CN100509785C - 通过反相制备色谱法分离和纯化芬太尼的工业方法 - Google Patents
通过反相制备色谱法分离和纯化芬太尼的工业方法 Download PDFInfo
- Publication number
- CN100509785C CN100509785C CNB2004800321721A CN200480032172A CN100509785C CN 100509785 C CN100509785 C CN 100509785C CN B2004800321721 A CNB2004800321721 A CN B2004800321721A CN 200480032172 A CN200480032172 A CN 200480032172A CN 100509785 C CN100509785 C CN 100509785C
- Authority
- CN
- China
- Prior art keywords
- acid
- fentanyl
- column
- solution
- aqueous
- 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.)
- Expired - Fee Related
Links
- 229960002428 fentanyl Drugs 0.000 title claims abstract description 71
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 238000000746 purification Methods 0.000 title claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 238000004237 preparative chromatography Methods 0.000 title abstract description 16
- 230000002441 reversible effect Effects 0.000 title abstract description 6
- 238000000926 separation method Methods 0.000 title description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 93
- 238000000034 method Methods 0.000 claims abstract description 61
- 238000011068 loading method Methods 0.000 claims abstract description 27
- 230000005526 G1 to G0 transition Effects 0.000 claims abstract description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- 239000012535 impurity Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- -1 aryl silane Chemical compound 0.000 claims description 17
- 239000003960 organic solvent Substances 0.000 claims description 15
- 150000007513 acids Chemical class 0.000 claims description 9
- 229930013930 alkaloid Natural products 0.000 claims description 9
- 239000003446 ligand Substances 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000012856 packing Methods 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 150000005215 alkyl ethers Chemical class 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
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- 239000000377 silicon dioxide Substances 0.000 claims description 3
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- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
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- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
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- 150000008378 aryl ethers Chemical class 0.000 claims description 2
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 claims description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000012264 purified product Substances 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 2
- 235000011054 acetic acid Nutrition 0.000 claims 2
- 235000019253 formic acid Nutrition 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- 229910000077 silane Inorganic materials 0.000 claims 2
- 239000011975 tartaric acid Substances 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- 125000003158 alcohol group Chemical group 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- QTLFDCJYRAHUCF-UHFFFAOYSA-N methoxy-[2-(oxiran-2-ylmethoxy)ethyl]silane Chemical compound CO[SiH2]CCOCC1CO1 QTLFDCJYRAHUCF-UHFFFAOYSA-N 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- 238000004262 preparative liquid chromatography Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 abstract 2
- 239000013110 organic ligand Substances 0.000 abstract 1
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 59
- 230000008569 process Effects 0.000 description 14
- 238000010828 elution Methods 0.000 description 12
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- 239000003814 drug Substances 0.000 description 9
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- 239000002245 particle Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 239000012527 feed solution Substances 0.000 description 4
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- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- MCMNRKCIXSYSNV-UHFFFAOYSA-N Zirconium dioxide Chemical compound O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
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- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
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- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
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- 241000208140 Acer Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- ADQRLSOASLQCON-UHFFFAOYSA-N CC[SiH](OC)OCC1CO1 Chemical compound CC[SiH](OC)OCC1CO1 ADQRLSOASLQCON-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 239000002535 acidifier Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
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- 235000019693 cherries Nutrition 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
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- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 229960004379 fentanyl hydrochloride Drugs 0.000 description 1
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- 239000012458 free base Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
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- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
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- 238000006317 isomerization reaction Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- DUGOZIWVEXMGBE-STQMWFEESA-N methyl (S)-phenyl[(S)-piperidin-2-yl]acetate Chemical compound C([C@H]1[C@@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 DUGOZIWVEXMGBE-STQMWFEESA-N 0.000 description 1
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- 229960005181 morphine Drugs 0.000 description 1
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- LHCBOXPPRUIAQT-UHFFFAOYSA-N n-phenyl-n-[1-(2-phenylethyl)piperidin-4-yl]propanamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 LHCBOXPPRUIAQT-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/32—Bonded phase chromatography
- B01D15/325—Reversed phase
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
- B01J20/287—Non-polar phases; Reversed phases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Neurology (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Hydrogenated Pyridines (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US51527403P | 2003-10-29 | 2003-10-29 | |
| US60/515,274 | 2003-10-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1874999A CN1874999A (zh) | 2006-12-06 |
| CN100509785C true CN100509785C (zh) | 2009-07-08 |
Family
ID=34572823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004800321721A Expired - Fee Related CN100509785C (zh) | 2003-10-29 | 2004-10-22 | 通过反相制备色谱法分离和纯化芬太尼的工业方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7728145B2 (deFl) |
| EP (1) | EP1682505B1 (deFl) |
| JP (1) | JP2007509945A (deFl) |
| CN (1) | CN100509785C (deFl) |
| AT (1) | ATE418544T1 (deFl) |
| AU (1) | AU2004287815B2 (deFl) |
| CA (1) | CA2544195A1 (deFl) |
| DE (1) | DE602004018674D1 (deFl) |
| ES (1) | ES2320136T3 (deFl) |
| MX (1) | MX264489B (deFl) |
| WO (1) | WO2005044798A1 (deFl) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104994924A (zh) * | 2013-01-29 | 2015-10-21 | 诺伊兰健康科学私人有限公司 | 使用在反相柱上的替代固定相纯化有机化合物 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7486949B2 (en) * | 2004-03-10 | 2009-02-03 | Broadcom Corporation | Method for re-establishing telephone calls after unintended termination |
| WO2006055321A2 (en) * | 2004-11-10 | 2006-05-26 | Boehringer Ingelheim Chemicals, Inc. | Process of making fentanyl intermediates |
| WO2010033540A1 (en) * | 2008-09-19 | 2010-03-25 | Mallinckrodt Inc. | Crystalline forms of fentanyl alkaloid |
| EP3046643A4 (en) * | 2013-09-20 | 2017-05-03 | Davuluri, Ramamohan Rao | Purification of organic compounds by surfactant mediated preparative hplc |
| US20220395767A1 (en) * | 2021-06-15 | 2022-12-15 | Perkinelmer Health Sciences, Inc. | Enhancing lcms analyte signals |
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|---|---|---|---|---|
| NL284196A (deFl) * | 1961-10-10 | |||
| US4234684A (en) * | 1979-12-11 | 1980-11-18 | Eli Lilly And Company | Method of preparing mycophenolic acid glucoside |
| US4293489A (en) * | 1979-12-13 | 1981-10-06 | Eli Lilly And Company | Derivatives of A-30912A nucleus |
| US4317903A (en) * | 1981-01-26 | 1982-03-02 | The Upjohn Company | Process for the purification of lincomycin |
| US4336333A (en) * | 1981-03-13 | 1982-06-22 | Eli Lilly And Company | Process for preparing tunicamycin |
| US4916142A (en) * | 1987-02-02 | 1990-04-10 | Boc, Inc. | N-heterocyclic-N-(4-piperidinyl)amides and pharmaceutical compositions and their use as analgesics |
| US4904590A (en) * | 1988-12-27 | 1990-02-27 | Eli Lilly And Company | Antibiotic A80915 and process for its production |
| US5780589A (en) * | 1994-11-30 | 1998-07-14 | The United States Of America As Represented By The Department Of Health And Human Services | Ultraselective opioidmimetic peptides and pharmacological and therapeutic uses thereof |
| AU744950B2 (en) * | 1998-02-03 | 2002-03-07 | Arqule, Inc. | Rapid method for separation of small molecules using reverse phase high performance liquid chromatography |
| WO2001040184A2 (en) * | 1999-12-06 | 2001-06-07 | Mallinckrodt Inc. | Methods for the syntheses of alfentanil, sufentanil and remifentanil |
| US7671203B2 (en) * | 2002-02-28 | 2010-03-02 | Mallinckrodt Inc. | Method and system for separation and purification of at least one narcotic alkaloid using reverse phase preparative chromatography |
| ITRM20020458A1 (it) | 2002-09-13 | 2004-03-14 | Ambiotec S A S Di Ammendola Sergio | Procedimento per la separazione preparativa degli epimeri di steroidi. |
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- 2004-10-22 CA CA002544195A patent/CA2544195A1/en not_active Abandoned
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- 2004-10-22 JP JP2006538157A patent/JP2007509945A/ja not_active Withdrawn
- 2004-10-22 CN CNB2004800321721A patent/CN100509785C/zh not_active Expired - Fee Related
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104994924A (zh) * | 2013-01-29 | 2015-10-21 | 诺伊兰健康科学私人有限公司 | 使用在反相柱上的替代固定相纯化有机化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1874999A (zh) | 2006-12-06 |
| WO2005044798A1 (en) | 2005-05-19 |
| MXPA06004711A (es) | 2006-07-20 |
| US7728145B2 (en) | 2010-06-01 |
| CA2544195A1 (en) | 2005-05-19 |
| ES2320136T3 (es) | 2009-05-19 |
| MX264489B (en) | 2009-02-12 |
| EP1682505B1 (en) | 2008-12-24 |
| AU2004287815A1 (en) | 2005-05-19 |
| JP2007509945A (ja) | 2007-04-19 |
| EP1682505A1 (en) | 2006-07-26 |
| DE602004018674D1 (de) | 2009-02-05 |
| US20070123710A1 (en) | 2007-05-31 |
| AU2004287815B2 (en) | 2009-05-28 |
| ATE418544T1 (de) | 2009-01-15 |
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