DK2776452T3 - Fremgangsmåde til rensning af teicoplanin - Google Patents
Fremgangsmåde til rensning af teicoplanin Download PDFInfo
- Publication number
- DK2776452T3 DK2776452T3 DK12784004.9T DK12784004T DK2776452T3 DK 2776452 T3 DK2776452 T3 DK 2776452T3 DK 12784004 T DK12784004 T DK 12784004T DK 2776452 T3 DK2776452 T3 DK 2776452T3
- Authority
- DK
- Denmark
- Prior art keywords
- teicoplanin
- solution
- water
- resin
- methanol
- Prior art date
Links
- 108010053950 Teicoplanin Proteins 0.000 title claims description 235
- DDTDNCYHLGRFBM-YZEKDTGTSA-N chembl2367892 Chemical compound CC(=O)N[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1O[C@@H]([C@H]1C(N[C@@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(O)C=C(C=4)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@H](CC=4C=C(Cl)C(O5)=CC=4)C(=O)N3)C(=O)N1)C(O)=O)=O)C(C=C1Cl)=CC=C1OC1=C(O[C@H]3[C@H]([C@@H](O)[C@H](O)[C@H](CO)O3)NC(C)=O)C5=CC2=C1 DDTDNCYHLGRFBM-YZEKDTGTSA-N 0.000 title claims description 233
- 229960001608 teicoplanin Drugs 0.000 title claims description 233
- 238000000034 method Methods 0.000 title claims description 63
- 230000008569 process Effects 0.000 title claims description 40
- 238000000746 purification Methods 0.000 title description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 177
- 229920005989 resin Polymers 0.000 claims description 99
- 239000011347 resin Substances 0.000 claims description 99
- 239000000243 solution Substances 0.000 claims description 81
- 238000001179 sorption measurement Methods 0.000 claims description 42
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 40
- 239000012528 membrane Substances 0.000 claims description 40
- 239000003960 organic solvent Substances 0.000 claims description 37
- 238000000108 ultra-filtration Methods 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 239000011148 porous material Substances 0.000 claims description 20
- 230000002378 acidificating effect Effects 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 18
- 230000002209 hydrophobic effect Effects 0.000 claims description 14
- 239000002609 medium Substances 0.000 claims description 14
- 150000002576 ketones Chemical class 0.000 claims description 11
- 150000002825 nitriles Chemical class 0.000 claims description 11
- 150000001298 alcohols Chemical class 0.000 claims description 9
- 241000187842 Actinoplanes teichomyceticus Species 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 239000012736 aqueous medium Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
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- 239000000872 buffer Substances 0.000 claims description 5
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
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- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims 1
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
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- 239000012465 retentate Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
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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 6
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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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- LCTCUBQFWLTHNS-MDZDMXLPSA-N 61036-64-4 Chemical compound CCCCC\C=C\CCC(=O)NC1C(O)C(O)C(CO)OC1OC(C(=C1)OC=2C(=CC(=CC=2)C(OC2C(C(O)C(O)C(CO)O2)NC(C)=O)C2C(NC(C3=CC(O)=CC(OC4C(C(O)C(O)C(CO)O4)O)=C3C=3C(O)=CC=C(C=3)C(NC3=O)C(=O)N2)C(=O)OC)=O)Cl)=C(OC=2C(=CC(=CC=2)C(O)C(C(N2)=O)NC(=O)C(N)C=4C=C(O5)C(O)=CC=4)Cl)C=C1C3NC(=O)C2C1=CC(O)=C(C)C5=C1 LCTCUBQFWLTHNS-MDZDMXLPSA-N 0.000 description 2
- 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
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- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 2
- BJNLLBUOHPVGFT-CAYRISATSA-N (1S,2R,19R,22R,34S,37R,40R,52S)-2-[(2R,3R,4R,5S,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-22-amino-5,15-dichloro-64-[(2S,3R,4R,5S,6R)-3-(decanoylamino)-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-26,31,44,49-tetrahydroxy-21,35,38,54,56,59-hexaoxo-47-[(3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-7,13,28-trioxa-20,36,39,53,55,58-hexazaundecacyclo[38.14.2.23,6.214,17.219,34.18,12.123,27.129,33.141,45.010,37.046,51]hexahexaconta-3,5,8,10,12(64),14,16,23(61),24,26,29(60),30,32,41(57),42,44,46(51),47,49,62,65-henicosaene-52-carboxylic acid Chemical compound CCCCCCCCCC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1Oc1c2Oc3ccc(C[C@H]4NC(=O)[C@H](N)c5ccc(O)c(Oc6cc(O)cc(c6)[C@H](NC4=O)C(=O)N[C@@H]4c(c2)cc1Oc1ccc(cc1Cl)[C@@H](O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O)[C@@H]1NC(=O)[C@H](NC4=O)c2ccc(O)c(c2)-c2c(OC4O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]4O)cc(O)cc2[C@H](NC1=O)C(O)=O)c5)cc3Cl BJNLLBUOHPVGFT-CAYRISATSA-N 0.000 description 1
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- BJNLLBUOHPVGFT-QRZIFLFXSA-N teichomycin Chemical compound CCCCCCCCCC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1)OC=2C(=CC(=CC=2)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@H]2C(N[C@H](C3=CC(O)=CC(O[C@@H]4[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)=C3C=3C(O)=CC=C(C=3)[C@@H](NC3=O)C(=O)N2)C(O)=O)=O)Cl)=C(OC=2C(=CC(C[C@H](C(N4)=O)NC(=O)[C@H](N)C=5C=C(O6)C(O)=CC=5)=CC=2)Cl)C=C1[C@H]3NC(=O)[C@@H]4C1=CC6=CC(O)=C1 BJNLLBUOHPVGFT-QRZIFLFXSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
- C07K9/006—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
- C07K9/008—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Claims (14)
1. Fremgangsmåde til fremstilling af renset teicoplanin, hvilken fremgangsmåde omfatter følgende trin: a) at absorbere teicoplanin til en hydrofob adsorptionsharpiks; b) at desorbere teicoplanin fra harpiksen under anvendelse af et medium, der indeholder vand og et vandblandbart organisk opløsningsmiddel; c) at behandle en opløsning, der omfatter teicoplanin, med aktivt kul efterfulgt af fjernelse af det aktive kul; d) at underkaste en opløsning, der omfatter teicoplanin, en ultrafiltrering på membraner med en udelukkelsesgrænse på 3-100 kDa, idet opløsningen indeholder mere end 20 rumfangs% af et vandblandbart organisk opløsningsmiddel og ikke mere end 90 rumfangs% af et vandblandbart organisk opløsningsmiddel; e) eventuelt at koncentrere og/eller afsalte en teicoplaninholdig opløsning efter ultrafiltrering som defineret i trin d) ved ultrafiltrering på membraner med en udelukkelsesgrænse på 1000 Da; f) at opnå renset teicoplanin.
2. Fremgangsmåde ifølge krav 1, hvori trin a) til f) udføres i den i krav 1 angivne rækkefølge.
3. Fremgangsmåde ifølge krav 1 eller 2, som endvidere omfatter et forudgående trin til tilsætning af et organisk opløsningsmiddel til en kultur af Actinoplanes teichomyceticus og frafiltrering og/eller fracentrifugering af mycelium og andet uopløseligt materiale.
4. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 3, ved hvilken den hydrofobe adsorptionsharpiks er en tværbunden ikke-ionisk makroretikulær polystyreneller polyacrylat-harpiks med en porestørrelse på 20 til 500 Å.
5. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 4, ved hvilken trinnet til at desorbere teicoplanin fra den hydrofobe adsorptionsharpiks udføres under anvendelse af et vandigt medium, der omfatter mindst 40 rumfangs% af et vandblandbart organisk opløsningsmiddel.
6. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 5, ved hvilken det vandblandbare organiske opløsningsmiddel er valgt blandt Ci-C4-alkoholer, C3-C4-ketoner eller C2-C4-nitriler.
7. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 6, ved hvilken trinnet til at desorbere teicoplanin fra den hydrofobe adsorptionsharpiks udføres under anvendelse af et vandigt medium med en pH-værdi under 4.
8. Fremgangsmåde ifølge krav 7, ved hvilken det vandige mediums pH-værdi indstilles ved tilsætning af en vandig opløsning af en mineralsyre, en organisk syre eller en sur puffer.
9. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 8, ved hvilket mediet i den opløsning, der undergår behandling med aktivt kul, stammer fra trin b) og omfatter mindst 40 rumfangs% af et organisk opløsningsmiddel valgt blandt Ci-C4-alkoholer, C3-C4-ketoner eller C2-C4-nitriler.
10. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 9, ved hvilken den i trin b) opnåede opløsning omfatter 60 til 80 rumfangs% methanol eller ved tilsætning af frisk opløsningsmiddel korrigeres til at have en methanolkoncentration på 60 til 80 rumfangs%.
11. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 10, ved hvilken ultrafiltreringen i trin d) udføres på en i trin c) opnået opløsning, som omfatter mere end 20 rumfangs% og op til 90 rumfangs% af en CrC4-alkohol, eller på en i trin c) opnået opløsning, som ved tilsætning af frisk opløsningsmiddel er blevet korrigeret til at omfatte mere end 20 rumfangs% og op til 90 rumfangs% af en Ci-C4-alkohol.
12. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 11, ved hvilken ultrafilteringen i trin d) udføres under anvendelse af en membran med en udelukkelsesgrænse på 3-100 kDa, fortrinsvis på 5-100 kDa og mere foretrukket 5-10 kDa, og/eller ved hvilken ultrafiltreringen i trin e) udføres under anvendelse af membraner med en udelukkelsesgrænse på 1000 Da.
13. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 12, ved hvilken opnåelsen af renset teicoplanin i trin f) gennemføres ved isolering af teicoplanin under involvering af fjernelse af opløsningsmidlet ved fordampning, vakuumfordampning, lyofilisering, spray-tørring eller udfældning ved tilsætning af et antiopløsningsmiddel.
14. Fremgangsmåde til fremstilling af en farmaceutisk sammensætning omfattende fremgangsmåden ifølge et hvilket som helst af kravene 1 til 13, og ved hvilken renset teicoplanin blandes med mindst ét farmaceutisk excipiens eller bærestof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11188759.2A EP2592089A1 (en) | 2011-11-11 | 2011-11-11 | Process of purification of teicoplanin |
| PCT/EP2012/072279 WO2013068538A1 (en) | 2011-11-11 | 2012-11-09 | Process of purification of teicoplanin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2776452T3 true DK2776452T3 (da) | 2016-01-18 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12784004.9T DK2776452T3 (da) | 2011-11-11 | 2012-11-09 | Fremgangsmåde til rensning af teicoplanin |
Country Status (10)
| Country | Link |
|---|---|
| EP (2) | EP2592089A1 (da) |
| KR (1) | KR20140091739A (da) |
| CN (1) | CN104066747A (da) |
| DK (1) | DK2776452T3 (da) |
| ES (1) | ES2558581T3 (da) |
| HU (1) | HUE026335T2 (da) |
| IN (1) | IN2014KN01209A (da) |
| PL (1) | PL2776452T3 (da) |
| SI (1) | SI2776452T1 (da) |
| WO (1) | WO2013068538A1 (da) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104231044B (zh) * | 2014-08-13 | 2017-03-22 | 甘肃汇能生物工程有限公司 | 那西肽过柱纯化工艺 |
| CN104371011A (zh) * | 2014-10-21 | 2015-02-25 | 福建省微生物研究所 | 高纯度替考拉宁精粉的纯化方法 |
| CN104910259A (zh) * | 2015-06-02 | 2015-09-16 | 苏州纳微科技有限公司 | 一种替考拉宁的层析纯化方法 |
| CN106589075B (zh) * | 2017-01-23 | 2020-05-05 | 福建省微生物研究所 | 一种替考拉宁的提纯方法 |
| CN109608523B (zh) * | 2018-11-23 | 2023-01-10 | 江苏九阳生物制药有限公司 | 一种高纯度替考拉宁的生产工艺 |
| CN113637050B (zh) * | 2021-09-15 | 2023-03-31 | 丽珠集团福州福兴医药有限公司 | 一种替考拉宁的脱色方法 |
| CN115260294B (zh) * | 2022-08-23 | 2025-09-02 | 北大方正集团有限公司 | 一种替考拉宁的分离纯化方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1496386A (en) | 1975-03-05 | 1977-12-30 | Lepetit Spa | Antibiotics |
| GB8608798D0 (en) | 1986-04-11 | 1986-05-14 | Lepetit Spa | Recovery of glycopeptide antibiotics from aqueous solutions |
| US4845194A (en) | 1987-02-27 | 1989-07-04 | Eli Lilly And Company | Glycopeptide recovery process |
| ATE127477T1 (de) | 1990-10-01 | 1995-09-15 | Lepetit Spa | Verfahren zur gewinnung von teicoplanin. |
| KR100321304B1 (ko) | 1999-04-16 | 2002-03-18 | 박호군 | 테이코플라닌의 정제방법 |
| KR100367890B1 (ko) | 2000-03-02 | 2003-01-14 | 은언기 | 랩핑/폴리싱 휠 및 그 제조방법 |
| KR20030017067A (ko) | 2001-08-23 | 2003-03-03 | 정용진 | 변이주 액티노플라네스 테이코마이세티커스 지안네시스 및이로부터 테이코플라닌을 생산하는 방법 |
| KR100459289B1 (ko) | 2002-05-30 | 2004-12-03 | 이연제약주식회사 | 발효액으로부터 테이코플라닌ａ₂의 회수방법 |
| KR100476818B1 (ko) | 2002-07-19 | 2005-03-17 | 종근당바이오 주식회사 | 테이코플라닌 에이 투 정제 방법 |
| KR100474653B1 (ko) | 2004-04-16 | 2005-03-14 | 동국제약 주식회사 | 타이코플라닌의 고순도 생산방법 |
| CN101423547B (zh) * | 2007-10-31 | 2012-10-17 | 浙江医药股份有限公司新昌制药厂 | 替考拉宁的提纯方法 |
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2011
- 2011-11-11 EP EP11188759.2A patent/EP2592089A1/en not_active Ceased
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2012
- 2012-11-09 CN CN201280066349.4A patent/CN104066747A/zh active Pending
- 2012-11-09 WO PCT/EP2012/072279 patent/WO2013068538A1/en not_active Ceased
- 2012-11-09 PL PL12784004T patent/PL2776452T3/pl unknown
- 2012-11-09 IN IN1209KON2014 patent/IN2014KN01209A/en unknown
- 2012-11-09 DK DK12784004.9T patent/DK2776452T3/da active
- 2012-11-09 HU HUE12784004A patent/HUE026335T2/en unknown
- 2012-11-09 SI SI201230427T patent/SI2776452T1/sl unknown
- 2012-11-09 ES ES12784004.9T patent/ES2558581T3/es active Active
- 2012-11-09 KR KR1020147015313A patent/KR20140091739A/ko not_active Ceased
- 2012-11-09 EP EP12784004.9A patent/EP2776452B1/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| PL2776452T3 (pl) | 2016-03-31 |
| ES2558581T3 (es) | 2016-02-05 |
| CN104066747A (zh) | 2014-09-24 |
| KR20140091739A (ko) | 2014-07-22 |
| EP2776452B1 (en) | 2015-10-07 |
| HUE026335T2 (en) | 2016-05-30 |
| IN2014KN01209A (da) | 2015-10-16 |
| WO2013068538A1 (en) | 2013-05-16 |
| SI2776452T1 (sl) | 2016-04-29 |
| EP2776452A1 (en) | 2014-09-17 |
| EP2592089A1 (en) | 2013-05-15 |
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