CN1724567A - Stable recombination human interferon alpha 1b water solution - Google Patents
Stable recombination human interferon alpha 1b water solution Download PDFInfo
- Publication number
- CN1724567A CN1724567A CN 200410069390 CN200410069390A CN1724567A CN 1724567 A CN1724567 A CN 1724567A CN 200410069390 CN200410069390 CN 200410069390 CN 200410069390 A CN200410069390 A CN 200410069390A CN 1724567 A CN1724567 A CN 1724567A
- Authority
- CN
- China
- Prior art keywords
- interferon alpha
- water solution
- human interferon
- recombination human
- interferon
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 108010002492 human interferon alfa-1b Proteins 0.000 title claims abstract description 15
- 102000000707 human interferon alfa-1b Human genes 0.000 title claims abstract description 15
- 238000005215 recombination Methods 0.000 title claims description 8
- 230000006798 recombination Effects 0.000 title claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 15
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 claims abstract description 5
- 102100040019 Interferon alpha-1/13 Human genes 0.000 claims abstract description 5
- 239000000243 solution Substances 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 5
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 4
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 4
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 claims description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 4
- 239000011780 sodium chloride Substances 0.000 abstract description 2
- 102000009027 Albumins Human genes 0.000 abstract 1
- 108010088751 Albumins Proteins 0.000 abstract 1
- 239000008280 blood Substances 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 abstract 1
- 229910000397 disodium phosphate Inorganic materials 0.000 abstract 1
- 239000001488 sodium phosphate Substances 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 102000014150 Interferons Human genes 0.000 description 10
- 108010050904 Interferons Proteins 0.000 description 10
- 229940079322 interferon Drugs 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000003889 eye drop Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 206010059313 Anogenital warts Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a stabilized recombinant human interferon alpha1b water solution, where the water solution with a total volume of 1000ml contains, therapeutic effective dose of interferon alpha1b, 2.5-27.0g of sodium chloride, 0.15-0.60g of citric acid, 1.5-6.0g of dodecahydro-disodium phosphate, and 5-20g of human blood albumin.
Description
Technical field
The present invention relates to the stable Interferon, rabbit aqueous solution.
Background technology
Since nineteen fifty-seven is found Interferon, rabbit, the history in existing more than 40 year.Up to the present, the research of the aspects such as basic theory, process for producing and clinical application of relevant Interferon, rabbit has all obtained great progress.
Recombinant human interferon alpha 1 b is applicable to chronic hepatitis B, hepatitis C, hairy cell leukemia, chronic myelocytic leukemia, pointed condyloma, and multiple transmissible disease and tumour, and clinical application range is wide, dosage is big.But this drug main will exist with the form of lyophilized injectable powder, need add water for injection during use, bring some inconvenience for clinical use, manufacturing cost that the more important thing is powder injection is higher, cost an arm and a leg, make many needs use the patient of Interferon, rabbit to be difficult to economically bear, seriously limited the universal use of Interferon, rabbit, also limited the performance of recombinant human interferon alpha 1 b pharmacological action widely.Recombinant human interferon alpha 1 b if can exist with the state of the aqueous solution, not only can make injection liquid easy to use, and can prepare multiple relevant formulations such as eye drop, sprays.
But when Interferon, rabbit existed with the state of the aqueous solution, its main drawback was unstable, can not long storage.
Summary of the invention
The object of the present invention is to provide a kind of stable Interferon, rabbit alpha 1 b water solution.
Consisting of of above-mentioned Interferon, rabbit alpha 1 b water solution is in the aqueous solution of 1000ml at cumulative volume, comprises following component:
A. treat the interferon alpha 1b of significant quantity;
B.2.5-27.0g sodium-chlor;
C.0.15-0.60g citric acid;
D.1.5-6.0g disodium hydrogen phosphate;
E.5-20g human serum albumin.
Wherein treat the interferon alpha 1b of significant quantity, should adjust accordingly according to indication and the different of patient.Typical concentrations is 10-60 μ g/ml, but when diseases such as treatment cancer, can use 300-500 μ g/ml.
The preferable range of sodium-chlor is 6.5-7.5g.
The preferable range of citric acid is 0.25-0.35g.
The preferable range of disodium hydrogen phosphate is 2.5-3.5g.
Those of ordinary skill in the art is easy to add other compositions on the basis of above-mentioned prescription; for example tween-80, N.F,USP MANNITOL, sucrose, cyclodextrin etc.; to reach the same or similar effects with the present invention, these prescriptions also should be included in protection scope of the present invention.
Recombination human interferon alpha 1 b water solution according to above-mentioned formulation can be stablized storage more than 2 years at 2-8 ℃, and its stability is basic identical with lyophilized injectable powder of preparation according to a conventional method.Can prepare injection liquid, eye drop, sprays etc. by this aqueous solution, both expand the range of application of interferon alpha 1b, reduced production cost again, avoided the secondary dissolving in use of conventional lyophilized injectable powder simultaneously, reduced opportunities for contamination, more convenient doctors and patients use.
Embodiment
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1
According to the formulated recombination human interferon alpha 1 b water solution of table 1, and will install in the eye-drop liquid bottle, make eye drop according to the solution branch of prescription A preparation; To install in the glass molding antibiotic bottle according to the solution branch of prescription B and C preparation, make injection liquid; To install in the aerosol container according to the solution branch of prescription D preparation, make sprays.
Table 1: the prescription of recombination human interferon alpha 1 b water solution
| Composition | Prescription A | Prescription B | Prescription C | Prescription D |
| α 1b interferon NaCl citric acid disodium hydrogen phosphate human serum albumin Tween 80 injects water to | 10mg 2.5g 0.6g 6.0g 5g - 1000ml | 30mg 7.0g 0.3g 3.0g 10g - 1000ml | 30mg 7.0g 0.3g 3.0g l0g 1ml 1000ml | 50mg 27g 0.15g 1.5g 20g - 1000ml |
Prepare the recombinant human interferon alpha 1 b lyophilized injectable powder then according to a conventional method, be summarized as follows: get 500ml water for injection, add 19.5ml 0.2mol/L NaH then
2PO
4, 30.5ml 0.2mol/L Na
2HPO4,10g human serum albumin, 31g N.F,USP MANNITOL, 30mg α 1b Interferon, rabbit are added water for injection to 1000ml, divide to be filled in the glass molding antibiotic bottle, and every bottle of 1ml according to the ordinary method freeze-drying, makes lyophilized injectable powder.Before use or survey are lived, add 1ml water for injection and make dissolving fully.
Recombinant human interferon alpha 1 b eye drop, injection liquid, sprays and the lyophilized injectable powder of above-mentioned preparation are placed 2-8 ℃ of long storage, and respectively in the time of 0,3,6,9,12,18,24 month, with conventional WISH-VSV systems measurement biological activity, and proofreaied and correct with the survey of the Nat'l Pharmaceutical ﹠ Biological Products Control Institute standard substance of living.
The result shows, recombinant human interferon alpha 1 b eye drop, injection liquid and sprays and lyophilized injectable powder have essentially identical stability, and after 24 months, activity is still more than 80%, and illustrating can long storage (referring to table 2) according to the recombination human interferon alpha 1 b water solution of the present invention's preparation.
Table 2: the stability of recombination human interferon alpha 1 b water solution
| Test item | Sample | 0 month | March | June | September | December | 18 months | 24 months |
| Active (1 * 10 5IU/ml) | Eye drop (A) | 1.12 | 1.10 | 1.07 | 1.04 | 1.01 | 0.97 | 0.93 |
| Injection liquid (B) | 3.78 | 3.70 | 3.64 | 3.55 | 3.47 | 3.34 | 3.21 | |
| Injection liquid (C) | 3.76 | 3.69 | 3.62 | 3.51 | 3.44 | 3.33 | 3.18 | |
| Sprays (D) | 6.12 | 5.92 | 5.59 | 5.46 | 5.34 | 5.19 | 5.02 | |
| Lyophilized injectable powder | 3.67 | 3.62 | 3.56 | 3.48 | 3.42 | 3.27 | 3.16 |
Claims (4)
1. stable recombination human interferon alpha 1 b water solution in the 1000ml aqueous solution, comprises following composition:
A. treat the interferon alpha 1b of significant quantity;
B.2.5-27.0g sodium-chlor;
C.0.15-0.60g citric acid;
D.1.5-6.0g disodium hydrogen phosphate;
E.5-20g human serum albumin.
2. the aqueous solution as claimed in claim 1 wherein contains 6.5-7.5g sodium-chlor.
3. the aqueous solution as claimed in claim 1 wherein contains the 0.25-0.35g citric acid.
4. the aqueous solution as claimed in claim 1 wherein contains the 2.5-3.5g disodium hydrogen phosphate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410069390 CN1724567B (en) | 2004-07-22 | 2004-07-22 | Stable recombination human interferon alpha 1b water solution |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410069390 CN1724567B (en) | 2004-07-22 | 2004-07-22 | Stable recombination human interferon alpha 1b water solution |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1724567A true CN1724567A (en) | 2006-01-25 |
| CN1724567B CN1724567B (en) | 2010-08-18 |
Family
ID=35924212
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410069390 Expired - Lifetime CN1724567B (en) | 2004-07-22 | 2004-07-22 | Stable recombination human interferon alpha 1b water solution |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1724567B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103649111A (en) * | 2011-07-05 | 2014-03-19 | 诺维信生物制药丹麦公司 | Albumin formulation and use |
| CN104888196A (en) * | 2015-06-25 | 2015-09-09 | 北京三元基因工程有限公司 | Stable interferon alpha multi-dose pen injection |
| CN111617031A (en) * | 2020-06-25 | 2020-09-04 | 长春生物制品研究所有限责任公司 | A kind of stable recombinant human interferon α1b eye drops and production method thereof |
| CN115804835A (en) * | 2022-12-30 | 2023-03-17 | 北京三元基因药业股份有限公司 | Oral preparation for treating diseases caused by rotavirus infection |
| CN117959251A (en) * | 2024-03-29 | 2024-05-03 | 长春生物制品研究所有限责任公司 | Recombinant human interferon α1b eye drops and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5766582A (en) * | 1994-10-11 | 1998-06-16 | Schering Corporation | Stable, aqueous alfa interferon solution formulations |
| CN1175901C (en) * | 1999-12-06 | 2004-11-17 | 天津华立达生物工程有限公司 | Stable water solution of interferon |
| CN1157226C (en) * | 2000-06-09 | 2004-07-14 | 天津华立达生物工程有限公司 | Stable alpha-interferon preparation |
| CN1443573A (en) * | 2003-04-28 | 2003-09-24 | 深圳市海王英特龙生物技术股份有限公司 | Recombinant human interferon alpha 2 b nose drops and its production method |
-
2004
- 2004-07-22 CN CN 200410069390 patent/CN1724567B/en not_active Expired - Lifetime
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103649111A (en) * | 2011-07-05 | 2014-03-19 | 诺维信生物制药丹麦公司 | Albumin formulation and use |
| CN103649111B (en) * | 2011-07-05 | 2018-03-13 | 阿尔布梅迪克斯医疗公司 | Albumin preparation and purposes |
| US10844349B2 (en) | 2011-07-05 | 2020-11-24 | Albumedix Ltd. | Albumin formulation and use |
| CN104888196A (en) * | 2015-06-25 | 2015-09-09 | 北京三元基因工程有限公司 | Stable interferon alpha multi-dose pen injection |
| CN104888196B (en) * | 2015-06-25 | 2018-07-06 | 北京三元基因药业股份有限公司 | A kind of interferon-' alpha ' multi-dose parenteral solution of stabilization |
| CN111617031A (en) * | 2020-06-25 | 2020-09-04 | 长春生物制品研究所有限责任公司 | A kind of stable recombinant human interferon α1b eye drops and production method thereof |
| CN115804835A (en) * | 2022-12-30 | 2023-03-17 | 北京三元基因药业股份有限公司 | Oral preparation for treating diseases caused by rotavirus infection |
| CN117959251A (en) * | 2024-03-29 | 2024-05-03 | 长春生物制品研究所有限责任公司 | Recombinant human interferon α1b eye drops and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1724567B (en) | 2010-08-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102662530B1 (en) | Method for preparing stable therapeutic formulations in anodic solvents. | |
| KR101084412B1 (en) | Stabilized Liquid Protein Formulations in Coated Pharmaceutical Containers | |
| EP3060240A1 (en) | Stable formulation of insulin glulisine | |
| CN112107544A (en) | Dexmedetomidine nasal spray, preparation method and application thereof | |
| US20030170207A1 (en) | Stable aqua formulation of interferon, the preparation method and the uses thereof | |
| KR102656841B1 (en) | Injectable pharmaceutical formulation of lefamulin | |
| EP1458355B1 (en) | Aqueous based pharmaceutical formulations of water-soluble prodrugs of propofol | |
| CN1724567B (en) | Stable recombination human interferon alpha 1b water solution | |
| US9468685B2 (en) | Methods of preparing a liquid formulation of G-CSF | |
| EP3679925B1 (en) | Pharmaceutical composition of docetaxel conjugate and preparation method | |
| WO2001087262A2 (en) | Stabilized steroidal suspension | |
| CN1449289A (en) | OCT preparation | |
| CN115192691B (en) | Argatroban injection and prefilled syringe | |
| CN115137713B (en) | Amphotericin B aerosol inhalation preparation and preparation method thereof | |
| CN1263451C (en) | Cinrofloxacin eye preparation formula and its using method | |
| HK40081665A (en) | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents | |
| WO2023027939A1 (en) | Method for preventing entry and replication of enveloped viruses | |
| WO2024011169A1 (en) | Stable, liquid pharmaceutical compositions comprising melphalan | |
| Nguyen-Xuan et al. | Stability of morphine sulfate in polypropylene infusion bags for use in patient-controlled analgesia pumps for postoperative pain management | |
| CN100502943C (en) | A drug injection of recombinant human erythropoietin | |
| CN112022803A (en) | A kind of highly stable salmon calcitonin injection and application thereof | |
| HK40033882A (en) | Pharmaceutical composition of docetaxel conjugate and preparation method | |
| CN113491668A (en) | Pharmaceutical composition preparation for injection and preparation method and application thereof | |
| CN1488350A (en) | Eye preparation for mulating prescription suitable for ciprofloxacin and use method thereof | |
| HK40033919B (en) | Pharmaceutical composition of docetaxel conjugate and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Free format text: FORMER OWNER: BEIJING BIO TECHNOLOGY DEVELOPMENT CO., LTD. Effective date: 20130829 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20130829 Address after: 102600 Beijing Jinyuan Daxing Industrial Development Zone Road No. 1 Patentee after: Beijing Tri-Prime Genetic Engineering Co.,Ltd. Address before: 102600 Beijing Jinyuan Daxing Industrial Development Zone Road No. 1 Patentee before: Beijing Tri-Prime Genetic Engineering Co.,Ltd. Patentee before: Beijing Biaio Technology Development Co.,Ltd. |
|
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 102600 Beijing Jinyuan Daxing Industrial Development Zone Road No. 1 Patentee after: BEIJING TRI-PRIME GENE PHARMACEUTICAL Co.,Ltd. Address before: 102600 Beijing Jinyuan Daxing Industrial Development Zone Road No. 1 Patentee before: Beijing Tri-Prime Genetic Engineering Co.,Ltd. |
|
| CX01 | Expiry of patent term |
Granted publication date: 20100818 |
|
| CX01 | Expiry of patent term |