CN111589199B - Separation device and method for ultralow aluminum ion residual quantity of human serum albumin - Google Patents
Separation device and method for ultralow aluminum ion residual quantity of human serum albumin Download PDFInfo
- Publication number
- CN111589199B CN111589199B CN202010488671.2A CN202010488671A CN111589199B CN 111589199 B CN111589199 B CN 111589199B CN 202010488671 A CN202010488671 A CN 202010488671A CN 111589199 B CN111589199 B CN 111589199B
- Authority
- CN
- China
- Prior art keywords
- stainless steel
- steel tank
- filter
- filter aid
- liquid
- 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.)
- Active
Links
- 229910052782 aluminium Inorganic materials 0.000 title claims abstract description 47
- 102000008100 Human Serum Albumin Human genes 0.000 title claims abstract description 30
- 108091006905 Human Serum Albumin Proteins 0.000 title claims abstract description 30
- 238000000926 separation method Methods 0.000 title claims abstract description 19
- 238000000034 method Methods 0.000 title claims description 19
- 229910001220 stainless steel Inorganic materials 0.000 claims abstract description 76
- 239000010935 stainless steel Substances 0.000 claims abstract description 76
- 239000007788 liquid Substances 0.000 claims abstract description 59
- -1 aluminum ion Chemical class 0.000 claims abstract description 42
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 17
- 239000008215 water for injection Substances 0.000 claims description 13
- 238000004140 cleaning Methods 0.000 claims description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 239000011780 sodium chloride Substances 0.000 claims description 9
- 238000007664 blowing Methods 0.000 claims description 8
- 239000010451 perlite Substances 0.000 claims description 7
- 235000019362 perlite Nutrition 0.000 claims description 7
- 239000001509 sodium citrate Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 7
- 229940038773 trisodium citrate Drugs 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 230000006835 compression Effects 0.000 claims description 4
- 238000007906 compression Methods 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 238000005086 pumping Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims 1
- 239000010836 blood and blood product Substances 0.000 abstract description 2
- 229940125691 blood product Drugs 0.000 abstract description 2
- 238000003860 storage Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 229910021645 metal ion Inorganic materials 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- LOHGGLZYTJNUAL-UHFFFAOYSA-M sodium;ethanol;chloride Chemical compound [Na+].[Cl-].CCO LOHGGLZYTJNUAL-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D25/00—Filters formed by clamping together several filtering elements or parts of such elements
- B01D25/12—Filter presses, i.e. of the plate or plate and frame type
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
- B01F27/05—Stirrers
- B01F27/11—Stirrers characterised by the configuration of the stirrers
- B01F27/112—Stirrers characterised by the configuration of the stirrers with arms, paddles, vanes or blades
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/80—Mixing plants; Combinations of mixers
- B01F33/81—Combinations of similar mixers, e.g. with rotary stirring devices in two or more receptacles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention discloses a separation device and a separation method for ultralow aluminum ion residual quantity of human serum albumin, and relates to the technical field of blood product production, wherein the device comprises a first stainless steel tank, a second stainless steel tank and a filter press; the top of the first stainless steel tank and the top of the second stainless steel tank are respectively provided with a liquid inlet, and the bottom of the first stainless steel tank and the bottom of the second stainless steel tank are respectively provided with a liquid outlet; the liquid outlets of the first stainless steel tank and the second stainless steel tank are connected with the liquid inlet of the filter press; the filter press is internally provided with a filter plate, the bottom of the filter press is provided with a liquid outlet, two sides of the top of the filter press are respectively provided with an air inlet and an air outlet, and the air inlet is connected with an air inlet pipeline for introducing compressed air. The invention reduces the initial content of aluminum ions in human serum albumin by reducing the content of aluminum ions in the filter aid.
Description
Technical Field
The invention relates to the technical field of blood product production, in particular to a separation device and a separation method for ultralow aluminum ion residual quantity of human serum albumin.
Background
In order to ensure the quality of medicines and ensure the safety and effectiveness of the medicines used by people, the quality standard of the medicines is continuously improved. Human serum albumin is a special clinical emergency biological product, and is a major concern for drug regulatory authorities. Because the filter plates, perlite and diatomite used in the production process of the human serum albumin contain a large amount of metal ion aluminum ions and other impurities, the high content of the human serum albumin aluminum ions becomes a high concern in the industry.
The hazard of aluminum ions includes the following points:
effects on bone metabolism: aluminum ions cause abnormal metabolism of minerals in bones, and various symptoms such as bone pain in load areas, reduced bone formation, osteomalacia, hypercalcemia, and serum thyroxine concentration lower than normal;
effects on liver metabolism: can lead to cholestatic liver disease, resulting in elevated serum-bound bilirubin levels, elevated transglutaminase and bile acid concentrations, increased bile duct transferrin excretion, and reduced concentrations of cytochrome P450. Children for long-term parenteral treatment may accumulate aluminum ions in the liver;
effects on the central nervous system: can cause senile dementia and dialytic encephalopathy caused by nerve fiber injury.
The aluminum ion content in human serum albumin also changes with the change of storage time and temperature, so that the control of the aluminum ion content in the production process control should be more in need of fine control.
For the control of aluminum ions in the existing human serum albumin, enterprises generally adopt saline water with different concentrations to increase ultrafiltration multiple to reduce the content of the aluminum ions, the method has a certain effect on reducing the content of the aluminum ions, when the aluminum ions and the albumin are firmly combined and reach an equilibrium point, the aluminum ions cannot be controlled at an ideal level after the ultrafiltration multiple is increased, meanwhile, the use amount of sodium chloride is increased, the material cost is increased, the process control time is prolonged, the microbial load is increased, and the quality control of products is not facilitated.
The human serum albumin of most of domestic manufacturers is stored in a cold storage at the temperature of 2-8 ℃ and is influenced by temperature, and in the storage process of the product, the glass bottle releases aluminum ions into the product, so that the content of the aluminum ions is relatively slowly increased. The human serum albumin of our company adopts a normal temperature (10-30 ℃) storage mode, is convenient to transport and store, and simultaneously, the release of aluminum ions in a glass bottle can be correspondingly accelerated under the influence of the storage temperature, so that the storage validity period of the product is shortened.
Therefore, there is a need to provide a new separation device and method for ultra-low aluminum ion residual amount of human serum albumin to solve the above problems in the prior art.
Disclosure of Invention
The invention aims to provide a separation device and a separation method for ultralow aluminum ion residual quantity of human serum albumin so as to reduce the initial aluminum ion content in the human serum albumin.
In order to achieve the above object, the present invention provides the following solutions: the invention provides a separation device for ultralow aluminum ion residual quantity of human serum albumin, which comprises a first stainless steel tank, a second stainless steel tank and a filter press; the top of the first stainless steel tank and the top of the second stainless steel tank are respectively provided with a liquid inlet, and the bottom of the first stainless steel tank and the bottom of the second stainless steel tank are respectively provided with a liquid outlet; the liquid outlets of the first stainless steel tank and the second stainless steel tank are connected with the liquid inlet of the filter press; the filter press is internally provided with a filter plate, the bottom of the filter press is provided with a liquid outlet, two sides of the top of the filter press are respectively provided with an air inlet and an air outlet, and the air inlet is connected with an air inlet pipeline for introducing compressed air.
Preferably, the first stainless steel tank and the second stainless steel tank are both internally provided with stirrers.
Preferably, the liquid outlets of the first stainless steel tank and the second stainless steel tank are connected with the liquid inlet of the filter press through a liquid pipeline, and a pneumatic pump is arranged on the liquid pipeline.
Preferably, cooling channels are arranged on the tank walls of the first stainless steel tank and the second stainless steel tank and used for introducing glycol for cooling.
Preferably, a plate heat exchanger is arranged on the air inlet pipeline.
Preferably, the filter press is also connected with a hydraulic pump for controlling the compression and release of the filter plates.
The invention also discloses a separation method of the ultralow aluminum ion residue of the human serum albumin, which comprises the following steps:
the first step: cleaning the first stainless steel tank, the second stainless steel tank, the pneumatic pump, the pipeline and the filter press by using water for injection until pH test paper is neutral;
and a second step of: assembling a filter press, installing a filter plate, taking a filter aid in a preset proportion, and connecting injection water with the total amount of the filter aid being 8-10 times in a second stainless steel tank, and simultaneously adding trisodium citrate with the total amount of the filter aid being 2% for dissolution;
and a third step of: adding a filter aid into a second stainless steel tank, stirring to enable the filter aid and the prepared trisodium citrate to be completely dissolved, and simultaneously adding water for injection, wherein the total amount of the filter aid is one time of that of the filter aid;
fourth step: preparing cleaning liquid by using a first stainless steel tank: adding sodium chloride solid into 20% ethanol solution with the total amount of filter aid being 3-5 times, so that the sodium chloride content in the solution is 0.7%, and uniformly stirring;
fifth step: pumping the filter aid suspension into a filter press by a pneumatic pump, and blowing compressed air for 15 minutes after filtering is finished, so that liquid in the filter press is blown out and most of the liquid is dried;
sixth step: cleaning a filter aid by using water for injection, and then blowing air by using compressed air for 15 minutes;
seventh step: replacing the injection water in the filter aid by the cleaning liquid prepared in the fourth step, and blowing by compressed air for more than 30 minutes until more than 90% of the water in the filter aid is dried by the compressed air;
eighth step: taking out the filter aid in the filter press to obtain a filter aid for removing a large amount of aluminum ions;
ninth step: adding a filter aid: in each production process, filter aid is added according to a certain proportion, so that the initial content of aluminum ions in human serum albumin can be reduced.
Preferably, the filter aid is diatomaceous earth or perlite.
Compared with the prior art, the invention has the following technical effects:
according to the invention, sodium ions and filter aid are mixed according to a certain concentration ratio, and the purpose of separating aluminum ions from metal ions by a process of replacing metal ions is achieved; thereby reducing the initial content of aluminum ions in human serum albumin, and reducing the content of aluminum ions in the product to the domestic leading level.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of the structure of a separation device for ultra-low aluminum ion residual quantity of human serum albumin;
wherein, 1 is the plate heat exchanger, 2 is first stainless steel tank, 3 is the stainless steel tank of second, 4 is the pneumatic pump, 5 is the pressure filter, 6 is the gas vent, 7 is the filter plate, 8 is the hydraulic pump, 9 is the liquid outlet.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In order that the above-recited objects, features and advantages of the present invention will become more readily apparent, a more particular description of the invention will be rendered by reference to the appended drawings and appended detailed description.
As shown in fig. 1, the embodiment provides a separation device for ultra-low aluminum ion residual quantity of human serum albumin, which comprises a first stainless steel tank 2, a second stainless steel tank 3 and a filter press 5; the top of the first stainless steel tank 2 and the top of the second stainless steel tank 3 are respectively provided with a liquid inlet, and the bottom of the first stainless steel tank and the bottom of the second stainless steel tank are respectively provided with a liquid outlet; the first stainless steel tank 2 is used for preparing a solvent to be used, and the second stainless steel tank 3 is used for dissolving a filter aid (diatomite or perlite); the liquid outlets of the first stainless steel tank 2 and the second stainless steel tank 3 are connected with the liquid inlet of the filter press 5; the filter press 5 is internally provided with a filter plate 7 for realizing solid-liquid separation of dissolved liquid, the bottom of the filter press 5 is provided with a liquid outlet 9, two sides of the top of the filter press 5 are respectively provided with an air inlet and an air outlet 6, and the air inlet is connected with an air inlet pipeline for introducing compressed air.
Preferably, the first stainless steel tank 2 and the second stainless steel tank 3 are both provided with stirrers, in this embodiment, the stirrers preferably use paddle stirrers, or other stirrers meeting the working requirements, and the stirrer is provided to stir the liquids in the first stainless steel tank 2 and the second stainless steel tank 3, so that the liquids are uniformly mixed or completely dissolved.
Preferably, the liquid outlets of the first stainless steel tank 2 and the second stainless steel tank 3 are connected with the liquid inlet of the filter press 5 through a liquid pipeline, and a pneumatic pump 4 is installed on the liquid pipeline to provide power for conveying liquid.
Preferably, cooling channels are arranged on the tank walls of the first stainless steel tank 2 and the second stainless steel tank 3 and used for introducing ethylene glycol at the temperature of minus 30 ℃ so as to cool liquid in the tank body.
In this embodiment, the liquid inlets of the first stainless steel tank 2 and the second stainless steel tank 3 are connected with liquid inlet pipes, each liquid inlet pipe comprises a main liquid inlet pipe and two liquid inlet branch pipes, the two liquid inlet branch pipes are connected with the stainless steel tank, and the two liquid inlet branch pipes are used for preparing reagents and are used for entering water for injection and other liquids.
Preferably, the plate heat exchanger 1 is arranged on the air inlet pipe, so that compressed air can be cooled, the plate heat exchanger 1 is an existing device in the field, and in the embodiment, the plate heat exchanger 1 also cools the compressed air through an ethylene glycol solution at the temperature of minus 30 ℃.
In this embodiment, the liquid in the first stainless steel tank 2 and the second stainless steel tank 3 and the compressed gas introduced into the first stainless steel tank are cooled, so that a lower temperature can be maintained, and the growth of aluminum ions can be reduced.
Preferably, the filter press 5 is further connected with a hydraulic pump 8, the hydraulic pump 8 adopts compression control as power, and is used for controlling the filter plate 7 to compress and loosen, the compression is used for fastening the filter plate 7 during filtering, and the loosening is used for installing the filter plate 7 and collecting the sediment after diatomite cleaning.
The invention also discloses a separation method of the ultralow aluminum ion residue of the human serum albumin, which comprises the following steps:
the first step: cleaning the first stainless steel tank, the second stainless steel tank, the pneumatic pump, the pipeline, the material barrel and the filter press by using water for injection until pH test paper is neutral;
and a second step of: assembling a filter press, installing a filter plate, taking diatomite in a certain proportion, and adding water for injection, the total amount of which is 8-10 times of that of the filter aid, into a second stainless steel tank, and simultaneously adding trisodium citrate, the total amount of which is 2% of that of the filter aid, for dissolution.
And a third step of: adding diatomite (or perlite) filter aid, stirring for more than 15 minutes, so that the diatomite and trisodium citrate prepared with a certain concentration are completely dissolved, and simultaneously adding water for injection, wherein the total amount of the water for injection is doubled;
fourth step: preparing cleaning liquid by using a first stainless steel tank: adding sodium chloride solid into 20% ethanol solution with 3-5 times of the total amount of filter aid to make the sodium chloride content in the solution be 0.7%, and uniformly stirring.
Fifth step: pumping the filter aid suspension into a filter press by a pneumatic pump by adopting a filtering method, and blowing compressed air for 15 minutes after the filtering is finished, so that liquid in the filter press is blown out and most of the liquid is dried;
sixth step: cleaning the filter aid by using water for injection with the weight 3-5 times of the precipitation weight, and blowing for 15 minutes;
seventh step: replacing water for injection in the filter aid by using an ethanol-sodium chloride solution with the concentration of 20% which is 3-5 times of the total amount of the filter aid prepared in the fourth step, and drying for more than 30 minutes until more than 90% of water in the filter aid is dried by compressed air;
eighth step: taking out the filter aid in the filter press to obtain diatomite (or perlite) for removing a large amount of aluminum ions;
ninth step: adding a filter aid: in each production process, a filter aid is added according to a certain proportion, so that the initial content of aluminum ions in human serum albumin can be reduced, and the content of aluminum ions in the product is reduced to the domestic leading level.
According to the invention, sodium ions in trisodium citrate and sodium chloride are mixed with diatomite, a filter plate or perlite according to a certain concentration ratio, and the purpose of separating aluminum ions from metal ions by a process of replacing the metal ions is achieved.
The principles and embodiments of the present invention have been described in detail with reference to specific examples, which are provided to facilitate understanding of the method and core ideas of the present invention; also, it is within the scope of the present invention to be modified by those of ordinary skill in the art in light of the present teachings. In view of the foregoing, this description should not be construed as limiting the invention.
Claims (5)
1. The separation method of the ultralow aluminum ion residue of the human serum albumin comprises the steps of adopting a separation device of the ultralow aluminum ion residue of the human serum albumin, wherein the separation device comprises a first stainless steel tank, a second stainless steel tank and a filter press; the top of the first stainless steel tank and the top of the second stainless steel tank are respectively provided with a liquid inlet, the bottom of the first stainless steel tank and the bottom of the second stainless steel tank are respectively provided with a liquid outlet, and the liquid outlets of the first stainless steel tank and the second stainless steel tank are connected with the liquid inlet of the filter press; the filter press is internally provided with a filter plate, the bottom of the filter press is provided with a liquid outlet, two sides of the top of the filter press are respectively provided with an air inlet and an air outlet, and the air inlet is connected with an air inlet pipeline for introducing compressed air;
cooling channels are arranged on the tank walls of the first stainless steel tank and the second stainless steel tank and used for introducing glycol for cooling, and a plate heat exchanger is arranged on the air inlet pipeline;
the method is characterized in that: the method comprises the following steps:
the first step: cleaning the first stainless steel tank, the second stainless steel tank, the pneumatic pump, the pipeline and the filter press by using water for injection until pH test paper is neutral;
and a second step of: assembling a filter press, installing a filter plate, taking a filter aid in a preset proportion, and connecting injection water with the total amount of the filter aid being 8-10 times in a second stainless steel tank, and simultaneously adding trisodium citrate with the total amount of the filter aid being 2% for dissolution;
and a third step of: adding a filter aid into a second stainless steel tank, stirring to enable the filter aid and the prepared trisodium citrate to be completely dissolved, and simultaneously adding water for injection, wherein the total amount of the filter aid is one time of that of the filter aid;
fourth step: preparing cleaning liquid by using a first stainless steel tank: adding sodium chloride solid into 20% ethanol solution with the total amount of filter aid being 3-5 times, so that the sodium chloride content in the solution is 0.7%, and uniformly stirring;
fifth step: pumping the filter aid suspension into a filter press by a pneumatic pump, and blowing compressed air for 15 minutes after filtering is finished, so that liquid in the filter press is blown out and most of the liquid is dried;
sixth step: cleaning a filter aid by using water for injection, and then blowing air by using compressed air for 15 minutes;
seventh step: replacing the injection water in the filter aid by the cleaning liquid prepared in the fourth step, and blowing by compressed air for more than 30 minutes until more than 90% of the water in the filter aid is dried by the compressed air;
eighth step: taking out the filter aid in the filter press to obtain a filter aid for removing a large amount of aluminum ions;
ninth step: adding a filter aid: in each production process, filter aid is added according to a certain proportion, so that the initial content of aluminum ions in the preparation and separation of human serum albumin can be reduced.
2. The method for separating ultralow aluminum ion residual amount of human serum albumin according to claim 1, wherein the method comprises the steps of: the filter aid is diatomite or perlite.
3. The method for separating ultralow aluminum ion residual amount of human serum albumin according to claim 1, wherein the method comprises the steps of: and stirrers are arranged in the first stainless steel tank and the second stainless steel tank.
4. The method for separating ultralow aluminum ion residual amount of human serum albumin according to claim 1, wherein the method comprises the steps of: the liquid outlets of the first stainless steel tank and the second stainless steel tank are connected with the liquid inlet of the filter press through liquid pipelines, and pneumatic pumps are arranged on the liquid pipelines.
5. The method for separating ultralow aluminum ion residual amount of human serum albumin according to claim 1, wherein the method comprises the steps of: the filter press is also connected with a hydraulic pump for controlling the compression and release of the filter plates.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010488671.2A CN111589199B (en) | 2020-06-02 | 2020-06-02 | Separation device and method for ultralow aluminum ion residual quantity of human serum albumin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010488671.2A CN111589199B (en) | 2020-06-02 | 2020-06-02 | Separation device and method for ultralow aluminum ion residual quantity of human serum albumin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111589199A CN111589199A (en) | 2020-08-28 |
| CN111589199B true CN111589199B (en) | 2023-10-27 |
Family
ID=72179471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010488671.2A Active CN111589199B (en) | 2020-06-02 | 2020-06-02 | Separation device and method for ultralow aluminum ion residual quantity of human serum albumin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111589199B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113694795B (en) * | 2021-09-27 | 2023-07-25 | 成都倍特药业股份有限公司 | Liquid preparation system and preparation method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101260145A (en) * | 2008-04-11 | 2008-09-10 | 北京未名福源基因药物研究中心有限公司 | Technique for separating and purifying recombination human serum albumin and fusion protein thereof |
| CN101851604A (en) * | 2010-04-20 | 2010-10-06 | 上海新都生物科技有限公司 | Method for producing human 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 |
| CN105754012A (en) * | 2016-03-21 | 2016-07-13 | 青岛海之林生物科技开发有限公司 | Preparation process of aluminum magnesium alginate |
| CN212631879U (en) * | 2020-06-02 | 2021-03-02 | 国药集团贵州血液制品有限公司 | Separating device for ultralow residual aluminum ions of human serum albumin |
-
2020
- 2020-06-02 CN CN202010488671.2A patent/CN111589199B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101260145A (en) * | 2008-04-11 | 2008-09-10 | 北京未名福源基因药物研究中心有限公司 | Technique for separating and purifying recombination human serum albumin and fusion protein thereof |
| CN101851604A (en) * | 2010-04-20 | 2010-10-06 | 上海新都生物科技有限公司 | Method for producing human 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 |
| CN105754012A (en) * | 2016-03-21 | 2016-07-13 | 青岛海之林生物科技开发有限公司 | Preparation process of aluminum magnesium alginate |
| CN212631879U (en) * | 2020-06-02 | 2021-03-02 | 国药集团贵州血液制品有限公司 | Separating device for ultralow residual aluminum ions of human serum albumin |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111589199A (en) | 2020-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6478966B2 (en) | System for extracting tetrodotoxin | |
| CN111589199B (en) | Separation device and method for ultralow aluminum ion residual quantity of human serum albumin | |
| CN212631879U (en) | Separating device for ultralow residual aluminum ions of human serum albumin | |
| KR20190028633A (en) | Nano-class collagen refining method with 96% absorption rate | |
| CN104004084B (en) | A kind of production method of human albumin | |
| CN114349842B (en) | Concentration and separation method of beta-lactoglobulin | |
| CN106676089A (en) | Method for preparing human prothrombin complex from plasma | |
| CN213357617U (en) | Processing system for automatically removing impurities and decoloring sugar liquor | |
| CN209791302U (en) | Gelatin concentration ultrafiltration equipment | |
| CN111165833B (en) | Fruit and vegetable juice beverage production system and method thereof | |
| CN209001070U (en) | A kind of device of lead-acid accumulator electrolyte cycling and reutilization | |
| CN207641300U (en) | A kind of classified concentration device of heparin sodium eluent | |
| CN210419589U (en) | Novel acid wastewater recovery equipment for semiconductor factory | |
| CN113061199A (en) | Process for concentrating and extracting crude heparin sodium by using nanofiltration membrane | |
| CN112574329A (en) | Method for preparing crude heparin sodium by using sow intestines through biological enzyme method | |
| CN110016525A (en) | A kind of functional food sugar grass syrup and preparation method thereof | |
| CN106635700B (en) | Method and system for reducing alcohol content and removing turbidity of white spirit | |
| CN210631794U (en) | Liquid filtering device for gelatin production | |
| CN201692711U (en) | Dialysis concentrate refining filter | |
| CN220939130U (en) | Concentrated spent acid joins in marriage sour device | |
| CN220788618U (en) | D-chiro-inositol's apparatus for producing | |
| CN108863763A (en) | A kind of preparation method and process units preventing citric acid condensation | |
| CN114940484B (en) | Preparation process of phosphorous acid cascade falling film evaporation | |
| CN220976666U (en) | Glycol chilled water purifying treatment equipment | |
| CN109110987A (en) | One kind being used for high concentrated organic wastewater dephosphorization denitrogenation processing system |
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 | ||
| CP03 | Change of name, title or address |
Address after: 556000 Chunhui West Avenue, Kaili Economic Development Zone, Miao and Dong Autonomous Prefecture, Southeast Guizhou Province Patentee after: China National Pharmaceutical Group Guizhou Biopharmaceutical Co.,Ltd. Country or region after: China Address before: 556000 No.16 Chunhui West Avenue, Kaili Economic Development Zone, Qiandongnan Miao and Dong Autonomous Prefecture, Guizhou Province Patentee before: SINOPHARM GUIZHOU BLOOD PRODUCTS Co.,Ltd. Country or region before: China |