause the endotoxemia of human body, these situations include: stress shape in severe trauma, infection etc.
Under state；The endotoxin of whole body reticuloendothelial system dysfunction, immunity function decline, intestinal absorption is excessive and is more than that body is removed
Ability；Gastrointestinal tract mucous ischemic, necrosis, barrier breakdown, a large amount of endotoxins are released into blood；The endotoxin of intestinal absorption is because of liver function
Obstacle directly enters body circulation by offshoot circulation；The infection of certain tissues, organ causes exogenous endotoxin to enter blood.
Endotoxemia typically results in lethal infection shock, multiple organ failure, disseminated intravascular coagulation etc.,
Case fatality rate is high.Exploitation endotoxin absorption columns can be applied to multiple disease areas, including pyemia, severe trauma sexuality contaminate, again
Type hepatitis, hepatic encephalopathy, Severe Acute Pancreatitis SAP concurrent infection, pulmonary infection etc., the patient populations of above-mentioned disease are huge.
Endotoxin absorbent be usually with macroreticular resin, active carbon or fiber etc. for carrier, activated load aglucon and obtain
It arrives.The dispensing of endotoxin absorbent mainly includes deoxycholic acid, polymyxin B, arginine, recombinant protein, polyethyleneimine at present
Amine (PEI) etc..
Macroporous absorbent resin as Endotoxin adsorption agent carrier would generally use hypertoxic, carcinogenicity during the preparation process
Chloromethyl ether and nitrobenzene, there are great security risks for health of the residual of these reagents to patient, while to production environment
Pressure is also very big.Active carbon carries out a large amount of impurity that can still fall off when blood perfusion after coating, into blood of human body, to patient
Still there is security risk.
In haemodialysis, the endotoxin that the water for dialysis produced from water making device contains would generally be more than relevant criterion
Regulation, excessive endotoxin, which enters blood of human body by dialysis membrane, should can send out Complication of dialysis a series of, seriously affect trouble
The life quality and dialysis-effect of person, therefore be also required to absorb and filter using endotoxin absorption columns excessive in removal water for dialysis
Endotoxin.
The Chinese patent of Publication No. CN104525151A is disclosed with polystyrene divinylbenzene resin and poly- methyl
Methacrylate resin is carrier, carries out epoxidation modification to the residual double bonds of vector resin, later immobilized aglucon again.But
The remaining double bond of porous carrier surface is less, therefore base unit weight is less, and the absorption property of induced by endotoxin is lower for immobilized matching.In addition,
Although the program reduces the residual of carcinogenicity substance, but used many hypertoxicity chemical reagent.Publication No.
JPH04270965A Japanese patent discloses a kind of endotoxin absorbent, be that polystyrene of the surface with polymyxin B is compiled
Textured fiber, polymyxin B other than expensive, also have sizable toxic effect, mainly renal toxicity, neurotoxicity and
Neuromuscular blockade.
Summary of the invention
In order to overcome the disadvantages of the prior art mentioned above with it is insufficient, the main purpose of the present invention is to provide one kind for
Endotoxic adsorbent is removed in blood perfusion and aqueous solution, the adsorbent with blood compatibility good, induced by endotoxin have compared with
Good selective absorption performance.
Another object of the present invention is to provide one kind for removing endotoxic absorption in blood perfusion and aqueous solution
The preparation method of agent.
Main purpose to realize the present invention, the present invention provides the absorption that blood perfusion and aqueous solution remove endotoxin
Agent, the adsorbent form the grafted chain with epoxy group or hydroxyl on non-woven fabrics, then by epoxy group and polyethyleneimine with
Covalent is connected or is connected to be formed in a manner of covalent groups by hydroxyl and polyethyleneimine.
By above scheme as it can be seen that adsorbent of the invention has the grafting of epoxy group or hydroxyl in nonwoven surface grafting
Chain, then pass through the immobilized polyethyleneimine of grafted chain.Wherein, the grafted chain with epoxy group or hydroxyl can pass through a variety of reaction sides
Formula obtains, and preparation method is relatively easy.Epoxy group or hydroxyl reactivity are higher, are easy immobilized polyethyleneimine aglucon, and anti-
Stable covalent bond or covalent groups should be formed afterwards, and aglucon is prevented to be detached from.Polyethyleneimine, which acts on combining by Electrostatic complexation, suffers from
The endotoxin in endotoxin or aqueous solution in person's blood, induced by endotoxin have good selectivity absorption property, Neng Goushi
The efficient removing of existing induced by endotoxin.Non-woven fabrics can be grafted a large amount of grafted chains, and grafted chain is stretched out from nonwoven surface, as connection
The intermediate arm of non-woven fabrics and polyethyleneimine aglucon, steric hindrance reduces when immobilized aglucon, so as to immobilized more polyethylene
Imines improves the absorption property of adsorbent.Grafted chain and polyethyleneimine with covalent bond or covalent groups in conjunction with, Covalent bonding together
Refer to that the group on grafted chain is directly reacted with the group in polyethyleneimine thus the covalent bond connection type formed, covalent base
Group is connected to one by crosslinking agent or other molecules in conjunction with the group in the group and polyethyleneimine referred on grafted chain
It rises.
Further technical solution is, when having epoxy group on grafted chain, the epoxy base density on non-woven fabrics is
0.7mmol/g to 1.6mmol/g；Or when having hydroxyl on grafted chain, the hydroxy density on non-woven fabrics is 0.64mmol/g
To 2.0mmol/g, hydroxyl reacts to form covalent groups by glutaraldehyde with polyethyleneimine.
By above scheme as it can be seen that grafted chain in adsorbent of the present invention by epoxy group thereon or hydroxyl come immobilized poly- second
The density of alkene imines aglucon, epoxy group or hydroxyl is conducive to connect more polyethyleneimines, avoid simultaneously in above range
Ethylene imine chain is overcrowding, since steric hindrance causes absorption property to decline.Epoxy base density and hydroxy density refer to phase
For the molal quantity of the non-woven fabrics group with grafted chain of unit mass.
Further technical solution is that grafted chain is grafted on non-woven fabrics poly- by glycidyl methacrylate (GMA)
It closes and is formed；Or grafted chain is existed by the mixture of hydroxyethyl methacrylate (HEMA), hydroxy-ethyl acrylate (HEA) or both
It is graft-polymerized and is formed on non-woven fabrics.
By above scheme as it can be seen that the grafted chain in adsorbent of the present invention can be by with double bond and epoxy group or hydroxyl
Reactive monomer be graft-polymerized on non-woven fabrics, wherein double bond participate in be graft-polymerized, epoxy group or hydroxyl are retained in and connect
In branch chain, reacted with polyethyleneimine.The grafted chain being consequently formed has a large amount of epoxy group or hydroxyl, can be immobilized a large amount of
Polyethyleneimine, to improve the absorption property of adsorbent.
Further technical solution is that non-woven fabrics is polyester non-woven fabric, polyethylene nonwoven or polypropylene non-woven fabric.
By above scheme as it can be seen that non-woven fabrics is preferably by with good blood compatibility, nontoxic, the polymer system that is not easily decomposed
Standby obtained non-woven fabrics.
Further technical solution is that the aperture of non-woven fabrics is 1 μm to 300 μm, and fibre diameter is 1 μm to 15 μm, monolithic
With a thickness of 0.2mm to 3.0mm.
By above scheme as it can be seen that using above-mentioned aperture, fibre diameter and single-sheet thickness non-woven fabrics, can guarantee nothing
More grafted chains are grafted in the fiber surface of non-woven fabrics on the basis of woven fabric support strength, improve absorption property.
Another object to realize the present invention, the present invention provides blood perfusions and aqueous solution to remove endotoxin adsorbent
Preparation method, method includes the following steps:
Step 1: carrying out graft reaction for non-woven fabrics in the grafting solution containing reactive monomer, initiator and solvent,
The grafted chain with hydroxyl or epoxy group is formed on non-woven fabrics；
Step 2: when grafted chain has epoxy group, the non-woven fabrics with grafted chain that step 1 is obtained is in polyethylene
It is reacted in imide liquor；When grafted chain has hydroxyl, the non-woven fabrics with grafted chain that step 1 is obtained is in poly- second
Glutaraldehyde is added in alkene imide liquor to be reacted.
By above scheme as it can be seen that the present invention preparation method for preparing endotoxin absorbent is simple, main includes activation nonwoven
The step of cloth and immobilized aglucon, first passes through and carries out graft modification activation to non-woven fabrics matrix fiber surface, then connected by grafted chain
Polyethyleneimine aglucon is connect, the adsorbent that induced by endotoxin there are good adsorption properties is obtained.When the grafted chain has epoxy group
When, after grafted chain is reacted with polyethyleneimine, ethanol amine and excessive epoxy reaction can also be added.
Further technical solution is that non-woven fabrics is polyester non-woven fabric, polyethylene nonwoven or polypropylene non-woven fabric；Nonwoven
The aperture of cloth is 1 μm to 300 μm, and fibre diameter is 1 μm to 15 μm, and single-sheet thickness is 0.2mm to 3.0mm；Reactive monomer is
Glycidyl methacrylate or reactive monomer are or mixtures thereof hydroxyethyl methacrylate, hydroxy-ethyl acrylate；
Initiator is photosensitizer, is selected from benzoin ethyl ether, anthraquinone -2,6- sodium disulfonate, azo dyes, benzophenone (BP) or xanthene
At least one of ketone；Solvent is n-butanol (BA).
By above scheme as it can be seen that the present invention passes through selection special pore size distribution, fibre diameter, single-sheet thickness and particular kind of
Non-woven fabrics can make carrier connect more grafted chains, and improve blood compatibility or safety；By selection with epoxy group or
The reactive monomer of hydroxyl is graft-polymerized, and can be improved the reactive group content of grafted chain, thus immobilized more aglucons；
Using environment-protecting and non-poisonous initiator and solvent, biocompatibility and the safety of adsorbent are improved, preparation process is also reduced
Destruction to environment.
Further technical solution is, in step 1, soaks non-woven fabrics with grafting solution before carrying out graft reaction；It connects
Branch reaction carries out under conditions of ultraviolet radioactive and ventilation；After carrying out graft reaction, grafted chain is had with dehydrated alcohol rinsing
Non-woven fabrics.
By above scheme as it can be seen that the present invention first sufficiently infiltrates non-woven fabrics with grafting solution between graft reaction, to guarantee
Reaction sufficiently carries out.Grafting is carried out under ventilation condition by ultraviolet light and polymerization reaction, safety and environmental protection are high-efficient.Grafting is anti-
Extra photosensitizer, monomer and copolymer should be removed afterwards, and processing is convenient.
Further technical solution is that polyethylenimine solution is aq. polyethyleneimine, and polyethyleneimine is straight chain
Type or branched chain type polyethyleneimine, molecular weight are 600 to 70000.
By above scheme as it can be seen that immobilized reaction of the invention carries out in water-based system, safety and environmental protection.Polyethyleneimine can
To select different structures as needed, also can choose different molecular weight, for example, 600,1800,10000,70000 or its
His suitable molecular weight.
Further technical solution is, in step 2, when grafted chain has epoxy group, reacts molten in polyethyleneimine
Liquid recycle stream is dynamic and carries out at room temperature；After reaction, product is washed to neutrality with distilled water, then the drying at 45 DEG C；
When grafted chain has hydroxyl, reaction circulates lower progress in polyethylenimine solution, glutaraldehyde solution is first added dropwise, then in room
Temperature is lower, and the reaction was continued；After reaction, product is washed to neutrality with distilled water, then the drying at 45 DEG C.
By above scheme as it can be seen that immobilized reaction method of the invention is simple, process warm and safe operation environmental protection.
Specific embodiment
Product of the invention, method and beneficial effect are described in detail below with reference to embodiment, with fully
Illustrate feature and effect of the invention.Raw material type, process conditions and the important parameter that can be used in the embodiment of the present invention
Range is as shown in table 1 below.
1 raw material type of table, process conditions or range
By the following examples 1 to 8 describe matrix non-woven fabrics fiber surface active specific steps, pass through embodiment 9
The specific steps for describing immobilized reaction to 16.
The surface active of matrix non-woven fabrics fiber
Embodiment 1
1) it is configured to the grafting solution of ultraviolet irradiation grafting: the grafting solution of configuration HEMA, BP and BA, wherein HEMA
The volume fraction that volume fraction is 10%, BA is that the concentration of 90%, BP is 0.2g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 300 μm, with a thickness of 2mm, diameter be the poly- to benzene of 10cm
Dioctyl phthalate fourth diester (PBT) disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: the non-woven fabrics after grafting solution sufficiently soaks is taken from grafting liquid
Out, it drains at room temperature 3 minutes, is placed under ultraviolet source and carries out ultraviolet radioactive graft reaction 20 minutes in the case where ventilation.It is purple
The main wave crest of outer light source is 365nm, and power 30W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:12, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activates the non-woven fabrics containing great amount of hydroxy group, and the hydroxy density on non-woven fabrics fiber surface is 0.64mmol/g.
Embodiment 2
1) it is configured to the grafting solution of ultraviolet irradiation grafting: the grafting solution of configuration HEMA, BP and BA, wherein HEMA
The volume fraction that volume fraction is 25%, BA is that the concentration of 75%, BP is 2g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 100 μm, with a thickness of 1mm, diameter be the poly- to benzene of 10cm
Dioctyl phthalate second diester (PET) disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: the non-woven fabrics after grafting solution sufficiently soaks is taken from grafting liquid
Out, it drains at room temperature 3 minutes, is placed under ultraviolet source and carries out ultraviolet radioactive graft reaction 40 minutes in the case where ventilation.It is purple
The main wave crest of outer light source is 365nm, and power 30W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:20, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activates the non-woven fabrics containing great amount of hydroxy group, and the hydroxy density on non-woven fabrics fiber surface is 1.5mmol/g.
Embodiment 3
1) it is configured to the grafting solution of ultraviolet irradiation grafting: configuring the grafting solution of HEA, BP and BA, wherein the body of HEA
The volume fraction that fraction is 10%, BA is that the concentration of 90%, BP is 1.0g/100mL, and stirring and dissolving is uniform, spare.
2) PBT non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 50 μm, be 10cm's with a thickness of 0.3mm, diameter
PBT disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: the non-woven fabrics after grafting solution sufficiently soaks is taken from grafting liquid
Out, it drains at room temperature 3 minutes, is placed under ultraviolet source and carries out ultraviolet radioactive graft reaction 15 minutes in the case where ventilation.It is purple
The main wave crest of outer light source is 365nm, and power 50W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:10, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activates the non-woven fabrics containing great amount of hydroxy group, and the hydroxy density on non-woven fabrics fiber surface is 0.8mmol/g.
Embodiment 4
1) it is configured to the grafting solution of ultraviolet irradiation grafting: configuring the grafting solution of HEA, BP and BA, wherein the body of HEA
The volume fraction that fraction is 30%, BA is that the concentration of 70%, BP is 2.0g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 50 μm, the PET circle that is 10cm with a thickness of 1.0mm, diameter
Piece immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: the non-woven fabrics after grafting solution sufficiently soaks is taken from grafting liquid
Out, it drains at room temperature 3 minutes, is placed under ultraviolet source and carries out ultraviolet radioactive graft reaction 15 minutes in the case where ventilation.It is purple
The main wave crest of outer light source is 365nm, and power 70W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activates the non-woven fabrics containing great amount of hydroxy group, and the hydroxy density on non-woven fabrics fiber surface is 2.0mmol/g.
Embodiment 5
1) it is configured to the grafting solution of ultraviolet irradiation grafting: configuring the grafting solution of GMA, BP and BA, wherein the body of GMA
The volume fraction that fraction is 15%, BA is that the concentration of 85%, BP is 1.0g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 150 μm, with a thickness of 1.0mm, diameter be poly- the third of 10cm
Alkene PP non-woven fabrics disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: by the non-woven fabrics after ultraviolet irradiation grafting solution sufficiently soaks from grafting
It takes out, drains at room temperature 3 minutes in liquid, progress ultraviolet radioactive graft reaction 15 under ultraviolet source is placed in the case where ventilation and is divided
Clock.The main wave crest of ultraviolet source is 365nm, and power 30W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activation contains the non-woven fabrics of a large amount of epoxy groups, and the epoxy base density on non-woven fabrics fiber surface is 0.7mmol/g.
Embodiment 6
1) it is configured to the grafting solution of ultraviolet irradiation grafting: configuring the grafting solution of GMA, BP and BA, wherein the body of GMA
The volume fraction that fraction is 30%, BA is that the concentration of 70%, BP is 2.0g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 150 μm, the poly- second that is 10cm with a thickness of 1.5mm, diameter
Alkene PE non-woven fabrics disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: by the non-woven fabrics after ultraviolet irradiation grafting solution sufficiently soaks from grafting
It takes out, drains at room temperature 3 minutes in liquid, progress ultraviolet radioactive graft reaction 15 under ultraviolet source is placed in the case where ventilation and is divided
Clock.The main wave crest of ultraviolet source is 365nm, and power 50W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:20, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activation contains the non-woven fabrics of a large amount of epoxy groups, and the epoxy base density on non-woven fabrics fiber surface is 1.6mmol/g.
Embodiment 7
1) it is configured to the grafting solution of ultraviolet irradiation grafting: the grafting solution of configuration HEMA, BP and BA, wherein HEMA
The volume fraction that volume fraction is 20%, BA is that the concentration of 80%, BP is 2.0g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 15 μm, the PBT nonwoven that is 10cm with a thickness of 1mm, diameter
Cloth disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: by the non-woven fabrics after ultraviolet irradiation grafting solution sufficiently soaks from grafting
It takes out, drains at room temperature 3 minutes in liquid, progress ultraviolet radioactive graft reaction 25 under ultraviolet source is placed in the case where ventilation and is divided
Clock.The main wave crest of ultraviolet source is 365nm, and power 70W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activates the non-woven fabrics containing great amount of hydroxy group, and the hydroxy density on non-woven fabrics fiber surface is 0.96mmol/g.
Embodiment 8
1) it is configured to the grafting solution of ultraviolet irradiation grafting: configuring the grafting solution of GMA, BP and BA, wherein the body of GMA
The volume fraction that fraction is 20%, BA is that the concentration of 80%, BP is 2.0g/100mL, and stirring and dissolving is uniform, spare.
2) non-woven fabrics is sufficiently soaked with grafting solution: by aperture being 15 μm, the PE nonwoven that is 10cm with a thickness of 1mm, diameter
Cloth disk immerses excessive grafting solution 3 minutes.
3) ultraviolet irradiation graft modification non-woven fabrics: by the non-woven fabrics after ultraviolet irradiation grafting solution sufficiently soaks from grafting
It takes out, drains at room temperature 3 minutes in liquid, progress ultraviolet radioactive graft reaction 25 under ultraviolet source is placed in the case where ventilation and is divided
Clock.The main wave crest of ultraviolet source is 365nm, and power 30W/cm, the vertical range of ultraviolet source to non-woven fabrics disk is 30cm.
4) treated non-woven fabrics the cleaning-drying of the non-woven fabrics of fiber surface activation: will be grafted through ultraviolet radioactive in excess
Dehydrated alcohol in rinse 4 times, the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, and dehydrated alcohol will carry out when rinsing
It circulates, every time rinsing 30 minutes.It is first drained after rinsing to no ethyl alcohol drop and is dripped, then dried 1 hour at 40 DEG C.Up to table
Face activation contains the non-woven fabrics of a large amount of epoxy groups, and the epoxy base density on non-woven fabrics fiber surface is 0.82mmol/g.
It is summarized as follows shown in table 2 as the parameter that embodiment 1 to 8 prepares the non-woven fabrics of surface active.
The parameter of 2 embodiment 1 to 8 of table
Immobilized reaction prepares endotoxin absorbent
Embodiment 9
The PBT non-woven fabrics that great amount of hydroxy group (0.64mmol/g) is had after taking the fiber surface being made by embodiment 1 to activate, adds
Enter the straight chain PEI aqueous solution 140mL that mass concentration is 5%, molecular weight is 600, circulates half an hour.It is dense that quality is gradually added dropwise
The glutaraldehyde solution 50mL that degree is 2%.Then reaction 4 hours is continued cycling through at room temperature.Non-woven fabrics is taken out, water washing is then distilled
To neutrality, in 45 DEG C of dryings.
Embodiment 10
The PET non-woven fabrics that great amount of hydroxy group (1.5mmol/g) is had after taking the fiber surface as made from embodiment 2 to activate, adds
Enter the straight chain PEI aqueous solution 340mL that mass concentration is 5%, molecular weight is 1800, circulates half an hour.Quality is gradually added dropwise
The glutaraldehyde solution 150mL that concentration is 2%.Then reaction 8 hours is continued cycling through at room temperature.Non-woven fabrics is taken out, then distilled water
Washing is to neutrality, in 45 DEG C of dryings.
Embodiment 11
The PBT non-woven fabrics that great amount of hydroxy group (0.8mmol/g) is had after taking the fiber surface as made from embodiment 3 to activate, adds
Enter the straight chain PEI aqueous solution 200mL that mass concentration is 5%, molecular weight is 4800, circulates half an hour.Quality is gradually added dropwise
The glutaraldehyde solution 80mL that concentration is 2%.Then reaction 6 hours is continued cycling through at room temperature.Non-woven fabrics is taken out, then distillation washing
It washs to neutrality, in 45 DEG C of dryings.
Embodiment 12
The PET non-woven fabrics that great amount of hydroxy group (2.0mmol/g) is had after taking the fiber surface as made from embodiment 4 to activate, adds
Enter the straight chain PEI aqueous solution 500mL that mass concentration is 5%, molecular weight is 70000, circulates half an hour.Quality is gradually added dropwise
The glutaraldehyde solution 180mL that concentration is 2%.Then reaction 12 hours is continued cycling through at room temperature.Non-woven fabrics is taken out, then distilled water
Washing is to neutrality, in 45 DEG C of dryings.
Embodiment 13
The PP non-woven fabrics that a large amount of epoxy groups (0.7mmol/g) is had after taking the fiber surface as made from embodiment 5 to activate, adds
The branch that enters that mass concentration is 5%, molecular weight is 600 PEI aqueous solution 180mL, room temperature cycles flowing reactive 4 hours.Take out nothing
Woven fabric is put into another container, and the ethanol amine that 20mL concentration is 1.5mol/L is then added, reacts 4 hours at room temperature.Take out nothing
Woven fabric is rinsed 4 times with dehydrated alcohol, and the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, and dehydrated alcohol is wanted when rinsing
It is circulated, every time rinsing 30 minutes.It is rinsed 30 minutes with water for injection again, in 45 DEG C of dryings.
Embodiment 14
The PE non-woven fabrics that a large amount of epoxy groups (1.6mmol/g) is had after taking the fiber surface as made from embodiment 6 to activate, adds
The branch that enters that mass concentration is 5%, molecular weight is 1800 PEI aqueous solution 400mL, room temperature cycles flowing reactive 8 hours.Take out nothing
Woven fabric is put into another container, and the ethanol amine that 20mL concentration is 1.5mol/L is then added, reacts 4 hours at room temperature.Take out nothing
Woven fabric is rinsed 4 times with dehydrated alcohol, and the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, and dehydrated alcohol is wanted when rinsing
It is circulated, every time rinsing 30 minutes.It is rinsed 30 minutes with water for injection again, in 45 DEG C of dryings.
Embodiment 15
The PBT non-woven fabrics that great amount of hydroxy group (0.96mmol/g) is had after taking the fiber surface as made from embodiment 7 to activate, adds
Enter the branch PEI aqueous solution 200mL that mass concentration is 5%, molecular weight is 4800, circulates half an hour.Quality is gradually added dropwise
The glutaraldehyde solution 80mL that concentration is 2%.Then reaction 12 hours is continued cycling through at room temperature.Non-woven fabrics is taken out, then distilled water
Washing is to neutrality, in 45 DEG C of dryings.
Embodiment 16
The PE non-woven fabrics of a large amount of epoxy groups (0.82mmol/g) is had after taking the fiber surface as made from embodiment 8 to activate,
Be added mass concentration be 5%, molecular weight is 10000 branch PEI aqueous solution 200mL, room temperature cycles flowing reactive 12 hours.It takes
Non-woven fabrics out is put into another container, and the ethanol amine that 20mL concentration is 1.5mol/L is then added, reacts 4 hours at room temperature.It takes
Non-woven fabrics out is rinsed 4 times with dehydrated alcohol, and the volume ratio of the volume of non-woven fabrics and dehydrated alcohol is 1:15, when rinsing anhydrous second
Alcohol will be circulated, every time rinsing 30 minutes.It is rinsed 30 minutes with water for injection again, in 45 DEG C of dryings.
The parameter of the immobilized PEI reaction of embodiment 9 to 16 is summarized as follows shown in table 3.
The parameter of 3 embodiment 9 to 16 of table
The performance detection of endotoxin absorbent
Endotoxic adsorption rate in blood plasma
At present it is believed that endotoxic concentration is lower than 0.1EU/mL, the blood of endotoxemia patient in human normal plasma
Slurry endotoxin concns are typically distributed on 0.1 to 1.0EU/mL, have the endotoxin concns of only a few patient to be distributed in 1.0 to 10EU/
mL.Configuration endotoxin concns are respectively the blood plasma of 0.5EU/mL, 1.0EU/mL and 2.0EU/mL, are prepared with embodiment 9 to 16
Endotoxin absorbent carries out Endotoxin adsorption, and the volume ratio of adsorbent and blood plasma is 1:8, when absorption frequency of oscillation be 100 ±
3Hz, 37 ± 1 DEG C of temperature, adsorption time 2 hours.The endotoxin concns of blood plasma, calculate endotoxin after being diluted with Nephelometric Determination
The Endotoxin adsorption rate of adsorbent, the results are shown in Table 3.
The endotoxin absorbent of 3 embodiment of table preparation is to adsorption rate endotoxic in blood plasma
Adsorbent in the embodiment of the present invention it can be seen from the Endotoxin adsorption result tested all has preferable endogenous toxic material
Plain adsorption rate can significantly reduce endotoxic concentration in blood plasma.For example, the Endotoxin adsorption rate of embodiment 12 even can achieve
70% or more.
The adsorption rate of albumen in blood plasma
With reference to " the disposable bilirubin plasorber of YY1290-2016 " standard, total protein when plasma adsorption is carried out
Loss experiment.
It measures adsorbent 1mL to be placed in conical flask, the volume ratio of adsorbent and blood plasma is 1:8, is put into water bath with thermostatic control oscillation
In device, 37 ± 1 DEG C of temperature are controlled, frequency of oscillation is 100 ± 3Hz, and oscillation absorption takes out conical flask after 2 hours, stands 3 at room temperature
Minute, sampling carries out concentration mensuration, the results are shown in Table 4.
Adsorption rate of the endotoxin absorbent to total protein in blood plasma in 4 embodiment of table
| Embodiment | Loss of proteins rate |
| Embodiment 9 | 3.6% |
| Embodiment 10 | 4.2% |
| Embodiment 11 | 5.3% |
| Embodiment 12 | 5.6% |
| Embodiment 13 | 7.2% |
| Embodiment 14 | 4.1% |
| Embodiment 15 | 3.9% |
| Embodiment 16 | 6.4% |
Adsorbent total protein loss in the embodiment of the present invention it can be seen from the total protein absorption result tested
Below 8%, hence it is evident that be lower than 15% specified in " the disposable bilirubin plasorber of YY1290-2016 ", from total egg
The angle of white loss illustrates that the endotoxin absorbent in the invention patent has preferable blood compatibility.
Therefore the present invention passes through ultraviolet irradiation crosslinking technology hydrophily on the surface grafting of matrix non-woven fabrics fiber
The intermediate arm with great amount of hydroxy group or epoxy group, it is solid by chemical covalent bonds to adsorb endotoxic main aglucon polyvinyl
It is scheduled on the hydroxyl or epoxy group of intermediate arm, so that the Endotoxin adsorption of blood perfusion and adsorption from aqueous solution be prepared
Agent, gained adsorbent has preferable Endotoxin adsorption performance, and has good blood compatibility.Preparation method of the invention
Simply, the use that severe toxicity, carcinogenicity chemical reagent are avoided in operating process, improves the safety of adsorbent, also reduces
Destruction to environment.
Specific embodiments of the present invention are described in detail above, but it is merely an example, the present invention is simultaneously unlimited
It is formed on particular embodiments described above.To those skilled in the art, any couple of present invention carries out equivalent modifications and
Substitution is also all among scope of the invention.Therefore, without departing from the spirit and scope of the invention made by equal transformation and
Modification, all should be contained within the scope of the invention.
Claims (10)
1. the adsorbent that blood perfusion and aqueous solution remove endotoxin, it is characterised in that:
The adsorbent forms the grafted chain with epoxy group or hydroxyl on non-woven fabrics, then passes through epoxy group and polyethyleneimine
It covalently connects or connects to be formed in a manner of covalent groups by hydroxyl and polyimides.
2. the adsorbent that blood perfusion according to claim 1 and aqueous solution remove endotoxin, it is characterised in that:
When the grafted chain has epoxy group, the epoxy base density on the non-woven fabrics is 0.7mmol/g to 1.6mmol/g；
When the grafted chain has hydroxyl, the hydroxy density on the non-woven fabrics is 0.64mmol/g to 2.0mmol/g, described
Hydroxyl reacts to form the covalent groups by glutaraldehyde with the polyethyleneimine.
3. the adsorbent that blood perfusion according to claim 2 and aqueous solution remove endotoxin, it is characterised in that:
The grafted chain is graft-polymerized on the non-woven fabrics by glycidyl methacrylate and is formed；
Or the grafted chain by the mixture of hydroxyethyl methacrylate, hydroxy-ethyl acrylate or both on the non-woven fabrics
It is graft-polymerized and is formed.
4. the adsorbent that blood perfusion according to claim 1 and aqueous solution remove endotoxin, it is characterised in that:
The non-woven fabrics is polyester non-woven fabric, polyethylene nonwoven or polypropylene non-woven fabric.
5. blood perfusion according to any one of claims 1 to 4 and aqueous solution remove the adsorbent of endotoxin, feature
It is:
The aperture of the non-woven fabrics is 1 μm to 300 μm, and fibre diameter is 1 μm to 15 μm, and single-sheet thickness is 0.2mm to 3.0mm.
6. the preparation method that blood perfusion and aqueous solution remove endotoxin adsorbent, it is characterised in that the method includes following
Step:
Step 1: non-woven fabrics is subjected to graft reaction in the grafting solution containing reactive monomer, initiator and solvent, in nothing
The grafted chain with epoxy group or hydroxyl is formed in woven fabric；
Step 2: when the grafted chain has epoxy group, the non-woven fabrics with grafted chain that step 1 is obtained is in polyethylene
It is reacted in imide liquor；When the grafted chain has hydroxyl, the non-woven fabrics with grafted chain that step 1 is obtained exists
Glutaraldehyde is added in polyethylenimine solution to be reacted.
7. blood perfusion according to claim 6 and aqueous solution remove the preparation method of endotoxin adsorbent, feature
It is:
The non-woven fabrics is polyester non-woven fabric, polyethylene nonwoven or polypropylene non-woven fabric；The aperture of the non-woven fabrics be 1 μm extremely
300 μm, fibre diameter is 1 μm to 15 μm, and single-sheet thickness is 0.2mm to 3.0mm；
The reactive monomer is glycidyl methacrylate or the reactive monomer is hydroxyethyl methacrylate second
Or mixtures thereof ester, hydroxy-ethyl acrylate；
The initiator is photosensitizer, is selected from benzoin ethyl ether, anthraquinone -2,6- sodium disulfonate, azo dyes, benzophenone or oxygen
At least one of miscellaneous anthrone；
The solvent is n-butanol.
8. blood perfusion according to claim 6 or 7 and aqueous solution remove the preparation method of endotoxin adsorbent, special
Sign is:
In step 1, the non-woven fabrics is soaked with the grafting solution before carrying out the graft reaction；
The graft reaction carries out under conditions of ultraviolet radioactive and ventilation；
After carrying out the graft reaction, the non-woven fabrics of grafted chain is had with dehydrated alcohol rinsing.
9. blood perfusion according to claim 6 and aqueous solution remove the preparation method of endotoxin adsorbent, feature
It is:
The polyethylenimine solution is aq. polyethyleneimine, and the polyethyleneimine is straight chain type or branched chain type polyethylene
Imines, molecular weight are 600 to 70000.
10. blood perfusion according to claim 6 or 9 and aqueous solution remove the preparation method of endotoxin adsorbent,
It is characterized in that:
In step 2, when the grafted chain has epoxy group, the reaction circulate in polyethylenimine solution and
It carries out at room temperature；It is described after reaction, product is washed to neutrality with distilled water, then is dried；
When the grafted chain has hydroxyl, the reaction circulates lower progress in polyethylenimine solution, is first added dropwise penta 2
Aldehyde solution, then the reaction was continued at room temperature；It is described after reaction, product is washed to neutrality with distilled water, then is dried.
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