JPH10511000A - 発酵ブイヨンから水不溶性化合物を回収する方法 - Google Patents
発酵ブイヨンから水不溶性化合物を回収する方法Info
- Publication number
- JPH10511000A JPH10511000A JP9502007A JP50200797A JPH10511000A JP H10511000 A JPH10511000 A JP H10511000A JP 9502007 A JP9502007 A JP 9502007A JP 50200797 A JP50200797 A JP 50200797A JP H10511000 A JPH10511000 A JP H10511000A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- solvent
- membrane
- broth
- filtration
- 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
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- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 4
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- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 3
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- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 claims description 2
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
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- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 2
- 229960002965 pravastatin Drugs 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 2
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 2
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- UCOQITKXMNKTKF-MXGZYYNMSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28,30-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23 Chemical compound C\C=C\C[C@@H](C)[C@@H](O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C)NC1=O UCOQITKXMNKTKF-MXGZYYNMSA-N 0.000 claims 1
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- 239000000155 melt Substances 0.000 description 1
- 238000000409 membrane extraction Methods 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 238000011027 product recovery Methods 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000000956 solid--liquid extraction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000010977 unit operation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/14—Ultrafiltration; Microfiltration
- B01D61/149—Multistep processes comprising different kinds of membrane processes selected from ultrafiltration or microfiltration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Water Supply & Treatment (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 原料発酵ブイヨンから水不溶性化合物を回収する方法であって、 a.溶媒適合性の多孔性濾過膜を横切る接線濾過により該発酵ブイヨンを濃縮し て、該膜を横切る透過物と該濃縮ブイヨンからなる滞留物とを生成させ、しかし て該水不溶性化合物は該滞留物中に保留され、しかも該滞留物を循環路に沿って 連続的に循環させて滞留物流を形成させかつ該原料ブイヨンのすべてが濃縮され るまで該原料ブイヨンを該滞留物流中に供給し、 b.該濃縮ブイヨンに溶媒を添加することにより該滞留物の該水不溶性化合物を 可溶化して、該化合物の溶液を生成させ、そして c.該溶液を工程(a)の該濾過膜を通じて濾過またはダイアフィルトレーショ ンして、該濾過膜を横切る溶媒透過物を生成させ、しかして該溶媒透過物は該可 溶化化合物を含む 工程からなる上記方法。 2. 該化合物が、免疫抑制剤、マクロライド系抗生物質、抗高コレステロー ル血症剤、シクロスポリン並びにそれらの誘 導体および中間体から成る群から選択される、請求の範囲第1項の方法。 3. 該化合物が、シクロスポリンA、シクロスポリンB、シクロスポリンG 、ラパマイシン、アスコマイシンおよびタクロリムスから選択された免疫抑制剤 である、請求の範囲第2項の方法。 4. 該免疫抑制剤がシクロスポリンAである、請求の範囲第3項の方法。 5. 該化合物が、ロバスタチン、プラバスタチン、シンバスタチンおよびフ ルバスタチンから選択された抗高コレステロール血症剤である、請求の範囲第2 項の方法。 6. 該化合物が、エリスロマイシンA、B、CおよびDから選択されたマク ロライド系抗生物質である、請求の範囲第2項の方法。 7. 該濾過膜が約0.001μmないし約5.0μmの孔サイズを有する、 請求の範囲第1項の方法。 8. 該濾過膜が約0.001μmないし約0.05μmの孔サイズを有する 、請求の範囲第1項の方法。 9. 該濾過膜が、セルロース、ポリスチレン、ポリスルホ ンおよびポリアミドから成る群から選択される、請求の範囲第1項の方法。 10. 該濾過膜がセラミックアルミナである、請求の範囲第1項の方法。 11. 該濾過膜が約0.05μmないし約5.0μmの孔サイズを有する、 請求の範囲第10項の方法。 12. 工程bの該溶媒が、低級アルコール、低級エステル、低級エーテルお よび低級ケトンから成る群から選択される、請求の範囲第1項の方法。 13. 該溶媒が、メタノール、エタノール、プロパノールおよびブタノール から選択されたアルコールである、請求の範囲第12項の方法。 14. 工程(b)において該化合物を可溶化するに先立って、該濃縮ブイヨ ンを工程(a)の該濾過膜を介してダイアフィルトレーションする工程を更に含 む、請求の範囲第1項の方法。 15. 該溶媒透過物を逆浸透または限外濾過膜にて濃縮する工程を更に含む 、請求の範囲第1項の方法。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/472,615 | 1995-06-07 | ||
US472,615 | 1995-06-07 | ||
US08/472,615 US5616595A (en) | 1995-06-07 | 1995-06-07 | Process for recovering water insoluble compounds from a fermentation broth |
PCT/US1996/009787 WO1996040758A1 (en) | 1995-06-07 | 1996-06-07 | Process for recovering water-insoluble compounds from a fermentation broth |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH10511000A true JPH10511000A (ja) | 1998-10-27 |
JP3146010B2 JP3146010B2 (ja) | 2001-03-12 |
Family
ID=23876243
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP50200797A Expired - Lifetime JP3146010B2 (ja) | 1995-06-07 | 1996-06-07 | 発酵ブイヨンから水不溶性化合物を回収する方法 |
Country Status (11)
Country | Link |
---|---|
US (1) | US5616595A (ja) |
EP (1) | EP0832108B1 (ja) |
JP (1) | JP3146010B2 (ja) |
AT (1) | ATE192162T1 (ja) |
CA (1) | CA2222810C (ja) |
DE (1) | DE69607961T2 (ja) |
DK (1) | DK0832108T3 (ja) |
ES (1) | ES2146007T3 (ja) |
GR (1) | GR3033795T3 (ja) |
PT (1) | PT832108E (ja) |
WO (1) | WO1996040758A1 (ja) |
Cited By (1)
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JP4818561B2 (ja) * | 2000-05-08 | 2011-11-16 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | クロスフロー精密濾過による封入体の精製 |
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GB9618952D0 (en) * | 1996-09-11 | 1996-10-23 | Sandoz Ltd | Process |
BE1009856A5 (fr) * | 1995-07-14 | 1997-10-07 | Sandoz Sa | Composition pharmaceutique sous la forme d'une dispersion solide comprenant un macrolide et un vehicule. |
US20030220234A1 (en) * | 1998-11-02 | 2003-11-27 | Selvaraj Naicker | Deuterated cyclosporine analogs and their use as immunodulating agents |
DE69832984T2 (de) | 1997-10-08 | 2006-09-21 | Isotechnika, Inc., Edmonton | DEUTERIERtE und undeuterierte CYCLOSPORIN-ANALOGA UND IHRE VERWENDUNG ALS IMMUNMODULIERENDE AGENtIEN |
AU3709199A (en) * | 1998-04-14 | 1999-11-01 | Dsm N.V. | Membrane filtration |
JP2002534370A (ja) | 1998-12-30 | 2002-10-15 | デクセル リミテッド | サイクロスポリンを送達するための分散可能な濃縮物 |
HU228268B1 (en) * | 1999-05-25 | 2013-02-28 | Astellas Pharma Inc | Method for separating analogous organic compounds |
RU2002114072A (ru) | 1999-11-30 | 2004-07-20 | Биогал Джиоджисзерджиар РТ (HU) | Способ выделения соединений статина из ферментационного бульона |
CA2394200C (en) * | 1999-12-14 | 2006-10-03 | Biogal Gyogyszergyar Rt. | Novel forms of pravastatin sodium |
US7732404B2 (en) * | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
AU3654301A (en) | 2000-02-24 | 2001-09-03 | Biogal Gyogyszergyar | Method of purifying a fermentation broth |
US20050215636A1 (en) * | 2000-10-05 | 2005-09-29 | Vilmos Keri | Pravastatin sodium substantially free of pravastatin lactone and EPI-pravastatin, and compositions containing same |
FR2821347A1 (fr) * | 2001-02-23 | 2002-08-30 | Vanlaer Fluides Et Automation | Systeme de traitement de solution aqueuse par membrane et fermentation |
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US7452692B2 (en) * | 2002-02-13 | 2008-11-18 | Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Method for extracting a macrolide from biomatter |
AU2003213024A1 (en) * | 2002-02-13 | 2003-09-04 | Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag | Method for extracting a macrolide from biomatter |
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WO2005019226A1 (en) * | 2003-08-26 | 2005-03-03 | Biocon Limited | A process for the recovery of substantially pure tricyclic macrolide |
PT1641447E (pt) * | 2003-11-24 | 2008-12-10 | Teva Gyogyszergyar Zartkoeruee | Método de purificação da pravastatina |
SI1697383T1 (sl) * | 2003-12-05 | 2014-09-30 | Biocon Limited | Postopek za čiščenje takrolimusa |
KR101335936B1 (ko) * | 2004-09-30 | 2013-12-03 | 바이엘 헬스케어, 엘엘씨 | 생물학적 분자의 통합된 연속 제조를 위한 장치 및 방법 |
JP2007523200A (ja) * | 2004-12-22 | 2007-08-16 | テバ ジョジセルジャール ザ−トケルエン ムケド レ−スベニュタ−ルシャシャ−グ | マクロライドを精製する方法 |
EP1833835A1 (en) * | 2005-01-05 | 2007-09-19 | Teva Gyogyszergyar Zartkoruen Müködö R Szv Nytarsa | Amorphous tacrolimus and preparation thereof |
WO2006086680A1 (en) * | 2005-02-09 | 2006-08-17 | Teva Gyógyszergyár Zártköruen Muködo Részvénytársaság | Methods of making pravastatin sodium |
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KR101101663B1 (ko) | 2009-01-13 | 2011-12-30 | (주) 제노텍 | 반코마이신 습체의 정제방법 |
WO2014072984A1 (en) | 2012-11-06 | 2014-05-15 | Natco Pharma Limited | Improved process for isolation and purification of rapamycin from fermentation broth |
US10183108B2 (en) | 2016-02-04 | 2019-01-22 | Pall Corporation | Inline diafiltration with multi-channel pump |
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-
1995
- 1995-06-07 US US08/472,615 patent/US5616595A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 ES ES96923254T patent/ES2146007T3/es not_active Expired - Lifetime
- 1996-06-07 DK DK96923254T patent/DK0832108T3/da active
- 1996-06-07 AT AT96923254T patent/ATE192162T1/de active
- 1996-06-07 EP EP96923254A patent/EP0832108B1/en not_active Expired - Lifetime
- 1996-06-07 JP JP50200797A patent/JP3146010B2/ja not_active Expired - Lifetime
- 1996-06-07 DE DE69607961T patent/DE69607961T2/de not_active Expired - Lifetime
- 1996-06-07 WO PCT/US1996/009787 patent/WO1996040758A1/en active Search and Examination
- 1996-06-07 CA CA002222810A patent/CA2222810C/en not_active Expired - Lifetime
- 1996-06-07 PT PT96923254T patent/PT832108E/pt unknown
-
2000
- 2000-06-27 GR GR20000401494T patent/GR3033795T3/el unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4818561B2 (ja) * | 2000-05-08 | 2011-11-16 | バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト | クロスフロー精密濾過による封入体の精製 |
Also Published As
Publication number | Publication date |
---|---|
CA2222810A1 (en) | 1996-12-19 |
WO1996040758A1 (en) | 1996-12-19 |
PT832108E (pt) | 2000-08-31 |
JP3146010B2 (ja) | 2001-03-12 |
ES2146007T3 (es) | 2000-07-16 |
ATE192162T1 (de) | 2000-05-15 |
GR3033795T3 (en) | 2000-10-31 |
DK0832108T3 (da) | 2000-09-25 |
US5616595A (en) | 1997-04-01 |
DE69607961T2 (de) | 2000-12-07 |
EP0832108A1 (en) | 1998-04-01 |
CA2222810C (en) | 2002-02-12 |
EP0832108B1 (en) | 2000-04-26 |
DE69607961D1 (de) | 2000-05-31 |
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