CN100503019C - polymer porous film material for adsorbing and separating blood plasma lipide component, its preparing and use - Google Patents
polymer porous film material for adsorbing and separating blood plasma lipide component, its preparing and use Download PDFInfo
- Publication number
- CN100503019C CN100503019C CNB2007100364065A CN200710036406A CN100503019C CN 100503019 C CN100503019 C CN 100503019C CN B2007100364065 A CNB2007100364065 A CN B2007100364065A CN 200710036406 A CN200710036406 A CN 200710036406A CN 100503019 C CN100503019 C CN 100503019C
- Authority
- CN
- China
- Prior art keywords
- cholesterol
- carrier materials
- membrane carrier
- blood plasma
- porous membrane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- External Artificial Organs (AREA)
Abstract
This invention aims at providing a plasma lipid composition selective adsorption separation porous membrane carrier materials, preparation methods and related applications. The porous membrane carrier used the average pore size of 0.05 m ~ 100 u medical nonwoven polymer as the starting raw materials, through a total of 60 Co-ray irradiation grafting copolymerization polyacrylic acid surface modification, it further fixed the cholesterol ligand by carboxyl and containing 0 to 10 carbon atoms hand cholesterol arm of covalent ligand, finally get the polymer porous membrane carrier materials of plasma lipid selective adsorption separation ability. The invention related to the preparation method is simple, safe, effective and easy to promote large-scale production. With good material blood compatibility, it can be used as a plasma lipid composition adsorption separation of hyperlipidemia, dynamic perfusion of clinic high plasma patients blood purification and waste blood separation renewable auxiliary materials.
Description
Technical field
The invention provides a kind of new function polymer porous film material, preparation method and blood plasma lipide component absorption with separate in application.The polymer porous film material that this invention provided relates to selective absorption, the separating medium material of blood plasma lipide component in the clinical blood purification applications, belongs to bio-medical material and medicine equipment material field.The related a kind of new polymers perforated membrane of this invention, is prepared through processes such as surperficial nuclear radiation graft modification and surperficial covalent coupling fixed series arm cholesterol absorption aglucons as setting out material by the medical grade non woven cloth in polymer of different average pore diameters size.
Background technology
Current diseases of cardiovascular and cerebrovascular systems has developed into one of three big main clinical diseases that threaten human health, and the whole world has 800～1,000 ten thousand people to die from cardiovascular related diseases every year." Chinese cardiovascular disease report 2005 " statistics according to issue on December 1st, 2006, the clinical number of dying from cardiovascular disease of China has reached about 3,000,000 every year now, account for about 45% of all total death tolls, and these cardiovascular and cerebrovascular disease deaths are most again dies from the artery sclerosis that high fat of blood causes.Clinic study shows that hyperlipidemia is key factor [the New Eng.J.Med.1990 that causes artery sclerosis and even coronary heart disease and miocardial infarction, 322,1700], find low-density lipoprotein (LDL) concentration abnormality in clinical crown worry and the patient's blood plasma lipide component simultaneously, there is close relation [Mayo Clin Proc in its too high levels, 1999,74,466].The content that reduces too high low-density lipoprotein (LDL) in patient's blood plasma lipide component is found the cardiovascular and cerebrovascular rheological characteristic and situation [the New Eng.J.Med that can improve clinical case effectively, 1995,333,1301], the treatment of the angiocardiopathy that is of value to hyperlipemia and is caused.Thereby, up-to-date u.s. national cholesterol education program (National Cholesterol Education Program, NCEP) guide is pointed out emphatically, the concentration that reduces low-density lipoprotein (LDL) in the blood plasma lipide component has become the prevention of arterial sclerosis, has reduced the important effective measure of Incidence of CHD, especially for all not having the heredity hypercholesterolemiapatients patients of effect to seem more important by meals control and clinical drug therapy.
For high efficiency more, remove harmful lipide component in clinical hyperlipemia patient's blood plasma safely, as low-density lipoprotein (LDL), VLDL (VLDL) and too high cholesterol and triglycerides (TG).Recent two decades comes, clinical medicine and biomaterial scientific research person continue, constantly explore new efficient clinical treatment method and the corresponding new bio medicine equipment of exploitation, wish that research obtains that biocompatibility is good, stable in the adsorbing separation selectivity height, human-body biological microenvironment, back functionalization is easy to low cost new blood purification material, in the hope of using the content of realizing reducing harmful lipide component in the clinical hyperlipemia blood plasma.The existing research and development of blood purification material shows: the plasma exchange method of purification (Plasma Exchange), the blood plasma Cured by Double Filtration Plasmapheresis method (Double-Filtration PlasmaPheresis) of early stage research and development is clinical up till now seldom to be used, and new immunity absorption (Immuno-adsorption), heparin-induced precipitation blood purification methods such as (HELP) and material are further developed.A large amount of clinical medicine application experiments shows that scavenging material and methods of treatment that these are new will cause new immune response, invivo anaphylaxis simultaneously, and blood purification operating process complexity, related medical equipment manufacturing cost costliness is difficult to widespread adoption and promotes, and therefore is superseded trend gradually.Use at present more relatively blood purification method sulfonation Sephacel absorption method (DSC) clinically, application result shows and still has cellulose bead bad mechanical strength, the high real shortcoming of manufacturing cost, is further improved.
On the other hand, the latest development of blood purification technology shows that the direct absorption method of whole blood (DALI) is more and more paid close attention to, and the core key that its relevant blood purification adsorption and separation material is this technology.Up to the present, still do not have really to be applied to the superior adsorbent of clinical whole blood dynamic perfusion absorption low-density lipoprotein (LDL) in the world wide, particularly use the successful report of multiporous biological separation membrane material adsorbing separation LDL less.People such as U.S. Parham report that series purifies the method [US Patent 5496637,5187010,5236644,5258149] of low-density lipoprotein LDL by carboxyl elecrtonegativity polyacrylic acid modification polysulfone fibre microporous barrier.But this method exists the microporous barrier preparation process very complicated, and conditional request is higher, and needs to use problems such as solvent in the preparation process.Simultaneously for the grappling polyacrylic acid better on the film surface, need to add pore-foaming agent, whether these can cause bad reaction in blood plasma dynamic perfusion purification process generation becomes new concern doubtful point.People such as Japanese H.Yokota reports that utilization terylene (PET) nonwoven is a base material in addition, by high energy electron irradiation induced surface graft copolymerization acrylic acid.On this basis, arm by certain-length combines little molecule (as the polypeptide of short chain, the little molecule of dextran sulfate etc.) covalent bonding with the acrylic acid carboxyl (COOH) of substrate surface and fixes with the specificity of low-density lipoprotein LDL, thereby prepare a series of LDL sorbing material (such as the flat 6-237997 ， of flat 6-178807 of Te Open Te Open Te Open flat 5-301043).Yet,, produce the required high energy electron irradiation apparatus expensive of above-mentioned adsorption cleaning material, and surface grafting combined polymerization efficient is not high although the dynamic perfusion effect of said method gained LDL scavenging material is comparatively desirable.Have realistic problems such as synthetic blood compatibility, the bio-toxicity with substrate surface carboxyl coupling process complexity, scavenging material in conjunction with little molecular agents of specificity be unclear simultaneously, therefore using apart from clinical practice still has longer distance.
Research about the blood purification material; domestic Nankai University has reported in the biomaterial research center low-density lipoprotein LDL adsorbent of several function admirables; reported LDL adsorbent [the Chinese biological engineering in medicine journal of the taurine absorption part that pearl crosslinked polyethylene alcogel is immobilized recently as Guo Xianquan etc.; 2001; 20 (4); 317]; also reported with the cross-linked poly-methyl methacrylate ethylene oxidic ester simultaneously and be the raw material that sets out; polymeric sorbent [the Chinese biological engineering in medicine journal that contains two sulfonic acid groups on the synthetic a series of different distance that prepare; 2001; 20 (1), 17].Fu Guoqi etc. are on activation porous chitosan bead surface, hydrocarbon arm chemical coupling tryptophan by certain-length is as aglucon, prepare successful LDL adsorbent, and test shows that it has higher adsorption capacity and adsorptive selectivity preferably to low-density lipoprotein LDL, has [the science communication of good blood compatibility simultaneously, 2003,48 (17), 1840].Yuan Yi etc. on the basis of similar absorption carrier, by sulfonation and fixedly the cholesterol part prepare successfully a kind of amphiphatic low-density lipoprotein LDL adsorbent [ion-exchange and absorption, 2003,19 (1), 49] that has.All in all; the medium carrier of above-mentioned several LDL adsorbents that compare better all is the polymer gel system; can its Mechanics of Machinery intensity bear the pressure and the multidirectional shearing force of association in the blood purification dynamic perfusion process for a long time; its material blood compatibility, bio-toxicity as adsorbent is still waiting further research simultaneously; and preparation method and engineering are relatively complicated, and large-scale production has certain difficulty.
Summary of the invention
The purpose of this invention is to provide a kind of blood plasma lipide component selective absorption isolating polymer porous film material;
Purpose of the present invention also provides a kind of preparation method of blood plasma lipide component selective absorption isolating polymer porous film material;
Another object of the present invention provides a kind of application of blood plasma lipide component selective absorption isolating polymer porous film material.To be used for blood plasma the dynamic perfusion optionally harmful lipide component low-density lipoprotein (LDL) of adsorbing separation, VLDL (VLDL) and too high T-CHOL (TC) and triglycerides (TG).
The present invention is that the medical polymer nonwoven with water-insoluble, serial average pore size that biological stability is good is the carrier material that sets out, by
60The acid of Co gamma-radiation irradiation grafting propylene copolymerization, the surface imports after hydrophily, the elecrtonegativity carboxyl functional group, further by the design and the covalent coupling of the hydrocarbon arm reagent of series length, on porous membrane carrier materials surface fixing can with the cholesterol aglucon of low-density lipoprotein (LDL) hydrophobic association of etc.ing, thereby finally prepare blood plasma lipide component selective absorption parting material based on surperficial elecrtonegativity carboxyl of above-mentioned absorption carrier and cholesterol aglucon.The absorption mechanism of new polymers porous film material provided by the present invention is the hydrophobic association interaction (the cholesterol aglucon on the cholesterol components of LDL and absorption carrier surface) and electrostatic attraction (the surperficial electropositive apolipoprotein B structure division of LDL and the elecrtonegativity acrylic acid carboxylic group of absorption carrier) of comprehensive utilization based on low-density lipoprotein (LDL) biological structure model, the cholesterol aglucon of coupling just can produce hydrophobic effect with the kernel cholesterol moiety of low-density lipoprotein (LDL), insert LDL inside, simultaneously the remaining elecrtonegativity carboxylic group of polymer-modified nonwoven porous membrane support can promote absorption carrier and LDL apolipoprotein B positively charged static adelphotaxy, improve comprehensive adsorbing separation ability and multiple lipoprotein (HDL, low-density lipoprotein, VLDL) adsorptive selectivity.Since in a kind of novel blood plasma lipide component adsorbing separation porous film material preparing carriers that this invention provided employing acrylic acid and cholesterol aglucon experimental results demonstrate have good biocompatibility, blood compatibility and blood plasma lipide component selective binding affinity, and adopted more easily
60Co gamma-radiation irradiation grafting combined polymerization support modification technology, so the present invention will provide the carrier material that microenvironment safety in a kind of organism, blood plasma lipide component separate effectively, biocompatibility is good, manufacturing cost is inexpensive.Novel carriers material provided by the invention might be applied to because the blood purification treatment of clinical patients such as unusual higher coronary heart disease of bringing out such as blood plasma lipide component such as low-density lipoprotein LDL, atherosclerotic.
A kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials of the present invention is in the fixing hydrophobic cholesterol aglucon of the carboxyl covalent coupling of the medical polymer nonwoven surface of irradiation grafting propylene copolymerization acid.The carboxyl of the medical polymer nonwoven surface of described irradiation grafting propylene copolymerization acid and the mol ratio of cholesterol aglucon are 8:1～4.
The medical polymer nonwoven of described irradiation grafting propylene copolymerization acid is to be the water-insoluble medical polymer nonwoven process of 0.05～100 μ m with average pore size
60The acid of Co gamma-radiation irradiation grafting propylene copolymerization.
Described medical polymer nonwoven is medical terylene non-woven fabric or polypropylene for medical article nonwoven, and material is 5～30 milligrams every square centimeter.
Acrylic acid percent grafting is 5～150 weight % on the medical polymer nonwoven of described irradiation grafting propylene copolymerization acid.
A kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention is the material that sets out with water-insoluble, biological microenvironment medical polymer nonwoven stable, avirulent different average pore diameters dimensions in its preparation process.
The nonwoven that is adopted in the above-mentioned preparation process material that sets out can be medical terylene non-woven fabric or polypropylene non-woven fabric, it uses possible material specification is 5～30 milligrams every square centimeter, more satisfactory is 5～20 milligrams every square centimeter, and optimal is 8～15 milligrams every square centimeter.
Preparation method according to a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, from synthetic, the possible scope of average pore size of the medical polymer nonwoven that adopts is 0.05～100 μ m, more satisfactory average pore size is 0.05～20 μ m, and the average pore size that relatively is fit to preparation and adsorption applications is 0.1～10.0 μ m.
The medical polymer nonwoven of the above-mentioned serial different average pore diameters material that sets out, at first through cutting in advance, be processed into 5.0 * 5.0cm
2The laboratory sample of size.Order utilization ultrasonic wave in acetone soln, the aqueous solution cleaned 15～30 minutes successively then, took out vacuum drying to constant weight, used in order to the subsequent preparation operation.
Preparation method according to a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, be soaked in the certain density acrylic acid solution through the unlike material specification that ultrasonic wave cleans, drying is later, the medical polymer nonwoven sample of different average pore diameters size above-mentioned, adopt
60Co gamma-radiation irradiation grafting process for copolymerization, the series polymer porous membrane carrier materials of preparation surface grafting propylene copolymerization acid modification.
Above-mentioned
60In the Co gamma-radiation irradiation grafting propylene copolymerization acid process, the possible range of acrylic acid aqueous solution concentration is 1～50wt%, the more satisfactory acrylic acid aqueous solution concentration that can avoid acrylic acid in the solution that obvious competitive homopolymerization takes place is 1～30wt%, using ideal acrylic acid aqueous solution concentration is 5～20wt%, wherein, wt represents weight.
According to the preparation method of a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, adopt
60In the Co gamma-radiation irradiation grafting propylene copolymerization acid preparation modification sample process,, improve the percent grafting of surfaces of carrier materials, therefore need to add suitable polymerization inhibitor in order to prevent the auto polymerization of acrylic monomers in the aqueous solution effectively.With ferrous sulfate commonly used is example, and inhibitor concentration scope possible in the acrylic acid aqueous solution is 0.1～5.0wt%, and the more satisfactory inhibitor concentration of graft copolymerization effect is 0.5～2.5wt% relatively.
Simultaneously, in the above-mentioned irradiation grafting copolymerization process, catalyst can promote a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials that this invention provides
60The acrylic acid efficient of Co gamma-radiation irradiating surface graft copolymerization.With sulfuric acid catalyst commonly used is example, and effectively consumption is the sulfuric acid that contains 0.1～5 weight %, and more satisfactory consumption is the sulfuric acid that contains 0.5～1.0 weight %.
Medical polymer nonwoven with above-mentioned unlike material specification, different average pore diameters is the raw material that set out,
60In the Co gamma-radiation irradiation grafting copolymerization process, after 16～24 hours, place through the aqueous solution soaking of the acrylic monomers, the polymerization inhibitor that contain above-mentioned concentration, catalyst
60In the radiation field of Co gamma-radiation source,, prepare the modified porous membrane carrier materials of co-polypropylene acid of serial percent grafting by the control of irradiation dose.
60Co gamma-radiation irradiation grafting combined polymerization preparation process is found, and is above-mentioned
60It is 10～50kGy that the Co gamma-radiation is used possible irradiation total dose range, and more satisfactory irradiation accumulated dose is 20～50kGy.
According to the preparation method of a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, the medical polymer nonwoven of above-mentioned unlike material specification, the different average pore diameters raw material sample that sets out exists
60After the acid of Co gamma-radiation irradiation grafting propylene copolymerization, from solution, take out, clean final vacuum repeatedly with pure water and be dried to the polyacrylic acid modified polyalcohol stephanoporate membrane carrier materials that obtains series specification, average pore size and grafting degree after the constant weight.By the variation of membrane carrier materials weight before and after the graft copolymerization, can quantitatively calculate corresponding percent grafting is 5～150wt%, and the content that can quantitatively measure film surface carboxyl by acid base titration is 10～200 μ mol/cm
2
According to the preparation method of a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, in order effectively to improve the selectivity and the adsorbing separation efficient of preparation gained absorption carrier, will be in above-mentioned process
60The serial porous membrane carrier materials surface of Co gamma-radiation irradiation grafting propylene copolymerization acid modification further fixedly has the cholesterol aglucon that strengthens the adsorbing separation effect by the hydrophobic association effect, and above-mentioned cholesterol aglucon fixedly is the method realization of adopting arm reagent covalent coupling on the porous membrane carrier materials surface.
The arm reagent of above-mentioned covalent coupling obtains by the glycol organic compound is synthetic usually, and possible carbon atom number range is 2～10 in the di-alcohols organic compound molecule structure, as ethylene glycol, 1,3-propane diols, 1,2-propane diols, 1,4-butanediol, 1,5-pentanediol, 1,6-hexylene glycol, 1,7-heptandiol, 1,8-ethohexadiol, 1,10-decanediol etc., wherein more satisfactory is ethylene glycol, 1,4-butanediol or 1,6-hexylene glycol.
According to the preparation method of a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, for
60Therefore the cholesterol aglucon that covalent coupling fixedly has the hydrocarbon arm of different carbon atom length (carbon number is 2～10) on the serial porous membrane carrier materials surface carboxyl of Co gamma-radiation irradiation grafting propylene copolymerization acid modification needs the synthetic in advance cholesterol aglucon [HO-(CH with the hydrocarbon arm of different carbon atom length
2)
n-O-CHOL], wherein CHOL is a cholesteryl.Its preparation method is: dewater, in the deoxygenation container or under nitrogen protection, rapidly p-methyl benzenesulfonic acid (OTs) is packed into wherein, slowly drip the dry pyridine that is dissolved with cholesterol then, solution is the pulverize redness gradually, continue stirring reaction 5～24 hours, and got the synthetic presoma CHOL-OTs of arm cholesterol aglucon; Can adopt following method post processing in the preparation process: reactant liquor is poured in 5% solution of potassium carbonate, and ice bath stirred 1 hour, and the solid behind the suction filtration is dissolved in the carrene, water cyclic washing, separatory, anhydrous sodium sulfate drying spends the night, and is spin-dried for carrene behind the suction filtration, and acetone recrystallization is able to purifying.Further described synthetic presoma is added dewater, in the reactor of deoxygenation, add a certain amount of above-mentioned possible aliphatic dihydroxy alcohol arm reagent compound simultaneously, refluxed in containing the oxygen organic solvent 5～24 hours, the described oxygen organic solvent that contains can be dioxane, ether etc.Thereafter removal of solvent under reduced pressure, residue is dissolved in the ethyl acetate, continuation is washed three times with saturated sodium bicarbonate aqueous solution washing three times, saturated sodium-chloride water solution, and anhydrous sodium sulfate drying spends the night, and finally obtains containing the hydrocarbon arm cholesterol of the carbon atom length aglucon [HO-(CH of n=2～10
2)
n-O-CHOL].The possible molar ratio of material of above-mentioned reaction is: p-methyl benzenesulfonic acid/aliphatic dihydroxy alcohol/cholesterol=2～10:5～20:1, more satisfactory scope is: p-methyl benzenesulfonic acid/aliphatic dihydroxy alcohol/cholesterol=2～5:5～10:1.
Preparation method according to a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials provided by the present invention, above-mentioned cholesterol aglucon with the hydrocarbon arm of different carbon atom length in the acrylic acid modified fixing method of polymer porous film surfaces of carrier materials covalent coupling of graft copolymerization is: at first dewatering, remove under the oxygen condition, acrylic acid carboxyl (COOH) content that has contained according to the acrylic acid modified polymer porous film surfaces of carrier materials of above-mentioned graft copolymerization, in certain design coupling part ratio, under logical condition of nitrogen gas, add cholesterol aglucon [HO-(CH
2)
n-O-CHOL], the coupling accelerant N, N '-dicyclohexylcarbodiimide (DCC) and 4-dimethylamino naphthyridine (DMAP).Inject the dichloromethane solvent of 40～80ml then, stir after 5～10 minutes, the different size that above-mentioned graft copolymerization is acrylic acid modified, the polyalcohol stephanoporate membrane carrier materials of different average pore diameters are put into reactor, keep at room temperature continuing stirring reaction 24～48 hours.After reaction is finished the above-mentioned porous membrane carrier materials of graft copolymerization cholesterol aglucon is taken out, with the carrene is solvent, adopt the extracting of Soxhlet extraction tube to remove unreacted little molecular reaction thing in 24 hours, vacuum drying obtains the acrylic acid modified polyalcohol stephanoporate membrane carrier materials of surperficial covalent coupling fixing arm cholesterol aglucon.
The material ratio of using in the reaction of above-mentioned covalent coupling is used possible scope: the polymer porous film carrier surface carboxyl amount (COOH) of acrylic acid surface grafting combined polymerization modification/cholesterol aglucon (HO-CHOL) or be connected with the cholesterol aglucon [HO-(CH of different hydrocarbon arms
2)
n-O-CHOL]/N, N '-dicyclohexylcarbodiimide (DCC)/4-dimethylamino naphthyridine (DMAP)=5～10:1～5:3～5:1～3, the more satisfactory scope of coupling reaction effect is polymer porous film carrier surface carboxyl amount (the COOH)/cholesterol aglucon (HO-CHOL) of acrylic acid surface grafting combined polymerization modification or the cholesterol aglucon [HO-(CH that is connected with different hydrocarbon arms
2)
n-O-CHOL]/N, N '-dicyclohexylcarbodiimide (DCC)/4-dimethylamino naphthyridine (DMAP)=8:1～4:3～5:2.
Advantage of the present invention
According to a kind of novel blood plasma lipide component adsorbing separation polymer porous film material, preparation and the application thereof that this invention provided, have following advantage:
(1) simple, the process conditions of preparation method are easy to control, and carrier material preparation repeatability is good.Key control parameter in the whole preparation process flow process is: the concentration of total radiation dose, graft copolymerization acrylic acid aqueous solution monomer concentration, cholesterol aglucon.The experimental result of porous adsorbing separation membrane material shows that preparation is subjected to other parameter influence less, and above-mentioned several key process parameter is easy to accurate control, and good reproducibility is fit to technical scale production.
(2) the raw material wide material sources that set out of the present invention, production cost is low.Material medical polymer nonwoven and the acrylic acid of mainly setting out of the present invention is cheap, and other Assisted Preparation material, and is also not high as cholesterol aglucon, coupling catalyst, coupling arm reagent aliphatic glycol price.
(3) a kind of novel blood plasma lipide component adsorbing separation polymer porous film material provided by the present invention, conventional medical disinfecting methods such as its blood compatibility is good, leaching liquor is nontoxic, suitable ultraviolet.
(4) according to a kind of novel blood plasma lipide component adsorbing separation polymer porous film material provided by the present invention, the active efficient of harmful lipide component low-density lipoprotein (LDL) adsorbed film of its blood plasma, the static adsorption capacity of low-density lipoprotein (LDL), T-CHOL (TC) and triglycerides (TG) reaches than the highest decline 54.1%, 48.3%, 49.5% before the adsorbing separation.Simultaneously, polyalcohol stephanoporate membrane carrier dynamic perfusion provided by the present invention absorption shows, LDL, TC and TG than adsorbing separation before the highest reduction by 32.0%, 55.3%, 49.4%.
(5) a kind of novel blood plasma lipide component adsorbing separation polymer porous film material application prospect provided by the present invention is extensive.Not only may be applied to clinical hyperlipemia blood purification, simultaneously may be applied to the blood product secondary industry, from meet the discarded blood plasma of blood transfusion standard, do not reclaim blood plasma, the processing blood product by adsorbing separation carrier material and the relevant auxiliary equipment of separating that this invention provided.
Specific implementation method
By the following examples the present invention is specifically described, will helps the understanding of the present invention, but do not limit content of the present invention.The chemical analysis method that is adopted among the embodiment specifies as follows:
(1) quantitative analysis method of porous adsorbing separation film surface carboxyl-content
Learnt from else's experience
60Co-ray mutual radiation graft copolymerization acrylic acid prepares (5 * 5cm of modification gained sample
2), put into the conical flask of 100ml volume, add the NaOH solution 50ml of 50mol/L then, static immersion is 24 hours under the room temperature.Extract soak 10ml, with the hydrochloric acid solution titration of having demarcated concentration, the volume of used salt acid solution during the record titration end-point, and each sample titrimetry three times are averaged.Therefore, the content of porous film surface graft acrylic acid carboxyl can calculate by following formula:
Wherein n is the concentration of hydrochloric acid, V
iBe the volume of sample titration used salt acid solution, V
0Be the porous membrane support blank of closing modification without acrylic graft copolymer volume with reference to titration used salt acid solution.
(2) analytical method of blood plasma low-density lipoprotein LDL concentration
Adopt one-step method (being enzyme process) analysis, its principle is: polyanion among human serum and the reagent R1 and polyion reaction, under the effect of surfactant, generation chemical reaction such as other lipoprotein except that low-density lipoprotein LDL and cholesterol esterase, cholesterol oxidase and being eliminated.After adding reagent R2, surfactant is wherein had an effect rapidly, and discharges LDL, and single catalysis LDL-C reaction under the enzyme effect, and existing colour response takes place, and its colour developing degree is directly proportional with LDL-C content in the serum.
Measure the specification and the composition of agents useful for same: (kit is supervised tool (standard) word 2005 No. 2401199 available from Shanghai Rongsheng Bioisystech Co., Ltd's Shanghai food medicine)
R1:2*40mlR2:2*10ml, calibration solution: 1*1ml (1ml distilled water redissolves during use).
R1: form by polyanion and cholesterol esterase, cholesterol oxidase, phenol, catalase, surfactant etc.
R2: form by peroxidase, 4-amino-antipyrine, buffer solution and surfactant etc.
The working solution preparation:
Reagent: R1:4ml and reagent R2:1ml mixing.
Working solution can be stablized 3 days at 2～8 ℃.(interim preparation before preferably using).
Test program: testing sample 10 μ l are added abundant mixing in the 1ml working solution, 37 ℃ of water-baths are after 10 minutes, with blank pipe (10 μ l distilled water add the 1ml working solution) zeroing, read respectively sample tube and calibration tube (10 μ l titers add 1ml working solution) in 546nm place ultraviolet absorptivity value, the content of calculating low-density lipoprotein LDL
(3) HDL HDL method for measurement of concentration
Adopt one-step method (being enzyme process) to measure; its principle: polyanion among human serum and the reagent R1 and polyion reaction; under the effect of surfactant, around lipoprotein, form stable protective layer; after adding reagent R2; surfactant discharges HDL rapidly; and single catalysis HDL-C reaction under the enzyme effect, its colour developing degree is directly proportional with serum middle-high density lipoprotein HDL-C content.
Measure the specification and the composition of agents useful for same: (kit is supervised tool (standard) word 2005 No. 2401199 available from Shanghai Rongsheng Bioisystech Co., Ltd's Shanghai food medicine)
R1:2*40ml R2:2*10ml, calibration solution: 1*1ml (1ml distilled water redissolves during use)
R1: compositions such as polyanion and cholesterol esterase, cholesterol oxidase, phenol, catalase, surfactant.
R2: compositions such as peroxidase, 4-amino-antipyrine, buffer solution and surfactant.
The working solution preparation: the R2 reagent mixing of 4ml R1 and 1ml, can under 2～8 ℃, can stablize 3 days.(interim preparation before preferably using).
Test program: sample to be tested 10 μ l are added abundant mixing in the 1ml working solution, water-bath is after 10 minutes in 37 ℃, with blank pipe (10 μ l distilled water add the 1ml working solution) zeroing, read sample tube and the calibration tube ultraviolet absorptivity value at the 546nm place of (10 μ l titers add the 1ml working solution) respectively, calculate the concentration of HDL HDL thus:
(4) assay method of total plasma cholesterol TC concentration
Adopt the CHOD-PAP method, its principle: the free cholesterol that reaches fatization in the sample to be tested, produce quinone imines through following reaction, available ultraviolet specrophotometer is measured its absorbance at the 500nm place, according to the variation of absorbance, calculate the content of plasma cholesterol.
Measure the specification and the composition of agents useful for same: (No. the 2401199th, Shanghai Rongsheng Bioisystech Co., Ltd's Shanghai food medicine prison tool (standard) word 2005)
R1 (buffer solution): 2 * 25ml R2 (enzyme reagent): 2 * 25ml
Calibration solution: (5.16mmol/l or 200mg/dl): 1 * 1ml
PiPes:35mmol/L, sodium taurocholate: 0.5mmol/L
Cholesteryl esterase〉0.2U/ml, cholesterol oxidase〉0.1U/ml
Phenol: 28mmol/l, peroxidase〉0.8U/ml
4-amino-antipyrine: 0.5mmol/l, pH7.0
The working solution preparation: 1 part of buffer solution and 1 part of equivalent mixing of enzyme reagent are stored in 2～8 ℃ and can stablize 30 days.
Test program: 10 μ l to be measured are added in the 1ml working solution, abundant mixing, 37 ℃ of water-baths are after 10 minutes, with blank pipe (10 μ l distilled water add the 1ml working solution) zeroing, read sample tube and calibration tube (10 μ l titers add the 1ml working solution) ultraviolet light absorption value respectively, calculate thus at the 500nm place
T-CHOL mmol/l=mg/dl * 0.0258
The assay method of (5) three ester TG concentration
Adopt TRIGLYCERIDES KIT (enzymic colorimetric) method, its principle: the triglycerides in the testing sample produces reddish violet pigment, available ultraviolet specrophotometer quantitative assay through following reaction.
Measure the specification and the composition of agents useful for same: (No. the 2401199th, Shanghai Rongsheng Bioisystech Co., Ltd's Shanghai food medicine prison tool (standard) word 2005)
2×25ml
Pipes:45mmol/L; Magnesium chloride: 5mmol/L; Peroxidase〉0.8U/ml;
Lipoproteinesterase〉100U/ml; ESBmT3mmol/l; 4-amino peace is for than 0.75mmol/L;
The glycerol 3-phosphate oxidizing ferment〉4U/ml; Glycerokinase〉1.5U/ml; ATP:0.9mmol/l, pH7.5.
Test program: testing sample 10 μ l are added abundant mixing in the 1ml working solution, 37 ℃ of water-baths are after 10 minutes, with blank pipe (10 μ l distilled water add the 1ml working solution) zeroing, read sample tube and calibration tube (10 μ l titers add the 1ml working solution) respectively and, calculate the concentration of triglycerides TG thus at 500nm place ultraviolet specrophotometer absorbance:
Triglycerides mg/dl=triglycerides mmol/L * 88.5
(6) surperficial total reflection infrared spectrum ATR-FITR analyzes
Sample is cut into the rectangular of 10mm * 80ml to be tested on fourier transform infrared spectroscopy instrument AVATAR-360.
Embodiment 1
The polypropylene for medical article nonwoven of average pore size 0.1 μ m is cut into 5 * 5cm
2Sample, ultrasonic wave cleaned 15～30 minutes in acetone and water successively, vacuum drying is standby.Then, said sample is soaked in the aqueous solution that contains acrylic monomers 10% (mass percent), contains 1.0% ferrous sulfate polymerization inhibitor, 0.5% sulfuric acid catalyst in the solution in addition, soak after 24 hours, sample is placed
60In the radiation field of Co gamma-radiation source, control accumulative total irradiation accumulated dose 30kGy.After taking out above-mentioned radiation treatment sample, clean, dry, to weigh and calculate acrylic acid copolymerized grafting rate be 30wt%, the surperficial carboxyl-content of corresponding gained porous membrane carrier materials is 25 μ mol/cm
2, the ATR-FITR infrared spectrum analysis finds that this sample is at 1700cm
-1Very strong absorption band of the new appearance in place is a carboxyl absorbing features signal, shows that acrylic acid by successful graft copolymerization introducing polypropylene non-woven fabric surface, obtains polyacrylic acid modified polypropylene non-woven fabric porous membrane carrier materials.
Embodiment 2
The polypropylene for medical article nonwoven of 0.45 μ m is cut into 5 * 5cm
2Sample, ultrasonic wave cleaned 15～30 minutes in acetone and water successively, vacuum drying is standby.Then said sample is soaked in the aqueous solution that contains 15% acrylic monomers.Contain 0.5% ferrous sulfate polymerization inhibitor, 1.0% sulfuric acid catalyst in the solution simultaneously, after the immersion 24 as a child, sample is placed
60In the radiation field of Co gamma-radiation source, control accumulative total irradiation accumulated dose is 20kGy.After taking out above-mentioned radiation treatment sample, clean, dry, to weigh and calculate acrylic acid combined polymerization percent grafting be 84%, quantitatively titration surface carboxyl-content is 70 μ mol/cm
2The ATR-FITR infrared spectrum analysis is found at 1700cm
-1A very strong absworption peak appears in the place, corresponding to the characteristic absorption signal of carboxyl, shows the polyacrylic acid modified polypropylene non-woven fabric porous membrane carrier materials of 84% percent grafting, 0.45 μ m average pore size.
Embodiment 3
Get one of 250ml volume there-necked flask, dewater, after the deoxygenation, under nitrogen protection, rapidly p-methyl benzenesulfonic acid 25 grams packed into wherein, slowly drip the 200ml dry pyridine that is dissolved with 25 gram cholesterol then, solution is the pulverize redness gradually.Continue stirring reaction after 24 hours, reactant liquor is poured in 5% solution of potassium carbonate, and ice bath stirred 1 hour, and the solid behind the suction filtration is dissolved in the carrene, water cyclic washing, separatory, and anhydrous sodium sulfate drying spends the night.Be spin-dried for carrene behind the suction filtration, be recrystallized in the acetone, obtain the cholesterol aglucon intermediate (CHOL-OTs) of p-methyl benzenesulfonic acid protection.Then its immigration is dewatered, in the reaction bulb of deoxygenation, add 1 of 20ml, 4-butanediol, with the dioxane is solvent, refluxes after 24 hours removal of solvent under reduced pressure, and residue is dissolved in the ethyl acetate, with saturated sodium bicarbonate aqueous solution washing three times, saturated sodium-chloride water solution washing three times, anhydrous sodium sulfate drying spends the night, and finally obtains containing 4 carbon atom length arm monohydroxy degree of functionality cholesterol aglucon [HO-(CH successively
2)
4-O-CHOL].
Embodiment 4
Get one of 250ml there-necked flask; dewater, after the deoxygenation; under nitrogen protection; rapidly p-methyl benzenesulfonic acid 25 grams are packed into; slowly drip the 200ml dry pyridine that is dissolved with 25 gram cholesterol then, solution is the pulverize redness gradually, continues stirring reaction 24 hours; reactant liquor is poured in 5% solution of potassium carbonate, and ice bath stirred 1 hour.Solid behind the suction filtration is dissolved in the carrene, water cyclic washing, separatory, and anhydrous sodium sulfate drying spends the night, and is spin-dried for carrene behind the suction filtration, and acetone recrystallization obtains the cholesterol aglucon intermediate CHOL-OTs that p-methyl benzenesulfonic acid is protected.In the reaction bulb that above-mentioned cholesterol aglucon intermediate CHOL-OTs adding dewaters, deoxygenation is handled, add 15 grams, 1,6-hexylene glycol again, be solvent with the dioxane, refluxed 24 hours.Then, removal of solvent under reduced pressure is dissolved in residue in the ethyl acetate, successively with saturated sodium bicarbonate aqueous solution washing three times, saturated sodium-chloride water solution washing three times, anhydrous sodium sulfate drying spends the night, and finally obtains containing 6 carbon atom length arm monohydroxy degree of functionality cholesterol aglucon [HO-(CH
2)
6-O-CHOL].
Embodiment 5
The reaction tube of getting the 100ml volume dewaters, after the deoxygenation, surperficial carboxyl-content according to the acrylic graft-modified polypropylene non-woven fabric perforated membrane of the foregoing description 2 gained, press carboxyl/cholesterol aglucon (HO-CHOL)/N, the molar ratio of material example of N '-dicyclohexylcarbodiimide (DCC)/4-dimethylamino naphthyridine (DMAP)=8:1:5:2, under logical condition of nitrogen gas, the cholesterol aglucon (HO-CHOL), the coupling catalyst N that add no hydrocarbon arm, N '-dicyclohexylcarbodiimide (DCC) and 4-dimethylamino naphthyridine (DMAP).Inject the 50ml carrene then, stir after 5～10 minutes, the acrylic graft-modified polypropylene non-woven fabric perforated membrane of the foregoing description 2 gained is put into reaction tube, stirring reaction is 24 hours under the room temperature.After cholesterol aglucon coupling reaction finishes, the acrylic graft-modified polypropylene non-woven fabric perforated membrane of coupling cholesterol aglucon is taken out, make solvent with carrene, utilization Soxhlet extraction tube extracting 24 hours is to remove unreacting substance, vacuum drying finally obtains not having the polyalcohol stephanoporate membrane carrier materials that the direct coupling cholesterol of arm adsorbs aglucon.
Embodiment 6
The reaction tube of getting the 100ml volume dewaters, after the deoxygenation, surperficial carboxyl-content according to the acrylic graft-modified polypropylene non-woven fabric perforated membrane of the foregoing description 2 gained, press carboxyl/cholesterol aglucon/N, the molar ratio of material example of N '-dicyclohexylcarbodiimide (DCC)/4-dimethylamino naphthyridine (DMAP)=8:4:3:2, under logical condition of nitrogen gas, add 4 carbon atom length of the foregoing description 3 preparation gained arm monohydroxy degree of functionality cholesterol aglucon [HO-(CH
2)
4-O-CHOL], coupling catalyst N, N '-dicyclohexylcarbodiimide (DCC) and 4-dimethylamino naphthyridine (DMAP).Inject the 50ml carrene then, stir after 5～10 minutes, the acrylic graft-modified polypropylene non-woven fabric perforated membrane of the foregoing description 2 gained is put into reaction tube, stirring reaction is 24 hours under the room temperature.After cholesterol aglucon coupling reaction finishes, the acrylic graft-modified polypropylene non-woven fabric perforated membrane of coupling cholesterol aglucon is taken out, make solvent with carrene, utilization Soxhlet extraction tube extracting 24 hours is to remove unreacting substance, vacuum drying, the cholesterol that finally obtains 4 carbon atom arms of coupling adsorbs the polyalcohol stephanoporate membrane carrier materials of aglucon.
Embodiment 7
The reaction tube of getting the 100ml volume dewaters, after the deoxygenation, surperficial carboxyl-content according to the acrylic graft-modified polypropylene non-woven fabric perforated membrane of the foregoing description 2 gained, press carboxyl/cholesterol aglucon/N, the ratio of N '-dicyclohexylcarbodiimide (DCC)/4-dimethylamino naphthyridine (DMAP)=8:2:5:2, under logical condition of nitrogen gas, add 6 carbon atom length of the foregoing description 4 preparation gained arm monohydroxy degree of functionality cholesterol aglucon [HO-(CH
2)
6-O-CHOL], coupling catalyst N, N '-dicyclohexylcarbodiimide (DCC) and 4-dimethylamino naphthyridine (DMAP).Inject the 50ml carrene then, stir after 5～10 minutes, the acrylic graft-modified polypropylene non-woven fabric perforated membrane of the foregoing description 2 gained is put into reaction tube, stirring reaction is 24 hours under the room temperature.After cholesterol aglucon coupling reaction finishes, the acrylic graft-modified polypropylene non-woven fabric perforated membrane of coupling cholesterol aglucon is taken out, make solvent with carrene, utilization Soxhlet extraction tube extracting 24 hours is to remove unreacting substance, vacuum drying, the cholesterol that finally obtains 6 carbon atom arms of coupling adsorbs the polyalcohol stephanoporate membrane carrier materials of aglucon.
Embodiment 8
The foregoing description 5,6,7 preparation resulting polymers porous membrane carrier materials are cut into fragment, pack in the 10ml sample bottle, draw 6ml simulated body fluid (pH=7.4) with its abundant swelling, with syringe the simulated body fluid in the sample bottle is thoroughly drained then, add the 2ml human plasma.Vibration is after 3 hours down to be sealed in 37 ℃ then, and the detection isothermal adsorbs the situation of change of front and back LDL, HDL, TG, TC, result's (wherein the blank sample is that the aperture is 0.45um, not the polypropylene non-woven fabric of graft acrylic acid) as shown in the table
Embodiment 9
To sample in the separated plasma 5ml of hyperlipemia dynamic perfusion through the porous membrane carrier materials adsorbing separation device of 6 layers of embodiment 4 gained is housed, dynamic perfusion speed 1ml/min, behind the perfusion 2 hours, the concentration of the LDL in the blood plasma is reduced to 75.9mg/dl, HDL by 111.64mg/dl concentration is reduced to 28.00mg/dl, TC by 51.77mg/dl content drops to 274.47mg/dl by the content that 160.31mg/dl drops to 71.65mg/dl, TG by 522.80mg/dl.
Claims (12)
1. blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials is characterized in that: described porous membrane carrier materials be by the carboxyl covalent coupling of the medical polymer nonwoven surface of irradiation grafting propylene copolymerization acid fixedly the hydrophobic cholesterol aglucon obtain; The carboxyl of the medical polymer nonwoven surface of described irradiation grafting propylene copolymerization acid and the mol ratio of described cholesterol aglucon are 8:1～4.
2. a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 1 is characterized in that: the medical polymer nonwoven of described irradiation grafting propylene copolymerization acid is to be the water-insoluble medical polymer nonwoven process of 0.1～50 μ m with average pore size
60The acid of Co gamma-radiation irradiation grafting propylene copolymerization, the content of film surface carboxyl is 10～200 μ mol/cm
2
3. a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 2, it is characterized in that: described medical polymer nonwoven is medical terylene non-woven fabric or polypropylene for medical article nonwoven, and material is 5～30 milligrams every square centimeter.
4. a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 1 or 2, it is characterized in that: acrylic acid percent grafting is 5～150 weight % on the medical polymer nonwoven of described irradiation grafting propylene copolymerization acid.
5. the preparation method of the described a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials of claim 1 is characterized in that may further comprise the steps:
(1)
60Co gamma-radiation irradiating surface graft copolymerization acrylic acid
With the medical polymer nonwoven that cleaned polymerization inhibitor and [H at the acrylic acid that contains 1～50 weight %, 0.1～5.0 weight %
+After soaking 16～24 hours in the aqueous solution of the catalyst of]=0.1～0.2M; Place
60In the Co gamma-radiation radiation field, control irradiation accumulated dose is 10～50kGy; Take out, clean, dry, obtain the polyalcohol stephanoporate membrane carrier materials of acrylic acid surface grafting modification by copolymerization;
(2) the fixing hydrophobic cholesterol aglucon of surperficial covalent coupling
Under anhydrous, oxygen free condition, with cholesterol aglucon, N, N '-dicyclohexylcarbodiimide and 4-dimethylamino naphthyridine mix, press carboxyl: cholesterol aglucon: N, N '-dicyclohexylcarbodiimide: the mol ratio of 4-dimethylamino naphthyridine is=8:1～4:3～5:2, add the polyalcohol stephanoporate membrane carrier materials of the acrylic acid surface grafting modification by copolymerization of above-mentioned steps (1) preparation gained, reacted drying under the room temperature 12～48 hours; Described cholesterol aglucon has molecular formula: HO-(CH
2)
n-O-CHOL, wherein, n=2～10, CHOL is a cholesteryl.
6. the preparation method of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 5, it is characterized in that: the cleaning of the described medical polymer nonwoven of step (1) be with the aperture be 0.1～50 μ m the medical polymer nonwoven successively in acetone and water ultrasonic wave cleaned vacuum drying 15～30 minutes.
7. the preparation method of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 5 is characterized in that: the described immersion of step (1) is with polymerization inhibitor and the [H of medical polymer nonwoven at the acrylic acid that contains 1～30 weight %, 0.5～2.5 weight %
+Soak in the aqueous solution of the catalyst of]=0.1～0.2M.
8. the preparation method of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 5 is characterized in that: the described polymerization inhibitor of step (1) is a ferrous sulfate.
9. the preparation method of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 5; it is characterized in that: the described cholesterol aglucon of step (2) is synthetic by the following method: under nitrogen protection; in p-methyl benzenesulfonic acid, slowly drip the dry pyridine that is dissolved with cholesterol; reacted 5～24 hours; get the reaction precursor body CHOL-OTs of cholesterol aglucon; with this presoma under the condition of deoxygenation that dewaters; in containing the oxygen organic solvent, be 2～10 arm reagent binary aliphatic alcohol reflux 5～24 hours with carbon number; obtain the cholesterol aglucon of n=2～hydrocarbon arm of 10 carbon atom length; wherein; OTs is the p-methyl benzenesulfonic acid base, described p-methyl benzenesulfonic acid; the mol ratio of the pure and mild cholesterol of binary aliphatic is 2～10:5～20:1.
10. the preparation method of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 9, it is characterized in that: the molar ratio range of reaction mass is: p-methyl benzenesulfonic acid/aliphatic dihydroxy alcohol/cholesterol=2～5:5～10:1.
11. the preparation method of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials as claimed in claim 9, it is characterized in that: described arm reagent aliphatic dihydroxy alcohol is an ethylene glycol, 1,3-propane diols, 1,2-propane diols, 1,4-butanediol, 1,5-pentanediol, 1,6-hexylene glycol, 1,7-heptandiol, 1,8-ethohexadiol or 1,10-decanediol.
12. the purposes of the described a kind of blood plasma lipide component selective absorption isolating polymer porous membrane carrier materials of claim 1 is characterized in that: be used for the adsorbing separation of blood plasma lipide component, clinical hyperlipemia patients'blood dynamic perfusion scavenging material or discarded plasma separation regeneration auxiliary material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100364065A CN100503019C (en) | 2007-01-12 | 2007-01-12 | polymer porous film material for adsorbing and separating blood plasma lipide component, its preparing and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100364065A CN100503019C (en) | 2007-01-12 | 2007-01-12 | polymer porous film material for adsorbing and separating blood plasma lipide component, its preparing and use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101024149A CN101024149A (en) | 2007-08-29 |
| CN100503019C true CN100503019C (en) | 2009-06-24 |
Family
ID=38742977
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100364065A Expired - Fee Related CN100503019C (en) | 2007-01-12 | 2007-01-12 | polymer porous film material for adsorbing and separating blood plasma lipide component, its preparing and use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100503019C (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2017311836B2 (en) * | 2016-08-18 | 2020-04-30 | Asahi Kasei Medical Co., Ltd. | Filter element for blood processing filter, blood processing filter and leukocyte removal method |
| JP6366025B2 (en) * | 2016-10-03 | 2018-08-01 | セルスペクト株式会社 | Plasma separator and plasma separation method |
| CN109046282B (en) * | 2018-08-31 | 2021-12-31 | 健帆生物科技集团股份有限公司 | Adsorbent for removing endotoxin by hemoperfusion and water solution and preparation method thereof |
| CN109316986B (en) * | 2018-11-07 | 2021-09-21 | 中南大学 | Acrylic acid and sulfonated dihydroxypropyl chitosan modified polysulfone membrane and preparation method thereof |
| CN109222999A (en) * | 2018-11-08 | 2019-01-18 | 郑州安图生物工程股份有限公司 | A kind of heparin tube with degreasing material |
| CN109580511A (en) * | 2018-12-06 | 2019-04-05 | 潍坊泽成生物技术有限公司 | A kind of detection method and detection kit of high-density lipoprotein cholesterol |
| CN117696017B (en) * | 2024-02-05 | 2024-05-07 | 四川大学华西医院 | Blood purification adsorption modified material and preparation method thereof |
-
2007
- 2007-01-12 CN CNB2007100364065A patent/CN100503019C/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 新型低密度脂蛋白吸附剂的制备及其吸附性能研究. 郭贤权，孙越，陈友安等.中国生物医学工程学报，第20卷第4期. 2001 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101024149A (en) | 2007-08-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101058058B (en) | Surface fixed taurine ligand porous membrane material, preparation method and its application in blood fat adsorption separation | |
| CN100503019C (en) | polymer porous film material for adsorbing and separating blood plasma lipide component, its preparing and use | |
| CN101024150A (en) | Porous film material fixed with heparin on surface, its preparing method and use | |
| CN100595225C (en) | Method for producing molecular engram polyalcohol microsphere and method for separating enrofloxacin thereof | |
| Baydemir et al. | Bilirubin recognition via molecularly imprinted supermacroporous cryogels | |
| CN107486176B (en) | Adsorbing material for blood purification and preparation method thereof | |
| CN103055822B (en) | Blood-purifying adsorbent for clearing blood bilirubin and preparation method thereof | |
| CN102532502B (en) | Biological functionalization degradable polyester and preparation method thereof | |
| Cao et al. | In vitro studies of PBT Nonwoven Fabrics adsorbent for the removal of low density lipoprotein from hyperlipemia plasma | |
| CN105126784A (en) | Adsorbent, preparation method thereof, and adsorption device for blood perfusion | |
| EP4331701A1 (en) | Modified macroporous adsorption resin, preparation method therefor and use thereof | |
| CN109437501A (en) | The method that tetracycline in water removal is removed in the activation persulfate degradation of sludge base hydro-thermal charcoal | |
| CN113045695B (en) | Preparation method and application of anticoagulant copolymer | |
| CN108514864A (en) | A kind of chitin/graphene oxide composite sponge and the preparation method and application thereof | |
| CN109734839A (en) | A kind of high anti-coagulation type polystyrene microsphere and the preparation method and application thereof | |
| CN111701581B (en) | Low-density lipoprotein, cholesterol and triglyceride adsorbent and preparation method and application thereof | |
| JPH07116268B2 (en) | Preparation of Copolymer of Dextran Anion Partially Substituted Compound and Olefin Compound | |
| CN113929082B (en) | Method for preparing rice straw carbon quantum dot nano enzyme and application of peroxidase activity thereof | |
| CN109248668A (en) | Adsorbent for blood extracorporeal circulation removal LDL and preparation method thereof and perfusion device | |
| CN110026248A (en) | The method and application of a kind of catalyst, the catalyst preparation aeroge adsorbent material | |
| CN109369850A (en) | A kind of porous resin microballoon and preparation method for heavy metal containing wastewater treatment | |
| CN109092262B (en) | Low-density lipoprotein adsorption microspheres and preparation method and adsorbent material | |
| CN102527341A (en) | Immunosorbent for blood purification and preparation method thereof | |
| CN100434180C (en) | Fiber base grafted polyglutamic acid ion exchange material and its preparing method and use in treating waste water | |
| Fu et al. | Chitosan adsorbents carrying amino acids for selective removal of low density lipoprotein |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090624 Termination date: 20160112 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |