CN1201815C - Stabilizer for recombinant alpha-interferon liquid - Google Patents
Stabilizer for recombinant alpha-interferon liquid Download PDFInfo
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- CN1201815C CN1201815C CNB021324654A CN02132465A CN1201815C CN 1201815 C CN1201815 C CN 1201815C CN B021324654 A CNB021324654 A CN B021324654A CN 02132465 A CN02132465 A CN 02132465A CN 1201815 C CN1201815 C CN 1201815C
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- interferon
- gelatin
- stabilizers
- stabilizing agent
- disaccharide
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Abstract
The present invention discloses a recombination alpha type interferon liquid stabilizer. The recombination alpha type interferon liquid stabilizer is formed by that gelatin and disaccharide are used as stabilizers of recombination alpha type interferon liquid formulations, and the gelatin and a disaccharide solution are added to an interferon stock solution, and the mixture is uniformly mixed, sterilized, filtered, subpacked and saved, wherein the titer of interferon is from 1, 000, 000 to 10, 000, 000 IU/ml, and the concentration of the gelatin is from 0.05 to 2.5%. The stabilizers of the present invention is not a product of human blood, and thus, the stabilizers have the advantages of nontoxicity, harmlessness, low production cost, obvious protective effect and long period of validity; the potential risks of carrying viruses by using human serum albumin (HSA) are avoided with the stabilizers, and the freeze-drying process of products is omitted. The stabilizers are used for preparing 'green' interferon injections with good quality, reasonable price and no pollution so that patients are convenient in use, and the economic burdens of the patients are relieved.
Description
Technical field:
The present invention discloses a kind of stabilizer for recombinant alpha-interferon liquid, belongs to the biological product protection
Technical field.
Background technology:
Interferon is the extensive bioactive albumen that has that exists in one group of body, has various effects such as antiviral, antitumor and adjusting body's immunity.Main at present treatment chronic viral hepatitis, tumor and other viral infection diseases.Interferon needs to protect its activity by stabilizing agent, otherwise very fast inactivation.Interferon human albumin commonly used because the human albumin costs an arm and a leg, causes the interferon product cost to improve as stabilizing agent at present, therefore brings very big financial burden to the patient; The human albumin has the potential danger of the virus of carrying in addition, to patient Yi Zaocheng viral infection.The applicant discloses a kind of with the protective agent of dextran as the recombined alpha-type interferon freeze-drying dosage form at Chinese patent 00110069.6; and as the stabilizing agent of liquid dosage form; its effect phase is lacked very much (keeping 1 year for 4 ℃), so this protective agent is not suitable for as recombinant alpha-interferon liquid dosage form protective agent.
Summary of the invention:
The present invention discloses a kind of stabilizer for recombinant alpha-interferon liquid, has avoided end user's blood albumin to carry the potential danger of virus, and has saved the freeze-drying process of goods.
Technical solution of the present invention is as follows: adopts gelatin and disaccharide stabilizing agent, in interferon stock solution, adds gelatin and two sugar juices as recombinant alpha-interferon, and mix homogeneously, packing is preserved after aseptic filtration.Wherein, in stabilizing agent, mixed proportion is that interferon is tired and is 100-1000 ten thousand IU/ml, and gelatin concentration is 0.05-2.5%, and the concentration of disaccharide is 0.2-10%.
Described disaccharide comprises sucrose, lactose, trehalose or maltose etc.,
When adopting gelatin and disaccharide to make stabilizing agent, also can increase Polyethylene Glycol 0.05～2.5% with (or) a kind of amino acids material.Amino acids comprises glycine, arginine and lysine, and its working concentration is 0.05-2.5%.
Good effect of the present invention is: used stabilizing agent is inhuman blood product, and nontoxic, harmless, production cost is low; the protection effect is obvious, and the effect phase is long, is used for preparation super quality and competitive price, free of contamination " green " interferon injection; make things convenient for extensive patients to use, alleviate patient economy burden.
The specific embodiment:
Embodiment 1
Get gelatin, sucrose, Polyethylene Glycol, glycine, prepare with 0.85% normal saline respectively, wherein gelatin, sucrose, Polyethylene Glycol, normal saline solution are through autoclaving, and glycine solution is degerming after filtration, prepare the 2-5 stabilizing agent respectively, each concentration is as follows, and No. 1 stabilizing agent is the human albumin, does matched group, every number sample all contains recombinant alpha-interferon 100-1000 ten thousand IU/ml, fully mix, carry out aseptic filtration, the branch loading amount is that 1ml/ props up.
Below be the stability of interferon injection under different condition that aforementioned stable agent and human albumin make stabilizing agent: (wherein interferon is tired in the 80-150% of labelled amount, represents that promptly interferon activity does not descend.)
No. 1 stabilizing agent: 1% human albumin, matched group.
No. 2 stabilizing agents: 0.4% gelatin+3% sucrose
No. 3 stabilizing agents: 0.4% gelatin+3% sucrose+0.3% Polyethylene Glycol
No. 4 stabilizing agents: 0.4% gelatin+3% sucrose+0.3% glycine
No. 5 stabilizing agents: 0.4% gelatin+3% sucrose+0.2% Polyethylene Glycol+0.2% glycine
Table 1: the different stabilizers interferon is at 4 ℃ of saving results: (300 ten thousand IU/ml)
Table 2: the different stabilizers interferon is 25 ℃ of saving results again: (300 ten thousand IU/ml)
Table 3: the different stabilizers interferon is at 37 ℃ of saving results: (300 ten thousand IU/ml)
3 as seen to, No. 1 stabilizing agent can be stablized interferon 12 months under 4 ℃ of conditions, kept 6 months in the time of 25 ℃, then kept 3 months at 37 ℃ by table 1.And 2 to No. 5 stabilizing agents can be protected interferon alpha-2 4 months at 4 ℃, are 15 months in the time of 25 ℃, can stablize 9 months for 37 ℃.Therefore, 2-5 number significantly better than No. 1 stabilizing agent; Slightly be better than 2,3 and No. 4 No. 5, but do not have significant difference.
Embodiment 2
The result of the test of gelatin and different two sugar composites.
2-1 number: 0.5% gelatin+2% sucrose
2-2 number: 0.5% gelatin+2% lactose
2-3 number: 0.5% gelatin+2% trehalose
Repeat above-mentioned processing step, the result is as follows:
Table 4: in the stability (containing interferon 500 ten thousand IU/ml) of 40 ℃ of accelerated test interferon
Embodiment 3
The result of the test of gelatin and two sugar composites and different aminoacids.
4-1 number: 0.4% gelatin+2% lactose+0.5% glycine
4-2 number: 0.4% gelatin+2% lactose+0.5% arginine
4-3 number: 0.4% gelatin+2% lactose+0.5% lysine
Table 5: in the stability (containing interferon 300 ten thousand IU/ml) of 40 ℃ of accelerated test interferon
Embodiment 4
The result of the test of gelatin and two sugar composites and Polyethylene Glycol (and aminoacid).
3-1 number: 0.4% gelatin+2% trehalose+0.4% Polyethylene Glycol
5-1 number: 0.3% gelatin+1% trehalose+0.4% Polyethylene Glycol+0.5% glycine
Table 6: in the stability (containing interferon 100 ten thousand IU/ml) of 40 ℃ of accelerated test interferon
Claims (4)
1, a kind of stabilizer for recombinant alpha-interferon liquid, it is characterized in that: adopt gelatin and disaccharide stabilizing agent as the recombinant alpha-interferon liquid preparation, in interferon stock solution, add gelatin and two sugar juices, in stabilizing agent, mixed proportion is that interferon is tired and is 100-1000 ten thousand IU/ml, gelatin concentration is 0.05-2.5%, and the concentration of disaccharide is 0.2～10%.
2, stabilizing agent according to claim 1 is characterized in that: disaccharide is taken from sucrose, lactose, trehalose or maltose.
3, stabilizing agent according to claim 1 and 2 is characterized in that: add Polyethylene Glycol 0.05～2.5%.
4, stabilizing agent according to claim 1 is characterized in that: add the amino acids material, amino acids comprises glycine, arginine and lysine, and its working concentration is 0.05-2.5%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021324654A CN1201815C (en) | 2002-06-21 | 2002-06-21 | Stabilizer for recombinant alpha-interferon liquid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021324654A CN1201815C (en) | 2002-06-21 | 2002-06-21 | Stabilizer for recombinant alpha-interferon liquid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1389470A CN1389470A (en) | 2003-01-08 |
| CN1201815C true CN1201815C (en) | 2005-05-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB021324654A Expired - Fee Related CN1201815C (en) | 2002-06-21 | 2002-06-21 | Stabilizer for recombinant alpha-interferon liquid |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512686B (en) * | 2010-12-21 | 2013-07-24 | 成都生物制品研究所有限责任公司 | Vaccine protectant, hydrophobia vaccine and preparation method thereof |
| CN103301443A (en) * | 2012-03-08 | 2013-09-18 | 河南省康星药业股份有限公司 | Preparation method of stable chicken lyophilized alpha-interferon dosage form |
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- 2002-06-21 CN CNB021324654A patent/CN1201815C/en not_active Expired - Fee Related
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Granted publication date: 20050518 Termination date: 20110621 |