CN1271621A - Process for synthesizing protein immunoadsorbent medium for removing pathogenic antibody and its compounds from plasm - Google Patents
Process for synthesizing protein immunoadsorbent medium for removing pathogenic antibody and its compounds from plasm Download PDFInfo
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- CN1271621A CN1271621A CN 99112880 CN99112880A CN1271621A CN 1271621 A CN1271621 A CN 1271621A CN 99112880 CN99112880 CN 99112880 CN 99112880 A CN99112880 A CN 99112880A CN 1271621 A CN1271621 A CN 1271621A
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- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 claims description 11
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 claims description 10
- 238000010189 synthetic method Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 7
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- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 claims description 6
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- 238000006722 reduction reaction Methods 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 2
- QVYARBLCAHCSFJ-UHFFFAOYSA-N butane-1,1-diamine Chemical compound CCCC(N)N QVYARBLCAHCSFJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000007142 ring opening reaction Methods 0.000 claims description 2
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 claims description 2
- 230000008878 coupling Effects 0.000 abstract description 7
- 238000010168 coupling process Methods 0.000 abstract description 7
- 238000005859 coupling reaction Methods 0.000 abstract description 7
- 238000001994 activation Methods 0.000 abstract description 5
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
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- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 abstract 2
- 239000011543 agarose gel Substances 0.000 abstract 2
- 239000003761 preservation solution Substances 0.000 abstract 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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Landscapes
- External Artificial Organs (AREA)
- Peptides Or Proteins (AREA)
Abstract
一种用于从血浆中去除致病抗体及其复合物的蛋白免疫吸附介质的合成方法,合成过程依下述步骤进行:(1)用环氧氯丙烷活化Sepharose CL－4B琼脂糖凝胶,反应温度40～80℃,时间1～4小时,环氧氯丙烷充分过量;(2)用环氧Sepharose CL－4B琼脂糖凝胶与ProteinA直接反应合成免疫吸附介质,反应温度为24～26℃,反应时间16～20小时,ProteinA充分过量,pH值控制在9～10范围内;用甘氨酸乙酯盐酸盐或乙醇氨封闭未反应活性基团;放入保存液中。本发明可以取代溴化氰活化工艺,无毒、无害,且偶联Protein A效果好。A method for synthesizing a protein immunoadsorption medium for removing pathogenic antibodies and their complexes from plasma, the synthesis process is carried out according to the following steps: (1) Sepharose CL-4B agarose gel is activated with epichlorohydrin, The reaction temperature is 40-80°C, the time is 1-4 hours, and the epichlorohydrin is sufficiently excessive; (2) Use epoxy Sepharose CL-4B agarose gel to directly react with Protein A to synthesize the immunoabsorption medium, and the reaction temperature is 24-26°C , the reaction time is 16-20 hours, the Protein A is sufficiently excessive, and the pH value is controlled within the range of 9-10; unreacted active groups are blocked with glycine ethyl ester hydrochloride or ethanol ammonia; put into the preservation solution. The invention can replace the cyanogen bromide activation process, is non-toxic and harmless, and has good effect of coupling Protein A.
Description
The present invention relates to a kind of synthetic method of ProteinA immunity adsorbing medium.Be matrix with the SepharoseCL-4B Ago-Gel specifically, adopt the method for epoxychloropropane activation, as open loop reagent, aldehyde radical carries out covalently bound as coupling group and genetic recombination Protein A with amino.This synthetic method is nontoxic, and the reliability height that Protein A combines with matrix is to the advantages of good adsorption effect of pathogenic antibody and compound thereof.
Immunity absorption therapy is the new method of a kind of disease that cures difficult and complicated cases of rising in recent years, its objective is by the blood of human body circulation branch road in external foundation makes blood adsorb the morbid substance of removing in the blood samples of patients by immunoabsorbent column, purify the human internal environment, reach the purpose of treatment disease.The immunosorbent that contains in the immunoabsorbent column can with the morbid substance specific bond in the blood, then harmless to other composition in the blood.Because immunity absorption therapy is directly to remove morbid substance from blood, for suddenly danger patient and malignant disorders such as cancer, AIDS, autoimmune disease, endotoxin shock etc. are evident in efficacy, side effect is little.The external method of using immunity absorption has successfully been treated several thousand cases, has reached the rescue urgent patient, prolongs the purpose of patient's life.The key of immunoadsorption therapy is the development of immunoabsorbent column, be exactly specifically immunosorbent selection and with the coupling of immobilized matrix, the immune adsorbing medium that immunosorbent and immobilized solid-phase matrix form must meet following requirement, just can carry out human body therapy:
(1) adsorbing medium should have higher selectivity, and non-special absorption is little;
(2) blood compatibility of adsorbing medium will be got well, promptly nontoxic, do not dissolve, not activating complement and blood coagulation system, non-sensitization;
(3) good stability is convenient to store and sterilization.
Protein A is a kind of protein on some aureus cell wall, its molecular weight is 42000, its amino terminal has 4 Fc lands highly roughly the same, can with the IgG in the human plasma and the Fc section specific bond of immune complex thereof, Protein A combines back vent and can be dissociated by the acid solution of pH2.3～2.5 with IgG and immune complex thereof.Human a lot of diseases all are to be caused by antibody and immune complex, as systemic loupus erythematosus, thrombocytopenic purpura, myasthenia gravis etc., these all are the difficult and complicated illness that can't cure, utilize the characteristic of Protein A and antibody and immune complex specific bond from blood, to remove these morbid substances, significantly mitigate the disease.Carry out a large amount of animals and clinical trial in this respect abroad, obtained better curative effect.The matrix of commercial Protein A immunoabsorbent column (the Sweden GABRO company) employing of using clinically now is Sepharose CL-4B Ago-Gel, with the coupling mode of Protein A be the cyanogen bromide-activated coupling, the shortcoming of this activation method is that cyanogen bromide is an extremely toxic substance, building-up process is bigger to human body and environmental hazard, another shortcoming is some experiment confirm, with the albumen group of the cyanogen bromide method coupling (Tesser etc. that come off easily, 1974), thus this synthesis technique not satisfactory.
The object of the present invention is to provide a kind of synthetic method that is used for removing from blood plasma the protein immunization adsorbing medium of pathogenic antibody and compound thereof, this method can replace cyanogen bromide-activated technology, and is nontoxic, harmless, and coupling Protein A is effective.
The invention provides a kind of synthetic method that is used for removing the protein immunization adsorbing medium of pathogenic antibody and compound thereof, it is characterized in that building-up process complies with following step and carry out from blood plasma:
(1) with epoxychloropropane activation Sepharose CL-4B Ago-Gel, 40～80 ℃ of reaction temperatures, 1～4 hour time, epoxychloropropane is fully excessive;
(2) directly react synthetic immune adsorbing medium with epoxy Sepharose CL-4B Ago-Gel and Protein A, reaction temperature is 24～26 ℃, and in 16～20 hours reaction time, Protin A is fully excessive, and the pH value is controlled in 9～10 scopes;
With glycine ethyl ester hydrochloride or ethanol ammonia sealing unreacted active group;
Put into and preserve liquid.
The present invention also provides the another kind of synthetic method that is used for removing from blood plasma the protein immunization adsorbing medium of pathogenic antibody and compound thereof, it is characterized in that building-up process is as follows:
(1) with epoxychloropropane activation Sepharose CL-4B Ago-Gel, 40～80 ℃ of reaction temperatures, 1～4 hour time, epoxychloropropane is fully excessive;
(2) with amino or two amino reagent the Sepherose CL-4B that has active epoxy group is carried out ring-opening reaction, two amino reagent are selected from a kind of of ethylenediamine, butanediamine, hexamethylene diamine, reaction temperature is 50～80 ℃, and in 1～4 hour reaction time, ammoniacal liquor or two amino reagent are fully excessive;
(3) obtain aldehyde radical Sepharose CL-4B with dialdehyde base reagent and the Sepharose CL-4B reaction that has active amino, dialdehyde base reagent is selected from defends a kind of of dialdehyde, terephthalaldehyde, reaction temperature is 30～40 ℃, and dialdehyde base reagent is fully excessive, and the pH value is controlled at 7.0～9.0;
(4) directly react synthetic immune adsorbing medium with aldehyde radical Sepharose CL-4B Ago-Gel and Protein A, reaction temperature is at 24～26 ℃, and in 16～20 hours reaction time, Protein A is fully excessive, and the pH value is controlled in 7.0～8.5 scopes;
With glycine ethyl ester hydrochloride or ethanol ammonia sealing unreacted active group;
With the two keys that produce in sodium borohydride or the sodium cyanoborohydride reduction reaction;
Put into and preserve liquid.
Adopt 0.2mol/l pH=2.3 glycine-HCl buffer solution as eluent among the present invention, make equilibrium liquid, the phosphate buffer that usefulness contains the 0.1mol/l pH=7.4 of 0.02～0.1% iteration sodium liquid storage of going bail for the phosphate buffer of 0.1mol/lpH=7.4.
In above-mentioned two kinds of methods provided by the invention second kind more superior.
The matrix that adopts among the present invention is Sepharose CL-4B Ago-Gel, and the Protein A of employing is the genetic recombination product, and purity reaches more than 98%.Experimental results show that Sepharose CL-4B Ago-Gel is a kind of good immune adsorbing base, satisfy the requirement of blood purification to immune adsorbing medium, genetic recombination Protein A than the Protein A purity height of from staphylococcus aureus, purifying, toxicity is little, price is low.Bonding in the experimentation between active group and medium is covalently bound, drops to Protein A leakage minimum.Below by embodiment in detail the present invention is described in detail.
Embodiment 1 has Sepharose CL-4B Ago-Gel synthetic of active epoxy group
Agitator is housed, temperature is taken into account in the 100ml there-necked flask of condenser, adds Sepharose CL-4B10ml, 1mol/l NaOH solution 10.5ml, heat temperature raising to 40 ℃, add epoxychloropropane 10ml,, will stir in the course of reaction 40 ℃ of isothermal reactions 2 hours.Stop reaction, reduce to room temperature after, remove unreacted epoxychloropropane and NaOH with a large amount of washings, filter is dried standby.
Embodiment 2 has Sepharose CL-4B Ago-Gel synthetic of amino active group
Agitator is housed, temperature is taken into account in the 100ml there-necked flask of condenser, adds the Sepharose CL-4B 10ml that has active epoxy group, adds hexamethylene diamine 5ml, add deionized water 20ml, 50 ℃ of isothermal reactions 2 hours are after reaction stops, with a large amount of neutrality that is washed to, filter is done standby.
Embodiment 3 has Sepharose CL-4B Ago-Gel synthetic of aldehyde radical active group
Agitator is housed, temperature is taken into account in the 100ml there-necked flask of condenser, add the Sepharose CL-4B 10ml that has active amino, add and defend dialdehyde 4ml, make buffer solution with borate or phosphate, the pH value is controlled in 9.0 scopes, adds buffer solution 20ml, 30 ℃ of isothermal reactions 2 hours, after reaction stops, removing the used dialdehyde of defending with a large amount of washings, filter is done standby.
Embodiment 4 directly reacts synthetic immunity by epoxy Sepharose CL-4B Ago-Gel and Protein A
Adsorbing medium
Agitator is housed, temperature is taken into account in the 100ml there-necked flask of condenser, adds epoxy Sepharose CL-4B 10ml, the NaHCO of 0.5mol/l
3-Na
2CO
3Cushioning liquid 20ml, pH=10,60mg Protein A is added wherein, 25 ℃ of isothermal reactions 20 hours, stop reaction, reclaim unreacted Protein A, with glycine ethyl ester hydrochloride or ethanol ammonia sealing unreacted active group, water is rinsed unreacted components well, is kept in the phosphate buffer of 50mmol/l pH=7.0, and the iteration sodium of adding 0.02～0.1% is made anticorrisive agent.Bonded amount with ultraviolet method absorbance detection Protein A is 2.0mg/ml, in conjunction with IgG amount 15mg/ml.
Embodiment 5 aldehyde radical Sepharose CL-4B Ago-Gels and Protein A directly react synthetic immunity and inhale
Attached medium
Agitator is being housed, temperature is taken into account in the 100ml there-necked flask of condenser, add aldehyde radical Sepharose CL-4B 10ml, the phosphoric acid or the borate buffer 20ml that add 0.1mol/l, the pH value is controlled in 7.0～8.5 scopes, add 60mg Protein A, 25 ℃ of isothermal reactions 20 hours, stop reaction, reclaim unreacted Protein A, with glycine ethyl ester hydrochloride or ethanol ammonia sealing unreacted active group, with the two keys that produce in sodium borohydride or the sodium cyanoborohydride reduction reaction, water is rinsed unreacted components well, be kept in the phosphate buffer of 0.1mol/lpH=7.4, the iteration sodium of adding 0.02～0.1% is made anticorrisive agent.The bonded amount that detects Protein A with ultraviolet method is 4.0mg/ml, in conjunction with IgG amount 25mg/ml.
The isolated experiment of embodiment 6 Protein A immunoabsorbent columns
By the synthetic Protein A immunity of above-mentioned synthetic method adsorbing medium 60ml, wherein the bonded amount of Protein A is 168mg, be loaded in the post of Φ 40 * 50, fully wash pillar with physiological saline, dog anesthesia with body weight 25Kg, from the femoral artery of dog, extract heparinized blood 600ml, isolate blood plasma 300ml, cross behind the post with the speed of 30ml/min and mix the femoral vein that together injects dog with blood cell.Going out in the post blood plasma with physiological saline is zero up to the absorption value at 280nm, with the antibody and the immune complex thereof that adsorb in 0.2mol/l pH=2.3 glycine-HCl buffer solution elution post, owing to be healthy dog, immune complex seldom, adsorbate is mainly antibody, the antibody amount that detects under the wash-out is 1.08g, and with the phosphate buffer balance pillar of 0.1mol/l pH=7.4, it is standby that the iteration sodium of adding 0.02～0.1% is made anticorrisive agent.In experimentation and after the experiment, the physiological status of dog does not change.
Embodiment 7 Protein A immunoabsorbent columns are tested continuously at the external blood circulation branch road of setting up
By the synthetic Protein A immunity of above-mentioned synthetic method adsorbing medium 120ml, equivalent is packed in the post of two Φ 40 * 50, and wherein the bonded amount of every pillar Protein A is 168mg.Fully wash pillar with physiological saline, with the dog anesthesia of body weight 13Kg, the switching pipeline with arterial end, vein end before the experiment connects, abundant fumigating reaches aseptic requirement, connects immunoabsorbent column, washes in a large number with physiological saline, what displace the inside iterates sodium, pipeline, the whole heparinizes of pillar.After the dog general anesthesia, arteria carotis intubate measuring blood pressure, pulsation, blood flow etc., blood is drawn from the back leg femoral artery of dog, through membrane separator blood is divided into blood cell, blood plasma two parts, plasma flow is crossed post 1 system, and post 2 system closings are crossed post blood plasma and mixed in blender with blood cell, in the input dog body, move after 10～15 minutes, close post 1 system entry, open post 2 systems, blood plasma in post 1 system is ejected with about 50ml physiological saline, enter blender.Close post 1 system outlet, post 1 system carries out wash-out, equilibrium process, and the first albumen of the eluent flush away absorption by 250ml again with the level pad balance pillar of about 150ml, falls level pad with the normal saline flushing of about 150ml, and regenerative process finishes.Open post 1 system entry, close post 2 system entries simultaneously, repeat above operation.Each post respectively switches 3 times, and blood sampling carries out the detection of various indexs 4 times altogether therebetween.Two blood pump flow velocitys, A pump: 80ml/min, B pump: 40ml/min.The index testing result shows, through 1 hour experiment, removes 6.5 gram antibody altogether from the blood plasma of dog, and the physical signs of dog, biochemical indicator, routine blood test etc. do not change, and behind the recovery from anesthesia, it is normal that physiological activity recovers.Same dog carries out twice experiment, has obtained similar result.
Above result confirms that Protein A immunoabsorbent column has security preferably and reliability.
Claims (2)
1. synthetic method that is used for removing from blood plasma the protein immunization adsorbing medium of pathogenic antibody and compound thereof is characterized in that building-up process complies with following step and carry out:
(1) with epoxychloropropane activation Sepharose CL-4B Ago-Gel, 40～60 ℃ of reaction temperatures, 1～4 hour time, epoxychloropropane is fully excessive;
(2) directly react synthetic immune adsorbing medium with epoxy Sepharose CL-4B Ago-Gel and Protein A, reaction temperature is 24～26 ℃, and in 16～20 hours reaction time, Protein A is fully excessive, and the pH value is controlled in 9～10 scopes;
With glycine ethyl ester hydrochloride or ethanol ammonia sealing unreacted active group;
Put into and preserve liquid.
2. one kind is used for it is characterized in that from the synthetic method of the protein immunization adsorbing medium of blood plasma removal pathogenic antibody and compound thereof building-up process is as follows:
(1) with epoxychloropropane activation Sepharose CL-4B Ago-Gel, 40～80 ℃ of reaction temperatures, 1～4 hour time, epoxychloropropane is fully excessive;
(2) with amino or two amino reagent the Sepherose CL-4B that has active epoxy group is carried out ring-opening reaction, two amino reagent are selected from a kind of of ethylenediamine, butanediamine, hexamethylene diamine, reaction temperature is 50～80 ℃, and in 1～4 hour reaction time, ammoniacal liquor or two amino reagent are fully excessive;
(3) obtain aldehyde radical SepharoseCL-4B with dialdehyde base reagent and the SepharoseCL-4B reaction that has active amino, dialdehyde base reagent is selected from defends a kind of of dialdehyde, terephthalaldehyde, reaction temperature is 30～40 ℃, and dialdehyde base reagent is fully excessive, and the pH value is controlled at 7.0～9.0;
(4) directly react synthetic immune adsorbing medium with aldehyde radical Sepharose CL-4B Ago-Gel and Protein A, reaction temperature is at 24～26 ℃, and in 16～20 hours reaction time, Protein A is fully excessive, and the pH value is controlled in 7.0～8.5 scopes;
With glycine ethyl ester hydrochloride or ethanol ammonia sealing unreacted active group;
With the two keys that produce in sodium borohydride or the sodium cyanoborohydride reduction reaction;
Put into and preserve liquid.
Priority Applications (1)
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| CN99112880A CN1100568C (en) | 1999-04-26 | 1999-04-26 | Process for synthesizing protein immunoadsorbent medium for removing pathogenic antibody and its compounds from plasm |
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| CN99112880A CN1100568C (en) | 1999-04-26 | 1999-04-26 | Process for synthesizing protein immunoadsorbent medium for removing pathogenic antibody and its compounds from plasm |
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| CN1100568C CN1100568C (en) | 2003-02-05 |
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Cited By (8)
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| CN100348302C (en) * | 2004-05-14 | 2007-11-14 | 华南理工大学 | Method for preparing water-soluble affinity ultrafiltration carrier |
| CN100371034C (en) * | 2004-03-12 | 2008-02-27 | 中国科学院大连化学物理研究所 | Application of Histidine in Affinity Adsorption Medium for Blood Purification |
| CN101185878B (en) * | 2006-11-17 | 2010-05-26 | 广州康盛生物科技有限公司 | A protein A immunoadsorbent material for removing pathogenic antibodies and their complexes, its synthesis method and application |
| CN101797493A (en) * | 2009-02-06 | 2010-08-11 | 上海抗体药物国家工程研究中心有限公司 | Method for preparing affinity chromatography medium in reaction kettle |
| CN103864960A (en) * | 2014-04-03 | 2014-06-18 | 福建省水产研究所 | Preparation method for hydroxypropyl low-melting-point agarose |
| CN108816208A (en) * | 2018-06-13 | 2018-11-16 | 云南师范大学 | A kind of protein A immunoadsorption material and preparation method thereof of high carrying capacity |
| CN110026166A (en) * | 2019-04-28 | 2019-07-19 | 广州康盛生物科技有限公司 | It is a kind of for targeting the albumin A adsorbent material and preparation method thereof of absorption |
| CN118304864A (en) * | 2024-03-06 | 2024-07-09 | 重庆希尔康血液净化器材研发有限公司 | Novel immunoadsorption material for fixed-point immobilized protein A and preparation method thereof |
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| CN100389325C (en) * | 2003-02-25 | 2008-05-21 | 上海实业科华生物技术有限公司 | A kind of preparation method of metal chelate chromatography filler |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3149360A1 (en) * | 1981-12-12 | 1983-06-16 | Biotest-Serum-Institut Gmbh, 6000 Frankfurt | "METHOD FOR PURIFYING AND / OR PHYTOHEMAGGLUTININE SEPARATION FROM HUMAN INTERLEUKIN-2" |
| US4689225A (en) * | 1984-11-02 | 1987-08-25 | Institut Merieux | Vaccine for cytomegalovirus |
| ZA902147B (en) * | 1989-03-28 | 1990-12-28 | Akzo Nv | Coccidiosis vaccine |
| CN1057607C (en) * | 1995-12-04 | 2000-10-18 | 广州市博普生物技术有限公司 | Double functional chromatographic material and preparing method and use |
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1999
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN100371034C (en) * | 2004-03-12 | 2008-02-27 | 中国科学院大连化学物理研究所 | Application of Histidine in Affinity Adsorption Medium for Blood Purification |
| CN100348302C (en) * | 2004-05-14 | 2007-11-14 | 华南理工大学 | Method for preparing water-soluble affinity ultrafiltration carrier |
| CN101185878B (en) * | 2006-11-17 | 2010-05-26 | 广州康盛生物科技有限公司 | A protein A immunoadsorbent material for removing pathogenic antibodies and their complexes, its synthesis method and application |
| CN101797493A (en) * | 2009-02-06 | 2010-08-11 | 上海抗体药物国家工程研究中心有限公司 | Method for preparing affinity chromatography medium in reaction kettle |
| CN101797493B (en) * | 2009-02-06 | 2014-05-21 | 上海抗体药物国家工程研究中心有限公司 | Method for preparing affinity chromatography medium in reaction kettle |
| CN103864960A (en) * | 2014-04-03 | 2014-06-18 | 福建省水产研究所 | Preparation method for hydroxypropyl low-melting-point agarose |
| CN108816208A (en) * | 2018-06-13 | 2018-11-16 | 云南师范大学 | A kind of protein A immunoadsorption material and preparation method thereof of high carrying capacity |
| CN108816208B (en) * | 2018-06-13 | 2022-03-01 | 云南师范大学 | High-load protein A immunoadsorption material and preparation method thereof |
| CN110026166A (en) * | 2019-04-28 | 2019-07-19 | 广州康盛生物科技有限公司 | It is a kind of for targeting the albumin A adsorbent material and preparation method thereof of absorption |
| CN118304864A (en) * | 2024-03-06 | 2024-07-09 | 重庆希尔康血液净化器材研发有限公司 | Novel immunoadsorption material for fixed-point immobilized protein A and preparation method thereof |
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