CN103550780A - Protein protective agent for Pasteur inactivating human intravenous immunoglobulin and inactivation method of protein protective agent - Google Patents
Protein protective agent for Pasteur inactivating human intravenous immunoglobulin and inactivation method of protein protective agent Download PDFInfo
- Publication number
- CN103550780A CN103550780A CN201310525253.6A CN201310525253A CN103550780A CN 103550780 A CN103550780 A CN 103550780A CN 201310525253 A CN201310525253 A CN 201310525253A CN 103550780 A CN103550780 A CN 103550780A
- Authority
- CN
- China
- Prior art keywords
- protein
- protective agent
- human normal
- normal immunoglobulin
- sorbitol
- 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
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention provides a protein protective agent for Pasteur inactivating human intravenous immunoglobulin and an inactivation method of the protein protective agent. A Pasteur inactivation method of human intravenous immunoglobulin comprises the following steps of adding the protein protective agent to a human intravenous immunoglobulin solution before inactivating; adjusting the content of sampled protein to be 40 to 60g/L, and adjusting pH (Potential of Hydrogen) to be 4.7 to 5.3; agitating for 30 minutes; transferring into a water bath under 60+/- 1 DEG C; maintaining the solution at temperature of 60+/ -0.5 DEG C for 10 hours after the solution temperature reaches 60 DEG C, thus accomplishing the inactivation of human intravenous immunoglobulin, wherein the protein protective agent is saccharose, arginine, glycine and sorbitol which are respective 50 to 70g/L, 20 to 40g/L, 30 to 60g/L and 240 to 260g/L in final content. According to the protein protective agent, simple sorbitol is used as the protective agent, the content of a polymer is decreased from 4.12% to 1.96%, thus the protein can be protected well, and the product quality can be improved.
Description
Technical field
The invention provides protein protectant and ablation method thereof, the quiet notes of especially a kind of pasteurization human normal immunoglobulin's protein protectant and ablation method thereof.
Background technology
Human normal immunoglobulin is one group of protein with antibody activity, after infusion, can improve rapidly the IgG level in receptor's blood, the anti-infection ability of enhancing body and immunoloregulation function.Because the quiet raw material of noting human normal immunoglobulin is human normal plasma, although Plasma donors is adopted various detectable to screen blood plasma and within 2007, comes into effect system 90 day quanrantine, make patient greatly away from the risk of virus attack, but still be subject to the potential threat of the susceptiveness of plasma screening reagent and the restriction of technology and unknown virus.Therefore blood products in process of production on the one hand, be by strict screening Plasma donors to reduce or to get rid of the virus that may exist in raw blood plasma; In preparation process, introduce on the other hand effective virus inactivation technology, this also fundamentally eliminate blood products may cause viral infection effective assurance.National Drug Administration issued a < < blood products removal/inactivation of viruses technical method and tests positive guideline > > in 2002 for this reason, in principle, enumerated conventional virus inactivating method and indicator virus, wherein pasteurization method is exactly a kind of conventional effective method in blood products production process.It shows in human albumin's application clinical practice decades result, and this method is safe to HIV and hepatitis virus.It is also the selection of numerous enterprises for quiet notes human normal immunoglobulin, but goods are after heating, all can occur the situation that polymer increases, and screening one or more protective agents becomes the required homework of numerous blood products enterprise.
Summary of the invention
The protein protectant and the ablation method thereof that the invention provides the quiet notes of a kind of pasteurization human normal immunoglobulin, solved in existing human albumin's inactivation process, and goods, after heating, occur the problem that polymer increases.
For solving the problems of the technologies described above, the technical solution used in the present invention is:
The quiet notes of pasteurization human normal immunoglobulin's a protein protectant, comprises sucrose, arginine, glycine and sorbitol, and its final content is respectively: 50g/L～70g/L, 20g/L～40g/L, 30g/L～60g/L and 240g/L～260g/L.
Further, a preferred embodiment of the present invention: described sucrose, arginine, glycine, final 60g/L, the 30g/L of sorbitol, 40g/L, 250g/L.
Protein protectant of the present invention can be widely used in the deactivation of blood products.
A pasteurization method of noting human normal immunoglobulin, comprises the following steps:
First the quiet notes human normal immunoglobulin solution before deactivation is added to protein protectant; then adjust sample protein matter content 40g/L～60g/L; pH value 4.7～5.3; stir after 30 minutes; put into 60 ℃ ± 1 ℃ water-bath; treat solution temperature to 60 ℃ timing; keep 60 ℃ ± 0.5 ℃ of solution temperature 10 hours; complete quiet notes human normal immunoglobulin's deactivation; described protein protectant comprises sucrose, arginine, glycine and sorbitol, and its final content is respectively: 50g/L～70g/L, 20g/L～40g/L, 30g/L～60g/L and 240g/L～260g/L.
Further, a preferred embodiment of the present invention: described sucrose, arginine, glycine, final 60g/L, the 30g/L of sorbitol, 40g/L, 250g/L.
The protectant selection research of different proteins:
First the quiet notes human normal immunoglobulin solution before deactivation is added to protein protectant; then adjust sample protein matter content 40g/L～60g/L; pH value 4.7～5.3; stir after 30 minutes; put into 60 ℃ ± 1 ℃ water-bath; treat products temperature to 60 ℃ timing, keep 60 ℃ ± 0.5 ℃ of products temperature 10 hours.Before and after measuring heating after rear taking-up, polymer changes, and compares.Assay method is measured according to three appendix VI R of < < Chinese Pharmacopoeia > > version in 2010 " human normal immunoglobulin's based article IgG monomer adds dimer algoscopy ".
1, take sorbitol as basic combination comparison, the results are shown in following table 1.
The result of table 1 various combination
Note: polymer 1.86% before heating, lower same.
By above experiment, can reach a conclusion: using sorbitol, glycine, sucrose, arginine as protein protectant, better than combined effect wherein.
2, the screening of arginine concentration
The concentration of sorbitol, glycine, sucrose is decided to be respectively to 15% (g/ml), 5% (g/ml), 5% (g/ml), arginine concentration is respectively by 1% (g/ml), 3% (g/ml), 5% (g/ml), 7% (g/ml), 10% (g/ml), and concrete outcome is in Table 2.
The selection result of table 2 arginine concentration
By this experiment, arginine is from 3%(g/ml) more than, its polymer changes little.We think arginine concentration location 3%(g/ml) comparatively suitable.
3, the screening of glycine concentration
Sorbitol, sucrose, arginic concentration are decided to be respectively to 15%(g/ml), 5%(g/ml), 3%(g/ml), glycine concentration is respectively by 2%(g/ml), 4%(g/ml), 6%(g/ml), 8%(g/ml), 10%(g/ml), concrete outcome is in Table 3.
The result of the screening of table 3 glycine concentration
As can be seen from the above table, glycine concentration location 4%(g/ml) better.
4, the screening of sucrose concentration
The concentration of sorbitol, arginine, glycine is decided to be respectively to 15%(g/ml), 3%(g/ml), 4%(g/ml), sucrose concentration is respectively by 2%(g/ml), 4%(g/ml), 6%(g/ml), 8%(g/ml), 10%(g/ml), concrete outcome is in Table 4.
The result of the screening of table 4 sucrose concentration
As can be seen from the above table, sucrose concentration location 6%(g/ml) better.
5, the screening of sorbitol concentration
The concentration of sucrose, arginine, glycine is decided to be respectively to 6%(g/ml), 3%(g/ml), 4%(g/ml), sorbitol concentration is respectively by 10%(g/ml), 15%(g/ml), 20%(g/ml), 25%(g/ml), 30%(g/ml), concrete outcome is in Table 5.
The selection result of table 5 sorbitol concentration
As can be seen from the above table, sorbitol concentration location 25%(g/ml) better.
In experiment, measure in addition other quiet notes human normal immunoglobulin's index with consistent as the result of protein protectant according to sorbitol, show to adopt protein protectant of the present invention on the not impact of other physical and chemical indexs of quiet notes human normal immunoglobulin.
Beneficial effect of the present invention:
Protein protectant of the present invention, can guarantee goods effectively, polymerization seldom after heating; with simple sorbitol as protective agent; polymeric content is 4.12% to have dropped to 1.96%, has well protected the protein in blood products, has improved product quality.
The specific embodiment
Below in conjunction with this specific embodiment, technical scheme of the present invention is clearly and completely described, obviously, described embodiment is only the present invention's part embodiment, rather than whole embodiment.Embodiment based in the present invention, those of ordinary skills, not making the every other embodiment obtaining under creative work prerequisite, belong to the scope of protection of the invention.
Embodiment 1
A pasteurization method of noting human normal immunoglobulin, comprises the following steps:
First the quiet notes human normal immunoglobulin solution before deactivation is added to protein protectant; then adjust sample protein matter content 40g/L～60g/L; pH value 4.7～5.3; stir after 30 minutes; put into 60 ℃ ± 1 ℃ water-bath, treat solution temperature to 60 ℃ timing, keep 60 ℃ ± 0.5 ℃ of solution temperature 10 hours; complete quiet notes human normal immunoglobulin's deactivation, described protein protectant comprises sucrose 60g/L, arginine 30g/L, glycine 40g/L and sorbitol 250g/L.After deactivation, before and after measuring heating after taking out, polymer changes, and assay method is measured according to three appendix VI R of < < Chinese Pharmacopoeia > > version in 2010 " human normal immunoglobulin's based article IgG monomer adds dimer algoscopy ".It is 1.90% that the polymer of measuring changes content, and it is 1.88% that the polymer before deactivation changes content.
Embodiment 2
A pasteurization method of noting human normal immunoglobulin, comprises the following steps:
First the quiet notes human normal immunoglobulin solution before deactivation is added to protein protectant; then adjust sample protein matter content 40g/L～60g/L; pH value 4.7～5.3; stir after 30 minutes; put into 60 ℃ ± 1 ℃ water-bath, treat solution temperature to 60 ℃ timing, keep 60 ℃ ± 0.5 ℃ of solution temperature 10 hours; complete quiet notes human normal immunoglobulin's deactivation, described protein protectant comprises sucrose 70g/L, arginase 12 0g/L, glycine 30g/L and sorbitol 260g/L.After deactivation, before and after measuring heating after taking out, polymer changes, and assay method is measured according to three appendix VI R of < < Chinese Pharmacopoeia > > version in 2010 " human normal immunoglobulin's based article IgG monomer adds dimer algoscopy "; It is 1.97% that the polymer of measuring changes content, and it is 1.88% that the polymer before deactivation changes content.
Embodiment 3
A pasteurization method of noting human normal immunoglobulin, comprises the following steps:
First the quiet notes human normal immunoglobulin solution before deactivation is added to protein protectant; then adjust sample protein matter content 40g/L～60g/L; pH value 4.7～5.3; stir after 30 minutes; put into 60 ℃ ± 1 ℃ water-bath, treat solution temperature to 60 ℃ timing, keep 60 ℃ ± 0.5 ℃ of solution temperature 10 hours; complete quiet notes human normal immunoglobulin's deactivation, described protein protectant comprises sucrose 50g/L, arginine 40g/L, glycine 20g/L l and sorbitol 240g/L.After deactivation, before and after measuring heating after taking out, polymer changes, and assay method is measured according to three appendix VI R of < < Chinese Pharmacopoeia > > version in 2010 " human normal immunoglobulin's based article IgG monomer adds dimer algoscopy "; It is 1.98% that the polymer of measuring changes content, and it is 1.88% that the polymer before deactivation changes content.
Passable by above embodiment, protein protectant of the present invention has good protective effect to quiet notes human normal immunoglobulin, and the Content of polymer before and after deactivation there is no variation, and on the not impact of quiet other physical and chemical index of notes human normal immunoglobulin.
The foregoing is only preferred embodiment of the present invention, in order to limit the present invention, within the spirit and principles in the present invention not all, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (4)
1. the quiet notes of pasteurization human normal immunoglobulin's protein protectant; it is characterized in that: comprise sucrose, arginine, glycine and sorbitol, its final content is respectively: 50g/L～7 0g/L, 20g/L～4 0g/L, 30g/L～6 0g/L and 240g/L～260g/L.
2. the quiet notes of a kind of pasteurization according to claim 1 human normal immunoglobulin's protein protectant, is characterized in that: described sucrose, arginine, glycine, its final content of sorbitol are respectively: 50g/L～7 0g/L, 20g/L～4 0g/L, 30g/L～6 0g/L and 240g/L～260g/L.
3. the quiet notes of pasteurization as claimed in claim 1 or 2 human normal immunoglobulin's protein protectant is for the deactivation of blood products.
4. quiet notes human normal immunoglobulin's a pasteurization method, is characterized in that, comprises the following steps:
First the quiet notes human normal immunoglobulin solution before deactivation is added to protein protectant, then adjust sample protein matter content 40g/L～6 0g/L, pH value 4.7～5.3, stir after 30 minutes, put into 60 ℃ ± 1 ℃ water-bath, treat solution temperature to 60 ℃ timing, keep 60 ℃ ± 0.5 ℃ of solution temperature 10 hours, complete quiet notes human normal immunoglobulin's deactivation, described protein protectant comprises sucrose, arginine, glycine and sorbitol, its final content is respectively: 50g/L～7 0g/L, 20g/L～4 0g/L, 30g/L～6 0g/L and 240g/L～260g/L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525253.6A CN103550780B (en) | 2013-10-30 | 2013-10-30 | Protein protective agent for Pasteur inactivating human intravenous immunoglobulin and inactivation method of protein protective agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525253.6A CN103550780B (en) | 2013-10-30 | 2013-10-30 | Protein protective agent for Pasteur inactivating human intravenous immunoglobulin and inactivation method of protein protective agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103550780A true CN103550780A (en) | 2014-02-05 |
| CN103550780B CN103550780B (en) | 2015-03-18 |
Family
ID=50005250
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310525253.6A Active CN103550780B (en) | 2013-10-30 | 2013-10-30 | Protein protective agent for Pasteur inactivating human intravenous immunoglobulin and inactivation method of protein protective agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103550780B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104826117A (en) * | 2015-05-05 | 2015-08-12 | 广东卫伦生物制药有限公司 | Storage stabilizer for human serum immunoglobulin solution preparation |
| CN104829709A (en) * | 2015-05-05 | 2015-08-12 | 广东卫伦生物制药有限公司 | Inactivation method of virus in human serum immunoglobulin |
| CN114099721A (en) * | 2021-11-30 | 2022-03-01 | 华兰生物工程重庆有限公司 | Globulin pasteurization process using combined protective agent |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1260171A (en) * | 2000-01-25 | 2000-07-19 | 长春长生基因药业股份有限公司 | Recombined alpha-type interferon freeze-drying protective agent |
| CN101612404A (en) * | 2009-07-29 | 2009-12-30 | 哈药集团生物疫苗有限公司 | Newcastle disease and infectious bronchitis of chicken bigeminal live vaccine heat-resisting lyophilized protecting agent |
| CN102018956A (en) * | 2010-11-16 | 2011-04-20 | 中国医学科学院医学生物学研究所 | F-gene type attenuated live mumps vaccine and preparation method and application thereof |
| CN102626520A (en) * | 2012-04-23 | 2012-08-08 | 青岛农业大学 | Heat-resisting cryoprotectant of mink canine distemper live vaccine and preparation method thereof |
-
2013
- 2013-10-30 CN CN201310525253.6A patent/CN103550780B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1260171A (en) * | 2000-01-25 | 2000-07-19 | 长春长生基因药业股份有限公司 | Recombined alpha-type interferon freeze-drying protective agent |
| CN101612404A (en) * | 2009-07-29 | 2009-12-30 | 哈药集团生物疫苗有限公司 | Newcastle disease and infectious bronchitis of chicken bigeminal live vaccine heat-resisting lyophilized protecting agent |
| CN102018956A (en) * | 2010-11-16 | 2011-04-20 | 中国医学科学院医学生物学研究所 | F-gene type attenuated live mumps vaccine and preparation method and application thereof |
| CN102626520A (en) * | 2012-04-23 | 2012-08-08 | 青岛农业大学 | Heat-resisting cryoprotectant of mink canine distemper live vaccine and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104826117A (en) * | 2015-05-05 | 2015-08-12 | 广东卫伦生物制药有限公司 | Storage stabilizer for human serum immunoglobulin solution preparation |
| CN104829709A (en) * | 2015-05-05 | 2015-08-12 | 广东卫伦生物制药有限公司 | Inactivation method of virus in human serum immunoglobulin |
| CN114099721A (en) * | 2021-11-30 | 2022-03-01 | 华兰生物工程重庆有限公司 | Globulin pasteurization process using combined protective agent |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103550780B (en) | 2015-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lei et al. | Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig | |
| Niu et al. | Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism | |
| Nowag et al. | Macroautophagy proteins assist Epstein Barr virus production and get incorporated into the virus particles | |
| ES2752137T3 (en) | Methods of treating inflammatory and autoimmune diseases with natalizumab | |
| TWI609690B (en) | Use of alphavirus for preparing anti-cancer drug | |
| Connolly et al. | Reovirus binding to cell surface sialic acid potentiates virus-induced apoptosis | |
| Yoon et al. | Cell-to-cell contact with hepatitis C virus-infected cells reduces functional capacity of natural killer cells | |
| Liao et al. | FasL/Fas pathway is involved in dengue virus induced apoptosis of the vascular endothelial cells | |
| US8663964B2 (en) | Methods of treating human papillomavirus | |
| CN103550780B (en) | Protein protective agent for Pasteur inactivating human intravenous immunoglobulin and inactivation method of protein protective agent | |
| EP2007392A2 (en) | Methods of treating inflammatory and autoimmune diseases with alpha-4 inhibitory compounds | |
| Baron et al. | Electroporation of antibodies, DNA, and other macromolecules into cells: a highly efficient method | |
| Carr et al. | Molecular responses of human retinal cells to infection with dengue virus | |
| Sun et al. | Endothelial Cell Sensitization by Death Receptor Fractions of an Anti–Dengue Nonstructural Protein 1 Antibody Induced Plasma Leakage, Coagulopathy, and Mortality in Mice | |
| Magge et al. | Inhibitors of C5 complement enhance vaccinia virus oncolysis | |
| Bandi et al. | Inhibition of type III interferon activity by orthopoxvirus immunomodulatory proteins | |
| Riabi et al. | Study of Coxsackie B viruses interactions with Coxsackie Adenovirus receptor and Decay-Accelerating Factor using Human CaCo-2 cell line | |
| Ng et al. | Two new species of betatorqueviruses identified in a human melanoma that metastasized to the brain | |
| Zhou et al. | Sars-cov-2 omicron ba. 2 variant evades neutralization by therapeutic monoclonal antibodies | |
| Strumillo et al. | Host–virus interaction and viral evasion | |
| Jin et al. | Differential virus replication, cytokine production, and antigen-presenting function by microglia from susceptible and resistant mice infected with Theiler's virus | |
| Cognasse et al. | Inflammatory markers and auto-Abs to type I IFNs in COVID-19 convalescent plasma cohort study | |
| Makuku et al. | Exploring the application of immunotherapy against HIV infection in the setting of malignancy: A detailed review article | |
| WO2019029081A1 (en) | Application of interferon κ in the preparation of anti enveloped virus drugs | |
| Saha et al. | Convalescent plasma therapy-a silver lining for COVID-19 management? |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: ZHENGZHOU LAISHI BLOOD PRODUCTS CO., LTD. Free format text: FORMER NAME: ZHENGZHOU BANGHE BIO-PHARMACEUTICAL CORPORATION |
|
| CP03 | Change of name, title or address |
Address after: Magnolia high tech Development Zone in Henan province 450000 Zhengzhou Street No. 22 Patentee after: ZHENGZHOU RAAS BLOOD PRODUCTS CO., LTD. Address before: Magnolia high tech Industrial Development Zone, Henan province Zhengzhou City 450000 Street No. 22 Patentee before: Zhengzhou Banghe Bio-Pharmaceutical Corporation |