JP5259624B2 - 炭酸水中に有機化合物を溶解させること、および凍結乾燥させることを含む精製方法 - Google Patents
炭酸水中に有機化合物を溶解させること、および凍結乾燥させることを含む精製方法 Download PDFInfo
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- JP5259624B2 JP5259624B2 JP2009545989A JP2009545989A JP5259624B2 JP 5259624 B2 JP5259624 B2 JP 5259624B2 JP 2009545989 A JP2009545989 A JP 2009545989A JP 2009545989 A JP2009545989 A JP 2009545989A JP 5259624 B2 JP5259624 B2 JP 5259624B2
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- rocuronium bromide
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims description 69
- 238000000034 method Methods 0.000 title claims description 62
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- 238000000746 purification Methods 0.000 title description 13
- 239000002904 solvent Substances 0.000 claims description 42
- OYTJKRAYGYRUJK-FMCCZJBLSA-M rocuronium bromide Chemical compound [Br-].N1([C@@H]2[C@@H](O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(CC=C)CCCC2)CCOCC1 OYTJKRAYGYRUJK-FMCCZJBLSA-M 0.000 claims description 33
- 229960003682 rocuronium bromide Drugs 0.000 claims description 31
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
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- 239000000842 neuromuscular blocking agent Substances 0.000 description 9
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- 238000001953 recrystallisation Methods 0.000 description 9
- 239000001569 carbon dioxide Substances 0.000 description 8
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- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
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- YXSLJKQTIDHPOT-UHFFFAOYSA-N Atracurium Dibesylate Chemical compound C1=C(OC)C(OC)=CC=C1CC1[N+](CCC(=O)OCCCCCOC(=O)CC[N+]2(C)C(C3=CC(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=CC=2)(C)CCC2=CC(OC)=C(OC)C=C21 YXSLJKQTIDHPOT-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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- YXRDKMPIGHSVRX-OOJCLDBCSA-N rocuronium Chemical compound N1([C@@H]2[C@@H](O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(CC=C)CCCC2)CCOCC1 YXRDKMPIGHSVRX-OOJCLDBCSA-N 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
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- GVEAYVLWDAFXET-XGHATYIMSA-N pancuronium Chemical compound C[N+]1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 GVEAYVLWDAFXET-XGHATYIMSA-N 0.000 description 2
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- 229960001844 tubocurarine Drugs 0.000 description 2
- 229960003819 vecuronium Drugs 0.000 description 2
- BGSZAXLLHYERSY-XQIGCQGXSA-N vecuronium Chemical compound N1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 BGSZAXLLHYERSY-XQIGCQGXSA-N 0.000 description 2
- GXFZCDMWGMFGFL-KKXMJGKMSA-N (+)-Tubocurarine chloride hydrochloride Chemical compound [Cl-].[Cl-].C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CC[NH+]3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 GXFZCDMWGMFGFL-KKXMJGKMSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- WMSYWJSZGVOIJW-ONUALHDOSA-L Mivacurium chloride Chemical compound [Cl-].[Cl-].C([C@@H]1C2=CC(OC)=C(OC)C=C2CC[N+]1(C)CCCOC(=O)CC/C=C/CCC(=O)OCCC[N+]1(CCC=2C=C(C(=CC=2[C@H]1CC=1C=C(OC)C(OC)=C(OC)C=1)OC)OC)C)C1=CC(OC)=C(OC)C(OC)=C1 WMSYWJSZGVOIJW-ONUALHDOSA-L 0.000 description 1
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
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- 229960002945 atracurium besylate Drugs 0.000 description 1
- XXZSQOVSEBAPGS-UHFFFAOYSA-L atracurium besylate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1.[O-]S(=O)(=O)C1=CC=CC=C1.C1=C(OC)C(OC)=CC=C1CC1[N+](CCC(=O)OCCCCCOC(=O)CC[N+]2(C)C(C3=CC(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=CC=2)(C)CCC2=CC(OC)=C(OC)C=C21 XXZSQOVSEBAPGS-UHFFFAOYSA-L 0.000 description 1
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- 230000020335 dealkylation Effects 0.000 description 1
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- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
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- 238000002635 electroconvulsive therapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
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- 150000003948 formamides Chemical class 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 229960002540 mivacurium Drugs 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- NPIJXCQZLFKBMV-YTGGZNJNSA-L pancuronium bromide Chemical compound [Br-].[Br-].C[N+]1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 NPIJXCQZLFKBMV-YTGGZNJNSA-L 0.000 description 1
- 229960003379 pancuronium bromide Drugs 0.000 description 1
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229960004804 rapacuronium Drugs 0.000 description 1
- LVQTUXZKLGXYIU-GWSNJHLMSA-M rapacuronium Chemical compound [Br-].N1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)CC)[N+]2(CC=C)CCCCC2)CCCCC1 LVQTUXZKLGXYIU-GWSNJHLMSA-M 0.000 description 1
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- 229960002655 tubocurarine chloride Drugs 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229960004298 vecuronium bromide Drugs 0.000 description 1
- VEPSYABRBFXYIB-PWXDFCLTSA-M vecuronium bromide Chemical compound [Br-].N1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 VEPSYABRBFXYIB-PWXDFCLTSA-M 0.000 description 1
- 210000001260 vocal cord Anatomy 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
- C07B63/04—Use of additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
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- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
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Description
(I) 前記化合物を6より低いpHを有する炭酸水に溶解させて溶液を生じること;および
(II) 前記溶液を凍結乾燥することを含む。
(I) 前記化合物を6より低いpHを有する炭酸水に溶解させて溶液を生じること;
(II) 溶解の間および/または溶解後に前記水をさらに炭酸塩化して、8より低いpHを維持するか、または回復させること;および
(III) 前記溶液を凍結乾燥することを含む。
(I) 前記化合物を6より低いpHを有する炭酸水に溶解させて溶液を生じること;任意に
(II) 溶解の間および/または溶解後に前記水をさらに炭酸塩化して、8より低いpHを維持するか、または回復させること;
(III) 前記炭酸水中に溶解している未精製の物質中に存在する残存溶媒を減らす中間の溶媒除去工程を行うこと、例えば真空蒸留工程;および
(IV) 前記溶液を凍結乾燥することを含む。
臭化ロクロニウムは、1.7kgのロクロニウムと、1.21Lの臭化アリルを17LのDCM中で反応させて、通常の化学を用いて合成した。
精製水(12L)を5℃に冷却し、二酸化炭素をpHが4.5より低くなるまで泡立てた。実施例1の湿った生成物を加え、二酸化炭素ガスをpHが8より低くなるまで再度、泡立てた。
MTBEとDCMのレベルは、工程の各ステージ後に測定し、その結果を以下に示す。
Claims (8)
- 未精製の臭化ロクロニウムの精製方法であって、臭化ロクロニウムを炭酸水に溶解させて溶液を生じること、および、前記溶液を凍結乾燥することを含む方法。
- 請求項1に記載の方法であって、前記炭酸水が、溶解前に、6より低いpHを有する方法。
- 請求項1または2に記載の、未精製の臭化ロクロニウムの精製方法であって、
(I) 臭化ロクロニウムを6より低いpHを有する炭酸水に溶解させて溶液を生じること;および
(II) 前記溶液を凍結乾燥することを含む方法。 - 請求項3に記載の方法であって、
(I) 臭化ロクロニウムを6より低いpHを有する炭酸水に溶解させて溶液を生じること;
(II) 溶解の間および/または溶解後、前記水をさらに炭酸塩化して、8より低いpHを維持するか、または回復させること;
(III) 前記溶液を凍結乾燥することを含む方法。 - 請求項3に記載の方法であって、
(I) 臭化ロクロニウムを6より低いpHを有する炭酸水に溶解させて溶液を生じること;任意に、
(II) 溶解の間および/または溶解後、前記水をさらに炭酸塩化して、8より低いpHを維持するか、または回復させること;
(III) 前記炭酸水中に溶解している未精製の物質中に存在する残存溶媒を減じる、中間の溶媒除去工程を行うこと;および
(IV) 前記溶液を凍結乾燥することを含む方法。 - 前記工程(III)における溶媒除去工程が、真空蒸留工程である請求項5に記載の方法。
- 臭化ロクロニウムが塩基性である請求項1〜6のいずれかに記載の方法。
- 少なくとも1種の残存溶媒を含む未精製の臭化ロクロニウムにおいて、残存溶媒を減じるかまたは、除去する方法であって、臭化ロクロニウムを炭酸水に溶解させて溶液を生じること、および、前記溶液を凍結乾燥することを含む方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GB0700878.2 | 2007-01-17 | ||
GB0700878A GB2445746A (en) | 2007-01-17 | 2007-01-17 | Use of carbonated water as a solvent for freeze drying, and method of purification comprising dissolution of material in carbonated water and freeze drying |
PCT/GB2008/000108 WO2008087383A1 (en) | 2007-01-17 | 2008-01-14 | Purification process comprising dissolving an organic compound in carbonated water and freeze-drying |
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JP2010516664A JP2010516664A (ja) | 2010-05-20 |
JP5259624B2 true JP5259624B2 (ja) | 2013-08-07 |
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JP2009545989A Expired - Fee Related JP5259624B2 (ja) | 2007-01-17 | 2008-01-14 | 炭酸水中に有機化合物を溶解させること、および凍結乾燥させることを含む精製方法 |
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US (1) | US8242265B2 (ja) |
EP (1) | EP2118096B1 (ja) |
JP (1) | JP5259624B2 (ja) |
ES (1) | ES2534036T3 (ja) |
GB (1) | GB2445746A (ja) |
WO (1) | WO2008087383A1 (ja) |
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CN101993470B (zh) * | 2009-08-27 | 2012-11-14 | 山东诺和诺泰生物制药有限公司 | 一种制备高纯度罗库溴铵的工艺 |
EP2703408B1 (en) * | 2011-04-25 | 2015-08-26 | Zhejiang Huahai Pharmaceutical Co., Ltd. | Method for purifying rocuronium bromide |
CN103435674B (zh) * | 2013-09-09 | 2015-05-06 | 山东新华制药股份有限公司 | 高纯度、高稳定性罗库溴铵的制备方法 |
JP2017507934A (ja) * | 2014-02-28 | 2017-03-23 | ヒカル リミテッド | ビルダグリプチンのための新規な実用的プロセス |
JP2016121073A (ja) * | 2014-12-24 | 2016-07-07 | ニプロ株式会社 | 注射剤用医薬組成物の製造方法 |
CN113372404B (zh) * | 2020-12-24 | 2023-04-04 | 上海药坦药物研究开发有限公司 | 一种泮库溴铵的纯化方法 |
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US3207780A (en) * | 1962-11-15 | 1965-09-21 | Upjohn Co | 1-deoxy-1-guanidino-3-o-carbamoyl-scyllo-inositol and acylates thereof |
JPS61119139A (ja) * | 1984-11-15 | 1986-06-06 | Morinaga & Co Ltd | 炭酸水による抽出物の製造法 |
GB8708886D0 (en) | 1987-04-14 | 1987-05-20 | Akzo Nv | 2beta-morpholino-androstane derivatives |
US5098908A (en) * | 1990-06-20 | 1992-03-24 | Merck & Co., Inc. | 17β-hydroxybenzoyl-4-aza-5α-androst-1-en-3-ones as testosterone reductase inhibitors |
US5795870A (en) * | 1991-12-13 | 1998-08-18 | Trustees Of Princeton University | Compositions and methods for cell transformation |
CZ300694A3 (en) | 1993-12-02 | 1996-05-15 | Akzo Nobel Nv | Substituted 2beta-morpholinandrostane derivatives, process of their preparation, their use for preparing pharmaceutical preparations and pharmaceutical compositions containing thereof |
US5605934A (en) * | 1995-03-23 | 1997-02-25 | Baxter International Inc. | Method of manufacturing and storing solutions |
IT1277700B1 (it) | 1995-12-22 | 1997-11-11 | Poli Ind Chimica Spa | Processo di preparazione di 2-beta, 16-beta-diamino 3-alfa, 17-beta- diacilossi 5-alfaandrostani, bloccanti neuromuscolari a struttura |
FR2832059B1 (fr) * | 2001-11-14 | 2004-05-21 | Oreal | Utilisation d'un extrait de myrsine africana en coloration d'oxydation pour la teinture des fibres keratiniques |
FR2841779B1 (fr) * | 2002-07-05 | 2006-01-27 | Oreal | Composition de teinture des fibres keratiniques contenant un precurseur d'aldehyde, une enzyme et une hydrazone et procede mettant en oeuvre cette composition |
DE112005000178T5 (de) | 2004-01-15 | 2007-01-25 | Chemagis Ltd. | Verfahren zur Herstellung von Rocuroniumbromid und Zwischenprodukte davon |
US7511051B2 (en) * | 2004-07-02 | 2009-03-31 | University Of Southern California | Cidofovir peptide conjugates as prodrugs |
US20060058276A1 (en) | 2004-07-15 | 2006-03-16 | Oded Friedman | Processes for the preparation and purification of rocuronium bromide |
US20060058275A1 (en) | 2004-07-15 | 2006-03-16 | Oded Friedman | Processes for preparing stabilized, highly pure rocuronium bromide |
US7361683B2 (en) * | 2004-11-24 | 2008-04-22 | Yung Shin Pharm. Ind., Co., Ltd | Paclitaxel aqueous injection solution and methods for preparing the same |
US20060009485A1 (en) * | 2005-06-23 | 2006-01-12 | Chemagis Ltd | Method of reprocessing quaternary ammonium-containing neuromuscular blocking agents |
JP2008522983A (ja) | 2005-09-13 | 2008-07-03 | シコール インコーポレイティド | ロクロニウムブロミドの合成方法 |
CN1864667B (zh) * | 2006-06-02 | 2010-10-06 | 重庆医药工业研究院有限责任公司 | 一种稳定的罗库溴铵冻干制剂及其制备方法 |
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- 2008-01-14 US US12/522,312 patent/US8242265B2/en not_active Expired - Fee Related
- 2008-01-14 WO PCT/GB2008/000108 patent/WO2008087383A1/en active Application Filing
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ES2534036T3 (es) | 2015-04-16 |
US20100105892A1 (en) | 2010-04-29 |
JP2010516664A (ja) | 2010-05-20 |
WO2008087383A1 (en) | 2008-07-24 |
GB2445746A (en) | 2008-07-23 |
EP2118096A1 (en) | 2009-11-18 |
GB0700878D0 (en) | 2007-02-21 |
EP2118096B1 (en) | 2015-03-04 |
US8242265B2 (en) | 2012-08-14 |
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