CN107199024A - It is a kind of to be used to remove adsorbent of blood low density lipoprotein and preparation method thereof - Google Patents
It is a kind of to be used to remove adsorbent of blood low density lipoprotein and preparation method thereof Download PDFInfo
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- CN107199024A CN107199024A CN201710308460.4A CN201710308460A CN107199024A CN 107199024 A CN107199024 A CN 107199024A CN 201710308460 A CN201710308460 A CN 201710308460A CN 107199024 A CN107199024 A CN 107199024A
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- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
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Abstract
The invention discloses a kind of adsorbent for being used to remove blood low density lipoprotein, coupling has hydrophobic aglucon and polyanion aglucon on its absorption carrier, wherein the mass ratio of the hydrophobic aglucon and polyanion aglucon is 1:5~5:1.The present invention on absorption carrier by being coupled hydrophobic aglucon and polyanion aglucon simultaneously, utilize the hydrophobic affinity interaction of the height of hydrophobic aglucon and lipoprotein, and acted on using the electrostatical binding of polyanion and lipoprotein, specific adsorption is carried out by both synergies to lipoprotein, so as to reach that specificity removes the purpose of TG, LDL in blood.The adsorbent is parental type adsorbent, and its adsorption capacity is high, and biocompatibility is good, it is adaptable to which whole blood perfusion treats hyperlipidemia.
Description
Technical field
The present invention relates to biomedicine field, more particularly to a kind of preparation for removing blood low density lipoprotein sorbent
Method.
Background technology
The number that China dies from cardiovascular and cerebrovascular disease every year is up to 3,000,000 people, accounts for the 51% of total Death causes, it has also become people
The number one killer of class Death causes.Epidemiological study shows that atherosclerosis is the main pathogenic of angiocardiopathy,
And low-density lipoprotein (LDL) excessive concentration is the main predisposing factors of atherosclerosis in blood.LDL is dense in blood
The rise of degree can cause the increase of blood viscosity, cause velocity of blood flow to decline, and in blood vessel breakage or stenosis, be oxidized low close
Spend lipoprotein (ox-LDL) easily and other albumen form patch, these patches little by little accumulate to cause Atherosclerosis
Change.Therefore LDL concentration can effectively prevent and treat atherosclerosis in reduction blood samples of patients, and further control
System and reduction cardiovascular and cerebrovascular disease odds.Serum triglyceride (TG) is that an important clinical blood fat conventional determining refers to
Mark, TG is increasingly subject to pay attention to as an independent hazards of coronary heart disease.TG is primarily present in extra-low density in serum
In lipoprotein (VLDL), LDL is changed into through intermediated-density lipoprotein (IDL) after its general metabolism.Therefore TG levels cross high energy actuating
Pulse atherosclerosis, make individual be in the danger for being susceptible to suffer from coronary heart disease.Therefore, except reduction LDL water for hyperlipidemia patient
Outside flat, also need to reduce internal TG levels.
At present, TG, LDL mainly have drug therapy, diet control and blood in the mode of concentration in reduction blood in clinic
Three kinds of the method for purification.But diet control can only be as a kind of regulative mode of auxiliary, and which needs to adhere to for a long time, and reality
Usually it can cause to make a futile effort because of can not for a long time adhere on border, and which also reduces the quality of life of patient.Medicine
Treatment mainly has lipid-regulation medicine (Statins and fibrates) and an anti-oxidation medicine, but can exist while medicine lipid-loweringing stomachache,
The side effects such as diarrhoea, muscle cramp, the problem of long-term use can also produce drug resistance and drug dependence.Further, for family
Property hereditary hyperlipidemia patient, due to there is gene defect, LDL can not be metabolized by normal approach, therefore can not
The purpose of reducing blood lipid is reached by drug therapy.
In recent years, blood purification remove LDL as a kind of new treatment method be used for the prevention of atherosclerosis with
Treatment, is particularly suitable for the patient of the hereditary hyperlipidemia of familial.Being applied to clinical blood purification method at present has：Blood plasma is put
Change, Cured by Double Filtration Plasmapheresis, the external heparin precipitation method, absorption method.Plasma exchange remove LDL while, also by other blood plasma it is useful into
Point discard, and displacement blood plasma is in itself containing VLDL, LDL, bradykinin etc., to prevent the generation of cardiovascular disease and development there is also
Disadvantageously.Double plasma filtration method also similar plasma exchange, can still cause part blood plasma component damages.External heparin precipitation
Method can effectively reduce blood plasma lipoprotein level, but equipment and cumbersome complexity used in this method, treatment time length and expense
It is fairly expensive.Absorption method has chemisorbed and immuno absorbence, and immunoabsorption is people's LDL covalently bondeds by purification together in agar
Sugared Sepharose CL-4B, being injected into goat body makes it produce specific anti-LDL antibody.This method specificity is high, and side effect is very
It is few, but there is treatment syndrome first and because immune response caused by dissident's antibody includes heating and low blood pressure in some patients,
And immune antiboidy is rare, adsorption column price is higher.Chemisorbed rule is in the immobilized negative electricity of carrier surface using electrostatic interaction
Lotus group adsorbs positively charged LDL.
At present existing commercial adsorbent can for ion adsorbent (the LiposoberD series of Japanese Kaneka companies and
The DALI series of German Fresenius companies) and the immunosorbent (LDL of German Miltenyi Biotec companies
Therasorb), wherein ion adsorbent will first rush equilibrium adsorption post in advance to blood ion using solion in use
Absorption, portioned product adsorbent also have activation clotting factor risk.Although its adsorptive selectivity of immunosorbent is high, absorption
Work well, but its antibody used is rare, and expensive and not easy to maintain, such product is mostly by the way of plasma adsorption
Treatment, although repeatable to utilize, but complex operation, consumptive material costliness is without the demand of tallying with the national condition.Although many in recent years learn
Person is directed to studying blood fat adsorbent, but achievement can't be applied to reality very well.
The content of the invention
It is an object of the invention to remove blood low density lipoprotein there is provided one kind for upper the deficiencies in the prior art to adsorb
Agent and preparation method thereof, the adsorbent specific can remove TG, LDL in blood, and adsorption capacity is high, and biocompatibility is good, fits
Hyperlipidemia is treated for whole blood perfusion.
The technical solution used in the present invention is：A kind of adsorbent for being used to remove blood low density lipoprotein, it is adsorbed
Coupling has hydrophobic aglucon and polyanion aglucon on carrier.The present invention is adsorbed using the affinity interaction of hydrophobic aglucon and lipid
VLDL and LDL.LDL apolipoprotein is mainly containing alkalescence such as a large amount of lysines, arginine and histidines in Apo B, Apo B
Amino acid residue, many Surface L DL exposed to apolipoprotein are positively charged under normal physiological pH environment, polyanion aglucon
LDL can be adsorbed by electrostatic interaction.And VLDL also contains part Apo B, therefore polyanion aglucon can also adsorb VLDL.That is this hair
Bright adsorbent is parental type adsorbent, to ensure that the synergy of hydrophobic aglucon and both polyanion aglucons can be to lipoprotein
Carry out efficient specific adsorption, the mass ratio of the hydrophobic aglucon and polyanion aglucon is 1:5~5:1.
As the further improvement of such scheme, the hydrophobic aglucon is tocopherol and its derivative.Tocopherol typically quilt
It is considered vitamin E, is a kind of important antioxidant.Tocopherol can promote human body sex hormone to secrete, and can improve mankind spermatozoon
Vigor and quantity and be used to prevent and treat male sterility, female fertility can also be improved and prevention of miscarriage, can additionally applied
In terms of burn, frostbite, capillary hemorrhage, climacteric metancholia, beauty.Vitamin E includes tocopherol and triolefin is given birth to
The class of phenol two totally 8 kinds of compounds, i.e. α, β, γ, methyltocol and α, β, γ, δ tocotrienol.The molecular structure of tocopherol contains hydroxyl
Base, phenyl ring and chain alkyl, are a kind of highly lipophilic compounds, and it is absorbed by the body and be distributed in along with the absorption of fat
In the lipoprotein such as VLDL, LDL.Tocopherol run in human body by the various interactions with lipoprotein biomembrane it
Between.The present invention, as hydrophobic aglucon, makes absorption carrier have very hydrophobic affine in lipoprotein using tocopherol and its derivative
Effect.
As the further improvement of such scheme, the polyanion aglucon is birdsed of the same feather flock together compound, acid selected from polyacids acidic amino acid
One of which in property polysaccharide polymer and polyacrylic polymer.Specifically, polyacids acidic amino acid compound of birdsing of the same feather flock together includes
Poly-aspartate, polyglutamic acid etc.；Acidic polysaccharose birdss of the same feather flock together compound including dextran sulfate, heparin, Sulfation rock algae pentasaccharides etc..
Further, it is contemplated that the water-soluble of polyanion aglucon and the viscosity of reaction system, the polymer is molecular weight
Less than 100000 polyanionic compound.
As the further improvement of such scheme, the absorption carrier is porous material, its pore diameter range is 50~
250nm, specific surface area is 300~1300m2/g.Absorption carrier swellbility in the present invention is small, and with good mechanicalness
The features such as energy, anti-wear performance, resistant to the sterilization performance, its shape can be microballoon, tunica fibrosa, flat board etc..Further, in the present invention
Absorption carrier be selected from porous cellulose microballoon, it is Sepharose microballoon, porous Chloropolystyrene divinyl microballoon, porous poly-
One of which in methyl acrylic ester microballoon, porous polyethylene alcohols microballoon.
A kind of preparation method as described above for being used to remove the adsorbent of blood low density lipoprotein, it includes following step
Suddenly：
Absorption carrier, rear immobilized hydrophobic aglucon are activated with bis-epoxy reagent；
Coupling has the absorption carrier re-activation of hydrophobic aglucon, rear immobilized polyanion aglucon；
The mass ratio of wherein described hydrophobic aglucon and polyanion aglucon is 1:5~5:1.
Specifically, the preparation method activates absorption carrier by the bis-epoxy reagent of long-chain first and preferential immobilized hydrophobic matched somebody with somebody
Base, is that make use of diepoxides as spacerarm, to reduce space of the hydrophobic aglucon of small molecule when adsorbing lipoprotein
Steric hindrance, then antithesis is associated with the polyanion aglucon that the absorption carrier of hydrophobic aglucon carries out immobilized macromolecular after re-activation again,
There is the adsorbent amphiphilic so as to synergistic sorption lipoprotein.
As the further improvement of above-mentioned preparation method, the bis-epoxy reagent of the activation absorption carrier is selected from resorcinol
Diglycidyl ether, ethylene glycol diglycidylether and its homologue, the polypropylene glycol diglycidyl ether of low molecule amount and its
One of which in homologue.Further, it is contemplated that the reactivity and molecular chain length of bis-epoxy reagent, the present invention is preferred
1,4- butanediol diglycidyl ethers.
In addition, the mode of the present invention for being coupled the absorption carrier re-activation for having hydrophobic aglucon can be according to the poly- of selection
The characteristic of anion aglucon is selected, typically conventional activation method, such as cyanogen bromide-activated, Epichlorohydrin activation.
The beneficial effects of the invention are as follows：The present invention on absorption carrier by being coupled hydrophobic aglucon and polyanion is matched somebody with somebody simultaneously
Base, using the hydrophobic affinity interaction of the height of hydrophobic aglucon and lipoprotein, and utilizes polyanion and the electrostatic knot of lipoprotein
Cooperation use, i.e., by both synergies to lipoprotein carry out specific adsorption so that reach specificity remove blood in TG,
LDL purpose.The adsorbent is parental type adsorbent, and its adsorption capacity is high, and biocompatibility is good, it is adaptable to which whole blood perfusion is controlled
Treat hyperlipidemia.The preparation method of adsorbent is easy in the present invention, and raw material is cheap and is easy to get.
Embodiment
The present invention is specifically described with reference to embodiment, in order to art personnel to the present invention
Understand.It is necessary that herein the present invention will be further described it is emphasized that embodiment is only intended to, it is impossible to be interpreted as to this
The limitation of invention protection domain, art person skilled in the art, the non-intrinsically safe made according to foregoing invention content to the present invention
The modifications and adaptations of property, should still fall within protection scope of the present invention.Simultaneously following mentioned raw materials are unspecified, are
Commercially available prod；The processing step or preparation method not referred in detail be processing step known to a person skilled in the art or
Preparation method.
A kind of preparation method for being used to remove the adsorbent of blood low density lipoprotein, comprises the following steps：
(1) bicyclic oxygen activation：The round bottom that real porous cellulose microballoon that 10~30mL has been sunk is placed in 50mL or 100mL burns
In bottle, 10~30mL dimethyl sulfoxide (DMSO)s (DMSO), 5~10mL 1.0mol/L NaOH solution, the 1 of 5~20mL are sequentially added,
4- butanediol diglycidyl ethers (BDE), 2~8h of stirring reaction at 20~40 DEG C.After question response is finished, suction filtration is taken out, first
Cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
(2) it is coupled hydrophobic aglucon：Porous microsphere prepared by step (1) is placed in 50mL or 100mL round-bottomed flask, plus
Enter 5~15mL DMSO, 5~15mL 0.5mol/L NaOH solution and 1~10g alpha-tocopherols, stirred at 20~50 DEG C
Lucifuge reacts 4~24h.Question response is finished, and first cleans unreacted alpha-tocopherol with 50% ethanol solution, then with distillation water washing
Totally.
(3) re-activation：Porous microsphere prepared by step (2) is placed in 50mL or 100mL round-bottomed flask, is added successively
Enter 5~15mL dimethyl sulfoxide (DMSO)s (DMSO), 5~15mL 2.0mol/L NaOH solution, 1~5mL epoxychloropropane (ECH),
2~6h of stirring reaction at 35~45 DEG C.After question response is finished, suction filtration is taken out, first two are cleaned with 0.1mol/L HCl solution
All over, cleaned again with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
(4) it is coupled polyanion aglucon：Porous microsphere prepared by step (3) is placed in 50mL or 100mL round-bottomed flask
In, add 5~15mL distilled water, 5~15mL 0.05mol/L NaOH solution and 1~10g dextran sulfate (average marks
Son amount is less than 100000, sulfur content is about 15~20%), 4~24h of stirring reaction at 40~60 DEG C.Question response is complete
Finish, use distilled water washes clean, produce parental type lipoprotein sorbent.
Simply prepare one of method of this parental type lipoprotein sorbent above.
Embodiment 1
Real porous cellulose microballoon that 10mL has been sunk is placed in 50mL conical flask, sequentially add 10mL DMSO,
10mL 1.0mol/L NaOH solution, 5mL BDDE (BDE), 4h is reacted at 25 DEG C.Treat anti-
After should finishing, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 50mL conical flask, adds 5mL DMSO, 5mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 2g, stirs lucifuge reaction 12h at 30 DEG C.Question response is finished, first clear with 50% ethanol solution
Unreacted alpha-tocopherol is washed, then with being transferred to after distilled water washes clean in conical flask, sequentially adds 5mL dimethyl sulfoxide (DMSO)
(DMSO), 5mL 2.0mol/L NaOH solution, 2mL epoxychloropropane, the stirring reaction 3h at 40 DEG C.Question response is finished
Afterwards, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 50mL conical flasks, 10mL distilled water, 5mL 0.05mol/ is added
L NaOH solution and 2g dextran sulfate (mean molecule quantity 3000, sulfur content about 16%), the stirring reaction 15h at 45 DEG C.
Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L1.
Embodiment 2
Real porous cellulose microballoon that 5mL has been sunk is placed in 50mL conical flask, sequentially adds 5mL DMSO, 2mL
1.0mol/L NaOH solution, 1mL BDDE (BDE), 6h is reacted at 30 DEG C.Question response is finished
Afterwards, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 50mL conical flask, adds 5mL DMSO, 3mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 1g, stirs lucifuge reaction 15h at 40 DEG C.Question response is finished, first clear with 50% ethanol solution
Unreacted alpha-tocopherol is washed, then with being transferred to after distilled water washes clean in conical flask, sequentially adds 5mL dimethyl sulfoxide (DMSO)
(DMSO), 5mL 2.0mol/L NaOH solution, 1mL epoxychloropropane, the stirring reaction 2.5h at 40 DEG C.Question response is complete
Bi Hou, takes out suction filtration, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 50mL conical flasks, 5mL distilled water, 1mL 0.05mol/L is added
NaOH solution and 0.5g dextran sulfates (mean molecule quantity is 5000, sulfur content about 17%), the stirring reaction at 45 DEG C
15h.Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L2.
Embodiment 3
Real Sepharose microballoon that 10mL has been sunk is placed in 50mL conical flask, sequentially adds 10mL DMSO, 6mL
1.0mol/L volumes NaOH solution, 3mL BDDE (BDE), react 8h at 25 DEG C.Question response is complete
Bi Hou, takes out suction filtration, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 50mL conical flask, adds 8mL DMSO, 6mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 3g, stirs lucifuge reaction 10h at 45 DEG C.Question response is finished, first clear with 50% ethanol solution
Unreacted alpha-tocopherol is washed, then with being transferred to after distilled water washes clean in conical flask, sequentially adds 5mL dimethyl sulfoxide (DMSO)
(DMSO), 5mL 2.0mol/L NaOH solution, 1.5mL epoxychloropropane, the stirring reaction 3h at 40 DEG C.Question response is complete
Bi Hou, takes out suction filtration, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 50mL conical flasks, 8mL distilled water, 2mL 0.05mol/L is added
NaOH solution and 3g dextran sulfates (mean molecule quantity is 5000, sulfur content about 17%), the stirring reaction 12h at 45 DEG C.
Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L3.
Embodiment 4
Real Porous Chitosan Microspheres that 3mL has been sunk are placed in 50mL conical flask, sequentially add 5mL DMSO, 5mL
1.0mol/L NaOH solution, 1mL BDDE (BDE), 6h is reacted at 25 DEG C.Question response is finished
Afterwards, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 50mL conical flask, adds 2mL DMSO, 2mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 0.5g, stirs lucifuge reaction 8h at 45 DEG C.Question response is finished, first clear with 50% ethanol solution
Unreacted alpha-tocopherol is washed, then with being transferred to after distilled water washes clean in conical flask, sequentially adds 2mL dimethyl sulfoxide (DMSO)
(DMSO), 2mL 2.0mol/L volumes NaOH solution, 0.5mL epoxychloropropane, the stirring reaction 2h at 40 DEG C.Question response is complete
Bi Hou, takes out suction filtration, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 50mL conical flasks, 5mL distilled water, 1mL 0.05mol/L is added
NaOH solution and 0.5g dextran sulfate (mean molecule quantity is 10000, sulfur content about 17%), the stirring reaction at 45 DEG C
12h.Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L4.
Embodiment 5
Real porous cellulose microballoon that 5mL has been sunk is placed in 50ml conical flask, sequentially adds 10mL DMSO, 5mL
1.0mol/L NaOH solution, 5mL BDDE (BDE), react 10h at 25 DEG C.Question response
After finishing, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 50ml conical flask, adds 10mL DMSO, 5mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 1g, stirs lucifuge reaction 8h at 45 DEG C.Question response is finished, and is first cleaned with 50% ethanol solution
Unreacted alpha-tocopherol, then with being transferred to after distilled water washes clean in conical flask, sequentially add 5mL dimethyl sulfoxide (DMSO)
(DMSO), 1mL 2.0mol/L NaOH solution, 1mL epoxychloropropane, the stirring reaction 4h at 40 DEG C.Question response is finished
Afterwards, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 50mL conical flasks, 10mL distilled water, 2mL 0.05mol/ is added
L NaOH solution and 2g dextran sulfate (mean molecule quantity is 50000, sulfur content about 17%), the stirring reaction at 45 DEG C
20h.Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L5.
Embodiment 6
Real Sepharose microballoon that 15mL has been sunk is placed in 100mL conical flask, sequentially add 20mL DMSO,
10mL 1.0mol/L NaOH solution, 5mL BDDE (BDE), 8h is reacted at 25 DEG C.Treat anti-
After should finishing, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 100mL conical flask, adds 10mL DMSO, 10mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 3g, stirs lucifuge reaction 15h at 45 DEG C.Question response is finished, first clear with 50% ethanol solution
Unreacted alpha-tocopherol is washed, then with being transferred to after distilled water washes clean in conical flask, sequentially adds 15mL dimethyl sulfoxide (DMSO)s
(DMSO), 5mL 2.0mol/L NaOH solution, 5mL epoxychloropropane, the stirring reaction 3.5h at 40 DEG C.Question response is complete
Bi Hou, takes out suction filtration, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 100mL conical flasks, 20mL distilled water, 5mL is added
0.05mol/L NaOH solution and 5g dextran sulfate (mean molecule quantity is 10000, sulfur content about 17%), at 45 DEG C
Stirring reaction 16h.Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L6.
Embodiment 7
Real porous polyethylene alcohol microballoon that 10mL has been sunk is placed in 100mL conical flask, sequentially add 15mL DMSO,
15mL 1.0mol/L NaOH solution, 4mL BDDE (BDE), 5h is reacted at 30 DEG C.Treat anti-
After should finishing, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 100mL conical flask, adds 10mL DMSO, 10mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 2g, stirs lucifuge reaction 11h at 40 DEG C.Question response is finished, first clear with 50% ethanol solution
Unreacted alpha-tocopherol is washed, then with being transferred to after distilled water washes clean in conical flask, sequentially adds 10mL dimethyl sulfoxide (DMSO)
(DMSO), 5mL 2.0mol/L NaOH solution, 3mL epoxychloropropane, the stirring reaction 3h at 45 DEG C.Question response is finished
Afterwards, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 100mL conical flasks, 10mL distilled water, 2mL is added
(mean molecule quantity is 3000, and about 16%) sulfur content, is stirred at 50 DEG C for 0.05mol/L NaOH solution and 2g dextran sulfate
Mix reaction 18h.Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L7.
Embodiment 8
Real porous polyethylene alcohol microballoon that 1mL has been sunk is placed in 50mL conical flask, sequentially adds 3mL DMSO, 1mL
1.0mol/L NaOH solution, 1mL BDDE (BDE), react 5h at 35 DEG C.Question response is complete
Bi Hou, takes out suction filtration, is first cleaned with 50% acetone soln to being remained without BDE, last distilled water is cleaned to without acetone residue.
The porous microsphere activated is placed in 50mL conical flask, adds 2mL DMSO, 2mL 0.5mol/L's
The alpha-tocopherol of NaOH solution and 1g, stirs lucifuge reaction 8h at 45 DEG C.Question response is finished, and is first cleaned with 50% ethanol solution
Unreacted alpha-tocopherol, then with being transferred to after distilled water washes clean in conical flask, sequentially add 2mL dimethyl sulfoxide (DMSO)
(DMSO), 2mL 2.0mol/L NaOH solution, 0.5mL epoxychloropropane, the stirring reaction 2.5h at 40 DEG C.Question response
After finishing, suction filtration is taken out, is first cleaned with 50% acetone soln to being remained without ECH, last distilled water is cleaned to without acetone residue.
The porous microsphere activated again is placed in 50mL conical flasks, 2mL distilled water, 1mL 0.05mol/L is added
NaOH solution and 0.2g dextran sulfate (mean molecule quantity is 3000, sulfur content about 16%), the stirring reaction at 45 DEG C
15h.Question response is finished, and uses distilled water washes clean, produces parental type lipoprotein sorbent L8.
Embodiment 9
Take adsorbent L1, L2, L3, L4, L5, L6, L7, L8 in 1mL case study on implementation to be placed in test tube respectively, add 5mL
Plug beyond the Great Wall after distilled water, 121 DEG C of steam sterilizing 30min of high pressure take out cooling.Sterilized adsorbent is drained after moisture,
Be separately added into 10mL hyperlipidemia patient blood plasma, in 37 DEG C of constant temperature oscillations absorption 2h, draw supernatant liquor determine TG, LDL, TC,
HDL concentration, and the calculating adsorption rate AP below formula.
AP=[(C0-C1)/C0] * 100%
C in formula0For the concentration of lipoprotein in solution before absorption, C1For the concentration of lipoprotein in solution after absorption.Experimental result
It is shown in Table 1.
TG, LDL, CH, HDL initial concentration are respectively in hyperlipidemia blood plasma：420.1mg/dL, 246.1mg/dL,
267.8mg/dL、30.7mg/dL.Data can be seen that the adsorbent that the present invention is prepared into has well to TG, LDL, CH in table 1
Adsorption capacity, and only adsorb a small amount of HDL.
The adsorbent Staticadsorption experiment of table 1
Embodiment 10：Adsorbent Hemocompatibility Tests
1mL adsorbent L1, L2, L3, L4, L5, L6, L7, L8 are taken respectively, and surface is blotted after soaking 30min with physiological saline
Moisture, adds the fresh human bloods of 2mL (EDTA-K2 anti-freezings), is put into constant temperature 2h in 37 DEG C of water-baths and is determined after blood cell analyzer
Blood corpuscle parameters situation.Blank blood without adsorbent is used as blank control.Table 2 between result of the test.
The adsorbent Hemocompatibility Tests of table 2
Embodiment 11：Adsorbent hemolytic test
Hemolytic test method investigates adsorbent L1, L2, L3, L4, L5, L6, L7, L8 method as defined in GB/T 14233.2
The hemolysis rate of the adsorbent of preparation.Result of the test is shown in Table 3.
The adsorbent hemolytic test of table 3
The hemolysis rate of adsorbent be below 5% meet mark GB/T 16886.4 provide.
Above-described embodiment is the preferred embodiments of the present invention, all with similar technique of the invention and the equivalence changes made,
The protection category of the present invention all should be belonged to.
Claims (10)
1. a kind of adsorbent for being used to remove blood low density lipoprotein, it is characterised in that：Coupling has hydrophobic match somebody with somebody on absorption carrier
The mass ratio of base and polyanion aglucon, the hydrophobic aglucon and polyanion aglucon is 1:5~5:1.
2. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 1, it is characterised in that：It is described
Hydrophobic aglucon is tocopherol and its derivative.
3. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 1, it is characterised in that：It is described
Polyanion aglucon is birdsed of the same feather flock together its in compound and polyacrylic polymer selected from birds of the same feather flock together compound, acidic polysaccharose of polyacids acidic amino acid
Middle one kind.
4. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 3, it is characterised in that：It is described
Polymer is polyanionic compound of the molecular weight below 100000.
5. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 1, it is characterised in that：It is described
Absorption carrier is porous material.
6. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 5, it is characterised in that：It is described
Absorption carrier is selected from porous cellulose microballoon, Sepharose microballoon, porous Chloropolystyrene divinyl microballoon, porous poly- first
One of which in base esters of acrylic acid microballoon, porous polyethylene alcohols microballoon.
7. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 1,5 or 6, its feature exists
In：The pore diameter range of the absorption carrier is 50~250nm.
8. a kind of adsorbent for being used to remove blood low density lipoprotein according to claim 1,5 or 6, its feature exists
In：The specific surface area of the absorption carrier is 300~1300m2/g。
9. a kind of being used for as described in any one of claim 1~8 removes the preparation side of the adsorbent of blood low density lipoprotein
Method, it is characterised in that comprise the following steps：
Absorption carrier, rear immobilized hydrophobic aglucon are activated with bis-epoxy reagent；
Coupling has the carrier re-activation of hydrophobic aglucon, rear immobilized polyanion aglucon；
The mass ratio of wherein described hydrophobic aglucon and polyanion aglucon is 1:5~5:1.
10. a kind of preparation method for being used to remove the adsorbent of blood low density lipoprotein according to claim 9, it is special
Levy and be：The bis-epoxy reagent of the activation absorption carrier is selected from resorcinolformaldehyde resin, ethylene glycol diglycidyl
One of which in ether and its homologue, the polypropylene glycol diglycidyl ether of low molecule amount and its homologue.
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| CN109092263A (en) * | 2018-08-28 | 2018-12-28 | 武汉瑞法医疗器械有限公司 | A kind of low-density lipoprotein adsorbent and preparation method thereof |
| CN116850977A (en) * | 2023-07-28 | 2023-10-10 | 广州康盛生物科技股份有限公司 | Directional coupling immunoadsorbent as well as preparation method and application thereof |
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