CA2265276C - Modified enantiomer content of crystalline alpha-lipoic acid (rs-thioctic acid) - Google Patents
Modified enantiomer content of crystalline alpha-lipoic acid (rs-thioctic acid) Download PDFInfo
- Publication number
- CA2265276C CA2265276C CA002265276A CA2265276A CA2265276C CA 2265276 C CA2265276 C CA 2265276C CA 002265276 A CA002265276 A CA 002265276A CA 2265276 A CA2265276 A CA 2265276A CA 2265276 C CA2265276 C CA 2265276C
- Authority
- CA
- Canada
- Prior art keywords
- thioctic acid
- acid
- enantiomers
- thioctic
- proportions
- 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
- 229960002663 thioctic acid Drugs 0.000 title claims abstract description 82
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 235000019136 lipoic acid Nutrition 0.000 title claims abstract description 57
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 claims abstract description 67
- 239000000843 powder Substances 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 20
- 238000002844 melting Methods 0.000 claims description 15
- 230000008018 melting Effects 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 7
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000008240 homogeneous mixture Substances 0.000 claims description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 4
- 230000003502 anti-nociceptive effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 239000002537 cosmetic Substances 0.000 claims description 3
- 230000001120 cytoprotective effect Effects 0.000 claims description 3
- 201000002342 diabetic polyneuropathy Diseases 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 235000016709 nutrition Nutrition 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000012986 modification Methods 0.000 abstract description 13
- 230000004048 modification Effects 0.000 abstract description 13
- 239000000243 solution Substances 0.000 description 11
- 239000013078 crystal Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- -1 pyruvic acid) Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- QVJPPFAOCXDDPW-UHFFFAOYSA-N 5-[chloro(difluoro)methyl]-1,2-oxazole Chemical compound FC(F)(Cl)C1=CC=NO1 QVJPPFAOCXDDPW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 102000012751 Pyruvate Dehydrogenase Complex Human genes 0.000 description 1
- 108010090051 Pyruvate Dehydrogenase Complex Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 238000005056 compaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000005895 oxidative decarboxylation reaction Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/02—Five-membered rings
- C07D339/04—Five-membered rings having the hetero atoms in positions 1 and 2, e.g. lipoic acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Seasonings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19810336.0 | 1998-03-11 | ||
| DE19810336A DE19810336A1 (de) | 1998-03-11 | 1998-03-11 | Alpha-Liponsäure mit neuartiger Modifikation |
| US09/074,645 US5994393A (en) | 1998-03-11 | 1998-05-08 | Alpha-lipoic acid with novel modification |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2265276A1 CA2265276A1 (en) | 1999-09-11 |
| CA2265276C true CA2265276C (en) | 2009-09-08 |
Family
ID=26044524
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002265276A Expired - Fee Related CA2265276C (en) | 1998-03-11 | 1999-03-11 | Modified enantiomer content of crystalline alpha-lipoic acid (rs-thioctic acid) |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5994393A (enExample) |
| EP (1) | EP0949258B1 (enExample) |
| AT (1) | ATE207914T1 (enExample) |
| CA (1) | CA2265276C (enExample) |
| CY (1) | CY1106435T1 (enExample) |
| DE (2) | DE19810336A1 (enExample) |
| DK (1) | DK0949258T3 (enExample) |
| ES (1) | ES2164474T3 (enExample) |
| IN (1) | IN186598B (enExample) |
| PT (1) | PT949258E (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19834608A1 (de) * | 1998-07-31 | 2000-02-03 | Basf Ag | Kristallmodifikation der Liponsäure |
| AU2001270554A1 (en) * | 2000-06-06 | 2001-12-17 | Basf Aktiengesellschaft | Use of an (r)-enantiomer of lipoic acid in cosmetics and dermatologicals |
| DE10151764A1 (de) * | 2001-10-19 | 2003-05-08 | Basf Ag | Kombination von Liponsäure und Glutamin in Lebens- und Arzneimitteln |
| WO2006058278A2 (en) * | 2004-11-24 | 2006-06-01 | Hill's Pet Nutrition, Inc. | Methods for improving liver clearance of xenobiotic substances in an animal |
| US20090176864A1 (en) * | 2004-11-24 | 2009-07-09 | Hill's Pet Nutrition, Inc. | Methods For Improving Hepatic and Immune Function In An Animal |
| BRPI0519610A2 (pt) | 2004-12-30 | 2009-02-25 | Hills Pet Nutrition Inc | mÉtodos para melhorar a qualidade de vida de um animal idoso ou muito idoso, de um canino de raÇa regular ou pequena, idoso ou muito idoso, de um cço de raÇa grande idoso ou muito idoso, e de um gato idoso ou muito idoso |
| US8252742B2 (en) | 2004-12-30 | 2012-08-28 | Hill's Pet Nutrition, Inc. | Methods for enhancing the quality of life of a senior animal |
| EP2389178A4 (en) * | 2008-12-01 | 2012-06-06 | Invasc Therapeutic Inc | COMPOSITIONS CONTAINING INHIBITORS OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND LIPOIC ACID COMPOUNDS, AND THEIR USE FOR THE TREATMENT OF RENIN-ANGIOTENSIN-ALDOSTERONE ASSOCIATED DISORDERS |
| CN108484570B (zh) * | 2018-05-15 | 2021-05-04 | 苏州富士莱医药股份有限公司 | 一种制备硫辛酸颗粒的方法及设备 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0427247T3 (da) * | 1989-11-09 | 1998-09-28 | Asta Medica Ag | Lægemiddel indeholdende R-alpha- lipoinsyre eller S-alphalipoinsyre som aktiv bestanddel |
| DE4218572A1 (de) * | 1992-06-05 | 1993-12-09 | Asta Medica Ag | Synergistische Kombination von Arzneimitteln enthaltend als Wirkstoff alpha-Liponsäure, Dihydroliponsäure, deren Metaboliten sowie die oxidierten und reduzierten Enantiomere der alpha-Liponsäure wie die R-alpha-Liponsäure oder S-alpha-Liponsäure sowie Metaboliten der alpha-Liponsäure mit den Vitaminen A, B1-6, B12, C und E |
| DE4235912C2 (de) * | 1992-10-23 | 2002-12-05 | Viatris Gmbh | Verfahren zur Herstellung kristalliner Thioctsäure und deren Verwendung |
| DE4433764A1 (de) * | 1994-09-22 | 1996-03-28 | Asta Medica Ag | Darreichungsformen enthaltend alpha-Liponsäure, feste Salze von R-Thioctsäure mit verbesserter Freisetzung und Bioverfügbarkeit |
-
1998
- 1998-03-11 DE DE19810336A patent/DE19810336A1/de not_active Withdrawn
- 1998-05-08 US US09/074,645 patent/US5994393A/en not_active Expired - Lifetime
-
1999
- 1999-03-02 ES ES99104155T patent/ES2164474T3/es not_active Expired - Lifetime
- 1999-03-02 AT AT99104155T patent/ATE207914T1/de active
- 1999-03-02 DE DE59900364T patent/DE59900364D1/de not_active Expired - Lifetime
- 1999-03-02 PT PT99104155T patent/PT949258E/pt unknown
- 1999-03-02 EP EP99104155A patent/EP0949258B1/de not_active Expired - Lifetime
- 1999-03-02 DK DK99104155T patent/DK0949258T3/da active
- 1999-03-11 CA CA002265276A patent/CA2265276C/en not_active Expired - Fee Related
- 1999-04-06 IN IN317CA1999 patent/IN186598B/en unknown
-
2002
- 2002-01-30 CY CY20021100024T patent/CY1106435T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE207914T1 (de) | 2001-11-15 |
| EP0949258A1 (de) | 1999-10-13 |
| EP0949258B1 (de) | 2001-10-31 |
| PT949258E (pt) | 2002-04-29 |
| US5994393A (en) | 1999-11-30 |
| CY1106435T1 (el) | 2011-04-06 |
| IN186598B (enExample) | 2001-10-06 |
| DE59900364D1 (de) | 2001-12-06 |
| DK0949258T3 (da) | 2002-01-28 |
| ES2164474T3 (es) | 2002-02-16 |
| CA2265276A1 (en) | 1999-09-11 |
| DE19810336A1 (de) | 1999-09-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130311 |