CN106676089A - Method for preparing human prothrombin complex from plasma - Google Patents
Method for preparing human prothrombin complex from plasma Download PDFInfo
- Publication number
- CN106676089A CN106676089A CN201710118663.7A CN201710118663A CN106676089A CN 106676089 A CN106676089 A CN 106676089A CN 201710118663 A CN201710118663 A CN 201710118663A CN 106676089 A CN106676089 A CN 106676089A
- Authority
- CN
- China
- Prior art keywords
- blood plasma
- eluent
- chromatographic column
- gel
- eluting
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6429—Thrombin (3.4.21.5)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21005—Thrombin (3.4.21.5)
Abstract
The invention discloses a method for preparing a human prothrombin complex from plasma. The method comprises: directly adsorbing the human prothrombin complex from the plasma by using DEAE A-50 gel, filling the adsorbed A-50 gel into a chromatographic column of a fixed bed, pumping eluant into the filled chromatographic column by using a peristaltic pump for online washing and elution, performing S/D inactivation on the eluant, and performing secondary chromatographic purification by using the chromatographic column of the fixed bed to obtain a high-purity human prothrombin complex product. According to the method, elution flow and speed can be accurately controlled by online elution after filling the gel into the column, the problems of contamination, cross contamination, gel leakage and the like caused by an open operation are reduced, an obtained product is high in purity, an IX factor titer can exceed 27IU/ml, and the IX factor specific activity exceeds 0.8IU/mg protein. Meanwhile, a self-flushing type filter with a pressure difference controller and an automatic solid matter stripping system is adopted, so the pressure difference in the whole filtering process is stable and controllable, gel particles can be well protected, broken colloidal particles flowing into a plasma tank in the filtering process are remarkably reduced, and gel losses in a production process can be reduced by above 20%.
Description
Technical field
The invention belongs to bio-pharmaceuticals and blood products technical field, and in particular to blood products are a kind of from blood plasma in preparing
The middle method for preparing Human Factor Ⅸ Complex.
Background technology
Human Factor Ⅸ Complex (Prothrombin complex concentrate, PCC) from human normal plasma,
It is a kind of traditional plasma protein products, except in addition to treating hemophilia B, it may also be used for treatment is because of vitamin K deficiency or liver
Disease and hemorrhage for causing etc., with the progressively accreditation of clinician, PCC usage amounts are also increasing year by year.At present, China's production
The producer of PCC is few, and in addition raw blood plasma is nervous, and critical shortage occurs in PCC, therefore, its production is prepared and causes each side
Concern.
The classical technique for preparing Human Factor Ⅸ Complex at present is the batch absorption that Dutch red cross blood center proposes
Technique:Adsorb II, tetra- kinds of blood coagulations of VII, IX, X from raw blood plasma with weak anion exchanger such as sephadex DEAE A-50
The factor, the A-50 gels after absorption are pulled out in batches using filter screen, remove absorption affinity with the buffer solution of low ionic strength weak
Foreign protein and the other compositions sticked, then increase the desired albumen of ionic strength elution of buffer, remake following process
Process.Batch absorbing process is open-sky technique, cumbersome, and easily causes pollution, cross-contamination, and gel leakage etc. is asked
Topic.Domestic Human Factor Ⅸ Complex also has the report being prepared as initiation material with the component III of cohn methods, but the method
Easily there is PROTHROMBIN ACTIVATOR phenomenon, cause drug user's Coagulation test, there is larger potential safety hazard.
The content of the invention
The invention provides one kind directly absorbs Human Factor Ⅸ Complex using DEAE A-50 gels from blood plasma,
A-50 gels after absorption are seated in fixed bed chromatographic column, the chromatographic column for filling pumps into eluent and carries out using peristaltic pump
Online washing and eluting, eluent Jing S/D inactivations, inactivation liquid is directly diluted to electric conductivity value without dialysis concentration<1000us, then
The preparation method of high-purity Human Factor Ⅸ Complex's product is obtained using the secondary chromatography purification of fixed bed chromatographic column.
The purpose of the present invention is achieved by following technical proposals:
A kind of method that Human Factor Ⅸ Complex is prepared from blood plasma is provided, is comprised the following steps:
(1) removal of blood plasma cryoprecipitate:With fresh food frozen human plasma as raw material, Jing melts the operations such as slurry, slurry, continuous centrifugal
The cryoprecipitate in blood plasma is removed, the blood plasma centrifuged supernatant without cryoprecipitate is obtained;
(2) gel batch absorption:Blood plasma temperature control at 10-15 DEG C, according to 1.0-1.5g xerogel/L blood plasma, to removing Cryoprecipitation
The DEAE A-50 gels after balance are added in the blood plasma of shallow lake, stirring, standing sedimentation 45min are closed after stirring and adsorbing 45min.Gel
Blood plasma after absorption automatically strips carrying out from wash type continuous filter for system using with differential pressure controller and solid content
Filter, collects the A-50 gels after absorption, and blood plasma filtered solution is incorporated to blood plasma tank;
(3) post eluting is filled:A-50 gels after absorption are seated in fixed bed chromatographic column, the chromatographic column for filling is used
Peristaltic pump pumps into cleaning mixture and carries out on-line rinsing, and washing flow velocity is 30-40cm/h, washing time about 60-90min.After washing
A-50 gels pump into eluent using peristaltic pump and carry out online eluting, eluent flow rate is 30-40cm/h, treats online ultraviolet inspection
The ultraviolet absorption value surveyed in device collects eluent and uses 0.45um filter element filterings less than eluting is stopped after 500Au;
(4) S/D is inactivated and diluted:The S/D for having configured is inactivated into liquid under gentle agitation and is slowly added to the eluent after filtering
In, addition stirs 30min after finishing.Adjustment liquid temperature is 24-26 DEG C, inactivates 6h.The side of addition diluted is taken after inactivation
Electric conductivity value is down to 800-1000us by method;
(5) fixed bed column chromatography:Capto DEAE anion-exchange gels are seated in fixed bed chromatographic column, are filled
Chromatographic column using balance liquid balance 2-5 column volume, S/D inactivation after diluent use peristaltic pump chromatographic column, loading flow velocity
For 30-40cm/h.Pumping into cleaning mixture using peristaltic pump after completion of the sample carries out on-line rinsing, and washing flow velocity is 30-40cm/h,
Washing time about 60-90min.Chromatographic column after washing pumps into eluent and carries out eluting using peristaltic pump, and eluent flow rate is 30-
40cm/h, after the ultraviolet absorption value in line UV-detector is less than 500Au eluting is stopped, and is collected eluent and is used
0.45um filter element filterings;
(6) it is concentrated by ultrafiltration:Ultrafiltration dialysis are carried out using dialysis solution, the electric conductivity value for giving liquid port is made less than after 1000us
It is concentrated by ultrafiltration, is controlled concentrated solution potency>35IU/ml;
(7) with liquid:Liquid is concentrated by ultrafiltration to be diluted using dialysis solution, it is 30-40IU/ml, pH7-7.5 to adjust vigor, is made
Use 0.45um filter element filterings;
(8) subpackage;
(9) lyophilizing;
The blood plasma after gel adsorption in step (2) is described from wash type mistake using being filtered from flushing type filter
Filter be with differential pressure controller and solid content automatically strip system from wash type continuous filter.
Cleaning mixture in step (3) by 20-30mmol/L sodium citrate, the Sodium Chloride of 0.1-0.5mol/L, 200-
The heparin sodium composition of 500IU/ml, pH is 6.8-7.0.The eluent by 20-30mmol/L sodium citrate, 0.5-
The Sodium Chloride of 1.0mol/L, the heparin sodium composition of 200-500IU/ml, pH is 6.8-7.0.
Type of elution in step (3) is that the A-50 gels after absorption are seated in fixed bed chromatographic column, is filled
Chromatographic column pumps into eluent and is washed online and eluting using peristaltic pump.
By the mode that electric conductivity value is down to 800-1000us it is by 1 after inactivation in step (4):2 ratio addition diluent
Dilution.
Compared with prior art, the present invention has following beneficial effect;
1. it is domestic at present predominantly to be inhaled using sephadex DEAE A-50 gels batch absorption-eluting-concentration-secondary batch
The method of attached-secondary concentration-subpackage-lyophilizing extracts Human Factor Ⅸ Complex from blood plasma, and batch absorbing process is open
Operation, easily causes pollution, cross-contamination, the problems such as gel is leaked.A-50 gels after absorption are seated in fixation by the present invention
In bed chromatographic column, the chromatographic column for filling pumps into eluent and is washed online and eluting using peristaltic pump, reduces open
The pollution that causes of operation, cross-contamination, the problems such as gel is leaked.Online eluting realizes the accurate control of eluting flow and speed
System, makes whole technical process more controllable, while the online UV-detector of fixed bed analysis system is made in elution process to mesh
Albumen collection it is highly efficient, reduce being mixed into for foreign protein, resulting product purity is higher, and IX factor potency is up to 27IU/
More than ml, IX factor specific activity is up to more than 0.8IU/mg albumen.
2. the method taken when in the present invention to the plasmapheresis after addition gel is different from traditional single strainer filtering,
During single strainer filtering, with the rising of solid concentration, the pressure reduction of filtration can be raised, and too high pressure reduction can make fragility
Sephadex gels are destroyed, and increased the material loss in production process, and the broken micelle after rupture is flowed into can be right after blood plasma tank
In follow-up blood plasma quiet third and it is albuminous production adversely affect.By modified technique, using with differential pressure controller and
Solid content automatically strips filtering to the blood plasma after addition gel from wash type continuous filter for system, greatlys save life
Time cost is produced, while making pressure reduction in whole filter process stablize controllable, preferable protective effect, mistake is served to gel particle
The broken micelle that blood plasma tank is flowed into during filter is substantially reduced, and the gel loss in production process can reduce by more than 20%.
3. after S/D inactivations need that eluent electric conductivity value is down to into 800-1000us side through ultrafiltration dialysis step in traditional handicraft
Chromatography sample introduction can be carried out, operation is relatively complicated, and ultrafilter membrane bag consumables cost is higher, by process modification, by sample introduction pre-treatment
Mode be improved to by 1:2 ratio addition diluted, the step of eliminate ultrafiltration dialysis, simplifies production technology and shows
Work reduces consumables cost.
Description of the drawings
Fig. 1 is the process chart that Human Factor Ⅸ Complex is prepared from blood plasma;
Specific embodiment
By combination accompanying drawing described further below it will be further appreciated that the features and advantages of the invention.The enforcement for being provided
Example is only the explanation to the inventive method, and limits remaining content of present invention announcement never in any form.
【Embodiment 1】
The removal of blood plasma cryoprecipitate:With fresh food frozen human plasma as raw material, Jing melts the operations such as slurry, slurry, continuous centrifugal and goes
Except the cryoprecipitate in blood plasma, blood plasma centrifuged supernatant 2kg without cryoprecipitate is obtained;
Gel batch absorption:Blood plasma temperature control at 10 DEG C, according to 1.0g xerogel/L blood plasma, to going in CPP plus
Enter the DEAE A-50 gels after balance, stirring is closed after stirring and adsorbing 45min.Blood plasma after gel adsorption is used from wash type
Filter is filtered, and collects the A-50 gels after absorption, and blood plasma filtered solution is incorporated to blood plasma tank;
Dress post eluting:A-50 gels after absorption are seated in fixed bed chromatographic column, the chromatographic column for filling uses compacted
Dynamic pump pumps into cleaning mixture and carries out on-line rinsing, and washing flow velocity is 35cm/h, washing time about 60min.A-50 after washing coagulates
Glue pumps into eluent and carries out online eluting using peristaltic pump, and eluent flow rate is 35cm/h, treats the purple in online UV-detector
Outer absorption value collects eluent 140ml, using 0.45um filter element filterings less than eluting is stopped after 500Au;
S/D is inactivated and diluted:The S/D for having configured is inactivated in the eluent after liquid is slowly added to filter under gentle agitation,
Addition stirs 30min after finishing.Adjustment liquid temperature is 24-26 DEG C, inactivates 6h.280ml diluents are added to drop electric conductivity value after inactivation
To 800us;
Fixed bed column is chromatographed:Capto DEAE anion-exchange gels are seated in fixed bed chromatographic column, are filled
Chromatographic column balances 3 column volumes using balance liquid, and using peristaltic pump chromatographic column, loading flow velocity is the diluent after S/D inactivations
35cm/h.Pumping into cleaning mixture using peristaltic pump after completion of the sample carries out on-line rinsing, and washing flow velocity is 35cm/h, washing time
About 60min.Chromatographic column after washing pumps into eluent and carries out eluting using peristaltic pump, and eluent flow rate is 35cm/h, treats online
Ultraviolet absorption value in UV-detector collects eluent less than eluting is stopped after 500Au;
Ultrafiltration dialysis:Ultrafiltration dialysis are carried out using dialysis solution, makes the electric conductivity value for giving liquid port laggard less than 1000us
Row is concentrated by ultrafiltration, and controls concentrated solution potency>35IU/ml, obtains Human Factor Ⅸ Complex's stock solution 75ml.
【Embodiment 2】
The removal of blood plasma cryoprecipitate:With fresh food frozen human plasma as raw material, Jing melts the operations such as slurry, slurry, continuous centrifugal and goes
Except the cryoprecipitate in blood plasma, blood plasma centrifuged supernatant 2kg without cryoprecipitate is obtained;
Gel batch absorption:Blood plasma temperature control at 15 DEG C, according to 1.5g xerogel/L blood plasma, to going in CPP plus
Enter the DEAE A-50 gels after balance, stirring, standing sedimentation 45min are closed after stirring and adsorbing 45min.Blood after gel adsorption
Slurry collects the A-50 gels after absorption using being filtered from flushing type filter, and blood plasma filtered solution is incorporated to blood plasma tank;
Dress post eluting:A-50 gels after absorption are seated in fixed bed chromatographic column, the chromatographic column for filling uses compacted
Dynamic pump pumps into cleaning mixture and carries out on-line rinsing, and washing flow velocity is 40cm/h, washing time about 70min.A-50 after washing coagulates
Glue pumps into eluent and carries out online eluting using peristaltic pump, and eluent flow rate is 40cm/h, treats the purple in online UV-detector
Outer absorption value collects eluent 170ml less than eluting is stopped after 500Au;
S/D is inactivated and diluted:The S/D for having configured is inactivated in the eluent after liquid is slowly added to filter under gentle agitation,
Addition stirs 30min after finishing.Adjustment liquid temperature is 24-26 DEG C, inactivates 6h.340ml diluents are added to drop electric conductivity value after inactivation
To 800us;
Fixed bed column is chromatographed:Capto DEAE anion-exchange gels are seated in fixed bed chromatographic column, are filled
Chromatographic column balances 5 column volumes using balance liquid, and using peristaltic pump chromatographic column, loading flow velocity is the diluent after S/D inactivations
40cm/h.Pumping into cleaning mixture using peristaltic pump after completion of the sample carries out on-line rinsing, and washing flow velocity is 40cm/h, washing time
About 70min.Chromatographic column after washing pumps into eluent and carries out eluting using peristaltic pump, and eluent flow rate is 40cm/h, treats online
Ultraviolet absorption value in UV-detector collects eluent less than eluting is stopped after 500Au;
Ultrafiltration dialysis:Ultrafiltration dialysis are carried out using dialysis solution, makes the electric conductivity value for giving liquid port laggard less than 1000us
Row is concentrated by ultrafiltration, and controls concentrated solution potency>35IU/ml, obtains Human Factor Ⅸ Complex's stock solution 85ml.Subpackage, lyophilizing is obtained
PCC products.After testing, gained PCC products IX factors potency is more than 27IU/ml, and IX factors specific activity reaches 0.8IU/mg albumen
More than.
Claims (5)
1. it is a kind of from blood plasma prepare Human Factor Ⅸ Complex method, it is characterised in that comprise the following steps:
(1) removal of blood plasma cryoprecipitate:With fresh food frozen human plasma as raw material, Jing melts the removal of the operations such as slurry, slurry, continuous centrifugal
Cryoprecipitate in blood plasma, obtains the blood plasma centrifuged supernatant without cryoprecipitate;
(2) gel batch absorption:Blood plasma temperature control at 10-15 DEG C, according to 1.0-1.5g xerogel/L blood plasma, to removing cryoprecipitate blood
The DEAE-sephadex A-50 gels after balance are added in slurry, stirring, standing sedimentation 45min are closed after stirring and adsorbing 45min.
Blood plasma after gel adsorption automatically strips entering from wash type continuous filter for system using with differential pressure controller and solid content
Row is filtered, and collects the A-50 gels after absorption, and blood plasma filtered solution is incorporated to blood plasma tank;
(3) post eluting is filled:A-50 gels after absorption are seated in fixed bed chromatographic column, the chromatographic column for filling uses wriggling
Pump pumps into cleaning mixture and carries out on-line rinsing, and washing flow velocity is 30-40cm/h, washing time about 60-90min.A- after washing
50 gels pump into eluent and carry out online eluting using peristaltic pump, and eluent flow rate is 30-40cm/h, treats online UV-detector
In ultraviolet absorption value less than eluting is stopped after 500Au, collect eluent and using 0.45um filter element filterings;
(4) S/D is inactivated and diluted:The S/D for having configured is inactivated in the eluent after liquid is slowly added to filter under gentle agitation, is added
Plus stir 30min after finishing.Adjustment liquid temperature is 24-26 DEG C, inactivates 6h.The method of addition diluted is taken after inactivation by electricity
Lead value and be down to 800-1000us;
(5) fixed bed column chromatography:Capto DEAE anion-exchange gels are seated in fixed bed chromatographic column, the layer for filling
Analysis post balances 2-5 column volume using balance liquid, and the diluent after S/D inactivations uses peristaltic pump chromatographic column, and loading flow velocity is 30-
40cm/h.Pumping into cleaning mixture using peristaltic pump after completion of the sample carries out on-line rinsing, and washing flow velocity is 30-40cm/h, is rinsed
Time about 60-90min.Chromatographic column after washing pumps into eluent and carries out eluting using peristaltic pump, and eluent flow rate is 30-
40cm/h, after the ultraviolet absorption value in line UV-detector is less than 500Au eluting is stopped, and is collected eluent and is used
0.45um filter element filterings;
(6) ultrafiltration dialysis:Ultrafiltration dialysis are carried out using dialysis solution, the electric conductivity value for giving liquid port is less than after 1000us is carried out
It is concentrated by ultrafiltration, controls concentrated solution potency>35IU/ml;
(7) with liquid:Liquid is concentrated by ultrafiltration to be diluted using dialysis solution, it is 30-40IU/ml, pH7-7.5 to adjust vigor, is used
0.45um filter element filterings;
(8) subpackage;
(9) lyophilizing.
2. it is according to claim 1 from blood plasma prepare Human Factor Ⅸ Complex method, it is characterised in that it is described
Using being filtered from flushing type filter, described be band from type filter is rinsed to the blood plasma after gel adsorption in step (2)
Have differential pressure controller and solid content automatically strip system from wash type continuous filter.
3. it is according to claim 1 from blood plasma prepare Human Factor Ⅸ Complex method, it is characterised in that it is described
Cleaning mixture in step (3) by 20-30mmol/L sodium citrate, the Sodium Chloride of 0.1-0.5mol/L, 200-500IU/ml's
Heparin sodium is constituted, and pH is 6.8-7.0.The eluent by 20-30mmol/L sodium citrate, the chlorination of 0.5-1.0mol/L
Sodium, the heparin sodium composition of 200-500IU/ml, pH is 6.8-7.0.
4. it is according to claim 1 from blood plasma prepare Human Factor Ⅸ Complex method, it is characterised in that it is described
Type of elution in step (3) is that the A-50 gels after absorption are seated in fixed bed chromatographic column, and the chromatographic column for filling makes
Pump into eluent with peristaltic pump to be washed online and eluting.
5. it is according to claim 1 from blood plasma prepare Human Factor Ⅸ Complex method, it is characterised in that it is described
By the mode that electric conductivity value is down to 800-1000us it is by 1 after inactivation in step (4):2 ratio addition diluted.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710118663.7A CN106676089B (en) | 2017-03-01 | 2017-03-01 | Method for preparing human prothrombin complex from blood plasma |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710118663.7A CN106676089B (en) | 2017-03-01 | 2017-03-01 | Method for preparing human prothrombin complex from blood plasma |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106676089A true CN106676089A (en) | 2017-05-17 |
CN106676089B CN106676089B (en) | 2020-01-10 |
Family
ID=58861631
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710118663.7A Active CN106676089B (en) | 2017-03-01 | 2017-03-01 | Method for preparing human prothrombin complex from blood plasma |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106676089B (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108048433A (en) * | 2018-01-19 | 2018-05-18 | 贵州泰邦生物制品有限公司 | A kind of preparation method of Human Factor Ⅸ Complex |
CN108245986A (en) * | 2018-03-24 | 2018-07-06 | 广东双林生物制药有限公司 | A kind of plasma adsorption filter device for the production of blood clotting factors blood product |
CN108441490A (en) * | 2018-04-02 | 2018-08-24 | 博雅生物制药集团股份有限公司 | A kind of technique that adsorption in turn method prepares Human Factor Ⅸ Complex |
CN109593747A (en) * | 2018-12-25 | 2019-04-09 | 山东泰邦生物制品有限公司 | A kind of method of Human Factor Ⅸ Complex's intermediate products liquid storage |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101974070A (en) * | 2010-11-08 | 2011-02-16 | 江西博雅生物制药股份有限公司 | Preparation process of human prothrombin compound |
CN102604920A (en) * | 2012-04-06 | 2012-07-25 | 湖南紫光古汉南岳制药有限公司 | Preparation method of human prothrombin complex |
CN102614219A (en) * | 2012-04-06 | 2012-08-01 | 湖南紫光古汉南岳制药有限公司 | Method for preparing human prothrombin complex with high yield |
CN104109202A (en) * | 2014-07-17 | 2014-10-22 | 山东泰邦生物制品有限公司 | Method for adsorbing human prothrombin complex from plasma |
CN104672328A (en) * | 2015-02-13 | 2015-06-03 | 山东泰邦生物制品有限公司 | Production method of human antithrombin III |
CN105039295A (en) * | 2015-09-15 | 2015-11-11 | 上海洲跃生物科技有限公司 | Method for preparing human thrombin from cold-removing glue plasma |
CN105175486A (en) * | 2015-10-20 | 2015-12-23 | 上海洲跃生物科技有限公司 | Preparation method of high-purity human coagulation factor IX |
-
2017
- 2017-03-01 CN CN201710118663.7A patent/CN106676089B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101974070A (en) * | 2010-11-08 | 2011-02-16 | 江西博雅生物制药股份有限公司 | Preparation process of human prothrombin compound |
CN102604920A (en) * | 2012-04-06 | 2012-07-25 | 湖南紫光古汉南岳制药有限公司 | Preparation method of human prothrombin complex |
CN102614219A (en) * | 2012-04-06 | 2012-08-01 | 湖南紫光古汉南岳制药有限公司 | Method for preparing human prothrombin complex with high yield |
CN104109202A (en) * | 2014-07-17 | 2014-10-22 | 山东泰邦生物制品有限公司 | Method for adsorbing human prothrombin complex from plasma |
CN104672328A (en) * | 2015-02-13 | 2015-06-03 | 山东泰邦生物制品有限公司 | Production method of human antithrombin III |
CN105039295A (en) * | 2015-09-15 | 2015-11-11 | 上海洲跃生物科技有限公司 | Method for preparing human thrombin from cold-removing glue plasma |
CN105175486A (en) * | 2015-10-20 | 2015-12-23 | 上海洲跃生物科技有限公司 | Preparation method of high-purity human coagulation factor IX |
Non-Patent Citations (2)
Title |
---|
A. V. ISERKAPOV 等: "Possible Production of Prothrombin Complex Concentrate by Anion-Exchange Column Chromatography", 《PHARMACEUTICAL CHEMISTRY JOURNAL》 * |
T. BURNOUF: "Chromatography in plasma fractionation: benefits and future trends", 《JOURNAL OF CHROMATOGRAPHY B 》 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108048433A (en) * | 2018-01-19 | 2018-05-18 | 贵州泰邦生物制品有限公司 | A kind of preparation method of Human Factor Ⅸ Complex |
CN108048433B (en) * | 2018-01-19 | 2020-07-21 | 贵州泰邦生物制品有限公司 | Preparation method of human prothrombin complex |
CN108245986A (en) * | 2018-03-24 | 2018-07-06 | 广东双林生物制药有限公司 | A kind of plasma adsorption filter device for the production of blood clotting factors blood product |
CN108245986B (en) * | 2018-03-24 | 2020-03-24 | 广东双林生物制药有限公司 | A plasma adsorption and filtration device for production of blood coagulation factor class blood products |
CN108441490A (en) * | 2018-04-02 | 2018-08-24 | 博雅生物制药集团股份有限公司 | A kind of technique that adsorption in turn method prepares Human Factor Ⅸ Complex |
CN109593747A (en) * | 2018-12-25 | 2019-04-09 | 山东泰邦生物制品有限公司 | A kind of method of Human Factor Ⅸ Complex's intermediate products liquid storage |
CN109593747B (en) * | 2018-12-25 | 2021-08-10 | 山东泰邦生物制品有限公司 | Method for liquid storage of human prothrombin complex intermediate product |
Also Published As
Publication number | Publication date |
---|---|
CN106676089B (en) | 2020-01-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104672328B (en) | A kind of production method of Human Antithrombin Ⅲ | |
CN106676089A (en) | Method for preparing human prothrombin complex from plasma | |
CN104109202B (en) | Method for adsorbing human prothrombin complex from plasma | |
CN101974070B (en) | Preparation process of human prothrombin compound | |
CN104328101B (en) | Preparation method of thrombin | |
CN107857811A (en) | A kind of preparation technology of human serum albumin | |
US5112949A (en) | Method of and apparatus for separating proteins | |
CN108048433B (en) | Preparation method of human prothrombin complex | |
CN104231073A (en) | Preparation method of human coagulation factor VIII | |
CN104402993A (en) | Method for preparing human immunoglobulin for intravenous injection | |
CN110257358B (en) | Production method of high-purity human coagulation factor IX preparation | |
CN110041425A (en) | A kind of high-purity sero-abluminous preparation method | |
CN109651502B (en) | Method for simultaneously separating and purifying blood coagulation factors IX, X and VII from human plasma | |
CN104558156A (en) | Method for extracting human serum albumin from plasma and increasing yield | |
CN106497903B (en) | A kind of technique for purifying blood coagulation proenzyme compound | |
CN106520882A (en) | Production method of extracting small-peptide ferroheme from animal blood | |
CN109705208A (en) | A kind of technique of single step chromatography preparation high-purity vWF ELISA | |
CN101439047B (en) | Technological process for improving stable FVII yield of human prothrombin complexes | |
CN108441490B (en) | Process for preparing human prothrombin complex by flow adsorption method | |
CN105821025B (en) | A kind of extracting method of fibrin ferment | |
CN107176999A (en) | A kind of preparation method of human serum albumin | |
CN111378029B (en) | Preparation method of human coagulation factor IX | |
SU513595A3 (en) | The method of selection orgoteina | |
CN104744585B (en) | A kind of Expanded Bed Adsorption(EBA)Technology prepares the process of fibrinogen | |
CN114605515B (en) | Separation and purification process of high-activity phytohemagglutinin |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |