DE10235168A1 - Verfahren zur Reinigung von Preproinsulin - Google Patents
Verfahren zur Reinigung von Preproinsulin Download PDFInfo
- Publication number
- DE10235168A1 DE10235168A1 DE10235168A DE10235168A DE10235168A1 DE 10235168 A1 DE10235168 A1 DE 10235168A1 DE 10235168 A DE10235168 A DE 10235168A DE 10235168 A DE10235168 A DE 10235168A DE 10235168 A1 DE10235168 A1 DE 10235168A1
- Authority
- DE
- Germany
- Prior art keywords
- gly
- leu
- glu
- ser
- gln
- 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.)
- Withdrawn
Links
- 108010066381 preproinsulin Proteins 0.000 title claims abstract description 94
- 238000000034 method Methods 0.000 title claims abstract description 38
- 238000000746 purification Methods 0.000 title claims description 5
- 102000004877 Insulin Human genes 0.000 claims abstract description 30
- 108090001061 Insulin Proteins 0.000 claims abstract description 30
- 238000004587 chromatography analysis Methods 0.000 claims abstract description 27
- 239000000126 substance Substances 0.000 claims abstract description 23
- 239000004026 insulin derivative Substances 0.000 claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 238000011097 chromatography purification Methods 0.000 claims abstract description 8
- 150000001768 cations Chemical class 0.000 claims abstract description 7
- 239000007864 aqueous solution Substances 0.000 claims abstract description 6
- 238000001179 sorption measurement Methods 0.000 claims abstract description 6
- 150000001450 anions Chemical class 0.000 claims abstract description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 72
- 239000000243 solution Substances 0.000 claims description 57
- 125000000539 amino acid group Chemical group 0.000 claims description 44
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 38
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- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 claims description 36
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- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
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- 239000003957 anion exchange resin Substances 0.000 description 5
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- 229960002869 insulin glargine Drugs 0.000 description 5
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- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- 230000001174 ascending effect Effects 0.000 description 4
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- 102000004169 proteins and genes Human genes 0.000 description 4
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- 238000003756 stirring Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 3
- 102000004142 Trypsin Human genes 0.000 description 3
- 108090000631 Trypsin Proteins 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
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- -1 insulin derivatives unmodified human insulin Chemical class 0.000 description 2
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
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- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
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- 108091005804 Peptidases Proteins 0.000 description 1
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- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
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- 125000003368 amide group Chemical group 0.000 description 1
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- 239000000538 analytical sample Substances 0.000 description 1
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- 150000002148 esters Chemical class 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
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Classifications
-
- 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
- C07K14/575—Hormones
- C07K14/62—Insulins
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Priority Applications (18)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10235168A DE10235168A1 (de) | 2002-08-01 | 2002-08-01 | Verfahren zur Reinigung von Preproinsulin |
| MXPA05001042A MXPA05001042A (es) | 2002-08-01 | 2003-07-18 | Un metodo para purificar preproinsulina. |
| JP2004525238A JP4519646B2 (ja) | 2002-08-01 | 2003-07-18 | プレプロインスリンの精製方法 |
| DE50309087T DE50309087D1 (https=) | 2002-08-01 | 2003-07-18 | |
| BR0313131-9A BR0313131A (pt) | 2002-08-01 | 2003-07-18 | Processo para a purificação de preproinsulina |
| AT03766211T ATE384742T1 (de) | 2002-08-01 | 2003-07-18 | Verfahren zur reinigung von preproinsulin |
| DK03766211T DK1527097T3 (da) | 2002-08-01 | 2003-07-18 | Fremgangsmåde til rensning af preproinsulin |
| CA2493539A CA2493539C (en) | 2002-08-01 | 2003-07-18 | A method for purifying preproinsulin |
| PT03766211T PT1527097E (pt) | 2002-08-01 | 2003-07-18 | Processo para a purificação de pré-proinsulina |
| PCT/EP2003/007820 WO2004013176A1 (de) | 2002-08-01 | 2003-07-18 | Verfahren zur reinigung von preproinsulin |
| ES03766211T ES2297223T3 (es) | 2002-08-01 | 2003-07-18 | Procedimiento para la purificacion de preproinsulina. |
| AU2003254375A AU2003254375B2 (en) | 2002-08-01 | 2003-07-18 | Method for purifying preproinsulin |
| SI200331119T SI1527097T1 (sl) | 2002-08-01 | 2003-07-18 | Postopek za ciscenje preproinzulina |
| EP03766211A EP1527097B1 (de) | 2002-08-01 | 2003-07-18 | Verfahren zur reinigung von preproinsulin |
| US10/632,414 US20050080000A1 (en) | 2002-08-01 | 2003-08-01 | Method of purifying preproinsulin |
| IL166438A IL166438A (en) | 2002-08-01 | 2005-01-23 | Method for purifying preproinsulin |
| US11/305,508 US7803763B2 (en) | 2002-08-01 | 2005-12-15 | Method of purifying preproinsulin |
| CY20081100198T CY1108046T1 (el) | 2002-08-01 | 2008-02-18 | Μεθοδος για τον καθορισμο προπροϊνσουλινης |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10235168A DE10235168A1 (de) | 2002-08-01 | 2002-08-01 | Verfahren zur Reinigung von Preproinsulin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10235168A1 true DE10235168A1 (de) | 2004-02-12 |
Family
ID=30128614
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10235168A Withdrawn DE10235168A1 (de) | 2002-08-01 | 2002-08-01 | Verfahren zur Reinigung von Preproinsulin |
| DE50309087T Expired - Lifetime DE50309087D1 (https=) | 2002-08-01 | 2003-07-18 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE50309087T Expired - Lifetime DE50309087D1 (https=) | 2002-08-01 | 2003-07-18 |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20050080000A1 (https=) |
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| SI (1) | SI1527097T1 (https=) |
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| US10307464B2 (en) | 2014-03-28 | 2019-06-04 | Mannkind Corporation | Use of ultrarapid acting insulin |
| CN106794156B (zh) * | 2014-07-08 | 2021-03-09 | 美药星制药股份有限公司 | 微粒化胰岛素、微粒化胰岛素类似物及其制备方法 |
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2002
- 2002-08-01 DE DE10235168A patent/DE10235168A1/de not_active Withdrawn
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2003
- 2003-07-18 PT PT03766211T patent/PT1527097E/pt unknown
- 2003-07-18 DE DE50309087T patent/DE50309087D1/de not_active Expired - Lifetime
- 2003-07-18 SI SI200331119T patent/SI1527097T1/sl unknown
- 2003-07-18 CA CA2493539A patent/CA2493539C/en not_active Expired - Fee Related
- 2003-07-18 ES ES03766211T patent/ES2297223T3/es not_active Expired - Lifetime
- 2003-07-18 BR BR0313131-9A patent/BR0313131A/pt active Search and Examination
- 2003-07-18 DK DK03766211T patent/DK1527097T3/da active
- 2003-07-18 EP EP03766211A patent/EP1527097B1/de not_active Expired - Lifetime
- 2003-07-18 MX MXPA05001042A patent/MXPA05001042A/es active IP Right Grant
- 2003-07-18 WO PCT/EP2003/007820 patent/WO2004013176A1/de not_active Ceased
- 2003-07-18 AU AU2003254375A patent/AU2003254375B2/en not_active Ceased
- 2003-07-18 JP JP2004525238A patent/JP4519646B2/ja not_active Expired - Fee Related
- 2003-07-18 AT AT03766211T patent/ATE384742T1/de active
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| Publication number | Publication date |
|---|---|
| US20050080000A1 (en) | 2005-04-14 |
| US7803763B2 (en) | 2010-09-28 |
| PT1527097E (pt) | 2008-02-25 |
| CY1108046T1 (el) | 2013-09-04 |
| WO2004013176A1 (de) | 2004-02-12 |
| EP1527097A1 (de) | 2005-05-04 |
| JP4519646B2 (ja) | 2010-08-04 |
| DK1527097T3 (da) | 2008-05-26 |
| CA2493539A1 (en) | 2004-02-12 |
| ES2297223T3 (es) | 2008-05-01 |
| IL166438A0 (en) | 2006-01-15 |
| CA2493539C (en) | 2012-01-31 |
| JP2006513978A (ja) | 2006-04-27 |
| AU2003254375B2 (en) | 2009-01-08 |
| DE50309087D1 (https=) | 2008-03-13 |
| US20060183666A1 (en) | 2006-08-17 |
| AU2003254375A1 (en) | 2004-02-23 |
| MXPA05001042A (es) | 2005-04-08 |
| EP1527097B1 (de) | 2008-01-23 |
| IL166438A (en) | 2010-11-30 |
| SI1527097T1 (sl) | 2008-04-30 |
| ATE384742T1 (de) | 2008-02-15 |
| BR0313131A (pt) | 2005-07-05 |
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