CN106008698B - A method of human serum albumin pyrogen is removed using cold ethanol method - Google Patents
A method of human serum albumin pyrogen is removed using cold ethanol method Download PDFInfo
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Abstract
The invention discloses a kind of methods using cold ethanol method removal human serum albumin pyrogen.Pyrogen, which is meant, can cause the raised pyrogenic substance of homeothermal animal abnormal body temperature, and adverse reaction, threat to life can be caused up to 1 μ g/kg containing pyrogen amount by injecting in the injection of human body.The present invention it is original prepare human serum albumin before, step is added: by the exceeded human blood albumin products of pyrogen, with 0 DEG C of normal saline dilution to 30g/L, FIV is added by every 100Kg albumin and precipitates 20~50Kg, stirring and dissolving, after with pH4.0 acetate buffer solution adjust solution ph to 5.80 ± 0.05；Coolant system cooling solution is opened to 0 DEG C ± 0.05 DEG C, temperature is added and is lower than -15 DEG C of 95%(V/V) ethyl alcohol to final ethanol concentration is 40%(V/V), add ethyl alcohol speed≤70L/h, controlling solution ph is 6.40~6.50, cool down when adding ethyl alcohol, makes the control of solution final temperature at -5.0 DEG C ± 0.5 DEG C.The pyrogen in injection can be effectively removed by this step.
Description
Technical field
The present invention relates to a kind of methods using cold ethanol method removal human serum albumin pyrogen, belong to bio-pharmaceuticals neck
Domain.
Background technique
Pyrogen (pyrogen), which is meant, can cause the raised pyrogenic substance of homeothermal animal abnormal body temperature, usually lipopolysaccharide
The compound being combined into protein, and lipopolysaccharides is endotoxic main component, has very strong pyrogenic activity.Inject human body
Injection in containing pyrogen amount can cause adverse reaction up to 1 μ g/kg, exothermic reaction usually occurs after injection 1 hour, can
Human body generation is set to feel cold, shiver, generate heat, perspire, the symptoms such as Nausea and vomiting, body temperature can rise to 40 DEG C or more sometimes, and serious person is very
To stupor, collapse, such as rescue not in time, it can threat to life.The phenomenon is known as " pyrogen reaction ", so the pyrogen in pharmacopoeia of each country
Inspection is the project that injection must be examined.Although increasingly strengthening in current GMP management, pyrogen contamination is still blood product production
The big critical point of enterprise faced.Once blood product pollution, caused by loss be huge, therefore produced in blood product
Cheng Zhong strengthens the emphasis that apyrogeneity operation is always manufacturing enterprise's training, and generally speaking the channel of pyrogen contamination, following nothing more than
It is several: raw material blood plasma, reaction vessel, added reagent, manual operation and working environment.Openly report the method for removing depyrogenation
Active carbon adsorption, ion-exchange, ultrafiltration etc..But these methods more or less some deficiencies, such as active carbon suction
Attached method, the process of addition have the potential danger of pollution cleaning shop, and such as a large amount of additions will cause the damage that target protein is adsorbed
It loses.Ion-exchange is processed the limitation of batch.Researcher thus invents a kind of side that depyrogenation is removed using cold ethanol method
Method, this will be benefited extensively for the enterprise for using cold ethanol method production human serum albumin, without additionally adding equipment, and
Handle of large quantities, pyrogen removal effect is obvious, is a kind of practicable method.
Summary of the invention
Heat source in cold ethanol method removal human serum albumin is utilized technical problem to be solved by the invention is to provide a kind of
The method of matter solves active carbon adsorption, ion-exchange etc. and goes deficiency existing for depyrogenation method.
In order to solve the above-mentioned technical problem, following technique measures are used, it is a kind of white using cold ethanol method removal people's blood
The method of heat source matter, mainly includes the following steps: in albumen
1. by the exceeded human blood albumin products of pyrogen, with 0 DEG C of normal saline dilution to 30g/L, by every 100Kg albumin
FIV is added and precipitates 20~50Kg, stirring and dissolving, after with pH4.0 acetate buffer solution adjust solution ph to 5.80 ± 0.05；
Coolant system cooling solution is opened to 0 DEG C ± 0.05 DEG C, temperature is added and is lower than -15 DEG C of 95%(V/V) ethyl alcohol is finally dense to ethyl alcohol
Degree is 40%(V/V), add ethyl alcohol speed≤70L/h, control solution ph is 6.40~6.50, cools down when adding ethyl alcohol, makes molten
Liquid final temperature is controlled at -5.0 DEG C ± 0.5 DEG C；
2, diatomite is added into solution, additional amount is every 1000L solution 2~4Kg diatomite, uses pressure after stirring 30min
Filter filters pressing obtains filtrate, during filters pressing, operating pressure control within 0.2MPa, filtrate temperature control -4.5 DEG C ±
1.0 DEG C, every 30min checks the temperature and clarity of first-time filtrate, and it is intracavitary with cold compression air to blow filter press after filters pressing
Liquid, to bubble out after stop.It is pumped into -5.0 DEG C of ± 0.5 DEG C of FIV equilibrium liquids and rinses filter presses, every 150 ~ 200L of flushing, finally
The intracavitary product of filter press is blown with cold compression air, collects filtrate, is i.e. IV pressing filtering liquid of component, precipitating discards；
Diatomite using preceding through 180 DEG C of dry roasting 2.5h, be cooled to 0 DEG C or less it is spare；
The preparation of FIV equilibrium liquid: amount of preparation is every filter press 400L；Preparation method: the ethyl alcohol containing 40%(V/V), 3.5
The sodium chloride of~4.5g/L, the anhydrous sodium acetate of 2.5~3.5g/L, with glacial acetic acid adjustment pH value to 6.4~6.5, solution temperature
± 0.5 DEG C of -5.0 DEG C of temperature;
The preparation of filter press: every 100Kg albumin fills 25 filter plates, after installing filter plate, rinses filter press with water for injection
It is feminine gender to bacterial endotoxin；Diatomite is added into FIV equilibrium liquid with the amount of every filter press 5Kg, is pumped into after stirring
Filter press carry out circulating cooling, filter press outlet temperature arrive -3 DEG C or less when, stop circulation, cleaning pre-cooling compressed air by pressure
Filter drying is spare；
3. the preparation that component V precipitates
1. measuring IV pressing filtering liquid volume of component, stirring, cooling are opened, product cools to -6~-7 DEG C, is slowly added to 2mol/
L HAC, addition speed are 50ml/min, and adjustment pH value of solution to 5.20~5.50 cools down IV pressing filtering liquid of component after having adjusted pH
To -8~-9 DEG C, 2h is stirred, it is quiet to put 6~8h；
2. opening stirring, diatomite is added in IV pressing filtering liquid of Xiang Zufen, additional amount is every 1000L solution 2~4Kg diatom
Soil starts filters pressing after stirring 30min；Filtered fluid is abandoned or carries out ethyl alcohol recovery processing after collecting；After filters pressing, filters pressing is unclamped
Machine, scraping component V precipitate；
Diatomite using preceding through 180 DEG C of dry roasting 2.5h, be cooled to 0 DEG C or less it is spare；
The preparation method of FV equilibrium liquid is that amount of preparation is every filter press 400L；Preparation method: water for injection 230L adds
95% ethyl alcohol 170L, cools to -8~-9 DEG C；
Filter press is first installing filter plate using preceding, and every 100Kg albumin fills 25 filter plates, after installing filter plate, uses injection
It is feminine gender that water, which rinses filter press to bacterial endotoxin,；Diatomite is added into FV equilibrium liquid with the amount of every filter press 5Kg, stirs
After be pumped into filter press and carry out circulating cooling, when filter press outlet temperature arrives -5 DEG C or less, stop circulation, the clean pressure being pre-chilled
Contracting air dries up filter press spare；
4. component V polishing purification
1. component V precipitates 8% ethanol solution stirring and dissolving of 5 times of volumes, after precipitating is completely dissolved, adjust pH value to 4.50
~4.70, the control of product final temperature is -3.0 DEG C ± 0.5 DEG C, continues stirring 2 ~ 3h filters pressing；
2. filters pressing: stirring in pressure-filtering process and do not stop, after filters pressing is complete, liquid in filter is blown out with low temperature cold air, until outlet
Stop after bubble, after with FV purification equilibrium liquid rinse filter plate, flushing liquor is incorporated into filtered fluid；Carry out ultrafiltration step.
FV purification balance liquid making method is amount of preparation: every filter press 250L.Preparation method are as follows: contain ethyl alcohol 12%, it is molten
Liquid pH value 4.50~4. 70 are cooled to -3.0 DEG C ± 0.5 DEG C；
Filter press is first installed using preceding, and every 100Kg component V precipitating installation filter plate 15~20 uses injection after installing filter plate
Being rinsed with water to bacterial endotoxin is feminine gender；Filter press is recycled with FV purification equilibrium liquid using preceding, answers filter press outlet temperature
Reach -2 DEG C or less, it is spare；
5. ultrafiltration
1. opening stirring, filtrate pH value is adjusted to 7.0~7.2 with 1M sodium bicarbonate；
2. refined solution to be concentrated into 100~150g/L of protein concentration for the first time, first with the sodium chloride solution etc. of 5 times of 9g/L
Volume dialysis, then dialysed in equal volume with 3 times of water for injection；After dialysis, product is finally concentrated to protein content
210g/L or more；Ultrafiltration membrane is washed with appropriate water for injection, collects film washing liquid, being incorporated to is human serum albumin in above-mentioned protein liquid
Stoste, sampling, which is done, carries out stoste detection；
6. semi-finished product are prepared
Preparation is diluted according to stoste calibrating: being prepared according to stock protein matter content, by every gram of protein
160mmol weighs Sodium Caprylate, weighs sodium chloride by every gram of 120~130mmol of protein, water-soluble with a small amount of injection after weighing
Solution is added product, then product is diluted to 195~200g/L of protein concentration, adjusts pH value 6.8~7.0；
7, pasteurization: product is subjected to 60 DEG C of 10h inactivation of viruses, degerming dispenses after inactivation.
Human serum albumin stoste prepared by the present invention, by semi-finished product prepare and inactivation of virus after can dispense for people's blood it is white
Albumen finished product, as the stoste of production human serum albumin, quality meets claimed below:
1. purity: by 0541 the second method of electrophoresis in four general rules of " Chinese Pharmacopoeia " version in 2015-acetate film electricity
The detection of swimming method, purity should be not less than 96%；
2. protein content: by 0731 protein determination third in four general rules of " Chinese Pharmacopoeia " version in 2015
The bis- contracting method urea method detections of method-, should be greater than 210g/L；
3. pH value: test sample protein content is diluted to 10g/L with physiological sodium chloride solution, pH value should be 6.4~
7.4。
4. Residual ethanol: by 3201 Residual ethanol measuring method (Kang Wei in four general rules of " Chinese Pharmacopoeia " version in 2015
Diffusion boat method) measurement, 0.025% should be not higher than.
5. pyrogen test: after the precipitating dissolution of component V, by 1143 bacteriums in four general rules of " Chinese Pharmacopoeia " version in 2015
Toxin inspection technique carries out, and Bacterial endotoxin limit should be less than 1.67EU/ml.
Embodiment
Embodiment 1
1. by the underproof human blood albumin products of pyrogen, with 0 DEG C of normal saline dilution to 30g/L, by the white egg of every 100Kg
White addition FIV precipitates 50Kg, stirring and dissolving, after with pH4.0 acetate buffer solution adjust solution ph to 5.80 ± 0.05.It opens
Coolant system cooling product is opened to 0 DEG C ± 0.05 DEG C, it is 40%(V/ that -15 DEG C of 95% ethyl alcohol below to final ethanol concentration, which is added,
), V add ethyl alcohol speed 60L/h.Repetition measurement solution ph should be 6.4 ~ 6.5, otherwise should correct so far range.It is dropped when adding ethyl alcohol
Temperature makes the control of product final temperature at -5.0 DEG C ± 0.5 DEG C.
2 diatomite is added into product, and additional amount is every 1000L solution 2Kg diatomite, uses filter press after stirring 30min
Filters pressing.During filters pressing, operating pressure is controlled within 0.2MPa, and filtrate temperature is controlled at -4.5 DEG C ± 1.0 DEG C, often
The temperature and clarity of 30min inspection first-time filtrate.Filter press intracavity liquid is blown with cold compression air after filters pressing, to out
Stop after bubble.It is pumped into -5.0 DEG C of ± 0.5 DEG C of FIV equilibrium liquids and rinses filter press, every flushing 200L finally uses cold compression air
Blow the intracavitary product of filter press.Filtrate, i.e. IV pressing filtering liquid of component are collected, precipitating is abandoned.
The preparation of diatomite: using preceding through 180 DEG C of dry roasting 2.5h, be cooled to 0 DEG C or less it is spare.
The preparation of FIV equilibrium liquid: amount of preparation is every filter press 400L.Preparation method: the ethyl alcohol containing 40%(V/V), 3.5
The sodium chloride of~4.5g/L, the anhydrous sodium acetate of 2.5~3.5g/L, with glacial acetic acid adjustment pH value to 6.4~6.5, solution temperature
± 0.5 DEG C of -5.0 DEG C of temperature.
The preparation of filter press: every 100Kg albumin fills 25 filter plates, after installing filter plate, rinses filter press with water for injection
It is feminine gender to bacterial endotoxin.Diatomite is added into FIV equilibrium liquid with the amount of every filter press 5Kg, is pumped into after stirring
Filter press carry out circulating cooling, filter press outlet temperature arrive -3 DEG C or less when, stop circulation, cleaning pre-cooling compressed air by pressure
Filter drying is spare.
3. the preparation that component V precipitates
1. measuring IV pressing filtering liquid volume of component, stirring, cooling are opened, product cools to -6~-7 DEG C, is slowly added to 2mol/
L HAC, addition speed are 50ml/min, and adjustment pH value of solution has been adjusted and product is cooled to -8~-9 DEG C after pH to 5.2~5.5,
2h is stirred, it is quiet to put 6~8h；
2. opening stirring, diatomite is added into product, additional amount is every 1000L solution 2~4Kg diatomite, stirring
Start filters pressing after 30min.Filtered fluid is abandoned or carries out ethyl alcohol recovery processing after collecting；After filters pressing, filter press, scraping group are unclamped
Divide V precipitating.
The preparation of diatomite: using preceding through 180 DEG C of dry roasting 2.5h, be cooled to 0 DEG C or less it is spare.
The preparation of FV equilibrium liquid: amount of preparation is every filter press 400L.Preparation method: water for injection 230L adds 95% second
Alcohol 170L cools to -8~-9 DEG C.
The preparation of filter press: every 100Kg albumin fills 25 filter plates, after installing filter plate, rinses filter press with water for injection
It is feminine gender to bacterial endotoxin.Diatomite is added into FV equilibrium liquid with the amount of every filter press 5Kg, pressure is pumped into after stirring
Filter carries out circulating cooling, when filter press outlet temperature arrives -5 DEG C or less, stops circulation, and the clean compressed air being pre-chilled is by filters pressing
Machine drying is spare.
4. component V polishing purification
1. component V precipitates 8% ethanol solution stirring and dissolving of 5 times of volumes, after precipitating is completely dissolved, adjust pH value to 4.50
~4.70, the control of product final temperature is -3.0 DEG C ± 0.5 DEG C, continues stirring 2 ~ 3h filters pressing.
2. filters pressing: stirring in pressure-filtering process and do not stop, after filters pressing is complete, liquid in filter is blown out with low temperature cold air, until outlet
Stop after bubble, after with FV purification equilibrium liquid rinse filter plate, flushing liquor is incorporated into filtered fluid, carries out ultrafiltration step；
FV refines equilibrium liquid and prepares: amount of preparation: every filter press 250L.Preparation method are as follows: contain ethyl alcohol 12%, solution ph
4.50 ~ 4. 70, it is cooled to -3.0 DEG C ± 0.5 DEG C.
The preparation of filter press: every 100Kg component V precipitating installation filter plate 15~20 is rushed after installing filter plate with water for injection
Bacterial endotoxin is washed till as feminine gender.Filter press is recycled with FV purification equilibrium liquid using preceding, makes filter press outlet temperature that should reach -2
DEG C or less, it is spare.
5. ultrafiltration
1. opening stirring, filtrate pH value is adjusted to 7.0~7.2 with 1M sodium bicarbonate.
2. refined solution to be concentrated into 100~150g/L of protein concentration for the first time, first with the sodium chloride solution etc. of 5 times of 9g/L
Volume dialysis, then dialysed in equal volume with 3 times of water for injection.After dialysis, product is finally concentrated to protein content
210g/L or more.Ultrafiltration membrane is washed with appropriate water for injection, collects film washing liquid, being incorporated to is human serum albumin in above-mentioned protein liquid
Stoste, sampling, which is done, carries out stoste detection.
6. semi-finished product are prepared
Preparation is diluted according to stoste calibrating: being prepared according to stock protein matter content, by every gram of protein
160mmol weighs Sodium Caprylate, weighs sodium chloride by every gram of 120~130mmol of protein, water-soluble with a small amount of injection after weighing
Solution is added product, then product is diluted to 195~200g/L of protein concentration, adjusts pH value 6.8~7.0.
7, pasteurization: product is subjected to 60 DEG C of 10h inactivation of viruses, degerming dispenses after inactivation.
| Lot number | Remove prepyrogen | Pyrogen after removal | Product loss | Remarks |
| 01 | The sum of heating 1.8 | 0.6 | 2.7% | |
| 02 | The sum of heating 2.0 | 0.8 | 2.5% | |
| 03 | The sum of heating 1.5 | 0.4 | 2.0% |
The present invention uses cold ethanol method it can be seen from above situation, and manufacturer does not need to increase additional equipment,
By the way that fraction IV Precipitation is added, adjusts five variable elements, can be effectively reduced product pyrogen, and protein losses only 3% hereinafter,
The reason is that being precipitated again using fraction IV Precipitation, pyrogen can be made coprecipitated, achieve the purpose that depyrogenation.Meanwhile
Original albumin in component IV can achieve the purpose of recycling, this is obtained to be double at one stroke, both eliminates original by dissolving again
There is the pyrogen in product, while having recycled the albumin in fraction IV Precipitation.
Claims (1)
1. a kind of method using cold ethanol method removal human serum albumin pyrogen, mainly includes the following steps:
(1) diatomite is added into human blood albumin products, additional amount is every 1000L solution 2~4Kg diatomite, stirs 30min
Afterwards use filter press filters pressing, during filters pressing, operating pressure control within 0.2MPa, filtrate temperature control -4.5 DEG C ±
1.0 DEG C, every 30min checks the temperature and clarity of first-time filtrate, and it is intracavitary with cold compression air to blow filter press after filters pressing
Liquid, to bubble out after stop；It is pumped into -5.0 DEG C of ± 0.5 DEG C of FIV equilibrium liquids and rinses filter presses, every 150 ~ 200L of flushing, finally
The intracavitary product of filter press is blown with cold compression air, collects filtrate, i.e. IV pressing filtering liquid of component, precipitating is abandoned；
Diatomite using preceding through 180 DEG C of dry roasting 2.5h, be cooled to 0 DEG C or less it is spare；
The preparation method of FIV equilibrium liquid are as follows: amount of preparation is every filter press 400L；Preparation method: the ethyl alcohol containing 40%(V/V),
The sodium chloride of 3.5~4.5g/L, the anhydrous sodium acetate of 2.5~3.5g/L, with glacial acetic acid adjustment pH value to 6.4~6.5, solution temperature
- 5.0 DEG C ± 0.5 DEG C of degree；
Filter press is first installing filter plate using preceding, and every 100Kg albumin fills 25 filter plates, after installing filter plate, is rushed with water for injection
Washing filter press to bacterial endotoxin is feminine gender；Diatomite is added into FIV equilibrium liquid with the amount of every filter press 5Kg, after stirring
It is pumped into filter press and carries out circulating cooling, when filter press outlet temperature arrives -3 DEG C or less, stop circulation, the clean compression being pre-chilled
Air dries up filter press spare；
(2) preparation that component V precipitates
1. measuring IV pressing filtering liquid volume of component, stirring, cooling are opened, product cools to -6~-7 DEG C, is slowly added to 2mol/L
HAC, addition speed are 50ml/min, and adjustment pH value of solution has been adjusted and product is cooled to -8~-9 DEG C after pH, stirred to 5.2~5.5
2h is mixed, it is quiet to put 6~8h；
2. opening stirring, diatomite is added into product, additional amount is every 1000L solution 2~4Kg diatomite, after stirring 30min
Start filters pressing；Filtered fluid is abandoned or carries out ethyl alcohol recovery processing after collecting；After filters pressing, filter press is unclamped, scraping component V is heavy
It forms sediment；
Diatomite using preceding through 180 DEG C of dry roasting 2.5h, be cooled to 0 DEG C or less it is spare；
The preparation method of FV equilibrium liquid is that amount of preparation is every filter press 400L；Preparation method: water for injection 230L adds 95%
Ethyl alcohol 170L cools to -8~-9 DEG C；
Filter press is first installing filter plate using preceding, and every 100Kg albumin fills 25 filter plates, after installing filter plate, is rushed with water for injection
Washing filter press to bacterial endotoxin is feminine gender；Diatomite is added into FV equilibrium liquid with the amount of every filter press 5Kg, it will after stirring
It is pumped into filter press and carries out circulating cooling, when filter press outlet temperature arrives -5 DEG C or less, stops circulation, the clean compression sky being pre-chilled
Gas dries up filter press spare；
(3) component V polishing purification
1. component V precipitates 8% ethanol solution stirring and dissolving of 5 times of volumes, after precipitating is completely dissolved, tune pH value to 4.50~
4.70, the control of product final temperature is -3.0 DEG C ± 0.5 DEG C, continues stirring 2 ~ 3h filters pressing；
2. filters pressing: stirring in pressure-filtering process and do not stop, after filters pressing is complete, liquid in filter is blown out with low temperature cold air, until out after bubble
Stop, after with FV purification equilibrium liquid rinse filter plate, flushing liquor is incorporated into filtered fluid, carries out ultrafiltration step；
The preparation method that FV refines equilibrium liquid is amount of preparation: every filter press 250L；Preparation method are as follows: contain ethyl alcohol 12%, solution
PH value 4.50 ~ 4. 70 are cooled to -3.0 DEG C ± 0.5 DEG C；
Filter press is first installing filter plate before using, and every 100Kg component V precipitating installs filter plate 15~20, uses and infuse after installation filter plate
Penetrate be rinsed with water to bacterial endotoxin for feminine gender；Filter press is recycled with FV purification equilibrium liquid using preceding, makes filter press outlet temperature
It should reach -2 DEG C or less, it is spare；
(4) ultrafiltration
1. opening stirring, filtrate pH value is adjusted to 7.0~7.2 with 1M sodium bicarbonate；
2. refined solution to be concentrated into 100~150g/L of protein concentration for the first time, first the sodium chloride solution with 5 times of 9g/L is saturating in equal volume
Analysis, then dialysed in equal volume with 3 times of water for injection；After dialysis, by product be finally concentrated to protein content 210g/L with
On；Ultrafiltration membrane is washed with appropriate water for injection, collects film washing liquid, being incorporated in above-mentioned protein liquid is human serum albumin stoste, is taken
Sample, which is done, carries out stoste detection；
(5) semi-finished product are prepared
Preparation is diluted according to stoste calibrating: being prepared according to stock protein matter content, is claimed by every gram of protein 160mmol
Sodium Caprylate is taken, weighs sodium chloride by every gram of 120~130mmol of protein, with the dissolution of a small amount of water for injection after weighing, system is added
Product, then product is diluted to 195~200g/L of protein concentration, pH value is adjusted 6.8~7.0；
(6) pasteurization: product is subjected to 60 DEG C of 10h inactivation of viruses, degerming dispenses after inactivation；
It is characterized by: further including following step before step (1):
The exceeded human blood albumin products of pyrogen are added with 0 DEG C of normal saline dilution to 30g/L by every 100Kg albumin
FIV precipitates 20~50Kg, stirring and dissolving, after with pH4.0 acetate buffer solution adjust solution ph to 5.80 ± 0.05；It opens
Coolant system cools down solution to 0 DEG C ± 0.05 DEG C, and it is 40% that 95% ethyl alcohol of the temperature lower than -15 DEG C to final ethanol concentration, which is added,
Add ethyl alcohol speed≤70L/h, control solution ph is 6.40~6.50, cools down when adding ethyl alcohol, controls solution final temperature
At -5.0 DEG C ± 0.5 DEG C.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102161702A (en) * | 2011-01-28 | 2011-08-24 | 哈尔滨派斯菲科生物制药股份有限公司 | Method for producing human blood albumin |
| CN103333240A (en) * | 2013-07-22 | 2013-10-02 | 北海开元生物科技有限公司 | Method for reclaiming human albumin from component IV precipitate |
| CN104558156A (en) * | 2015-01-23 | 2015-04-29 | 郑州莱士血液制品有限公司 | Method for extracting human serum albumin from plasma and increasing yield |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102161702A (en) * | 2011-01-28 | 2011-08-24 | 哈尔滨派斯菲科生物制药股份有限公司 | Method for producing human blood albumin |
| CN103333240A (en) * | 2013-07-22 | 2013-10-02 | 北海开元生物科技有限公司 | Method for reclaiming human albumin from component IV precipitate |
| CN104558156A (en) * | 2015-01-23 | 2015-04-29 | 郑州莱士血液制品有限公司 | Method for extracting human serum albumin from plasma and increasing yield |
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